SU-F-T-414: Mathematical Formulation of Gantry Starting Angle for Right Medial Tangential Arc in Left Intact Partial Breast Irradiation Using Volumetric Modulated Arc Therapy (VMAT)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Giri, U; Sarkar, B; Kaur, H

Purpose: To choose appropriate gantry starting angle for partial left breast irradiation using volumetric modulated arc therapy (VMAT). Methods: A random patient of left breast carcinoma was selected for this study. The slice which was selected for this mathematical formulation was having maximum breast thickness and maximum medial and lateral tangential distance. After this appropriate isocenter was chosen on that CT slice. The distances between various points were measured by the measuring tool in Monaco 5.00.04. Using the various trigonometric equations, a final equation was derived which shows the relationship between Gantry start angle, isocenter Location and tissue thickness. Results:more » The final equation for gantry start for right medial tangential arc is given asStarting angle = 270°+tan^(−1)(sin(θ)/(x-1/x-2 +cosθ))The above equation was tested for 10 cases and it was found to be appropriate for all the cases. Conclusion: Gantry starting angle for partial arc irradiation depends upon Breast thickness, Distance between Medial and lateral tangent and isocenter location.« less

Decline of Cosmetic Outcomes Following Accelerated Partial Breast Irradiation Using Intensity Modulated Radiation Therapy: Results of a Single-Institution Prospective Clinical Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liss, Adam L.; Ben-David, Merav A.; Jagsi, Reshma

2014-05-01

Purpose: To report the final cosmetic results from a single-arm prospective clinical trial evaluating accelerated partial breast irradiation (APBI) using intensity modulated radiation therapy (IMRT) with active-breathing control (ABC). Methods and Materials: Women older than 40 with breast cancer stages 0-I who received breast-conserving surgery were enrolled in an institutional review board-approved prospective study evaluating APBI using IMRT administered with deep inspiration breath-hold. Patients received 38.5 Gy in 3.85-Gy fractions given twice daily over 5 consecutive days. The planning target volume was defined as the lumpectomy cavity with a 1.5-cm margin. Cosmesis was scored on a 4-category scale by themore » treating physician. Toxicity was scored according to National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 3.0). We report the cosmetic and toxicity results at a median follow-up of 5 years. Results: A total of 34 patients were enrolled. Two patients were excluded because of fair baseline cosmesis. The trial was terminated early because fair/poor cosmesis developed in 7 of 32 women at a median follow-up of 2.5 years. At a median follow-up of 5 years, further decline in the cosmetic outcome was observed in 5 women. Cosmesis at the time of last assessment was 43.3% excellent, 30% good, 20% fair, and 6.7% poor. Fibrosis according to CTCAE at last assessment was 3.3% grade 2 toxicity and 0% grade 3 toxicity. There was no correlation of CTCAE grade 2 or greater fibrosis with cosmesis. The 5-year rate of local control was 97% for all 34 patients initially enrolled. Conclusions: In this prospective trial with 5-year median follow-up, we observed an excellent rate of tumor control using IMRT-planned APBI. Cosmetic outcomes, however, continued to decline, with 26.7% of women having a fair to poor cosmetic result. These results underscore the need for continued cosmetic assessment for patients treated with APBI by technique.« less

Accelerated partial breast irradiation using intensity-modulated radiotherapy versus whole breast irradiation: 5-year survival analysis of a phase 3 randomised controlled trial.

PubMed

Livi, Lorenzo; Meattini, Icro; Marrazzo, Livia; Simontacchi, Gabriele; Pallotta, Stefania; Saieva, Calogero; Paiar, Fabiola; Scotti, Vieri; De Luca Cardillo, Carla; Bastiani, Paolo; Orzalesi, Lorenzo; Casella, Donato; Sanchez, Luis; Nori, Jacopo; Fambrini, Massimiliano; Bianchi, Simonetta

2015-03-01

Accelerated partial breast irradiation (APBI) has been introduced as an alternative treatment method for selected patients with early stage breast cancer (BC). Intensity-modulated radiotherapy (IMRT) has the theoretical advantage of a further increase in dose conformity compared with three-dimensional techniques, with more normal tissue sparing. The aim of this randomised trial is to compare the local recurrence and survival of APBI using the IMRT technique after breast-conserving surgery to conventional whole-breast irradiation (WBI) in early stage BC. This study was performed at the University of Florence (Florence, Italy). Women aged more than 40years affected by early BC, with a maximum pathological tumour size of 25mm, were randomly assigned in a 1:1 ratio to receive either WBI or APBI using IMRT. Patients in the APBI arm received a total dose of 30 Gy to the tumour bed in five daily fractions. The WBI arm received 50Gy in 25 fractions, followed by a boost on the tumour bed of 10Gy in five fractions. The primary end-point was occurrence of ipsilateral breast tumour recurrences (IBTRs); the main analysis was by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT02104895. A total of 520 patients were randomised (260 to external WBI and 260 to APBI with IMRT) between March 2005 and June 2013. At a median follow-up of 5.0 years (Interquartile Range (IQR) 3.4-7.0), the IBTR rate was 1.5% (three cases) in the APBI group (95% confidence interval (CI) 0.1-3.0) and in the WBI group (three cases; 95% CI 0.0-2.8). No significant difference emerged between the two groups (log rank test p=0.86). We identified seven deaths in the WBI group and only one in the APBI group (p=0.057). The 5-year overall survival was 96.6% for the WBI group and 99.4% for the APBI group. The APBI group presented significantly better results considering acute (p=0.0001), late (p=0.004), and cosmetic outcome (p=0.045). To our knowledge, this is the first randomised study using the IMRT technique for APBI delivery. No significant difference in terms of IBTR and overall survival was observed between the two arms. APBI displayed a significantly better toxicity profile. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reproducible deep-inspiration breath-hold irradiation with forward intensity-modulated radiotherapy for left-sided breast cancer significantly reduces cardiac radiation exposure compared to inverse intensity-modulated radiotherapy.

PubMed

Bolukbasi, Yasemin; Saglam, Yucel; Selek, Ugur; Topkan, Erkan; Kataria, Anglina; Unal, Zeynep; Alpan, Vildan

2014-01-01

To investigate the objective utility of our clinical routine of reproducible deep-inspiration breath-hold irradiation for left-sided breast cancer patients on reducing cardiac exposure. Free-breathing and reproducible deep-inspiration breath-hold scans were evaluated for our 10 consecutive left-sided breast cancer patients treated with reproducible deep-inspiration breath-hold. The study was based on the adjuvant dose of 50 Gy in 25 fractions of 2 Gy/fraction. Both inverse and forward intensity-modulated radiotherapy plans were generated for each computed tomography dataset. Reproducible deep-inspiration breath-hold plans with forward intensity-modulated radiotherapy significantly spared the heart and left anterior descending artery compared to generated free-breathing plans based on mean doses - free-breathing vs reproducible deep-inspiration breath-hold, left ventricle (296.1 vs 94.5 cGy, P = 0.005), right ventricle (158.3 vs 59.2 cGy, P = 0.005), left anterior descending artery (171.1 vs 78.1 cGy, P = 0.005), and whole heart (173.9 vs 66 cGy, P = 0.005), heart V20 (2.2% vs 0%, P = 0.007) and heart V10 (4.2% vs 0.3%, P = 0.007) - whereas they revealed no additional burden on the ipsilateral lung. Reproducible deep-inspiration breath-hold and free-breathing plans with inverse intensity-modulated radiotherapy provided similar organ at risk sparing by reducing the mean doses to the left ventricle, left anterior descending artery, heart, V10-V20 of the heart and right ventricle. However, forward intensity-modulated radiotherapy showed significant reduction in doses to the left ventricle, left anterior descending artery, heart, right ventricle, and contralateral breast (mean dose, 248.9 to 12.3 cGy, P = 0.005). The mean doses for free-breathing vs reproducible deep-inspiration breath-hold of the proximal left anterior descending artery were 1.78 vs 1.08 Gy and of the distal left anterior descending artery were 8.11 vs 3.89 Gy, whereas mean distances to the 50 Gy isodose line of the proximal left anterior descending artery were 6.6 vs 3.3 cm and of the distal left anterior descending artery were 7.4 vs 4.1 cm, with forward intensity-modulated radiotherapy. Overall reduction in mean doses to proximal and distal left anterior descending artery with deep-inspiration breath-hold irradiation was 39% (P = 0.02) and 52% (P = 0.002), respectively. We found a significant reduction of radiation exposure to the contralateral breast, left and right ventricles, as well as of proximal and especially distal left anterior descending artery with the deep-inspiration breath-hold technique with forward intensity-modulated radiotherapy planning.

Intensity modulated radiotherapy and 3D conformal radiotherapy for whole breast irradiation: a comparative dosimetric study and introduction of a novel qualitative index for plan evaluation, the normal tissue index

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yim, Jackie; Suttie, Clare; Bromley, Regina

We report on a retrospective dosimetric study, comparing 3D conformal radiotherapy (3DCRT) and hybrid intensity modulated radiotherapy (hIMRT). We evaluated plans based on their planning target volume coverage, dose homogeneity, dose to organs at risk (OARs) and exposure of normal tissue to radiation. The Homogeneity Index (HI) was used to assess the dose homogeneity in the target region, and we describe a new index, the normal tissue index (NTI), to assess the dose in the normal tissue inside the tangent treatment portal. Plans were generated for 25 early-stage breast cancer patients, using a hIMRT technique. These were compared with themore » 3DCRT plans of the treatment previously received by the patients. Plan quality was evaluated using the HI, NTI and dose to OARs. The hIMRT technique was significantly more homogenous than the 3DCRT technique, while maintaining target coverage. The hIMRT technique was also superior at minimising the amount of tissue receiving D{sub 105%} and above (P < 0.0001). The ipsilateral lung and contralateral breast maximum were significantly lower in the hIMRT plans (P < 0.05 and P < 0.005), but the 3DCRT technique achieved a lower mean heart dose in left-sided breast cancer patients (P < 0.05). Hybrid intensity modulated radiotherapy plans achieved improved dose homogeneity compared to the 3DCRT plans and superior outcome with regard to dose to normal tissues. We propose that the addition of both HI and NTI in evaluating the quality of intensity modulated radiotherapy (IMRT) breast plans provides clinically relevant comparators which more accurately reflect the new paradigm of treatment goals and outcomes in the era of breast IMRT.« less

Three dimensional intensity modulated brachytherapy (IMBT): dosimetry algorithm and inverse treatment planning.

PubMed

Shi, Chengyu; Guo, Bingqi; Cheng, Chih-Yao; Esquivel, Carlos; Eng, Tony; Papanikolaou, Niko

2010-07-01

The feasibility of intensity modulated brachytherapy (IMBT) to improve dose conformity for irregularly shaped targets has been previously investigated by researchers by means of using partially shielded sources. However, partial shielding does not fully explore the potential of IMBT. The goal of this study is to introduce the concept of three dimensional (3D) intensity modulated brachytherapy and solve two fundamental issues regarding the application of 3D IMBT treatment planning: The dose calculation algorithm and the inverse treatment planning method. A 3D IMBT treatment planning system prototype was developed using the MATLAB platform. This system consists of three major components: (1) A comprehensive IMBT source calibration method with dosimetric inputs from Monte Carlo (EGSnrc) simulations; (2) a "modified TG-43" (mTG-43) dose calculation formalism for IMBT dosimetry; and (3) a physical constraint based inverse IMBT treatment planning platform utilizing a simulated annealing optimization algorithm. The model S700 Axxent electronic brachytherapy source developed by Xoft, Inc. (Fremont, CA), was simulated in this application. Ten intracavitary accelerated partial breast irradiation (APBI) cases were studied. For each case, an "isotropic plan" with only optimized source dwell time and a fully optimized IMBT plan were generated and compared to the original plan in various dosimetric aspects, such as the plan quality, planning, and delivery time. The issue of the mechanical complexity of the IMBT applicator is not addressed in this study. IMBT approaches showed superior plan quality compared to the original plans and tht isotropic plans to different extents in all studied cases. An extremely difficult case with a small breast and a small distance to the ribs and skin, the IMBT plan minimized the high dose volume V200 by 16.1% and 4.8%, respectively, compared to the original and the isotropic plans. The conformity index for the target was increased by 0.13 and 0.04, respectively. The maximum dose to the skin was reduced by 56 and 28 cGy, respectively, per fraction. Also, the maximum dose to the ribs was reduced by 104 and 96 cGy, respectively, per fraction. The mean dose to the ipsilateral and contralateral breasts and lungs were also slightly reduced by the IMBT plan. The limitations of IMBT are the longer planning and delivery time. The IMBT plan took around 2 h to optimize, while the isotropic plan optimization could reach the global minimum within 5 min. The delivery time for the IMBT plan is typically four to six times longer than the corresponding isotropic plan. In this study, a dosimetry method for IMBT sources was proposed and an inverse treatment planning system prototype for IMBT was developed. The improvement of plan quality by 3D IMBT was demonstrated using ten APBI case studies. Faster computers and higher output of the source can further reduce plan optimization and delivery time, respectively.

Dosimetric and radiobiological comparison of Forward Tangent Intensity Modulated Radiation Therapy (FT-IMRT) and Volumetric Modulated Arc Therapy (VMAT) for early stage whole breast cancer

NASA Astrophysics Data System (ADS)

Moshiri Sedeh, Nader

Intensity Modulated Radiation Therapy (IMRT) is a well-known type of external beam radiation therapy. The advancement in technology has had an inevitable influence in radiation oncology as well that has led to a newer and faster dose delivery technique called Volumetric Modulated Arc Therapy (VMAT). Since the presence of the VMAT modality in clinics in the late 2000, there have been many studies in order to compare the results of the VMAT modality with the current popular modality IMRT for various tumor sites in the body such as brain, prostate, head and neck, cervix and anal carcinoma. This is the first study to compare VMAT with IMRT for breast cancer. The results show that the RapidArc technique in Eclipse version 11 does not improve all aspects of the treatment plans for the breast cases automatically and easily, but it needs to be manipulated by extra techniques to create acceptable plans thus further research is needed.

Comparison of chronic toxicities between brachytherapy-based accelerated partial breast irradiation and whole breast irradiation using intensity modulated radiotherapy.

PubMed

Wobb, Jessica L; Shah, Chirag; Jawad, Maha S; Wallace, Michelle; Dilworth, Joshua T; Grills, Inga S; Ye, Hong; Chen, Peter Y

2015-12-01

Brachytherapy-based APBI (bAPBI) shortens treatment duration and limits dose to normal tissue. While studies have demonstrated similar local control when comparing bAPBI and whole breast irradiation using intensity modulated radiotherapy (WBI-IMRT), comparison of late side effects is limited. Here, we report chronic toxicity profiles associated with these two treatment modalities. 1034 patients with early stage breast cancer were treated at a single institution; 489 received standard-fractionation WBI-IMRT between 2000 and 2013 and 545 received bAPBI (interstitial 40%, applicator-based 60%) between 1993 and 2013. Chronic toxicity was evaluated ≥6 months utilizing CTCAE version 3.0; cosmesis was evaluated using the Harvard scale. Median follow-up was 4.6 years (range 0.1-13.4) for WBI-IMRT versus 6.7 years (range 0.1-20.1) for bAPBI (p < 0.001). Compared to WBI-IMRT, bAPBI was associated with higher rates of ≥grade 2 seroma formation (14.4% vs 2.9%, p < 0.001), telangiectasia (12.3% vs 2.1%, p = 0.002) and symptomatic fat necrosis (10.2% vs 3.6%, p < 0.001). Lower rates of hyperpigmentation were observed (5.8% vs 14.5%; p = 0.001). Infection rates were similar (3.3% vs 1.3%, p = 0.07). There was no difference between rates of fair (6.1% vs. 4.1%, p = 0.30) or poor (0.2% vs. 0.5%, p = NS) cosmesis. Mastectomy rates for local recurrence (3.1% for WBI-IMRT and 1.2% for bAPBI, p = 0.06), or for other reasons (0.8% and 0.6%, p = 0.60) were similar between groups. With 5-year follow-up, WBI-IMRT and bAPBI are associated with similar, acceptable rates of toxicity. These data further support the utilization of bAPBI as a modality to deliver adjuvant radiation in a safe and efficacious manner. Copyright © 2015 Elsevier Ltd. All rights reserved.

Estimation of the risk of secondary malignancy arising from whole-breast irradiation: comparison of five radiotherapy modalities, including TomoHDA.

PubMed

Han, Eun Young; Paudel, Nava; Sung, Jiwon; Yoon, Myonggeun; Chung, Weon Kuu; Kim, Dong Wook

2016-04-19

The risk of secondary cancer from radiation treatment remains a concern for long-term breast cancer survivors, especially those treated with radiation at the age younger than 45 years. Treatment modalities optimally maximize the dose delivery to the tumor while minimizing radiation doses to neighboring organs, which can lead to secondary cancers. A new TomoTherapy treatment machine, TomoHDATM, can treat an entire breast with two static but intensity-modulated beams in a slice-by-slice fashion. This feature could reduce scattered and leakage radiation doses. We compared the plan quality and lifetime attributable risk (LAR) of a second malignancy among five treatment modalities: three-dimensional conformal radiation therapy, field-in-field forward-planned intensity-modulated radiation therapy, inverse-planned intensity-modulated radiation therapy (IMRT), volumetric modulated arc therapy, and TomoDirect mode on the TomoHDA system. Ten breast cancer patients were selected for retrospective analysis. Organ equivalent doses, plan characteristics, and LARs were compared. Out-of-field organ doses were measured with radio-photoluminescence glass dosimeters. Although the IMRT plan provided overall better plan quality, including the lowest probability of pneumonitis, it caused the second highest LAR. The TomoTherapy plan provided plan quality comparable to the IMRT plan and posed the lowest total LAR to neighboring organs. Therefore, it can be a better treatment modality for younger patients who have a longer life expectancy.

Preoperative Single-Fraction Partial Breast Radiation Therapy: A Novel Phase 1, Dose-Escalation Protocol With Radiation Response Biomarkers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Horton, Janet K., E-mail: janet.horton@duke.edu; Blitzblau, Rachel C.; Yoo, Sua

Purpose: Women with biologically favorable early-stage breast cancer are increasingly treated with accelerated partial breast radiation (PBI). However, treatment-related morbidities have been linked to the large postoperative treatment volumes required for external beam PBI. Relative to external beam delivery, alternative PBI techniques require equipment that is not universally available. To address these issues, we designed a phase 1 trial utilizing widely available technology to 1) evaluate the safety of a single radiation treatment delivered preoperatively to the small-volume, intact breast tumor and 2) identify imaging and genomic markers of radiation response. Methods and Materials: Women aged ≥55 years with clinically node-negative,more » estrogen receptor–positive, and/or progesterone receptor–positive HER2−, T1 invasive carcinomas, or low- to intermediate-grade in situ disease ≤2 cm were enrolled (n=32). Intensity modulated radiation therapy was used to deliver 15 Gy (n=8), 18 Gy (n=8), or 21 Gy (n=16) to the tumor with a 1.5-cm margin. Lumpectomy was performed within 10 days. Paired pre- and postradiation magnetic resonance images and patient tumor samples were analyzed. Results: No dose-limiting toxicity was observed. At a median follow-up of 23 months, there have been no recurrences. Physician-rated cosmetic outcomes were good/excellent, and chronic toxicities were grade 1 to 2 (fibrosis, hyperpigmentation) in patients receiving preoperative radiation only. Evidence of dose-dependent changes in vascular permeability, cell density, and expression of genes regulating immunity and cell death were seen in response to radiation. Conclusions: Preoperative single-dose radiation therapy to intact breast tumors is well tolerated. Radiation response is marked by early indicators of cell death in this biologically favorable patient cohort. This study represents a first step toward a novel partial breast radiation approach. Preoperative radiation should be tested in future clinical trials because it has the potential to challenge the current treatment paradigm and provide a path forward to identify radiation response biomarkers.« less

Sentinel Lymph Node Biopsy: Quantification of Lymphedema Risk Reduction

DTIC Science & Technology

2006-10-01

dimensional internal mammary lymphoscintigraphy: implications for radiation therapy treatment planning for breast carcinoma. Int J Radiat Oncol Biol Phys...techniques based on conventional photon beams, intensity modulated photon beams and proton beams for therapy of intact breast. Radiother Oncol. Feb...Harris JR. Three-dimensional internal mammary lymphoscintigraphy: implications for radiation therapy treatment planning for breast carcinoma. Int J

Dosimetric comparison of 3D conformal, IMRT, and V-MAT techniques for accelerated partial-breast irradiation (APBI)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiu, Jian-Jian; Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai

2014-07-01

The purpose is to dosimetrically compare the following 3 delivery techniques: 3-dimensional conformal radiation therapy (3D-CRT), intensity-modulated arc therapy (IMRT), and volumetric-modulated arc therapy (V-MAT) in the treatment of accelerated partial-breast irradiation (APBI). Overall, 16 patients with T1/2N0 breast cancer were treated with 3D-CRT (multiple, noncoplanar photon fields) on the RTOG 0413 partial-breast trial. These cases were subsequently replanned using static gantry IMRT and V-MAT technology to understand dosimetric differences among these 3 techniques. Several dosimetric parameters were used in plan quality evaluation, including dose conformity index (CI) and dose-volume histogram analysis of normal tissue coverage. Quality assurance studies includingmore » gamma analysis were performed to compare the measured and calculated dose distributions. The IMRT and V-MAT plans gave more conformal target dose distributions than the 3D-CRT plans (p < 0.05 in CI). The volume of ipsilateral breast receiving 5 and 10 Gy was significantly less using the V-MAT technique than with either 3D-CRT or IMRT (p < 0.05). The maximum lung dose and the ipsilateral lung volume receiving 10 (V{sub 10}) or 20 Gy (V{sub 20}) were significantly less with both V-MAT and IMRT (p < 0.05). The IMRT technique was superior to 3D-CRT and V-MAT of low dose distributions in ipsilateral lung (p < 0.05 in V{sub 5} and D{sub 5}). The total mean monitor units (MUs) for V-MAT (621.0 ± 111.9) were 12.2% less than those for 3D-CRT (707.3 ± 130.9) and 46.5% less than those for IMRT (1161.4 ± 315.6) (p < 0.05). The average machine delivery time was 1.5 ± 0.2 minutes for the V-MAT plans, 7.0 ± 1.6 minutes for the 3D-CRT plans, and 11.5 ± 1.9 minutes for the IMRT plans, demonstrating much less delivery time for V-MAT. Based on this preliminary study, V-MAT and IMRT techniques offer improved dose conformity as compared with 3D-CRT techniques without increasing dose to the ipsilateral lung. In terms of MU and delivery time, V-MAT is significantly more efficient for APBI than for conventional 3D-CRT and static-beam IMRT.« less

SU-E-T-583: Operated Left Breast and Chest Wall Radiotherapy: A Dosimetric Comparison Between 3DCRT, IMRT and VMAT

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sarkar, B; Roy, S; Munshi, A

2015-06-15

Purpose: To evaluate the comparative dosimetric efficacy between field and field 3DCRT(FnF), multiple field Intensity modulated radiotherapy (SnS IMRT) and, partial arc volumetric modulated arc therapy (VMAT) in case of post operative left side breast and chest wall irradiation. Methods: CT study set of fifteen post-operative left breast and chest wall patient was tested for a treatment plan of 50Gy in 25 fraction using partial arc VMAT, SnSIMRT and tangential beam 3DCRT . 3DCRT FnF gantry angle was ranging for left medial tangential 290±17{sup 0} and Lt lateral tangential l14°±12{sup 0}. For IMRT four fixed beam at gantry angle G130{supmore » 0} G110{sup 0} G300{sup 0} and G330{sup 0} was used, in case of insufficient dose another beam G150{sup 0} was added. In case of partial arc VMAT, lateral tangential arc G130{sup 0}-G100{sup 0} and medial tangential arc G280{sup 0}-G310{sup 0}. Inverse optimization was opted to cover at least 95%PTV by 95% prescription dose (RxD) and a strong weightage on reduction of heart and lung dose. PTV coverage was evaluated for it’s clinically acceptability depending on the tumor spatial location and its quadrant. Out of the three plans, any one was used for the actual patient treatment. Results: Dosimetric analysis done for breast PTV, left lung, heart and the opposite breast. PTV mean dose and maximum dose was 5129.8±214.8cGy, 4749.0±329.7cGy, 5024.6±73.4cGy and 5855.2±510.7cGy, 5340.7±146.1cGy, 5347.2±196.8cGy for FnF, VMAT and IMRT respectively. Ipsilateral lung volume receiving 20Gy and 5Gy was 23.6±9.5cGy and 32.7±10.3cGy for FnF, 18.6±8.7cGy and 38.8±15.2cGy for VMAT and 25.7±9.6cGy and 50.7±8.4cGy for IMRT respectively. Heart mean and 2cc dose was 867.9±456.7cGy and 5038.5±184.3cGy for FnF, 532.6±263cGy and 3632.1±990.6 for VMAT, 711±229.9cGy and 4421±463.7cGy for IMRT respectively. VMAT shows minimum contralateral breast dose 168±113.8cGy. Conclusion: VMAT shows a better tumor conformity, minimum heart, ipsilateral lung and opposite breast dose. Cardiac Toxicity and risk of contralateral breast cancer can be reduce using VMAT.« less

Reducing radiation dose to the female breast during CT coronary angiography: A simulation study comparing breast shielding, angular tube current modulation, reduced kV, and partial angle protocols using an unknown-location signal-detectability metric

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rupcich, Franco; Gilat Schmidt, Taly; Badal, Andreu

2013-08-15

Purpose: The authors compared the performance of five protocols intended to reduce dose to the breast during computed tomography (CT) coronary angiography scans using a model observer unknown-location signal-detectability metric.Methods: The authors simulated CT images of an anthropomorphic female thorax phantom for a 120 kV reference protocol and five “dose reduction” protocols intended to reduce dose to the breast: 120 kV partial angle (posteriorly centered), 120 kV tube-current modulated (TCM), 120 kV with shielded breasts, 80 kV, and 80 kV partial angle (posteriorly centered). Two image quality tasks were investigated: the detection and localization of 4-mm, 3.25 mg/ml and 1-mm,more » 6.0 mg/ml iodine contrast signals randomly located in the heart region. For each protocol, the authors plotted the signal detectability, as quantified by the area under the exponentially transformed free response characteristic curve estimator (A-caret{sub FE}), as well as noise and contrast-to-noise ratio (CNR) versus breast and lung dose. In addition, the authors quantified each protocol's dose performance as the percent difference in dose relative to the reference protocol achieved while maintaining equivalent A-caret{sub FE}.Results: For the 4-mm signal-size task, the 80 kV full scan and 80 kV partial angle protocols decreased dose to the breast (80.5% and 85.3%, respectively) and lung (80.5% and 76.7%, respectively) with A-caret{sub FE} = 0.96, but also resulted in an approximate three-fold increase in image noise. The 120 kV partial protocol reduced dose to the breast (17.6%) at the expense of increased lung dose (25.3%). The TCM algorithm decreased dose to the breast (6.0%) and lung (10.4%). Breast shielding increased breast dose (67.8%) and lung dose (103.4%). The 80 kV and 80 kV partial protocols demonstrated greater dose reductions for the 4-mm task than for the 1-mm task, and the shielded protocol showed a larger increase in dose for the 4-mm task than for the 1-mm task. In general, the CNR curves indicate a similar relative ranking of protocol performance as the corresponding A-caret{sub FE} curves, however, the CNR metric overestimated the performance of the shielded protocol for both tasks, leading to corresponding underestimates in the relative dose increases compared to those obtained when using the A-caret{sub FE} metric.Conclusions: The 80 kV and 80 kV partial angle protocols demonstrated the greatest reduction to breast and lung dose, however, the subsequent increase in image noise may be deemed clinically unacceptable. Tube output for these protocols can be adjusted to achieve a more desirable noise level with lesser breast dose savings. Breast shielding increased breast and lung dose when maintaining equivalent A-caret{sub FE}. The results demonstrated that comparisons of dose performance depend on both the image quality metric and the specific task, and that CNR may not be a reliable metric of signal detectability.« less

Accelerated partial breast irradiation using robotic radiotherapy: a dosimetric comparison with tomotherapy and three-dimensional conformal radiotherapy.

PubMed

Rault, Erwann; Lacornerie, Thomas; Dang, Hong-Phuong; Crop, Frederik; Lartigau, Eric; Reynaert, Nick; Pasquier, David

2016-02-27

Accelerated partial breast irradiation (APBI) is a new breast treatment modality aiming to reduce treatment time using hypo fractionation. Compared to conventional whole breast irradiation that takes 5 to 6 weeks, APBI is reported to induce worse cosmetic outcomes both when using three-dimensional conformal radiotherapy (3D-CRT) and intensity-modulated radiotherapy (IMRT). These late normal tissue effects may be attributed to the dose volume effect because a large portion of the non-target breast tissue volume (NTBTV) receives a high dose. In the context of APBI, non-coplanar beams could spare the NTBTV more efficiently. This study evaluates the dosimetric benefit of using the Cyberknife (CK) for APBI in comparison to IMRT (Tomotherapy) and three dimensional conformal radiotherapy (3D-CRT). The possibility of using surgical clips, implanted during surgery, to track target movements is investigated first. A phantom of a female thorax was designed in-house using the measurements of 20 patients. Surgical clips of different sizes were inserted inside the breast. A treatment plan was delivered to the mobile and immobile phantom. The motion compensation accuracy was evaluated using three radiochromic films inserted inside the breast. Three dimensional conformal radiotherapy (3D-CRT), Tomotherapy (TOMO) and CK treatment plans were calculated for 10 consecutive patients who received APBI in Lille. To ensure a fair comparison of the three techniques, margins applied to the CTV were set to 10 mm. However, a second CK plan was prepared using 3 mm margins to evaluate the benefits of motion compensation. Only the larger clips (VITALITEC Medium-Large) could be tracked inside the larger breast (all gamma indices below 1 for 1 % of the maximum dose and 1 mm). All techniques meet the guidelines defined in the NSABP/RTOG and SHARE protocols. As the applied dose volume constraints are very strong, insignificant dosimetric differences exist between techniques regarding the PTV coverage and the sparing of the lung and heart. However, the CK may be used to reduce high doses received by the NTBTV more efficiently. Robotic stereotactic radiotherapy may be used for APBI to more efficiently spare the NTBTV and improve cosmetic results of APBI.

Accelerated Partial Breast Irradiation: What is Dosimetric Effect of Advanced Technology Approaches?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moran, Jean M.; Ben-David, Merav A.; Marsh, Robin B.

2009-09-01

Purpose: The present treatment planning study compared whole breast radiotherapy (WBRT) to accelerated partial breast irradiation (APBI) for different external beam techniques and geometries (e.g., free breathing [FB] and deep inspiration breath hold [DIBH]). Methods and Materials: After approval by our institutional review board, a treatment planning study was performed of 10 patients with left-sided Stage 0-I breast cancer enrolled in a Phase I-II study of APBI using intensity-modulated radiotherapy (IMRT). After lumpectomy, patients underwent planning computed tomography scans during FB and using an active breathing control device at DIBH. For the FB geometry, standard WBRT and three-dimensional conformal radiotherapymore » (3D-CRT) APBI plans were created. For the DIBH geometry with active breathing control, WBRT, 3D-CRT, and IMRT APBI plans were created. Results: All APBI techniques had excellent planning target volume coverage. The maximal planning target volume dose was reduced from 116% of the prescription dose to 108% with the IMRT(DIBH) APBI plan. The maximal heart dose was >30 Gy for the WBRT techniques, 8.2 Gy for 3D-CRT(FB), and <5.0 Gy for 3D-CRT(DIBH) and IMRT(DIBH) techniques. The mean left anterior descending artery dose was significantly reduced from 11.4 Gy with WBRT(FB) to 4.2 with WBRT(DIBH) and <2.0 Gy with all APBI techniques. Conclusion: Although planning target volume coverage was acceptable with all techniques, the plans using the DIBH geometry resulted in a marked reduction in the normal tissue dose compared with WBRT planned in the absence of cardiac blocking. Additional study is needed to determine whether these techniques result in clinical benefits.« less

Patient-Reported Outcomes following Breast Conservation Therapy and Barriers to Referral for Partial Breast Reconstruction.

PubMed

Vrouwe, Sebastian Q; Somogyi, Ron B; Snell, Laura; McMillan, Catherine; Vesprini, Danny; Lipa, Joan E

2018-01-01

The purpose of this study was to evaluate the self-reported aesthetic outcome of breast conservation therapy in a generalized sample of patients, and to describe potential barriers to referral for partial breast reconstruction. Consecutive breast conservation therapy patients completing radiotherapy over a 1-year period at a regional cancer center were identified. Eligible patients were contacted by means of mail/e-mail and invited to participate. Participants completed the BREAST-Q breast conservation therapy module along with a questionnaire examining feelings about breast reconstruction. Multiple regression analysis was performed using the satisfaction with breasts scale as the dependent variable. Surveys were completed by 185 of 592 eligible participants (response rate, 31.3 percent; mean age, 61 years) an average of 38 months after lumpectomy. The mean score for the BREAST-Q satisfaction with breasts scale was 59 of 100. Younger age (p = 0.038), lumpectomy reexcision (p = 0.018), and lumpectomy at a nonacademic center (p = 0.026) were significantly associated with lower satisfaction. Bra size, months from lumpectomy, and tumor quadrant/size were not significantly associated with satisfaction (p > 0.05). The most common statements regarding reconstruction were "I don't feel the need for it" (60.0 percent), "I don't like the thought of having breast implants" (22.7 percent), and "I don't want any more surgeon/doctor visits" (22.2 percent). Before lumpectomy, only 1.6 percent had a consultation for reconstruction, and only 22.7 percent were aware of this option. If offered, 33.1 percent of patients would have attended this consultation. There is an unmet demand for partial breast reconstruction, with an opportunity to advocate and increase awareness on behalf of patients undergoing breast conservation therapy.

Radiation therapy for breast cancer: Literature review

DOE Office of Scientific and Technical Information (OSTI.GOV)

Balaji, Karunakaran, E-mail: karthik.balaji85@gmail.com; School of Advanced Sciences, VIT University, Vellore; Subramanian, Balaji

Concave shape with variable size target volume makes treatment planning for the breast/chest wall a challenge. Conventional techniques used for the breast/chest wall cancer treatment provided better sparing of organs at risk (OARs), with poor conformity and uniformity to the target volume. Advanced technologies such as intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) improve the target coverage at the cost of higher low dose volumes to OARs. Novel hybrid techniques present promising results in breast/chest wall irradiation in terms of target coverage as well as OARs sparing. Several published data compared these technologies for the benefit ofmore » the breast/chest wall with or without nodal volumes. The aim of this article is to review relevant data and identify the scope for further research in developing optimal treatment plan for breast/chest wall cancer treatment.« less

Dosimetric comparison of hybrid volumetric-modulated arc therapy, volumetric-modulated arc therapy, and intensity-modulated radiation therapy for left-sided early breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lin, Jia-Fu; Yeh, Dah-Cherng; Yeh, Hui-Ling, E-mail: hlyeh@vghtc.gov.tw

2015-10-01

To compare the dosimetric performance of 3 different treatment techniques: hybrid volumetric-modulated arc therapy (hybrid-VMAT), pure-VMAT, and fixed-field intensity-modulated radiation therapy (F-IMRT) for whole-breast irradiation of left-sided early breast cancer. The hybrid-VMAT treatment technique and 2 other treatment techniques—pure-VMAT and F-IMRT—were compared retrospectively in 10 patients with left-sided early breast cancer. The treatment plans of these patients were replanned using the same contours based on the original computed tomography (CT) data sets. Dosimetric parameters were calculated to evaluate plan quality. Total monitor units (MUs) and delivery time were also recorded and evaluated. The hybrid-VMAT plan generated the best results inmore » dose coverage of the target and the dose uniformity inside the target (p < 0.0001 for conformal index [CI]; p = 0.0002 for homogeneity index [HI] of planning target volume [PTV]{sub 50.4} {sub Gy} and p < 0.0001 for HI of PTV{sub 62} {sub Gy}). Volumes of ipsilateral lung irradiated to doses of 20 Gy (V{sub 20} {sub Gy}) and 5 Gy (V{sub 5} {sub Gy}) by the hybrid-VMAT plan were significantly less than those of the F-IMRT and the pure-VMAT plans. The volume of ipsilateral lung irradiated to a dose of 5 Gy was significantly less using the hybrid-VMAT plan than that using the F-IMRT or the pure-VMAT plan. The total mean MUs for the hybrid-VMAT plan were significantly less than those for the F-IMRT or the pure-VMAT plan. The mean machine delivery time was 3.23 ± 0.29 minutes for the hybrid-VMAT plans, which is longer than that for the pure-VMAT plans but shorter than that for the F-IMRT plans. The hybrid-VMAT plan is feasible for whole-breast irradiation of left-sided early breast cancer.« less

Prone breast forward intensity-modulated radiotherapy for Asian women with early left breast cancer: factors for cardiac sparing and clinical outcomes

PubMed Central

Chen, Jenny Ling-Yu; Cheng, Jason Chia-Hsien; Kuo, Sung-Hsin; Chan, Hsing-Min; Huang, Yu-Sen; Chen, Yu-Hsuan

2013-01-01

Since December 2009, after breast-conserving surgery for Stage 0–I cancer of the left breast, 21 women with relatively pendulous breasts underwent computed tomography prone and supine simulations. The adjuvant radiotherapy was 50 Gy in 25 fractions to the left breast alone. Four plans—conventional wedged tangents and forward intensity-modulated radiotherapy (fIMRT) in supine and prone positions—were generated. fIMRT generated better homogeneity in both positions. Prone position centralized the breast tissue by gravity and also shortened the breast width which led to better conformity in both planning techniques. Prone fIMRT significantly reduced doses to left lung, Level I and Level II axilla. The mean cardiac doses did not differ between positions. Among the four plans, prone fIMRT produced the best target dosimetry and normal organ sparing. In subgroup analysis, patients with absolute breast depth > 7 cm in the prone position or breast depth difference > 3 cm between positions had significant cardiac sparing with prone fIMRT. Sixteen patients with significant cardiac sparing in prone position were treated using prone fIMRT and the others using supine fIMRT. All patients received a supine electron tumor bed boost of 10 Gy in 5 fractions. No patients developed Grade 2 or worse acute or late toxicities. There was no difference in the number of segments or beams, monitor units, treatment time, or positioning reproducibility between prone and supine positions. At a median follow-up time of 26.8 months, no locoregional or distant recurrence or death was noted. PMID:23504450

Second cancer risk after 3D-CRT, IMRT and VMAT for breast cancer.

PubMed

Abo-Madyan, Yasser; Aziz, Muhammad Hammad; Aly, Moamen M O M; Schneider, Frank; Sperk, Elena; Clausen, Sven; Giordano, Frank A; Herskind, Carsten; Steil, Volker; Wenz, Frederik; Glatting, Gerhard

2014-03-01

Second cancer risk after breast conserving therapy is becoming more important due to improved long term survival rates. In this study, we estimate the risks for developing a solid second cancer after radiotherapy of breast cancer using the concept of organ equivalent dose (OED). Computer-tomography scans of 10 representative breast cancer patients were selected for this study. Three-dimensional conformal radiotherapy (3D-CRT), tangential intensity modulated radiotherapy (t-IMRT), multibeam intensity modulated radiotherapy (m-IMRT), and volumetric modulated arc therapy (VMAT) were planned to deliver a total dose of 50 Gy in 2 Gy fractions. Differential dose volume histograms (dDVHs) were created and the OEDs calculated. Second cancer risks of ipsilateral, contralateral lung and contralateral breast cancer were estimated using linear, linear-exponential and plateau models for second cancer risk. Compared to 3D-CRT, cumulative excess absolute risks (EAR) for t-IMRT, m-IMRT and VMAT were increased by 2 ± 15%, 131 ± 85%, 123 ± 66% for the linear-exponential risk model, 9 ± 22%, 82 ± 96%, 71 ± 82% for the linear and 3 ± 14%, 123 ± 78%, 113 ± 61% for the plateau model, respectively. Second cancer risk after 3D-CRT or t-IMRT is lower than for m-IMRT or VMAT by about 34% for the linear model and 50% for the linear-exponential and plateau models, respectively. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

SU-E-P-56: Dosimetric Comparison of Three Post Modified Radical Mastectomy Radiotherapy Techniques for Locally Advanced Left-Sided Breast Cancer and Beyond

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ma, C; Zhang, W; Lu, J

2015-06-15

Purpose: To compare the dosimetry of post modified radical mastectomy radiotherapy (PMRMRT) for left-sided breast cancer using 3-dimensional conformal radiotherapy (3DCRT), intensity-modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Methods: We created ten sets of PMRMRT plans for ten consecutive patients and utilized two tangential and one or two supraclavicular beams in 3DCRT, a total of 5 beams in IMRT and two optimized partial arcs in VMAT. The difference in results between any two of the three new plans, between new and previous 3DCRT plans were compared and analyzed by ANOVA (α =0.05) and paired-sample t-test respectively. Pmore » values less than 0.05 were considered statistically significant. Results: Both IMRT and VMAT plans had similar PTV coverage, hotspot area and conformity (all p>0.05), and significantly higher PTV coverage compared with new 3DCRT (both p<0.001). IMRT plans had significantly less heart and left lung radiation exposure compared with VMAT (all p<0.05). The 3DCRT plans with larger estimated CTV displacement had better target coverage but worse OARs sparing compared to those with smaller one. Conclusion: IMRT has dosimetrical advantages over the other two techniques in PMRMRT for left-sided breast cancer. Individually quantifying and minimizing CTV displacement can significantly improve dosage distribution. This work was supported by the Medical Scientific Research Foundation of Guangdong Procvince (A2014455 to Changchun Ma)« less

Modulation transfer function of partial gating detector by liquid crystal auto-controlling light intensity

NASA Astrophysics Data System (ADS)

Yang, Xusan; Tang, Yuanhe; Liu, Kai; Liu, Hanchen; Gao, Haiyang; Li, Qing; Zhang, Ruixia; Ye, Na; Liang, Yuan; Zhao, Gaoxiang

2008-12-01

Based on the electro-optical properties of liquid crystal, we have designed a novel partial gating detector. Liquid crystal can be taken to change its own transmission according to the light intensity outside. Every single pixel of the image is real-time modulated by liquid crystal, thus the strong light is weakened and low light goes through the detector normally .The purpose of partial-gating strong light (>105lx) can be achieved by this detector. The modulation transfer function (MTF) equations of the main optical sub-systems are calculated in this paper, they are liquid crystal panels, linear fiber panel and CCD array detector. According to the relevant size, the MTF value of this system is fitted out. The result is MTF= 0.518 at Nyquist frequency.

SU-E-P-51: Dosimetric Comparison to Organs at Risk Sparing Using Volumetric-Modulated Arc Therapy Versus Intensity-Modulated Radiotherapy in Postoperative Radiotherapy of Left-Sided Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qiao, L; Deng, G; Xie, J

2015-06-15

Purpose: To compare the dosimetric characteristics of volumetric-modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) techniques in treatment planning for left-sided breast cancer patients with modified radical mastectomy. Methods: Twenty-four left-sided breast cancer patients treated with modified radical mastectomy were selected in this study. The planning target volume (PTV) was generated by using 7-mm uniform expansion of the clinical target volume (CTV) in all direction except the skin surface. The organs at risk (OARs) included heart, left lung, right lung, and right breast. Dose volume histograms (DVHs) were utilized to evaluate the dose distribution in PTV and OARs. Results: Bothmore » VMAT and IMRT plans met the requirement of PTV coverage. VMAT was superior to IMRT in terms of conformity, with a statistically significant difference (p=0.024). Mean doses, V5 and V10 of heart and both lungs in VMAT plans were significantly decreased compared to IMRT plans (P<0.05), but in terms of heart volume irradiated by high doses (V30 and V45), no significant differences were observed (P>0.05). For right breast, VMAT showed the reduction of V5 in comparison with IMRT (P<0.05). Additionally, the mean number of monitor units (MU) and treatment time in VMAT (357.21, 3.62 min) were significantly less than those in IMRT (1132.85, 8.74 min). Conclusion: VMAT showed similar PTV coverage and significant advantage in OARs sparing compared with IMRT, especially in terms of decreased volumes irradiated by low doses, while significantly reducing the treatment time and MU number.« less

Radiation therapy planning with photons and protons for early and advanced breast cancer: an overview

PubMed Central

Weber, Damien C; Ares, Carmen; Lomax, Antony J; Kurtz, John M

2006-01-01

Postoperative radiation therapy substantially decreases local relapse and moderately reduces breast cancer mortality, but can be associated with increased late mortality due to cardiovascular morbidity and secondary malignancies. Sophistication of breast irradiation techniques, including conformal radiotherapy and intensity modulated radiation therapy, has been shown to markedly reduce cardiac and lung irradiation. The delivery of more conformal treatment can also be achieved with particle beam therapy using protons. Protons have superior dose distributional qualities compared to photons, as dose deposition occurs in a modulated narrow zone, called the Bragg peak. As a result, further dose optimization in breast cancer treatment can be reasonably expected with protons. In this review, we outline the potential indications and benefits of breast cancer radiotherapy with protons. Comparative planning studies and preliminary clinical data are detailed and future developments are considered. PMID:16857055

Electron intensity modulation for mixed-beam radiation therapy with an x-ray multi-leaf collimator

NASA Astrophysics Data System (ADS)

Weinberg, Rebecca

The current standard treatment for head and neck cancer at our institution uses intensity-modulated x-ray therapy (IMRT), which improves target coverage and sparing of critical structures by delivering complex fluence patterns from a variety of beam directions to conform dose distributions to the shape of the target volume. The standard treatment for breast patients is field-in-field forward-planned IMRT, with initial tangential fields and additional reduced-weight tangents with blocking to minimize hot spots. For these treatment sites, the addition of electrons has the potential of improving target coverage and sparing of critical structures due to rapid dose falloff with depth and reduced exit dose. In this work, the use of mixed-beam therapy (MBT), i.e., combined intensity-modulated electron and x-ray beams using the x-ray multi-leaf collimator (MLC), was explored. The hypothesis of this study was that addition of intensity-modulated electron beams to existing clinical IMRT plans would produce MBT plans that were superior to the original IMRT plans for at least 50% of selected head and neck and 50% of breast cases. Dose calculations for electron beams collimated by the MLC were performed with Monte Carlo methods. An automation system was created to facilitate communication between the dose calculation engine and the treatment planning system. Energy and intensity modulation of the electron beams was accomplished by dividing the electron beams into 2x2-cm2 beamlets, which were then beam-weight optimized along with intensity-modulated x-ray beams. Treatment plans were optimized to obtain equivalent target dose coverage, and then compared with the original treatment plans. MBT treatment plans were evaluated by participating physicians with respect to target coverage, normal structure dose, and overall plan quality in comparison with original clinical plans. The physician evaluations did not support the hypothesis for either site, with MBT selected as superior in 1 out of the 15 head and neck cases (p=1) and 6 out of 18 breast cases (p=0.95). While MBT was not shown to be superior to IMRT, reductions were observed in doses to critical structures distal to the target along the electron beam direction and to non-target tissues, at the expense of target coverage and dose homogeneity.

Dosimetric aspects of breast radiotherapy with three-dimensional and intensity-modulated radiotherapy helical tomotherapy planning modules

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yadav, Poonam; Service of Radiation Therapy, University of Wisconsin Aspirus Cancer Center, Wisconsin Rapids, WI; Yan, Yue, E-mail: yyan5@mdanderson.org

In this work, we investigated the dosimetric differences between the intensity-modulated radiotherapy (IMRT) plans and the three-dimensional (3D) helical plans based on the TomoTherapy system. A total of 15 patients with supine setup were randomly selected from the data base. For patients with lumpectomy planning target volume (PTV), regional lymph nodes were also included as part of the target. For dose sparing, the significant differences between the helical IMRT and helical 3D were only found in the heart and contralateral breast. For the dose to the heart, helical IMRT reduced the maximum point dose by 6.98 Gy compared to themore » helical 3D plan (p = 0.01). For contralateral breast, the helical IMRT plans significantly reduced the maximum point dose by 5.6 Gy compared to the helical 3D plan. However, compared to the helical 3D plan, the helical IMRT plan increased the volume for lower dose (13.08% increase in V{sub 5} {sub Gy}, p = 0.01). In general, there are no significant differences in dose sparing between helical IMRT and helical 3D plans.« less

Development of three-dimensional radiotherapy techniques in breast cancer

NASA Astrophysics Data System (ADS)

Coles, Charlotte E.

Radiotherapy following conservation surgery decreases local relapse and death from breast cancer. Currently, the challenge is to minimise the morbidity caused by this treatment without losing efficacy. Despite many advances in radiation techniques in other sites of the body, the majority of breast cancer patients are still planned and treated using 2-dimensional simple radiotherapy techniques. In addition, breast irradiation currently consumes 30% of the UK's radiotherapy workload. Therefore, any change to more complex treatment should be of proven benefit. The primary objective of this research is to develop and evaluate novel radiotherapy techniques to decrease irradiation of normal structures and improve localisation of the tumour bed. I have developed a forward-planned intensity modulated (IMRT) breast radiotherapy technique, which has shown improved dosimetry results compared to standard breast radiotherapy. Subsequently, I have developed and implemented a phase III randomised controlled breast IMRT trial. This National Cancer Research Network adopted trial will answer an important question regarding the clinical benefit of breast IMRT. It will provide DNA samples linked with high quality clinical outcome data, for a national translational radiogenomics study investigating variation in normal tissue toxicity. Thus, patients with significant late normal tissue side effects despite good dose homogeneity will provide the best model for finding differences due to underlying genetics. I evaluated a novel technique using high definition free-hand 3-dimensional (3D) ultrasound in a phantom study, and the results suggested that this is an accurate and reproducible method for tumour bed localisation. I then compared recognised methods of tumour bed localisation with the 3D ultrasound method in a clinical study. The 3D ultrasound technique appeared to accurately represent the shape and spatial position of the tumour cavity. This tumour bed localisation research facilitated protocol development of a proposed national breast radiotherapy trial investigating IMRT and partial breast irradiation.

Depressed mood in breast cancer survivors: associations with physical activity, cancer-related fatigue, quality of life, and fitness level.

PubMed

Galiano-Castillo, Noelia; Ariza-García, Angelica; Cantarero-Villanueva, Irene; Fernández-Lao, Carolina; Díaz-Rodríguez, Lourdes; Arroyo-Morales, Manuel

2014-04-01

One out of five cancer survivors suffer from depression after oncology treatment. The aim of this study was to examine the relationship between depression and quality of life (QoL), cancer-related symptoms, physical activity level, health-related fitness, and salivary flow rate in breast cancer survivors. 108 breast cancer survivors in the year after the conclusion of treatment were included in this cross-sectional study. Demographic and clinically relevant information, cancer-related fatigue (Piper Fatigue Scale), QoL (QLQ-Br23 module), pain intensity VAS scale, salivary flow rate, physical activity level (Minnesota Leisure Time Physical Activity Questionnaire), and health-related fitness were assessed in all participants. Depressed mood was measured with the Profile of Mood States (POMS) Depression subscale. Significant positive correlations between depressed mood and fatigue, systemic side effects, perceived shoulder pain, and breast-arms symptoms (r ranged between .57 and .28, P < .01) were found. In addition, significant negative correlations between depressed mood and body image, future perspective, force handgrip, and physical activity level (r ranged between -.41 and -.19; p < .05) were found. Regression analyses revealed that cancer-related fatigue, physical activity level, systemic side effects, and body image were significant predictors of depressed mood, and when combined, they explained 39.6% of the variance in depressed mood. Cancer-related fatigue, physical activity level, and QoL partially explain the variability of depressed mood in breast cancer survivors. This paper facilitates a better understanding of the relationship between depressed mood and possible factors associated with it. Copyright © 2013 Elsevier Ltd. All rights reserved.

Accelerated partial breast irradiation using intensity modulated radiotherapy versus whole breast irradiation: Health-related quality of life final analysis from the Florence phase 3 trial.

PubMed

Meattini, Icro; Saieva, Calogero; Miccinesi, Guido; Desideri, Isacco; Francolini, Giulio; Scotti, Vieri; Marrazzo, Livia; Pallotta, Stefania; Meacci, Fiammetta; Muntoni, Cristina; Bendinelli, Benedetta; Sanchez, Luis Jose; Bernini, Marco; Orzalesi, Lorenzo; Nori, Jacopo; Bianchi, Simonetta; Livi, Lorenzo

2017-05-01

Accelerated partial breast irradiation (APBI) represents a valid option for selected early breast cancer (BC). We recently published the 5-year results of the APBI-IMRT-Florence phase 3 randomised trial (NCT02104895), showing a very low rate of disease failure, with acute and early-late toxicity in favour of APBI. We present the early and 2-year follow-up health-related quality of life (HRQoL) results. Eligible patients were women aged more than 40 years with early BC suitable for breast-conserving surgery. APBI consisted of 30 Gy in five fractions delivered with IMRT technique. Standard whole breast irradiation (WBI) consisted of 50 Gy in 25 fractions plus a 10 Gy in five fractions boost on tumour bed. A total of 520 patients were enrolled in the phase 3 trial. Overall, 205 patients (105 APBI and 100 WBI) fully completed all the given questionnaires and were therefore included in the present analysis. As HRQoL assessment, patients were asked to complete the European Organisation for Research and Treatment of Cancer QLQ-C30, and the BR23 questionnaires at the beginning (T0), at the end (T1) and after 2 years from radiation (T2). No significant difference between the two arms at QLQ-C30 and BR23 scores emerged at T0. Global health status (p = 0.0001), and most scores of the functional and symptom scales of QLQ-C30 at T1 showed significant differences in favour of the APBI arm. Concerning the BR23 functional and symptom scales, the body image perception, future perspective and breast and arm symptoms were significantly better in the APBI group. Similar significant results emerged at T2: significant differences in favour of APBI emerged for GHS (p = 0.0001), and most functional and symptom QLQ-C30 scales. According to QLQ-BR23 module, among the functional scales, the body image perception and the future perspective were significantly better in the APBI group (p = 0.0001), whereas among the symptom scales significant difference emerged by breast and arm symptoms with better outcomes in APBI arm (p < 0.01). Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. Early BC treated with APBI showed an improved short-term, and 2-year follow-up HRQoL outcome as compared with WBI. APBI should be strongly considered in the treatment choice for selected low-risk patients. Mature local control results from ongoing adequately powered randomised trials are awaited. Copyright © 2017 Elsevier Ltd. All rights reserved.

Statistical process control analysis for patient quality assurance of intensity modulated radiation therapy

NASA Astrophysics Data System (ADS)

Lee, Rena; Kim, Kyubo; Cho, Samju; Lim, Sangwook; Lee, Suk; Shim, Jang Bo; Huh, Hyun Do; Lee, Sang Hoon; Ahn, Sohyun

2017-11-01

This study applied statistical process control to set and verify the quality assurances (QA) tolerance standard for our hospital's characteristics with the criteria standards that are applied to all the treatment sites with this analysis. Gamma test factor of delivery quality assurances (DQA) was based on 3%/3 mm. Head and neck, breast, prostate cases of intensity modulated radiation therapy (IMRT) or volumetric arc radiation therapy (VMAT) were selected for the analysis of the QA treatment sites. The numbers of data used in the analysis were 73 and 68 for head and neck patients. Prostate and breast were 49 and 152 by MapCHECK and ArcCHECK respectively. C p value of head and neck and prostate QA were above 1.0, C pml is 1.53 and 1.71 respectively, which is close to the target value of 100%. C pml value of breast (IMRT) was 1.67, data values are close to the target value of 95%. But value of was 0.90, which means that the data values are widely distributed. C p and C pml of breast VMAT QA were respectively 1.07 and 2.10. This suggests that the VMAT QA has better process capability than the IMRT QA. Consequently, we should pay more attention to planning and QA before treatment for breast Radiotherapy.

Reducing radiation dose to the female breast during conventional and dedicated breast computed tomography

NASA Astrophysics Data System (ADS)

Rupcich, Franco John

The purpose of this study was to quantify the effectiveness of techniques intended to reduce dose to the breast during CT coronary angiography (CTCA) scans with respect to task-based image quality, and to evaluate the effectiveness of optimal energy weighting in improving contrast-to-noise ratio (CNR), and thus the potential for reducing breast dose, during energy-resolved dedicated breast CT. A database quantifying organ dose for several radiosensitive organs irradiated during CTCA, including the breast, was generated using Monte Carlo simulations. This database facilitates estimation of organ-specific dose deposited during CTCA protocols using arbitrary x-ray spectra or tube-current modulation schemes without the need to run Monte Carlo simulations. The database was used to estimate breast dose for simulated CT images acquired for a reference protocol and five protocols intended to reduce breast dose. For each protocol, the performance of two tasks (detection of signals with unknown locations) was compared over a range of breast dose levels using a task-based, signal-detectability metric: the estimator of the area under the exponential free-response relative operating characteristic curve, AFE. For large-diameter/medium-contrast signals, when maintaining equivalent AFE, the 80 kV partial, 80 kV, 120 kV partial, and 120 kV tube-current modulated protocols reduced breast dose by 85%, 81%, 18%, and 6%, respectively, while the shielded protocol increased breast dose by 68%. Results for the small-diameter/high-contrast signal followed similar trends, but with smaller magnitude of the percent changes in dose. The 80 kV protocols demonstrated the greatest reduction to breast dose, however, the subsequent increase in noise may be clinically unacceptable. Tube output for these protocols can be adjusted to achieve more desirable noise levels with lesser dose reduction. The improvement in CNR of optimally projection-based and image-based weighted images relative to photon-counting was investigated for six different energy bin combinations using a bench-top energy-resolving CT system with a cadmium zinc telluride (CZT) detector. The non-ideal spectral response reduced the CNR for the projection-based weighted images, while image-based weighting improved CNR for five out of the six investigated bin combinations, despite this non-ideal response, indicating potential for image-based weighting to reduce breast dose during dedicated breast CT.

Objectively-Measured Physical Activity and Cognitive Functioning in Breast Cancer Survivors

PubMed Central

Marinac, Catherine R.; Godbole, Suneeta; Kerr, Jacqueline; Natarajan, Loki; Patterson, Ruth E.; Hartman, Sheri J.

2015-01-01

Purpose To explore the relationship between objectively measured physical activity and cognitive functioning in breast cancer survivors. Methods Participants were 136 postmenopausal breast cancer survivors. Cognitive functioning was assessed using a comprehensive computerized neuropsychological test. 7-day physical activity was assessed using hip-worn accelerometers. Linear regression models examined associations of minutes per day of physical activity at various intensities on individual cognitive functioning domains. The partially adjusted model controlled for primary confounders (model 1), and subsequent adjustments were made for chemotherapy history (model 2), and BMI (model 3). Interaction and stratified models examined BMI as an effect modifier. Results Moderate-to-vigorous physical activity (MVPA) was associated with Information Processing Speed. Specifically, ten minutes of MVPA was associated with a 1.35-point higher score (out of 100) on the Information Processing Speed domain in the partially adjusted model, and a 1.29-point higher score when chemotherapy was added to the model (both p<.05). There was a significant BMI x MVPA interaction (p=.051). In models stratified by BMI (<25 vs. ≥25 kg/m2), the favorable association between MVPA and Information Processing Speed was stronger in the subsample of overweight and obese women (p<.05), but not statistically significant in the leaner subsample. Light-intensity physical activity was not significantly associated with any of the measured domains of cognitive function. Conclusions MVPA may have favorable effects on Information Processing Speed in breast cancer survivors, particularly among overweight or obese women. Implications for Cancer Survivors Interventions targeting increased physical activity may enhance aspects of cognitive function among breast cancer survivors. PMID:25304986

Intensity modulated radiotherapy with fixed collimator jaws for locoregional left-sided breast cancer irradiation.

PubMed

Wang, Juanqi; Yang, Zhaozhi; Hu, Weigang; Chen, Zhi; Yu, Xiaoli; Guo, Xiaomao

2017-05-16

The purpose of this study is to evaluate the intensity modulated radiotherapy (IMRT) with the fixed collimator jaws technique (FJT) for the left breast and regional lymph node. The targeted breast tissue and the lymph nodes, and the normal tissues were contoured for 16 left-sided breast cancer patients previously treated with radiotherapy after lumpectomy. For each patient, treatment plans using different planning techniques, i.e., volumetric modulated arc therapy (VMAT), tangential IMRT (tangential-IMRT), and IMRT with FJT (FJT-IMRT) were developed for dosimetric comparisons. A dose of 50Gy was prescribed to the planning target volume. The dose-volume histograms were generated, and the paired t-test was used to analyze the dose differences. FJT-IMRT had similar mean heart volume receiving 30Gy (V30 Gy) with tangential-IMRT (1.5% and 1.6%, p = 0.41), but inferior to the VMAT (0.8%, p < 0.001). In the average heart mean dose comparison, FJT-IMRT had the lowest value, and it was 0.6Gy lower than that for the VMAT plans (p < 0.01). A significant dose increase in the contralateral breast and lung was observed in VMAT plans. Compared with tangential-IMRT and VMAT plans, FJT-IMRT reduced the mean dose of thyroid, humeral head and cervical esophageal by 47.6% (p < 0.01) and 45.7% (p < 0.01), 74.3% (p =< 0.01) and 73% (p =< 0.01), and 26.7% (p =< 0.01) and 29.2% (p =< 0.01). In conclusion, compared with tangential-IMRT and VMAT, FJT-IMRT plan has the lowest thyroid, humeral head and cervical esophageal mean dose and it can be a reasonable treatment option for a certain subgroup of patients, such as young left-breast cancer patients and/or patients with previous thyroid disease.

Intensity modulated radiotherapy with simultaneous integrated boost vs. conventional radiotherapy with sequential boost for breast cancer - A preliminary result.

PubMed

Lee, Hsin-Hua; Hou, Ming-Feng; Chuang, Hung-Yi; Huang, Ming-Yii; Tsuei, Le-Ping; Chen, Fang-Ming; Ou-Yang, Fu; Huang, Chih-Jen

2015-10-01

This study was aimed to assess the acute dermatological adverse effect from two distinct RT techniques for breast cancer patients. We compared intensity-modulated radiotherapy with simultaneous integrated boost (IMRT-SIB) and conventional radiotherapy followed by sequential boost (CRT-SB). The study population was composed of 126 consecutive female breast cancer patients treated with breast conserving surgery. Sixty-six patients received IMRT-SIB to 2 dose levels simultaneously. They received 50.4 Gy at 1.8 Gy per fraction to the whole breast and 60.2 Gy at 2.15 Gy per fraction to the tumor bed by integral boost. Sixty patients in the CRT-SB group received 50 Gy in 25 fractions to the whole breast followed by a boost irradiation to tumor bed in 5-7 fractions to a total dose of 60-64 Gy. Acute skin toxicities were documented in agreement with the Common Terminology Criteria for Adverse Events version 3 (CTCAE v.3.0). Ninety-eight patients had grade 1 radiation dermatitis while 14 patients had grade 2. Among those with grade 2, there were 3 patients in IMRT-SIB group (4.5%) while 11 in CRT-SB group (18.3%). (P = 0.048) There was no patient with higher than grade 2 toxicity. Three year local control was 99.2%, 3-year disease free survival was 97.5% and 3-year overall survival was 99.2%. A significant reduction in the severity of acute radiation dermatitis from IMRT-SIB comparing with CRT-SB is demonstrated. Copyright © 2015 Elsevier Ltd. All rights reserved.

Multibeam inverse intensity-modulated radiotherapy (IMRT) for whole breast irradiation: a single center experience in China.

PubMed

Yang, Zhaozhi; Zhang, Li; Chen, Xingxing; Ma, Jinli; Mei, Xin; Chen, Jiayi; Yu, Xiaoli; Guo, Xiaomao

2015-10-27

To present the clinical experience in our cancer center with multibeam inverse intensity-modulated radiotherapy (IMRT) for early stage breast cancer (BC) patients with whole breast irradiation (WBI). We retrospectively analyzed 622 patients with Stage 0 to III BC treated from 2008 to 2011 with wide local excision and WBI, using an inverse IMRT technique. All of the patients were prescribed a total dose of 50 Gy to the whole breast in 2-Gy fractions, followed by a tumor bed boost of 10 Gy in 5 fractions using an electron beam. Of all of the patients, 132 (21.2%) received whole breast plus regional lymph node (RLN) irradiation. 438 of 622 patients had records of acute skin toxicity based on common terminology criteria (CTC) for adverse events. Two hundred eighty (64%) patients had Grade 0/1 toxicity, 153 (35%) had Grade 2 and only 4 patients experienced grade 3 toxicity. Seventy patients (16%) had moist desquamation. Univariate analysis revealed that breast planning target volume was the only predictive factor for Grade ≥2 acute dermatitis (P = 0.002). After 4 years, 170 patients reported cosmetic results by self-assessment, of whom 151 (89%) patients reported good/excellent cosmetic results, and 17 (11%) patients reported fair assessments. For invasive cancer, the four-year rate of freedom from locoregional recurrence survival was 98.3%. Regarding carcinoma in situ, no patients experienced recurrence. BC patients who underwent conservative surgery followed by inverse IMRT plan exhibited acceptable acute toxicities and clinical outcomes. Longer follow-up is needed.

Proton therapy for locally advanced breast cancer: A systematic review of the literature.

PubMed

Kammerer, Emmanuel; Guevelou, Jennifer Le; Chaikh, Abdulhamid; Danhier, Serge; Geffrelot, Julien; Levy, Christelle; Saloux, Eric; Habrand, Jean-Louis; Thariat, Juliette

2018-02-01

Radiation therapy plays a major role in the management of adjuvant breast cancer with nodal involvement, with an iatrogenic increase of cardio-vascular risk. Photon therapy, even with intensity modulation, has the downsides of high mean heart dose and heterogeneous target coverage, particularly in the case of internal mammary irradiation. This systematic review of the literature aims to evaluate proton therapy in locally advanced breast cancer. PubMed was searched for original full-text articles with the following search terms: «Proton Therapy» and «Breast Cancer». On-going trials were collected using the words "Breast Cancer" and "Protons". 13 articles met the criteria: 6 with passive proton therapy (Double Scattering), 5 with Pencil Beam Scanning (PBS) and 2 with a combination of both. Proton therapy offered a better target coverage than photons, even compared with intensity modulation radiation therapy (including static or rotational IMRT or tomotherapy). With proton therapy, volumes receiving 95% of the dose were around 98%, with low volumes receiving 105% of the dose. Proton therapy often decreased mean heart dose by a factor of 2 or 3, i.e. 1 Gy with proton therapy versus 3 Gy with conventional 3D, and 6 Gy for IMRT. Lungs were better spared with proton therapy than with photon therapy. Cutaneous toxicity observed with double scattering is improved with PBS. Proton therapy reduces mean heart dose in breast cancer irradiation, probably reducing late cardio-vascular toxicity. Large clinical studies will likely confirm a clinical benefit of proton therapy. Copyright © 2017 Elsevier Ltd. All rights reserved.

A comparative analysis of 3D conformal deep inspiratory–breath hold and free-breathing intensity-modulated radiation therapy for left-sided breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reardon, Kelli A.; Read, Paul W.; Morris, Monica M.

2013-07-01

Patients undergoing radiation for left-sided breast cancer have increased rates of coronary artery disease. Free-breathing intensity-modulated radiation therapy (FB-IMRT) and 3-dimensional conformal deep inspiratory–breath hold (3D-DIBH) reduce cardiac irradiation. The purpose of this study is to compare the dose to organs at risk in FB-IMRT vs 3D-DIBH for patients with left-sided breast cancer. Ten patients with left-sided breast cancer had 2 computed tomography scans: free breathing and voluntary DIBH. Optimization of the IMRT plan was performed on the free-breathing scan using 6 noncoplanar tangential beams. The 3D-DIBH plan was optimized on the DIBH scan and used standard tangents. Mean volumesmore » of the heart, the left anterior descending coronary artery (LAD), the total lung, and the right breast receiving 5% to 95% (5% increments) of the prescription dose were calculated. Mean volumes of the heart and the LAD were lower (p<0.05) in 3D-DIBH for volumes receiving 5% to 80% of the prescription dose for the heart and 5% for the LAD. Mean dose to the LAD and heart were lower in 3D-DIBH (p≤0.01). Mean volumes of the total lung were lower in FB-IMRT for dose levels 20% to 75% (p<0.05), but mean dose was not different. Mean volumes of the right breast were not different for any dose; however, mean dose was lower for 3D-DIBH (p = 0.04). 3D-DIBH is an alternative approach to FB-IMRT that provides a clinically equivalent treatment for patients with left-sided breast cancer while sparing organs at risk with increased ease of implementation.« less

MDA-9/Syntenin (SDCBP) modulates small GTPases RhoA and Cdc42 via transforming growth factor β1 to enhance epithelial-mesenchymal transition in breast cancer.

PubMed

Menezes, Mitchell E; Shen, Xue-Ning; Das, Swadesh K; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B

2016-12-06

Epithelial-mesenchymal transition (EMT) is one of the decisive steps regulating cancer invasion and metastasis. However, the molecular mechanisms underlying this transition require further clarification. MDA-9/syntenin (SDCBP) expression is elevated in breast cancer patient samples as well as cultured breast cancer cells. Silencing expression of MDA-9 in mesenchymal metastatic breast cancer cells triggered a change in cell morphology in both 2D- and 3D-cultures to a more epithelial-like phenotype, along with changes in EMT markers, cytoskeletal rearrangement and decreased invasion. Conversely, over expressing MDA-9 in epithelial non-metastatic breast cancer cells instigated a change in morphology to a more mesenchymal phenotype with corresponding changes in EMT markers, cytoskeletal rearrangement and an increase in invasion. We also found that MDA-9 upregulated active levels of known modulators of EMT, the small GTPases RhoA and Cdc42, via TGFβ1. Reintroducing TGFβ1 in MDA-9 silenced cells restored active RhoA and cdc42 levels, modulated cytoskeletal rearrangement and increased invasion. We further determined that MDA-9 interacts with TGFβ1 via its PDZ1 domain. Finally, in vivo studies demonstrated that silencing the expression of MDA-9 resulted in decreased lung metastasis and TGFβ1 re-expression partially restored lung metastases. Our findings provide evidence for the relevance of MDA-9 in mediating EMT in breast cancer and support the potential of MDA-9 as a therapeutic target against metastatic disease.

Multipixel frequency-domain imaging of spontaneous canine breast disease using fluorescent contrast agents

NASA Astrophysics Data System (ADS)

Reynolds, Jeffery S.; Thompson, Alan B.; Troy, Tamara L.; Mayer, Ralf H.; Waters, David J.; Sevick-Muraca, Eva M.

1999-07-01

In this paper we demonstrate the ability to detect the frequency-domain fluorescent signal from the contrast agent indocyanine green within the mammary chain of dogs with spontaneous mammary tumors. We use a gain-modulated image intensifier to rapidly capture multi-pixel images of the fluorescent modulation amplitude, modulation phase, and average intensity signals. Excitation is provided by a 100 MHz amplitude-modulated, 780 nm laser diode. Time series images of the uptake and clearance of the contrast agent in the diseased tissue are also presented.

Five-year Results of Whole Breast Intensity Modulated Radiation Therapy for the Treatment of Early Stage Breast Cancer: The Fox Chase Cancer Center Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Keller, Lanea M.M., E-mail: Lanea.Keller@fccc.edu; Sopka, Dennis M.; Li Tianyu

Purpose: To report the 5-year outcomes using whole-breast intensity-modulated radiation therapy (IMRT) for the treatment of early-stage-breast cancer at the Fox Chase Cancer Center. Methods and Materials: A total of 946 women with early-stage breast cancer (stage 0, I, or II) were treated with IMRT after surgery with or without systemic therapy from 2003-2010. Whole-breast radiation was delivered via an IMRT technique with a median whole-breast radiation dose of 46 Gy and median tumor bed boost of 14 Gy. Endpoints included local-regional recurrence, cosmesis, and late complications. Results: With a median follow-up of 31 months (range, 1-97 months), there weremore » 12 ipsilateral breast tumor recurrences (IBTR) and one locoregional recurrence. The 5-year actuarial IBTR and locoregional recurrence rates were 2.0% and 2.4%. Physician-reported cosmestic outcomes were available for 645 patients: 63% were considered 'excellent', 33% 'good', and <1.5% 'fair/poor'. For physician-reported cosmesis, boost doses {>=}16 Gy, breast size >900 cc, or boost volumes >34 cc were significantly associated with a 'fair/poor' cosmetic outcome. Fibrosis, edema, erythema, and telangectasia were also associated with 'fair/poor' physician-reported cosmesis; erythema and telangectasia remained significant on multivariate analysis. Patient-reported cosmesis was available for 548 patients, and 33%, 50%, and 17% of patients reported 'excellent', 'good', and 'fair/poor' cosmesis, respectively. The use of a boost and increased boost volume: breast volume ratio were significantly associated with 'fair/poor' outcomes. No parameter for patient-reported cosmesis was significant on multivariate analysis. The chances of experiencing a treatment related effect was significantly associated with a boost dose {>=}16 Gy, receipt of chemotherapy and endocrine therapy, large breast size, and electron boost energy. Conclusions: Whole-breast IMRT is associated with very low rates of local recurrence at 5 years, 83%-98% 'good/excellent' cosmetic outcomes, and minimal chronic toxicity, including late fibrosis.« less

Automation and Intensity Modulated Radiation Therapy for Individualized High-Quality Tangent Breast Treatment Plans

DOE Office of Scientific and Technical Information (OSTI.GOV)

Purdie, Thomas G., E-mail: Tom.Purdie@rmp.uhn.on.ca; Department of Radiation Oncology, University of Toronto, Toronto, Ontario; Techna Institute, University Health Network, Toronto, Ontario

Purpose: To demonstrate the large-scale clinical implementation and performance of an automated treatment planning methodology for tangential breast intensity modulated radiation therapy (IMRT). Methods and Materials: Automated planning was used to prospectively plan tangential breast IMRT treatment for 1661 patients between June 2009 and November 2012. The automated planning method emulates the manual steps performed by the user during treatment planning, including anatomical segmentation, beam placement, optimization, dose calculation, and plan documentation. The user specifies clinical requirements of the plan to be generated through a user interface embedded in the planning system. The automated method uses heuristic algorithms to definemore » and simplify the technical aspects of the treatment planning process. Results: Automated planning was used in 1661 of 1708 patients receiving tangential breast IMRT during the time interval studied. Therefore, automated planning was applicable in greater than 97% of cases. The time for treatment planning using the automated process is routinely 5 to 6 minutes on standard commercially available planning hardware. We have shown a consistent reduction in plan rejections from plan reviews through the standard quality control process or weekly quality review multidisciplinary breast rounds as we have automated the planning process for tangential breast IMRT. Clinical plan acceptance increased from 97.3% using our previous semiautomated inverse method to 98.9% using the fully automated method. Conclusions: Automation has become the routine standard method for treatment planning of tangential breast IMRT at our institution and is clinically feasible on a large scale. The method has wide clinical applicability and can add tremendous efficiency, standardization, and quality to the current treatment planning process. The use of automated methods can allow centers to more rapidly adopt IMRT and enhance access to the documented improvements in care for breast cancer patients, using technologies that are widely available and already in clinical use.« less

Automation and intensity modulated radiation therapy for individualized high-quality tangent breast treatment plans.

PubMed

Purdie, Thomas G; Dinniwell, Robert E; Fyles, Anthony; Sharpe, Michael B

2014-11-01

To demonstrate the large-scale clinical implementation and performance of an automated treatment planning methodology for tangential breast intensity modulated radiation therapy (IMRT). Automated planning was used to prospectively plan tangential breast IMRT treatment for 1661 patients between June 2009 and November 2012. The automated planning method emulates the manual steps performed by the user during treatment planning, including anatomical segmentation, beam placement, optimization, dose calculation, and plan documentation. The user specifies clinical requirements of the plan to be generated through a user interface embedded in the planning system. The automated method uses heuristic algorithms to define and simplify the technical aspects of the treatment planning process. Automated planning was used in 1661 of 1708 patients receiving tangential breast IMRT during the time interval studied. Therefore, automated planning was applicable in greater than 97% of cases. The time for treatment planning using the automated process is routinely 5 to 6 minutes on standard commercially available planning hardware. We have shown a consistent reduction in plan rejections from plan reviews through the standard quality control process or weekly quality review multidisciplinary breast rounds as we have automated the planning process for tangential breast IMRT. Clinical plan acceptance increased from 97.3% using our previous semiautomated inverse method to 98.9% using the fully automated method. Automation has become the routine standard method for treatment planning of tangential breast IMRT at our institution and is clinically feasible on a large scale. The method has wide clinical applicability and can add tremendous efficiency, standardization, and quality to the current treatment planning process. The use of automated methods can allow centers to more rapidly adopt IMRT and enhance access to the documented improvements in care for breast cancer patients, using technologies that are widely available and already in clinical use. Copyright © 2014 Elsevier Inc. All rights reserved.

Automated planning of tangential breast intensity-modulated radiotherapy using heuristic optimization.

PubMed

Purdie, Thomas G; Dinniwell, Robert E; Letourneau, Daniel; Hill, Christine; Sharpe, Michael B

2011-10-01

To present an automated technique for two-field tangential breast intensity-modulated radiotherapy (IMRT) treatment planning. A total of 158 planned patients with Stage 0, I, and II breast cancer treated using whole-breast IMRT were retrospectively replanned using automated treatment planning tools. The tools developed are integrated into the existing clinical treatment planning system (Pinnacle(3)) and are designed to perform the manual volume delineation, beam placement, and IMRT treatment planning steps carried out by the treatment planning radiation therapist. The automated algorithm, using only the radio-opaque markers placed at CT simulation as inputs, optimizes the tangential beam parameters to geometrically minimize the amount of lung and heart treated while covering the whole-breast volume. The IMRT parameters are optimized according to the automatically delineated whole-breast volume. The mean time to generate a complete treatment plan was 6 min, 50 s ± 1 min 12 s. For the automated plans, 157 of 158 plans (99%) were deemed clinically acceptable, and 138 of 158 plans (87%) were deemed clinically improved or equal to the corresponding clinical plan when reviewed in a randomized, double-blinded study by one experienced breast radiation oncologist. In addition, overall the automated plans were dosimetrically equivalent to the clinical plans when scored for target coverage and lung and heart doses. We have developed robust and efficient automated tools for fully inversed planned tangential breast IMRT planning that can be readily integrated into clinical practice. The tools produce clinically acceptable plans using only the common anatomic landmarks from the CT simulation process as an input. We anticipate the tools will improve patient access to high-quality IMRT treatment by simplifying the planning process and will reduce the effort and cost of incorporating more advanced planning into clinical practice. Crown Copyright © 2011. Published by Elsevier Inc. All rights reserved.

Predicted Risk of Radiation-Induced Cancers After Involved Field and Involved Node Radiotherapy With or Without Intensity Modulation for Early-Stage Hodgkin Lymphoma in Female Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Weber, Damien C., E-mail: damien.weber@unige.ch; Johanson, Safora; Peguret, Nicolas

2011-10-01

Purpose: To assess the excess relative risk (ERR) of radiation-induced cancers (RIC) in female patients with Hodgkin lymphoma (HL) female patients treated with conformal (3DCRT), intensity modulated (IMRT), or volumetric modulated arc (RA) radiation therapy. Methods and Materials: Plans for 10 early-stage HL female patients were computed for 3DCRT, IMRT, and RA with involved field RT (IFRT) and involvednode RT (INRT) radiation fields. Organs at risk dose--volume histograms were computed and inter-compared for IFRT vs. INRT and 3DCRT vs. IMRT/RA, respectively. The ERR for cancer induction in breasts, lungs, and thyroid was estimated using both linear and nonlinear models. Results:more » The mean estimated ERR for breast, lung, and thyroid were significantly lower (p < 0.01) with INRT than with IFRT planning, regardless of the radiation delivery technique used, assuming a linear dose-risk relationship. We found that using the nonlinear model, the mean ERR values were significantly (p < 0.01) increased with IMRT or RA compared to those with 3DCRT planning for the breast, lung, and thyroid, using an IFRT paradigm. After INRT planning, IMRT or RA increased the risk of RIC for lung and thyroid only. Conclusions: In this comparative planning study, using a nonlinear dose--risk model, IMRT or RA increased the estimated risk of RIC for breast, lung, and thyroid for HL female patients. This study also suggests that INRT planning, compared to IFRT planning, may reduce the ERR of RIC when risk is predicted using a linear model. Observing the opposite effect, with a nonlinear model, however, questions the validity of these biologically parameterized models.« less

Role of extracellular matrix in regulation of staurosporine-induced apoptosis in breast cancer cells.

PubMed

Vasaturo, F; Malacrino, C; Sallusti, E; Coppotelli, G; Birarelli, P; Giuffrida, A; Albonici, L; Simonelli, L; Modesti, A; Modesti, M; Scarpa, S

2005-04-01

Autocrine and paracrine mechanisms modulate the synthesis and secretion of extracellular matrix (ECM); moreover, each component of the ECM is capable of modulating the synthesis and release of other ECM molecules. Therefore, the synthesis of ECM glycoprotein fibronectin and laminin was studied in the human breast cancer cell lines MCF7 and MDA MB 23, plated on different ECM. Our results showed that the cells plated on a fibronectin substrate increased laminin synthesis: this event correlated with an increase in alpha2 and alpha3 integrin subunits. Staurosporine-induced apoptosis was then analyzed in the cell lines plated on different ECM. Staurosporine treatment determined the apoptosis of 35 and 33% respectively of MDA MB 231 and MCF7; these values increased to 60 and 64% in cells plated on laminin, to 48 and 63% in cells plated on fibronectin and to 64 and 69% in cells plated on matrigel. Moreover, staurosporine treatment decreased bcl-2 expression in the cells plated on fibronectin and laminin. Yet, staurosporine treatment determined PARP cleavage and PARP partial disappearance when the cells were plated on matrigel. Finally, a partial loss of function mutant Ras protein that activated only Raf pathway, was expressed in MCF7, in order to identify whether the increase of apoptosis induced by extracellular matrix involved the Raf/MAP kinase pathway. The increase of apoptosis of the cells plated on matrigel suggested that the activation of the Raf pathway is probably involved in the decrease of survival on matrigel. These data demonstrate that the modification of ECM modulates the apoptotic process of breast cancer cells and suggest that it is worthwhile to dissect the role of ECM in the control of apoptotic process.

Heart-sparing radiotherapy in patients with breast cancer: What are the techniques used in the clinical routine?: A pattern of practice survey in the German-speaking countries.

PubMed

Duma, Marciana-Nona; Münch, Stefan; Oechsner, Markus; Combs, Stephanie E

2017-01-01

The aim of this study was to understand the practice of care in German-speaking countries with regard to heart-sparing radiotherapy techniques. Between August 2015 and September 2015, an e-mail/fax-based survey was sent to radiation oncology departments in Germany, Austria, and the German-speaking Switzerland. The questionnaire was divided into 3 chapters: a general chapter on the department, a chapter specific for heart-sparing techniques in patients with breast cancer, and a third chapter on personal beliefs on the topic of heart sparing in patients with breast cancer. A total of 82 radiation oncology departments answered the questionnaire: 16 university clinics and 66 other departments. In general, heart-sparing techniques are being offered by 90.2% of departments for radiation oncology in the German-speaking countries. However, in the clinical routine, 87.7% of institutions use heart-sparing techniques in less than 50% of patients with breast cancer. Heart-sparing techniques are especially provided for patients with left-sided breast cancer (80%), patients after mastectomy (52.5%), and when the mammaria interna lymph drainage vessels are irradiated (41.3%). In 46.3% of departments, there are written internal guidelines for heart sparing in patients with breast cancer. Breathing-adapted radiotherapy is used as the most frequent heart-sparing technique in 64.7% of the institutions, followed by intensity-modulated radiation therapy, which is most frequently used by 22.1%. The only significant difference between university hospitals and other departments was seen for the offering of partial breast irradiation. The most commonly used heart-sparing technique is breathing-adapted radiotherapy, but there is no coherent approach for heart sparing in patients with breast cancer in the German-speaking countries. Overall, all options for cardiac protection/cardiac avoidance have their advantages and disadvantages, with deep inspiration breath-hold radiotherapyhaving the most clear data, which should be the preferred choice when using heart-sparing techniques. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Arsenic induces functional re-expression of estrogen receptor α by demethylation of DNA in estrogen receptor-negative human breast cancer.

PubMed

Du, Juan; Zhou, Nannan; Liu, Hongxia; Jiang, Fei; Wang, Yubang; Hu, Chunyan; Qi, Hong; Zhong, Caiyun; Wang, Xinru; Li, Zhong

2012-01-01

Estrogen receptor α (ERα) is a marker predictive for response of breast cancers to endocrine therapy. About 30% of breast cancers, however, are hormone- independent because of lack of ERα expression. New strategies are needed for re-expression of ERα and sensitization of ER-negative breast cancer cells to selective ER modulators. The present report shows that arsenic trioxide induces reactivated ERα, providing a target for therapy with ER antagonists. Exposure of ER-negative breast cancer cells to arsenic trioxide leads to re-expression of ERα mRNA and functional ERα protein in in vitro and in vivo. Luciferase reporter gene assays and 3-(4,5-dimethylthiazol-2-yl)- 5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (MTS) assays show that, upon exposure to arsenic trioxide, formerly unresponsive, ER-negative MDA-MB-231 breast cancer cells become responsive to ER antagonists, 4-hydroxytamoxifen and ICI 182,780. Furthermore, methylation- specific PCR and bisulfite-sequencing PCR assays show that arsenic trioxide induces partial demethylation of the ERα promoter. A methyl donor, S-adenosylmethionine (SAM), reduces the degree of arsenic trioxide-induced re-expression of ERα and demethylation. Moreover, Western blot and ChIP assays show that arsenic trioxide represses expression of DNMT1 and DNMT3a along with partial dissociation of DNMT1 from the ERα promoter. Thus, arsenic trioxide exhibits a previously undefined function which induces re-expression ERα in ER-negative breast cancer cells through demethylation of the ERα promoter. These findings could provide important information regarding the application of therapeutic agents targeting epigenetic changes in breast cancers and potential implication of arsenic trioxide as a new drug for the treatment of ER-negative human breast cancer.

Radiographic findings after treatment with balloon brachytherapy accelerated partial breast irradiation.

PubMed

Ibrahim, Nafisa B; Anandan, Srividya; Hartman, Audrey L; McSweeney, Michelle; Chun, Jeanette; McKee, Andrea; Yang, Rebecca; Kim, Cathleen

2015-01-01

The use of accelerated partial breast irradiation (APBI) following breast-conserving surgery is rapidly gaining popularity as an alternative to whole-breast irradiation (WBI) in selected patients with early-stage breast cancer. Although data on the long-term effectiveness and safety of APBI accelerated partial breast irradiation are still being gathered, the shorter treatment course and narrowed radiation target of APBI accelerated partial breast irradiation provide an attractive alternative for carefully selected patients. These patients include those with relatively small tumors (≤3 cm), negative or close margins, and negative sentinel lymph nodes. Possible long-term complications include telangiectasia and the development of a palpable mass at the lumpectomy site. Mammographic findings in patients who have undergone APBI accelerated partial breast irradiation are distinct from those in patients who have undergone conventional WBI whole-breast irradiation . The most common post-APBI accelerated partial breast irradiation radiographic findings include formation of seromas at the lumpectomy site, focal parenchymal changes such as increased trabeculation and parenchymal distortion, fat necrosis, and skin changes such as thickening or retraction. Given the continued evolution of breast cancer treatment, it is important that radiologists have a comprehensive understanding of APBI accelerated partial breast irradiation in terms of rationale, patient selection criteria, common postprocedural radiographic findings (and how they differ from post-WBI whole-breast irradiation findings), and advantages and potential complications. RSNA, 2015

[Do breast-feeding and "diet" milks have any preventive or curative effect in the management of atopic dermatitis in children?].

PubMed

de Boissieu, D

2005-01-01

A) The preventive interest of infants' food in the onset of atopic dermatitis. Measures of prevention of atopic dermatitis concern predisposed children. Most studies agree on the protective effect of breast feeding for at least 3 to 4 months, compared with industrial milk products, on the onset of atopic dermatitis. Partial breast feeding is not protective. There is no preventive effect of breast feeding on the onset of atopic dermatitis in the absence of a family history of atopy. However, a few studies have raised the question of the aggravation of eczema during prolonged breast feeding. The "breast fed" group is probably not a homogenous group. Mothers' milk contains IgA, TGFb-type cytokines and long-chain polyinsaturated fatty acids that may play an important part in the acquisition of tolerance to food and the prevention of atopic dermatitis. The administration of a protein hydrolysate is preferable in terms of prevention of an allergy to a formula based on cow's milk, but does not provide any benefit compared with breast feeding. The preventive effect on atopic dermatitis of a casein hydrolysate is greater than that of a partial hydrolysate, which itself is greater than a formula based on cow's milk. In conclusion, the first preventive measure is breast feeding for 3 to 4 months, associated with intensive protein hydrolysate in the case of mixed feeding. In the absence of breast feeding, intensive hydrolysate is recommended in children at high risk. B) The curative interest of infants' food in the management of atopic dermatitis. The curative interest implies the responsibility of food in the triggering-off or maintenance of atopic dermatitis. This concerns non-diversified infants exhibiting severe or moderate eczema concomitant to digestive disorders. In such cases, the diagnosis of food allergy should be evoked. If the infant is fed on industrial milk, a test diet should be proposed with a hydrolysate or based on amino acids, followed by the re-introduction of the formula used previously. If the infant is exclusively breast fed, diagnosis of an allergy to one of the foodstuffs ingested by the mother should be searched for and treated. Early diagnosis of food allergy in infants, before diversification, is the optimal factor of prognosis.

Male breast cancer arising in ectopic axillary breast tissue: A diagnostic dilemma.

PubMed

Xie, Yangchun; Huang, Jin; Xiao, Desheng; Zhong, Meizuo

2013-06-01

Male breast cancer arising in ectopic axillary breast tissue is a rare occurrence and few cases have been reported in the literature. Due to its rarity, male axillary breast cancer is easy to misdiagnose. As for adenocarcinoma in the axilla, it is difficult to identify whether the origin is the mammary tissue or the skin appendages, particularly in cases where there is a poor differentiation. The present study reports the case of a male patient with a right axillary lesion that had been present for 6 months. A histological evaluation revealed the features of a poorly-differentiated adenocarcinoma with regards to the pathological report. The patient was diagnosed with a metastatic adenocarcinoma with unknown primary origin. However, following 4 cycles of intensive chemotherapy, the patient experienced bone metastasis while the local lesion was in partial remission. Further immunohistochemistry confirmed its mammary origin. There is limited literature relating to male ectopic axillary breast cancer, and a high probability of misdiagnosis of this disease.

Male breast cancer arising in ectopic axillary breast tissue: A diagnostic dilemma

PubMed Central

XIE, YANGCHUN; HUANG, JIN; XIAO, DESHENG; ZHONG, MEIZUO

2013-01-01

Male breast cancer arising in ectopic axillary breast tissue is a rare occurrence and few cases have been reported in the literature. Due to its rarity, male axillary breast cancer is easy to misdiagnose. As for adenocarcinoma in the axilla, it is difficult to identify whether the origin is the mammary tissue or the skin appendages, particularly in cases where there is a poor differentiation. The present study reports the case of a male patient with a right axillary lesion that had been present for 6 months. A histological evaluation revealed the features of a poorly-differentiated adenocarcinoma with regards to the pathological report. The patient was diagnosed with a metastatic adenocarcinoma with unknown primary origin. However, following 4 cycles of intensive chemotherapy, the patient experienced bone metastasis while the local lesion was in partial remission. Further immunohistochemistry confirmed its mammary origin. There is limited literature relating to male ectopic axillary breast cancer, and a high probability of misdiagnosis of this disease. PMID:23833669

Crocetin shifts autophagic cell survival to death of breast cancer cells in chemotherapy.

PubMed

Zhang, Ailian; Li, Jincheng

2017-03-01

The chemotherapy with fluorouracil is not always effective, in which some breast cancer cells may survive the fluorouracil treatment through enhanced autophagy. Crocetin is the major constituent of saffron, a Chinese traditional herb, which has recently found to have multiple pharmacological effects, including anticancer. However, the effects of Crocetin on the outcome of fluorouracil therapy for breast cancer have not been studied. Here, we showed that fluorouracil treatment inhibited the growth of breast cancer cells, in either a Cell Counting Kit-8 assay or an MTT assay. Inhibition of autophagy further suppressed breast cancer cell growth, suggesting that the breast cancer cells increased autophagic cell survival during fluorouracil treatment. However, Crocetin significantly increased the suppressive effects of fluorouracil on breast cancer cell growth, without affecting either cell apoptosis or autophagy. Inhibition of autophagy at the presence of Crocetin partially abolished the suppressive effects on breast cancer cell growth, suggesting that Crocetin may increase autophagic cell death in fluorouracil-treated breast cancer cells. Furthermore, Crocetin decreased Beclin-1 levels but increased ATG1 levels in fluorouracil-treated breast cancer cells. Together, these data suggest that Crocetin may shift autophagic cell survival to autophagic cell death in fluorouracil-treated breast cancer cells, possibly through modulation of the expression of ATG1 and Beclin-1.

Wavelength-Modulated Differential Photoacoustic Spectroscopy (WM-DPAS): Theory of a High-Sensitivity Methodology for the Detection of Early-Stage Tumors in Tissues

NASA Astrophysics Data System (ADS)

Choi, S.; Mandelis, A.; Guo, X.; Lashkari, B.; Kellnberger, S.; Ntziachristos, V.

2015-06-01

In the field of medical diagnostics, biomedical photoacoustics (PA) is a non-invasive hybrid optical-ultrasonic imaging modality. Due to the unique hybrid capability of optical and acoustic imaging, PA imaging has risen to the frontiers of medical diagnostic procedures such as human breast cancer detection. While conventional PA imaging has been mainly carried out by a high-power pulsed laser, an alternative technology, the frequency domain biophotoacoustic radar (FD-PAR) is under intensive development. It utilizes a continuous wave optical source with the laser intensity modulated by a frequency-swept waveform for acoustic wave generation. The small amplitude of the generated acoustic wave is significantly compensated by increased signal-to-noise ratio (several orders of magnitude) using matched-filter and pulse compression correlation processing in a manner similar to radar systems. The current study introduces the theory of a novel FD-PAR modality for ultra-sensitive characterization of functional information for breast cancer imaging. The newly developed theory of wavelength-modulated differential PA spectroscopy (WM-DPAS) detection has been introduced to address angiogenesis and hypoxia monitoring, two well-known benchmarks of breast tumor formation. Based on the WM-DPAS theory, this modality efficiently suppresses background absorptions and is expected to detect very small changes in total hemoglobin concentration and oxygenation levels, thereby identifying pre-malignant tumors before they are anatomically apparent. An experimental system design for the WM-DPAS is presented and preliminary single-ended laser experimental results were obtained and compared to a limiting case of the developed theoretical formalism.

Anterior Myocardial Territory May Replace the Heart as Organ at Risk in Intensity-Modulated Radiotherapy for Left-Sided Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tan Wenyong; Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology, Huazhong University of Science and Technology, Wuhan; Liu Dong

Purpose: We investigated whether the heart could be replaced by the anterior myocardial territory (AMT) as the organ at risk (OAR) in intensity-modulated radiotherapy (IMRT) of the breast for patients with left-sided breast cancer. Methods and Materials: Twenty-three patients with left-sided breast cancer who received postoperative radiation after breast-conserving surgery were studied. For each patient, we generated five IMRT plans including heart (H), left ventricle (LV), AMT, LV+AMT, and H+LV as the primary OARs, respectively, except both lungs and right breast, which corresponded to IMRT(H), IMRT(LV), IMRT(AMT), IMRT(LV+AMT), and IMRT(H+LV). For the planning target volumes and OARs, the parameters ofmore » dose-volume histograms were compared. Results: The homogeneity index, conformity index, and coverage index were not compromised significantly in IMRT(AMT), IMRT(LV) and IMRT(LV+ AMT), respectively, when compared with IMRT(H). The mean dose to the heart, LV, and AMT decreased 5.3-21.5% (p < 0.05), 19.9-29.5% (p < 0.05), and 13.3-24.5% (p < 0.05), respectively. Similarly, the low (e.g., V5%), middle (e.g., V20%), and high (e.g., V30%) dose-volume of the heart, LV, and AMT decreased with different levels. The mean dose and V10% of the right lung increased by 9.2% (p < 0.05) and 27.6% (p < 0.05), respectively, in IMRT(LV), and the mean dose and V5% of the right breast decreased significantly in IMRT(AMT) and IMRT(LV+AMT). IMRT(AMT) was the preferred plan and was then compared with IMRT(H+LV); the majority of dose-volume histogram parameters of OARs including the heart, LV, AMT, both lungs, and the right breast were not statistically different. However, the low dose-volume of LV increased and the middle dose-volume decreased significantly (p < 0.05) in IMRT(AMT). Also, those of the right lung (V10%, V15%) and right breast (V5%, V10%) decreased significantly (p < 0.05). Conclusions: The AMT may replace the heart as the OAR in left-sided breast IMRT after breast-conserving surgery to decrease the radiation dose to the heart.« less

Individualized Selection of Beam Angles and Treatment Isocenter in Tangential Breast Intensity Modulated Radiation Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Penninkhof, Joan, E-mail: j.penninkhof@erasmusmc.nl; Spadola, Sara; Department of Physics and Astronomy, Alma Mater Studiorum, University of Bologna, Bologna

Purpose and Objective: Propose a novel method for individualized selection of beam angles and treatment isocenter in tangential breast intensity modulated radiation therapy (IMRT). Methods and Materials: For each patient, beam and isocenter selection starts with the fully automatic generation of a large database of IMRT plans (up to 847 in this study); each of these plans belongs to a unique combination of isocenter position, lateral beam angle, and medial beam angle. The imposed hard planning constraint on patient maximum dose may result in plans with unacceptable target dose delivery. Such plans are excluded from further analyses. Owing to differencesmore » in beam setup, database plans differ in mean doses to organs at risk (OARs). These mean doses are used to construct 2-dimensional graphs, showing relationships between: (1) contralateral breast dose and ipsilateral lung dose; and (2) contralateral breast dose and heart dose (analyzed only for left-sided). The graphs can be used for selection of the isocenter and beam angles with the optimal, patient-specific tradeoffs between the mean OAR doses. For 30 previously treated patients (15 left-sided and 15 right-sided tumors), graphs were generated considering only the clinically applied isocenter with 121 tangential beam angle pairs. For 20 of the 30 patients, 6 alternative isocenters were also investigated. Results: Computation time for automatic generation of 121 IMRT plans took on average 30 minutes. The generated graphs demonstrated large variations in tradeoffs between conflicting OAR objectives, depending on beam angles and patient anatomy. For patients with isocenter optimization, 847 IMRT plans were considered. Adding isocenter position optimization next to beam angle optimization had a small impact on the final plan quality. Conclusion: A method is proposed for individualized selection of beam angles in tangential breast IMRT. This may be especially important for patients with cardiac risk factors or an enhanced risk for the development of contralateral breast cancer.« less

Evolution of singularities in a partially coherent vortex beam.

PubMed

van Dijk, Thomas; Visser, Taco D

2009-04-01

We study the evolution of phase singularities and coherence singularities in a Laguerre-Gauss beam that is rendered partially coherent by letting it pass through a spatial light modulator. The original beam has an on-axis minumum of intensity--a phase singularity--that transforms into a maximum of the far-field intensity. In contrast, although the original beam has no coherence singularities, such singularities are found to develop as the beam propagates. This disappearance of one kind of singularity and the gradual appearance of another is illustrated with numerical examples.

SU-F-T-314: Estimation of Dose Distributions with Different Types of Breast Implants in Various Radiation Treatment Techniques for Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, M; Lee, S; Suh, T

Purpose: This study investigates the effects of different kinds and designs of commercialized breast implants on the dose distributions in breast cancer radiotherapy under a variety of conditions. Methods: The dose for the clinical conventional tangential irradiation, Intensity Modulated Radiation Therapy (IMRT), volumetric modulated arc therapy (VMAT) breast plans was measured using radiochromic films and stimulated luminescence dosimeter (OSLD). The radiochromic film was used as an integrating dosimeter, while the OSLDs were used for real-time dosimetry to isolate the contribution of dose from individual segment. The films were placed at various slices in the Rando phantom and between the bodymore » and breast surface OSLDs were used to measure skin dose at 18 positions spaced on the two (right/left) breast. The implant breast was placed on the left side and the phantom breast was remained on the right side. Each treatment technique was performed on different size of the breasts and different shape of the breast implant. The PTV dose was prescribed 50.4 Gy and V47.88≥95%. Results: In different shapes of the breast implant, because of the shadow formed extensive around the breast implant, dose variation was relatively higher that of prescribed dose. As the PTV was delineated on the whole breast, maximum 5% dose error and average 3% difference was observed averagely. VMAT techniques largely decrease the contiguous hot spot in the skin by an average of 25% compared with IMRT. The both IMRT and VMAT techniques resulted in lower doses to normal critical structures than tangential plans for nearly all dose analyzation. Conclusion: Compared to the other technique, IMRT reduced radiation dose exposure to normal tissues and maintained reasonable target homogeneity and for the same target coverage, VMAT can reduce the skin dose in all the regions of the body.« less

First clinical experience with a dedicated MRI-guided high-intensity focused ultrasound system for breast cancer ablation.

PubMed

Merckel, Laura G; Knuttel, Floor M; Deckers, Roel; van Dalen, Thijs; Schubert, Gerald; Peters, Nicky H G M; Weits, Teun; van Diest, Paul J; Mali, Willem P Th M; Vaessen, Paul H H B; van Gorp, Joost M H H; Moonen, Chrit T W; Bartels, Lambertus W; van den Bosch, Maurice A A J

2016-11-01

To assess the safety and feasibility of MRI-guided high-intensity focused ultrasound (MR-HIFU) ablation in breast cancer patients using a dedicated breast platform. Patients with early-stage invasive breast cancer underwent partial tumour ablation prior to surgical resection. MR-HIFU ablation was performed using proton resonance frequency shift MR thermometry and an MR-HIFU system specifically designed for breast tumour ablation. The presence and extent of tumour necrosis was assessed by histopathological analysis of the surgical specimen. Pearson correlation coefficients were calculated to assess the relationship between sonication parameters, temperature increase and size of tumour necrosis at histopathology. Ten female patients underwent MR-HIFU treatment. No skin redness or burns were observed in any of the patients. No correlation was found between the applied energy and the temperature increase. In six patients, tumour necrosis was observed with a maximum diameter of 3-11 mm. In these patients, the number of targeted locations was equal to the number of areas with tumour necrosis. A good correlation was found between the applied energy and the size of tumour necrosis at histopathology (Pearson = 0.76, p = 0.002). Our results show that MR-HIFU ablation with the dedicated breast system is safe and results in histopathologically proven tumour necrosis. • MR-HIFU ablation with the dedicated breast system is safe and feasible • In none of the patients was skin redness or burns observed • No correlation was found between the applied energy and the temperature increase • The correlation between applied energy and size of tumour necrosis was good.

Second cancer incidence risk estimates using BEIR VII models for standard and complex external beam radiotherapy for early breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Donovan, E. M.; James, H.; Bonora, M.

2012-10-15

Purpose: To compare organ specific cancer incidence risks for standard and complex external beam radiotherapy (including cone beam CT verification) following breast conservation surgery for early breast cancer.Method: Doses from breast radiotherapy and kilovoltage cone beam CT (CBCT) exposures were obtained from thermoluminescent dosimeter measurements in an anthropomorphic phantom in which the positions of radiosensitive organs were delineated. Five treatment deliveries were investigated: (i) conventional tangential field whole breast radiotherapy (WBRT), (ii) noncoplanar conformal delivery applicable to accelerated partial beast irradiation (APBI), (iii) two-volume simultaneous integrated boost (SIB) treatment, (iv) forward planned three-volume SIB, and (v) inverse-planned three volume SIB.more » Conformal and intensity modulated radiotherapy methods were used to plan the complex treatments. Techniques spanned the range from simple methods appropriate for patient cohorts with a low cancer recurrence risk to complex plans relevant to cohorts with high recurrence risk. Delineated organs at risk included brain, salivary glands, thyroid, contralateral breast, left and right lung, esophagus, stomach, liver, colon, and bladder. Biological Effects of Ionizing Radiation (BEIR) VII cancer incidence models were applied to the measured mean organ doses to determine lifetime attributable risk (LAR) for ages at exposure from 35 to 80 yr according to radiotherapy techniques, and included dose from the CBCT imaging. Results: All LAR decreased with age at exposure and were lowest for brain, thyroid, liver, and bladder (<0.1%). There was little dependence of LAR on radiotherapy technique for these organs and for colon and stomach. LAR values for the lungs for the three SIB techniques were two to three times those from WBRT and APBI. Uncertainties in the LAR models outweigh any differences in lung LAR between the SIB methods. Constraints in the planning of the SIB methods ensured that contralateral breast doses and LAR were comparable to WBRT, despite their added complexity. The smaller irradiated volume of the ABPI plan contributed to a halving of LAR for contralateral breast compared with the other plan types. Daily image guided radiotherapy (IGRT) for a left breast protocol using kilovoltage CBCT contributed <10% to LAR for the majority of organs, and did not exceed 22% of total organ dose. Conclusions: Phantom measurements and calculations of LAR from the BEIR VII models predict that complex breast radiotherapy techniques do not increase the theoretical risk of second cancer incidence for organs distant from the treated breast, or the contralateral breast where appropriate plan constraints are applied. Complex SIB treatments are predicted to increase the risk of second cancer incidence in the lungs compared to standard whole breast radiotherapy; this is outweighed by the threefold reduction in 5 yr local recurrence risk for patients of high risk of recurrence, and young age, from the use of radiotherapy. APBI may have a favorable impact on risk of second cancer in the contralateral breast and lung for older patients at low risk of recurrence. Intensive use of IGRTincreased the estimated values of LAR but these are dominated by the effect of the dose from the radiotherapy, and any increase in LAR from IGRT is much lower than the models' uncertainties.« less

Quality-of-life results for accelerated partial breast irradiation with interstitial brachytherapy versus whole-breast irradiation in early breast cancer after breast-conserving surgery (GEC-ESTRO): 5-year results of a randomised, phase 3 trial.

PubMed

Schäfer, Rebekka; Strnad, Vratislav; Polgár, Csaba; Uter, Wolfgang; Hildebrandt, Guido; Ott, Oliver J; Kauer-Dorner, Daniela; Knauerhase, Hellen; Major, Tibor; Lyczek, Jaroslaw; Guinot, Jose Luis; Dunst, Jürgen; Miguelez, Cristina Gutierrez; Slampa, Pavel; Allgäuer, Michael; Lössl, Kristina; Kovács, György; Fischedick, Arnt-René; Fietkau, Rainer; Resch, Alexandra; Kulik, Anna; Arribas, Leo; Niehoff, Peter; Guedea, Ferran; Schlamann, Annika; Gall, Christine; Polat, Bülent

2018-04-20

Previous results from the GEC-ESTRO trial showed that accelerated partial breast irradiation (APBI) using multicatheter brachytherapy in the treatment of early breast cancer after breast-conserving surgery was non-inferior to whole-breast irradiation in terms of local control and overall survival. Here, we present 5-year results of patient-reported quality of life. We did this randomised controlled phase 3 trial at 16 hospitals and medical centres in seven European countries. Patients aged 40 years or older with 0-IIA breast cancer were randomly assigned (1:1) after breast-conserving surgery (resection margins ≥2 mm) to receive either whole-breast irradiation of 50 Gy with a boost of 10 Gy or APBI using multicatheter brachytherapy. Randomisation was stratified by study centre, tumour type, and menopausal status, with a block size of ten and an automated dynamic algorithm. There was no masking of patients or investigators. The primary endpoint of the trial was ipsilateral local recurrence. Here, we present 5-year results of quality of life (a prespecified secondary endpoint). Quality-of-life questionnaires (European Organisation for Research and Treatment of Cancer QLQ-C30, breast cancer module QLQ-BR23) were completed before radiotherapy (baseline 1), immediately after radiotherapy (baseline 2), and during follow-up. We analysed the data according to treatment received (as-treated population). Recruitment was completed in 2009, and long-term follow-up is continuing. The trial is registered at ClinicalTrials.gov, number NCT00402519. Between April 20, 2004, and July 30, 2009, 633 patients had accelerated partial breast irradiation and 551 patients had whole-breast irradiation. Quality-of-life questionnaires at baseline 1 were available for 334 (53%) of 663 patients in the APBI group and 314 (57%) of 551 patients in the whole-breast irradiation group; the response rate was similar during follow-up. Global health status (range 0-100) was stable in both groups: at baseline 1, APBI group mean score 65·5 (SD 20·6) versus whole-breast irradiation group 64·6 (19·6), p=0·37; at 5 years, APBI group 66·2 (22·2) versus whole-breast irradiation group 66·0 (21·8), p=0·94. The only moderate, significant difference (difference of 10-20 points) between the groups was found in the breast symptoms scale. Breast symptom scores were significantly higher (ie, worse) after whole-breast irradiation than after APBI at baseline 2 (difference of means 13·6, 95% CI 9·7-17·5; p<0·0001) and at 3-month follow-up (difference of means 12·7, 95% CI 9·8-15·6; p<0·0001). APBI with multicatheter brachytherapy was not associated with worse quality of life compared with whole-breast irradiation. This finding supports APBI as an alternative treatment option after breast-conserving surgery for patients with early breast cancer. German Cancer Aid. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dosimetric comparison of moderate deep inspiration breath-hold and free-breathing intensity-modulated radiotherapy for left-sided breast cancer.

PubMed

Chi, F; Wu, S; Zhou, J; Li, F; Sun, J; Lin, Q; Lin, H; Guan, X; He, Z

2015-05-01

This study determined the dosimetric comparison of moderate deep inspiration breath-hold using active breathing control and free-breathing intensity-modulated radiotherapy (IMRT) after breast-conserving surgery for left-sided breast cancer. Thirty-one patients were enrolled. One free breathe and two moderate deep inspiration breath-hold images were obtained. A field-in-field-IMRT free-breathing plan and two field-in-field-IMRT moderate deep inspiration breath-holding plans were compared in the dosimetry to target volume coverage of the glandular breast tissue and organs at risks for each patient. The breath-holding time under moderate deep inspiration extended significantly after breathing training (P<0.05). There was no significant difference between the free-breathing and moderate deep inspiration breath-holding in the target volume coverage. The volume of the ipsilateral lung in the free-breathing technique were significantly smaller than the moderate deep inspiration breath-holding techniques (P<0.05); however, there was no significant difference between the two moderate deep inspiration breath-holding plans. There were no significant differences in target volume coverage between the three plans for the field-in-field-IMRT (all P>0.05). The dose to ipsilateral lung, coronary artery and heart in the field-in-field-IMRT were significantly lower for the free-breathing plan than for the two moderate deep inspiration breath-holding plans (all P<0.05); however, there was no significant difference between the two moderate deep inspiration breath-holding plans. The whole-breast field-in-field-IMRT under moderate deep inspiration breath-hold with active breathing control after breast-conserving surgery in left-sided breast cancer can reduce the irradiation volume and dose to organs at risks. There are no significant differences between various moderate deep inspiration breath-holding states in the dosimetry of irradiation to the field-in-field-IMRT target volume coverage and organs at risks. Copyright © 2015 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Incorporating partial shining effects in proton pencil-beam dose calculation

NASA Astrophysics Data System (ADS)

Li, Yupeng; Zhang, Xiaodong; Fwu Lii, Ming; Sahoo, Narayan; Zhu, Ron X.; Gillin, Michael; Mohan, Radhe

2008-02-01

A range modulator wheel (RMW) is an essential component in passively scattered proton therapy. We have observed that a proton beam spot may shine on multiple steps of the RMW. Proton dose calculation algorithms normally do not consider the partial shining effect, and thus overestimate the dose at the proximal shoulder of spread-out Bragg peak (SOBP) compared with the measurement. If the SOBP is adjusted to better fit the plateau region, the entrance dose is likely to be underestimated. In this work, we developed an algorithm that can be used to model this effect and to allow for dose calculations that better fit the measured SOBP. First, a set of apparent modulator weights was calculated without considering partial shining. Next, protons spilled from the accelerator reaching the modulator wheel were simplified as a circular spot of uniform intensity. A weight-splitting process was then performed to generate a set of effective modulator weights with the partial shining effect incorporated. The SOBPs of eight options, which are used to label different combinations of proton-beam energy and scattering devices, were calculated with the generated effective weights. Our algorithm fitted the measured SOBP at the proximal and entrance regions much better than the ones without considering partial shining effect for all SOBPs of the eight options. In a prostate patient, we found that dose calculation without considering partial shining effect underestimated the femoral head and skin dose.

SU-F-T-537: Prone Breast Accelerated Partial Breast Irradiation Using Non-Coplanar Volumetric Arc Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beninati, G; Barbiere, J; Godfrey, L

2016-06-15

Purpose: To demonstrate that Volumetric Modulated Arc Therapy (VMAT) can be an alternative technique to Brachytherapy Accelerated Partial Breast Irradiation (APBI) for treating large breasted women. The non-coplanar VMAT technique uses a commercially available couch and a small number of angles. This technique with the patient in the prone position can reduce high skin and critical structure doses in large breasted women, which are usually associated with Brachytherapy APBI. Methods: Philips Pinnacle treatment planning system with Smart Arc was used to plan a left sided laterally located excision cavity on a standard prone breast patient setup. Three thirty-degree arcs enteredmore » from the lateral side at respective couch angles of 345, 0, and 15 degrees. A fourth thirty degree arc beam entered from the medial side at a couch angle of 0 degrees. The arcs were selected to avoid critical structures as much as possible. A test run was then performed to verify that the beams did not collide with the patient nor support structures. NSABP B-39/RTOG 0413 protocol guidelines were used for dose prescription, normal tissue, and target definition. Results: Dose Volume Histogram analysis indicated that all parameters were equal or better than RTOG recommendations. Of particular note regarding the plan quality:1.(a) For a prescribed dose of 3850cGy the PTV-EVAL target volume receiving 100 percent of the dose(V100) was 93; protocol recommendation is V90 > 90 percent. (b) Maximum dose was 110 percent versus the allowed 120 percent .2. Uninvolved percentage of normal breast V100 and V50 were 17 and 47 versus allowed 35 and 60 percent respectively.3. For the skin, V100 was 5.7cc and the max dose to 0.1 cc was 4190cGy. Conclusion: Prone Breast non-coplanar VMAT APBI can achieve better skin cosmesis and lower critical structure doses than Brachytherapy APBI.« less

Defining the Role of Free Flaps in Partial Breast Reconstruction.

PubMed

Smith, Mark L; Molina, Bianca J; Dayan, Erez; Jablonka, Eric M; Okwali, Michelle; Kim, Julie N; Dayan, Joseph H

2018-03-01

 Free flaps have a well-established role in breast reconstruction after mastectomy; however, their role in partial breast reconstruction remains poorly defined. We reviewed our experience with partial breast reconstruction to better understand indications for free tissue transfer.  A retrospective review was performed of all patients undergoing partial breast reconstruction at our center between February 2009 and October 2015. We evaluated the characteristics of patients who underwent volume displacement procedures versus volume replacement procedures and free versus pedicled flap reconstruction.  There were 78 partial breast reconstructions, with 52 reductions/tissue rearrangements (displacement group) and 26 flaps (replacement group). Bra cup size and body mass index (BMI) were significantly smaller in the replacement group. Fifteen pedicled and 11 free flaps were performed. Most pedicled flaps (80.0%) were used for lateral or upper pole defects. Most free flaps (72.7%) were used for medial and inferior defects or when there was inadequate donor tissue for a pedicled flap. Complications included hematoma, cellulitis, and one aborted pedicled flap.  Free and pedicled flaps are useful for partial breast reconstruction, particularly in breast cancer patients with small breasts undergoing breast-conserving treatment (BCT). Flap selection depends on defect size, location, and donor tissue availability. Medial defects are difficult to reconstruct using pedicled flaps due to arc of rotation and intervening breast tissue. Free tissue transfer can overcome these obstacles. Confirming negative margins before flap reconstruction ensures harvest of adequate volume and avoids later re-operation. Judicious use of free flaps for oncoplastic reconstruction expands the possibility for breast conservation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

From technological advances to biological understanding: The main steps toward high-precision RT in breast cancer.

PubMed

Leonardi, Maria Cristina; Ricotti, Rosalinda; Dicuonzo, Samantha; Cattani, Federica; Morra, Anna; Dell'Acqua, Veronica; Orecchia, Roberto; Jereczek-Fossa, Barbara Alicja

2016-10-01

Radiotherapy improves local control in breast cancer (BC) patients which increases overall survival in the long term. Improvements in treatment planning and delivery and a greater understanding of BC behaviour have laid the groundwork for high-precision radiotherapy, which is bound to further improve the therapeutic index. Precise identification of target volumes, better coverage and dose homogeneity have had a positive impact on toxicity and local control. The conformity of treatment dose due to three-dimensional radiotherapy and new techniques such as intensity modulated radiotherapy makes it possible to spare surrounding normal tissue. The widespread use of dose-volume constraints and histograms have increased awareness of toxicity. Real time image guidance has improved geometric precision and accuracy, together with the implementation of quality assurance programs. Advances in the precision of radiotherapy is also based on the choice of the appropriate fractionation and approach. Adaptive radiotherapy is not only a technical concept, but is also a biological concept based on the knowledge that different types of BC have distinctive patterns of locoregional spread. A greater understanding of cancer biology helps in choosing the treatment best suited to a particular situation. Biomarkers predictive of response play a crucial role. The combination of radiotherapy with molecular targeted therapies may enhance radiosensitivity, thus increasing the cytotoxic effects and improving treatment response. The appropriateness of an alternative fractionation, partial breast irradiation, dose escalating/de-escalating approaches, the extent of nodal irradiation have been examined for all the BC subtypes. The broadened concept of adaptive radiotherapy is vital to high-precision treatments. Copyright © 2016 Elsevier Ltd. All rights reserved.

Breast cancer instructs dendritic cells to prime interleukin 13–secreting CD4+ T cells that facilitate tumor development

PubMed Central

Aspord, Caroline; Pedroza-Gonzalez, Alexander; Gallegos, Mike; Tindle, Sasha; Burton, Elizabeth C.; Su, Dan; Marches, Florentina; Banchereau, Jacques; Palucka, A. Karolina

2007-01-01

We previously reported (Bell, D., P. Chomarat, D. Broyles, G. Netto, G.M. Harb, S. Lebecque, J. Valladeau, J. Davoust, K.A. Palucka, and J. Banchereau. 1999. J. Exp. Med. 190: 1417–1426) that breast cancer tumors are infiltrated with mature dendritic cells (DCs), which cluster with CD4+ T cells. We now show that CD4+ T cells infiltrating breast cancer tumors secrete type 1 (interferon γ) as well as high levels of type 2 (interleukin [IL] 4 and IL-13) cytokines. Immunofluorescence staining of tissue sections revealed intense IL-13 staining on breast cancer cells. The expression of phosphorylated signal transducer and activator of transcription 6 in breast cancer cells suggests that IL-13 actually delivers signals to cancer cells. To determine the link between breast cancer, DCs, and CD4+ T cells, we implanted human breast cancer cell lines in nonobese diabetic/LtSz-scid/scid β2 microglobulin–deficient mice engrafted with human CD34+ hematopoietic progenitor cells and autologous T cells. There, CD4+ T cells promote early tumor development. This is dependent on DCs and can be partially prevented by administration of IL-13 antagonists. Thus, breast cancer targets DCs to facilitate its development. PMID:17438063

Five-year Local Control in a Phase II Study of Hypofractionated Intensity Modulated Radiation Therapy With an Incorporated Boost for Early Stage Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Freedman, Gary M., E-mail: Gary.Freedman@uphs.upenn.edu; Anderson, Penny R.; Bleicher, Richard J.

Purpose: Conventional radiation fractionation of 1.8-2 Gy per day for early stage breast cancer requires daily treatment for 6-7 weeks. We report the 5-year results of a phase II study of intensity modulated radiation therapy (IMRT), hypofractionation, and incorporated boost that shortened treatment time to 4 weeks. Methods and Materials: The study design was phase II with a planned accrual of 75 patients. Eligibility included patients aged {>=}18 years, Tis-T2, stage 0-II, and breast conservation. Photon IMRT and an incorporated boost was used, and the whole breast received 2.25 Gy per fraction for a total of 45 Gy, and themore » tumor bed received 2.8 Gy per fraction for a total of 56 Gy in 20 treatments over 4 weeks. Patients were followed every 6 months for 5 years. Results: Seventy-five patients were treated from December 2003 to November 2005. The median follow-up was 69 months. Median age was 52 years (range, 31-81). Median tumor size was 1.4 cm (range, 0.1-3.5). Eighty percent of tumors were node negative; 93% of patients had negative margins, and 7% of patients had close (>0 and <2 mm) margins; 76% of cancers were invasive ductal type: 15% were ductal carcinoma in situ, 5% were lobular, and 4% were other histology types. Twenty-nine percent of patients 29% had grade 3 carcinoma, and 20% of patients had extensive in situ carcinoma; 11% of patients received chemotherapy, 36% received endocrine therapy, 33% received both, and 20% received neither. There were 3 instances of local recurrence for a 5-year actuarial rate of 2.7%. Conclusions: This 4-week course of hypofractionated radiation with incorporated boost was associated with excellent local control, comparable to historical results of 6-7 weeks of conventional whole-breast fractionation with sequential boost.« less

Light-driven phase shifter

DOEpatents

Early, James W.

1990-01-01

A light-driven phase shifter is provided for modulating a transmission light beam. A gaseous medium such as argon is provided with electron energy states excited to populate a metastable state. A tunable dye laser is selected with a wavelength effective to deplete the metastable electron state and may be intensity modulated. The dye laser is directed through the gaseous medium to define a first optical path having an index of refraction determined by the gaseous medium having a depleted metastable electron state. A transmission laser beam is also directed through the gaseous medium to define a second optical path at least partially coincident with the first optical path. The intensity of the dye laser beam may then be varied to phase modulate the transmission laser beam.

Treatment of left sided breast cancer for a patient with funnel chest: Volumetric-modulated arc therapy vs. 3D-CRT and intensity-modulated radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Haertl, Petra M., E-mail: petra.haertl@klinik.uni-regensburg.de; Pohl, Fabian; Weidner, Karin

2013-04-01

This case study presents a rare case of left-sided breast cancer in a patient with funnel chest, which is a technical challenge for radiation therapy planning. To identify the best treatment technique for this case, 3 techniques were compared: conventional tangential fields (3D conformal radiotherapy [3D-CRT]), intensity-modulated radiotherapy (IMRT), and volumetric-modulated arc therapy (VMAT). The plans were created for a SynergyS® (Elekta, Ltd, Crawley, UK) linear accelerator with a BeamModulator™ head and 6-MV photons. The planning system was Oncentra Masterplan® v3.3 SP1 (Nucletron BV, Veenendal, Netherlands). Calculations were performed with collapsed cone algorithm. Dose prescription was 50.4 Gy to themore » average of the planning target volume (PTV). PTV coverage and homogeneity was comparable for all techniques. VMAT allowed reducing dose to the ipsilateral organs at risk (OAR) and the contralateral breast compared with IMRT and 3D-CRT: The volume of the left lung receiving 20 Gy was 19.3% for VMAT, 26.1% for IMRT, and 32.4% for 3D-CRT. In the heart, a D{sub 15%} of 9.7 Gy could be achieved with VMAT compared with 14 Gy for IMRT and 46 Gy for 3D-CRT. In the contralateral breast, D{sub 15%} was 6.4 Gy for VMAT, 8.8 Gy for IMRT, and 10.2 Gy for 3D-CRT. In the contralateral lung, however, the lowest dose was achieved with 3D-CRT with D{sub 10%} of 1.7 Gy for 3D-CRT, and 6.7 Gy for both IMRT and VMAT. The lowest number of monitor units (MU) per 1.8-Gy fraction was required by 3D-CRT (192 MU) followed by VMAT (518 MU) and IMRT (727 MU). Treatment time was similar for 3D-CRT (3 min) and VMAT (4 min) but substantially increased for IMRT (13 min). VMAT is considered the best treatment option for the presented case of a patient with funnel chest. It allows reducing dose in most OAR without compromising target coverage, keeping delivery time well below 5 minutes.« less

Adoption of Hypofractionated Radiation Therapy for Breast Cancer After Publication of Randomized Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jagsi, Reshma, E-mail: rjagsi@med.umich.edu; Falchook, Aaron D.; Hendrix, Laura H.

2014-12-01

Purpose: Large randomized trials have established the noninferiority of shorter courses of “hypofractionated” radiation therapy (RT) to the whole breast compared to conventional courses using smaller daily doses in the adjuvant treatment of selected breast cancer patients undergoing lumpectomy. Hypofractionation is more convenient and less costly. Therefore, we sought to determine uptake of hypofractionated breast RT over time. Methods and Materials: In the Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database, we identified 16,096 women with node-negative breast cancer and 4269 with ductal carcinoma in situ (DCIS) who received lumpectomy followed by more than 12 fractions of RT between 2004 andmore » 2010. Based on Medicare claims, we determined the number of RT treatments given and grouped patients into those receiving hypofractionation (13-24) or those receiving conventional fractionation (≥25). We also determined RT technique (intensity modulated RT or not) using Medicare claims. We evaluated patterns and correlates of hypofractionation receipt using bivariate and multivariable analyses. Results: Hypofractionation use was similar in patients with DCIS and those with invasive disease. Overall, the use of hypofractionation increased from 3.8% in 2006 to 5.4% in 2007, to 9.4% in 2008, and to 13.6% in 2009 and 2010. Multivariable analysis showed increased use of hypofractionation in recent years and in patients with older age, smaller tumors, increased comorbidity, higher regional education, and Western SEER regions. However, even in patients over the age of 80, the hypofractionation rate in 2009 to 2010 was only 25%. Use of intensity modulated RT (IMRT) also increased over time (from 9.4% in 2004 to 22.7% in 2009-2010) and did not vary significantly between patients receiving hypofractionation and those receiving traditional fractionation. Conclusions: Hypofractionation use increased among low-risk older US breast cancer patients with publication and maturation of evidence from randomized trials, but overall use of this cost-saving approach remained low. This contrasts with the more rapid rate of adoption of IMRT in the same time period, a costly innovation supported by less strong evidence of benefit.« less

Modulating emission intensity of GaN-based green light emitting diodes on c-plane sapphire

DOE Office of Scientific and Technical Information (OSTI.GOV)

Du, Chunhua; Ma, Ziguang; Zhou, Junming

2014-04-14

The asymmetric dual-wavelength (green/blue) coupled InGaN/GaN multiple quantum wells were proposed to modulate the green emission intensity. Electroluminescent measurements demonstrate the conspicuous increment of the green light intensity by decreasing the coupled barrier thickness. This was partly attributed to capture of more carriers when holes tunnel across the thinner barrier from the blue quantum wells, as a hole reservoir, to the green quantum wells. While lower effective barrier height of the blue quantum wells benefits improved hole transportation from p-GaN to the active region. Efficiency droop of the green quantum wells was partially alleviated due to the enhanced injection efficiencymore » of holes.« less

Robust analysis of semiparametric renewal process models

PubMed Central

Lin, Feng-Chang; Truong, Young K.; Fine, Jason P.

2013-01-01

Summary A rate model is proposed for a modulated renewal process comprising a single long sequence, where the covariate process may not capture the dependencies in the sequence as in standard intensity models. We consider partial likelihood-based inferences under a semiparametric multiplicative rate model, which has been widely studied in the context of independent and identical data. Under an intensity model, gap times in a single long sequence may be used naively in the partial likelihood with variance estimation utilizing the observed information matrix. Under a rate model, the gap times cannot be treated as independent and studying the partial likelihood is much more challenging. We employ a mixing condition in the application of limit theory for stationary sequences to obtain consistency and asymptotic normality. The estimator's variance is quite complicated owing to the unknown gap times dependence structure. We adapt block bootstrapping and cluster variance estimators to the partial likelihood. Simulation studies and an analysis of a semiparametric extension of a popular model for neural spike train data demonstrate the practical utility of the rate approach in comparison with the intensity approach. PMID:24550568

Iterative dataset optimization in automated planning: Implementation for breast and rectal cancer radiotherapy.

PubMed

Fan, Jiawei; Wang, Jiazhou; Zhang, Zhen; Hu, Weigang

2017-06-01

To develop a new automated treatment planning solution for breast and rectal cancer radiotherapy. The automated treatment planning solution developed in this study includes selection of the iterative optimized training dataset, dose volume histogram (DVH) prediction for the organs at risk (OARs), and automatic generation of clinically acceptable treatment plans. The iterative optimized training dataset is selected by an iterative optimization from 40 treatment plans for left-breast and rectal cancer patients who received radiation therapy. A two-dimensional kernel density estimation algorithm (noted as two parameters KDE) which incorporated two predictive features was implemented to produce the predicted DVHs. Finally, 10 additional new left-breast treatment plans are re-planned using the Pinnacle 3 Auto-Planning (AP) module (version 9.10, Philips Medical Systems) with the objective functions derived from the predicted DVH curves. Automatically generated re-optimized treatment plans are compared with the original manually optimized plans. By combining the iterative optimized training dataset methodology and two parameters KDE prediction algorithm, our proposed automated planning strategy improves the accuracy of the DVH prediction. The automatically generated treatment plans using the dose derived from the predicted DVHs can achieve better dose sparing for some OARs without compromising other metrics of plan quality. The proposed new automated treatment planning solution can be used to efficiently evaluate and improve the quality and consistency of the treatment plans for intensity-modulated breast and rectal cancer radiation therapy. © 2017 American Association of Physicists in Medicine.

Mueller matrix polarimetry imaging for breast cancer analysis (Conference Presentation)

NASA Astrophysics Data System (ADS)

Gribble, Adam; Vitkin, Alex

2017-02-01

Polarized light has many applications in biomedical imaging. The interaction of a biological sample with polarized light reveals information about its biological composition, both structural and functional. The most comprehensive type of polarimetry analysis is to measure the Mueller matrix, a polarization transfer function that completely describes how a sample interacts with polarized light. However, determination of the Mueller matrix requires tissue analysis under many different states of polarized light; a time consuming and measurement intensive process. Here we address this limitation with a new rapid polarimetry system, and use this polarimetry platform to investigate a variety of tissue changes associated with breast cancer. We have recently developed a rapid polarimetry imaging platform based on four photoelastic modulators (PEMs). The PEMs generate fast polarization modulations that allow the complete sample Mueller matrix to be imaged over a large field of view, with no moving parts. This polarimetry system is then demonstrated to be sensitive to a variety of tissue changes that are relevant to breast cancer. Specifically, we show that changes in depolarization can reveal tumor margins, and can differentiate between viable and necrotic breast cancer metastasized to the lymph nodes. Furthermore, the polarimetric property of linear retardance (related to birefringence) is dependent on collagen organization in the extracellular matrix. These findings indicate that our polarimetry platform may have future applications in fields such as breast cancer diagnosis, improving the speed and efficacy of intraoperative pathology, and providing prognostic information that may be beneficial for guiding treatment.

A new breast cancer risk analysis approach using features extracted from multiple sub-regions on bilateral mammograms

NASA Astrophysics Data System (ADS)

Sun, Wenqing; Tseng, Tzu-Liang B.; Zheng, Bin; Zhang, Jianying; Qian, Wei

2015-03-01

A novel breast cancer risk analysis approach is proposed for enhancing performance of computerized breast cancer risk analysis using bilateral mammograms. Based on the intensity of breast area, five different sub-regions were acquired from one mammogram, and bilateral features were extracted from every sub-region. Our dataset includes 180 bilateral mammograms from 180 women who underwent routine screening examinations, all interpreted as negative and not recalled by the radiologists during the original screening procedures. A computerized breast cancer risk analysis scheme using four image processing modules, including sub-region segmentation, bilateral feature extraction, feature selection, and classification was designed to detect and compute image feature asymmetry between the left and right breasts imaged on the mammograms. The highest computed area under the curve (AUC) is 0.763 ± 0.021 when applying the multiple sub-region features to our testing dataset. The positive predictive value and the negative predictive value were 0.60 and 0.73, respectively. The study demonstrates that (1) features extracted from multiple sub-regions can improve the performance of our scheme compared to using features from whole breast area only; (2) a classifier using asymmetry bilateral features can effectively predict breast cancer risk; (3) incorporating texture and morphological features with density features can boost the classification accuracy.

Simultaneous integrated boost with intensity modulated radiation therapy in brain oligometastases: A feasible technique for developing countries

PubMed Central

Tiwari, Vivek; Pande, Subodh C.; Verma, Kamal; Goel, Sandeep

2015-01-01

Introduction: To analyze the pattern of brain metastasis (BM), and to use intensity modulated radiation therapy (IMRT) for target dose escalation in cases with ≤3 metastatic lesions (oligometastases). Materials and Methods: Thirty-two consecutive cases of BM treated during September 2009 to August 2012 were analyzed retrospectively. Results: The study comprised 13 males (40.62%) and 19 females (59.37%). Thirteen (40%) patients presented with disseminated intracranial metastases, while 19 (60%) had ≤3 foci. In 25 cases (78%), the primary was located either in the breast (14 cases) or lung (11 cases). The 13 patients with disseminated intracranial metastases received whole brain radiation therapy to a dose of 30 Gy/10-12 daily fractions (Group A) while the 19 cases with ≤3 lesions received an additional dose of 6-10 Gy to gross lesions using a simultaneous integrated boost (SIB) with IMRT thus receiving a total dose of 36-40 Gy/12-15 fractions (Group B). Overall survival (OS) for the breast primary was 6.3 and lung primary was 5.3 months, respectively. The mean OS for breast cases in Group B was higher (9.5 months) as compared to Group A cases (1.9 months) and was statistically significant (P = 0.0056). Similarly, primary lung cancer cases in Group B showed a mean OS of 8.75 months versus 2.6 months for Group A cases (P = 0.213). Conclusions: IMRT is a safe and effective technique in cases with oligometastases for dose escalation in the form of SIB. PMID:25839012

Does the 1H-NMR plasma metabolome reflect the host-tumor interactions in human breast cancer?

PubMed

Richard, Vincent; Conotte, Raphaël; Mayne, David; Colet, Jean-Marie

2017-07-25

Breast cancer (BC) is the most common diagnosed cancer and the leading cause of cancer death in women worldwide. There is an obvious need for a better understanding of BC biology. Alterations in the serum metabolome of BC patients have been identified but their clinical significance remains elusive. We evaluated by 1H-Nuclear Magnetic Resonance (1H-NMR) spectroscopy, filtered plasma metabolome of 50 early (EBC) and 15 metastatic BC (MBC) patients. Using Principal Component Analysis, Partial Least-Squares Discriminant Analysis and Hierarchical Clustering we show that plasma levels of glucose, lactate, pyruvate, alanine, leucine, isoleucine, glutamate, glutamine, valine, lysine, glycine, threonine, tyrosine, phenylalanine, acetate, acetoacetate, β-hydroxy-butyrate, urea, creatine and creatinine are modulated across patients clusters. In particular lactate levels are inversely correlated with the tumor size in the EBC cohort (Pearson correlation r = -0.309; p = 0.044). We suggest that, in BC patients, tumor cells could induce modulation of the whole patient's metabolism even at early stages. If confirmed in a lager study these observations could be of clinical importance.

Cyclophosphamide dose intensification may circumvent anthracycline resistance of p53 mutant breast cancers.

PubMed

Lehmann-Che, Jacqueline; André, Fabrice; Desmedt, Christine; Mazouni, Chafika; Giacchetti, Sylvie; Turpin, Elisabeth; Espié, Marc; Plassa, Louis-François; Marty, Michel; Bertheau, Philippe; Sotiriou, Christos; Piccart, Martine; Symmans, W Fraser; Pusztai, Lajos; de Thé, Hugues

2010-01-01

The predictive value of p53 for the efficacy of front-line anthracycline-based chemotherapy regimens has been a matter of significant controversy. Anthracyclines are usually combined with widely different doses of alkylating agents, which may significantly modulate tumor response to these combinations. We analyzed three series of de novo stage II-III breast cancer patients treated front line with anthracycline-based regimens of various cyclophosphamide dose intensities: 65 patients with estrogen receptor (ER)(-) tumors treated with anthracyclines alone (Institut Jules Bordet, Brussels), 51 unselected breast cancer patients treated with intermediate doses of cyclophosphamide (MD Anderson Cancer Center, Houston, TX), and 128 others treated with a dose-dense anthracycline-cyclophosphamide combination (St. Louis, Paris). After chemotherapy and surgery, pathologic complete response (pCR) was evaluated. p53 status was determined by a yeast functional assay on the pretreatment tumor sample. In a multivariate analysis of the pooled results, a lack of ER expression and high-dose cyclophosphamide administration were associated with a higher likelihood of pCR. A sharp statistical interaction was detected between p53 status and cyclophosphamide dose intensity. Indeed, when restricting our analysis to patients with ER(-) tumors, we confirmed that a mutant p53 status was associated with anthracycline resistance, but found that p53 inactivation was required for response to the dose-intense alkylating regimen. The latter allowed very high levels of pCR in triple-negative tumors. Thus, our data strongly suggest that cyclophosphamide dose intensification in ER(-) p53-mutated breast cancer patients could significantly improve their response.

Two distinct mTORC2-dependent pathways converge on Rac1 to drive breast cancer metastasis.

PubMed

Morrison Joly, Meghan; Williams, Michelle M; Hicks, Donna J; Jones, Bayley; Sanchez, Violeta; Young, Christian D; Sarbassov, Dos D; Muller, William J; Brantley-Sieders, Dana; Cook, Rebecca S

2017-06-30

The importance of the mTOR complex 2 (mTORC2) signaling complex in tumor progression is becoming increasingly recognized. HER2-amplified breast cancers use Rictor/mTORC2 signaling to drive tumor formation, tumor cell survival and resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapy. Cell motility, a key step in the metastatic process, can be activated by mTORC2 in luminal and triple negative breast cancer cell lines, but its role in promoting metastases from HER2-amplified breast cancers is not yet clear. Because Rictor is an obligate cofactor of mTORC2, we genetically engineered Rictor ablation or overexpression in mouse and human HER2-amplified breast cancer models for modulation of mTORC2 activity. Signaling through mTORC2-dependent pathways was also manipulated using pharmacological inhibitors of mTOR, Akt, and Rac. Signaling was assessed by western analysis and biochemical pull-down assays specific for Rac-GTP and for active Rac guanine nucleotide exchange factors (GEFs). Metastases were assessed from spontaneous tumors and from intravenously delivered tumor cells. Motility and invasion of cells was assessed using Matrigel-coated transwell assays. We found that Rictor ablation potently impaired, while Rictor overexpression increased, metastasis in spontaneous and intravenously seeded models of HER2-overexpressing breast cancers. Additionally, migration and invasion of HER2-amplified human breast cancer cells was diminished in the absence of Rictor, or upon pharmacological mTOR kinase inhibition. Active Rac1 was required for Rictor-dependent invasion and motility, which rescued invasion/motility in Rictor depleted cells. Rictor/mTORC2-dependent dampening of the endogenous Rac1 inhibitor RhoGDI2, a factor that correlated directly with increased overall survival in HER2-amplified breast cancer patients, promoted Rac1 activity and tumor cell invasion/migration. The mTORC2 substrate Akt did not affect RhoGDI2 dampening, but partially increased Rac1 activity through the Rac-GEF Tiam1, thus partially rescuing cell invasion/motility. The mTORC2 effector protein kinase C (PKC)α did rescue Rictor-mediated RhoGDI2 downregulation, partially rescuing Rac-guanosine triphosphate (GTP) and migration/motility. These findings suggest that mTORC2 uses two coordinated pathways to activate cell invasion/motility, both of which converge on Rac1. Akt signaling activates Rac1 through the Rac-GEF Tiam1, while PKC signaling dampens expression of the endogenous Rac1 inhibitor, RhoGDI2.

Can Intensity-Modulated Radiotherapy Preserve Oral Health-Related Quality of Life of Nasopharyngeal Carcinoma Patients?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pow, Edmond H.N., E-mail: ehnpow@hku.hk; Kwong, Dora L.W.; Sham, Jonathan S.T.

Purpose: To investigate the changes in salivary function and oral health-related quality of life for patients with nasopharyngeal carcinoma treated by intensity-modulated radiotherapy (IMRT). Methods and Materials: A total of 57 patients with early-stage nasopharyngeal carcinoma received IMRT. The parotid and whole saliva flow was measured, and the Medical Outcomes Study 36-item short form, European Organization for Research and Treatment of Cancer Quality of Life questionnaire-C30, European Organization for Research and Treatment of Cancer Quality of Life questionnaire 35-item head-and-neck module, and Oral Health Impact Profile questionnaires were completed at baseline and 2, 6, 12, 18, and 24 months aftermore » IMRT. Results: Parotid saliva flow recovered fully after 1 year and maintained. Whole saliva flow recovered partially to 40% of baseline. A general trend of deterioration in most quality of life scales was observed after IMRT, followed by gradual recovery. Persistent oral-related symptoms were found 2 years after treatment. Conclusion: IMRT for early-stage nasopharyngeal carcinoma could only partially preserve the whole salivary function and oral health-related quality of life.« less

Breast feeding and the older infant.

PubMed

Prentice, A

1991-01-01

The possible benefits and disadvantages to the older infant of breast-feeding being continued after the introduction of solid foods are reviewed. The limited evidence from industrialised countries suggests that prolonged partial breast-feeding has little influence on child health and growth. In contrast, in poor areas of the developing world, the continuation of breast-feeding for 1-2 years after the introduction of other foods appears to have several major benefits. These include the supply of nutrients, the delivery of protective, digestive and trophic agents, and extending the period of infertility in the mother. Partial breast-feeding after 6 months is associated with reduced severity of infectious diseases particularly in severely malnourished individuals. There is no evidence that partial breast-feeding plays a causal role in poor growth performance. In poor areas of the developing world, breast-feeding, together with the provision of adequate amounts of other foods, should be encouraged for the first two years of life.

A novel biphenyl urea derivate inhibits the invasion of breast cancer through the modulation of CXCR4

PubMed Central

Zhan, Yingzhuan; Zhang, Han; Li, Jing; Zhang, Yanmin; Zhang, Jie; He, Langchong

2015-01-01

The increased migration and invasion of breast carcinoma cells are key events in the development of metastasis to the lymph nodes and distant organs. CXCR4, the receptor for stromal-derived factor-1, is reportedly involved in breast carcinogenesis and invasion. In this study, we investigated a novel biphenyl urea derivate, TPD7 for its ability to affect CXCR4 expression as well as function in breast cancer cells. We demonstrated that TPD7 inhibited the breast cancer proliferation and down-regulated the CXCR4 expression on breast cancer cells both over-expressing and low-expressing HER2, an oncogene known to induce the chemokine receptor. Treatments with pharmacological proteasome inhibitors partial suppressed TPD7-induced decrease in CXCR4 expression. Real-time PCR analysis revealed that down-regulation of CXCR4 by TPD7 also occurred at the translational level. Inhibition of CXCR4 expression by TPD7 further correlated with the suppression of SDF-1α-induced migration and invasion in breast tumour cells, knockdown of CXCR4 attenuated TPD7-inhibitory effects. In addition, TPD7 treatment significantly suppressed matrix metalloproteinase (MMP)-2 and MMP-9 expression, the downstream targets of CXCR4, perhaps via inactivation of the ERK signaling pathway. Overall, our results showed that TPD7 exerted its anti-invasive effect through the down-regulation of CXCR4 expression and thus had the potential for the treatment of breast cancer. PMID:25753200

Partially coherent polarized atmospheric transmission characteristics and application technology research

NASA Astrophysics Data System (ADS)

Fu, Qiang; Gao, Duorui; Liu, Zhi; Chen, Chunyi; Lou, Yan; Jiang, Huilin

2014-11-01

Based on partially coherent polarized light transmission characteristics of the atmosphere, an intensity expression of completely coherent flashing light is derived from Andrews scale modulation method. According to the generalized Huygens-Fresnel principle and Rytov theory, the phase fluctuation structure function is obtained on condition that the refractive index profile in the atmosphere meet Von Karman spectrum, then get the arrival Angle fluctuation variance. Through the RMS beam width of gaussian beams in turbulent atmosphere, deviation angle formula of fully coherent gaussian beams in turbulence atmosphere is attained, then get the RMS beam width of partially coherent and derivation angle expression of GSM beam in turbulent atmosphere. Combined with transmission properties of radial polarized laser beam, cross spectral density matrix of partially coherent radially polarized light can be gained by using generalized huygens-fresnel principle. And light intensity and polarization after transmission can be known according to the unity of coherence and polarization theory. On the basis of the analysis model and numerical simulation, the simulation results show that: the light spot caused by atmospheric turbulence of partially coherent polarization will be superior to completely polarized light.Taking advantage of this feature, designed a new wireless suppression technology of atmospheric turbulence, that is the optimization criterion of initial degree of coherent light beam. The optimal initial degree of coherent light beam will change along with the change of atmospheric turbulence conditions,make control the beam's initial degree of coherence to realize the initial degree of coherence of light beam in real time and dynamic control. A spatial phase screen before emission aperture of fully coherent light is to generate the partially coherent light, liquid crystal spatial light modulator is is a preferable way to realize the dynamic random phase. Finally look future of the application research of partially coherent light.

In-depth characterization of breast cancer tumor-promoting cell transcriptome by RNA sequencing and microarrays

PubMed Central

Soldà, Giulia; Merlino, Giuseppe; Fina, Emanuela; Brini, Elena; Moles, Anna; Cappelletti, Vera; Daidone, Maria Grazia

2016-01-01

Numerous studies have reported the existence of tumor-promoting cells (TPC) with self-renewal potential and a relevant role in drug resistance. However, pathways and modifications involved in the maintenance of such tumor subpopulations are still only partially understood. Sequencing-based approaches offer the opportunity for a detailed study of TPC including their transcriptome modulation. Using microarrays and RNA sequencing approaches, we compared the transcriptional profiles of parental MCF7 breast cancer cells with MCF7-derived TPC (i.e. MCFS). Data were explored using different bioinformatic approaches, and major findings were experimentally validated. The different analytical pipelines (Lifescope and Cufflinks based) yielded similar although not identical results. RNA sequencing data partially overlapped microarray results and displayed a higher dynamic range, although overall the two approaches concordantly predicted pathway modifications. Several biological functions were altered in TPC, ranging from production of inflammatory cytokines (i.e., IL-8 and MCP-1) to proliferation and response to steroid hormones. More than 300 non-coding RNAs were defined as differentially expressed, and 2,471 potential splicing events were identified. A consensus signature of genes up-regulated in TPC was derived and was found to be significantly associated with insensitivity to fulvestrant in a public breast cancer patient dataset. Overall, we obtained a detailed portrait of the transcriptome of a breast cancer TPC line, highlighted the role of non-coding RNAs and differential splicing, and identified a gene signature with a potential as a context-specific biomarker in patients receiving endocrine treatment. PMID:26556871

Benefits of donor human milk for preterm infants: current evidence.

PubMed

Bertino, Enrico; Giuliani, Francesca; Occhi, Luciana; Coscia, Alessandra; Tonetto, Paola; Marchino, Federica; Fabris, Claudio

2009-10-01

It's undoubted that optimum nutrition for term infants is breastfeeding, exclusive for the first six months, then followed by a complementary diet and carried on, if possible, for the first year of life or even more. During the last decades several data confirmed the great advantages of fresh mother's milk use also for feeding very low and extremely low birthweight preterm infants. When mother's milk is unavailable or in short supply, pasteurized donor breast milk is widely used in neonatal intensive care units. Pasteurization partially affects nutritional and immunological properties of breast milk, however it is known that pasteurized milk maintains some biological properties and clinical benefits. The substantial benefits of mother's own milk feeding of preterm infants are supported by strong evidence. However, there is increasing evidence also on specific benefits of donor breast milk. Future research is needed to compare formula vs. nutrient fortified donor breast milk, to compare formula and DM as supplements to maternal milk rather than as sole diet and to compare effects of different methods of heat treatments on donor human milk quality.

Omega-3 docosahexaenoic acid induces pyroptosis cell death in triple-negative breast cancer cells.

PubMed

Pizato, Nathalia; Luzete, Beatriz Christina; Kiffer, Larissa Fernanda Melo Vasconcelos; Corrêa, Luís Henrique; de Oliveira Santos, Igor; Assumpção, José Antônio Fagundes; Ito, Marina Kiyomi; Magalhães, Kelly Grace

2018-01-31

The implication of inflammation in pathophysiology of several type of cancers has been under intense investigation. Omega-3 fatty acids can modulate inflammation and present anticancer effects, promoting cancer cell death. Pyroptosis is an inflammation related cell death and so far, the function of docosahexaenoic acid (DHA) in pyroptosis cell death has not been described. This study investigated the role of DHA in triggering pyroptosis activation in breast cancer cells. MDA-MB-231 breast cancer cells were supplemented with DHA and inflammation cell death was analyzed. DHA-treated breast cancer cells triggered increased caspase-1and gasdermin D activation, enhanced IL-1β secretion, translocated HMGB1 towards the cytoplasm, and membrane pore formation when compared to untreated cells, suggesting DHA induces pyroptosis programmed cell death in breast cancer cells. Moreover, caspase-1 inhibitor (YVAD) could protect breast cancer cells from DHA-induced pyroptotic cell death. In addition, membrane pore formation showed to be a lysosomal damage and ROS formation-depended event in breast cancer cells. DHA triggered pyroptosis cell death in MDA-MB-231by activating several pyroptosis markers in these cells. This is the first study that shows the effect of DHA triggering pyroptosis programmed cell death in breast cancer cells and it could improve the understanding of the omega-3 supplementation during breast cancer treatment.

Poster — Thur Eve — 10: Partial kV CBCT, complete kV CBCT and EPID in breast treatment: a dose comparison study for skin, breasts, heart and lungs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roussin, E; Archambault, L K; Wierzbicki, W

The advantages of kilovoltage cone beam CT (kV CBCT) imaging over electronic portal imaging device (EPID) such as accurate 3D anatomy, soft tissue visualization, fast rigid registration and enhanced precision on patient positioning has lead to its increasing use in clinics. The benefits of this imaging technique are at the cost of increasing the dose to healthy surrounding organs. Our center has moved toward the use of daily partial rotation kV CBCT to restrict the dose to healthy tissues. This study aims to better quantify radiation doses from different image-guidance techniques such as tangential EPID, complete and partial kV CBCTmore » for breast treatments. Cross-calibrated ionization chambers and kV calibrated Gafchromic films were used to measure the dose to the heart, lungs, breasts and skin. It was found that performing partial kV CBCT decreases the heart dose by about 36%, the lungs dose by 31%, the contralateral breast dose by 41% and the ipsilateral breast dose by 43% when compared to a full rotation CBCT. The skin dose measured for a full rotation CBCT was about 0.8 cGy for the contralateral breast and about 0.3 cGy for the ipsilateral breast. The study is still ongoing and results on skin doses for partial rotation kV CBCT as well as for tangential EPID images are upcoming.« less

Assessment of female breast dose for thoracic cone-beam CT using MOSFET dosimeters.

PubMed

Sun, Wenzhao; Wang, Bin; Qiu, Bo; Liang, Jian; Xie, Weihao; Deng, Xiaowu; Qi, Zhenyu

2017-03-21

To assess the breast dose during a routine thoracic cone-beam CT (CBCT) check with the efforts to explore the possible dose reduction strategy. Metal oxide semiconductor field-effect transistor (MOSFET) dosimeters were used to measure breast surface doses during a thorax kV CBCT scan in an anthropomorphic phantom. Breast doses for different scanning protocols and breast sizes were compared. Dose reduction was attempted by using partial arc CBCT scan with bowtie filter. The impact of this dose reduction strategy on image registration accuracy was investigated. The average breast surface doses were 20.02 mGy and 11.65 mGy for thoracic CBCT without filtration and with filtration, respectively. This indicates a dose reduction of 41.8% by use of bowtie filter. It was found 220° partial arc scanning significantly reduced the dose to contralateral breast (44.4% lower than ipsilateral breast), while the image registration accuracy was not compromised. Breast dose reduction can be achieved by using ipsilateral 220° partial arc scan with bowtie filter. This strategy also provides sufficient image quality for thorax image registration in daily patient positioning verification.

Dosimetric comparison of three intensity-modulated radiation therapies for left breast cancer after breast-conserving surgery.

PubMed

Zhang, Huai-Wen; Hu, Bo; Xie, Chen; Wang, Yun-Lai

2018-05-01

This study aimed to evaluate dosimetric differences of intensity-modulated radiation therapy (IMRT) in target and normal tissues after breast-conserving surgery. IMRT five-field plan I, IMRT six-field plan II, and field-in-field-direct machine parameter optimization-IMRT plan III were designed for each of the 50 patients. One-way analysis of variance was performed to compare differences, and P < 0.05 was considered statistically significant. Homogeneity index of plan III is lower than those of plans I and II. No difference was identified in conformity index of targets. Plan I exhibited difference in mean dose (D mean ) for the heart (P < 0.05). Plan I featured smaller irradiation dose volumes in V 5 , V 20 (P < 0.05) of the left lung than II. Plan I exhibited significantly higher V 5 in the right lung than plans II and III (P < 0.05). Under plan I, irradiation dose at V 5 in the right breast is higher than that in plans II and III. Patients in plan III presented less total monitor unit and total treatment time than those in plans I and II (P < 0.05). IMRT six-field plans II, and field-in-field-direct machine parameter optimization-IMRT plans III can reduce doses and volumes to the lungs and heart better while maintaining satisfying conformity index and homogeneity index of target. Nevertheless, plan II neglects target movements caused by respiration. In the same manner, plan III can substantially reduce MU and shorten patient treatment time. Therefore, plan III, which considers target movement caused by respiration, is a more practical radiation mode. © 2018 The Authors. Journal of Applied Clinical Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Planning hybrid intensity modulated radiation therapy for whole-breast irradiation.

PubMed

Farace, Paolo; Zucca, Sergio; Solla, Ignazio; Fadda, Giuseppina; Durzu, Silvia; Porru, Sergio; Meleddu, Gianfranco; Deidda, Maria Assunta; Possanzini, Marco; Orrù, Sivia; Lay, Giancarlo

2012-09-01

To test tangential and not-tangential hybrid intensity modulated radiation therapy (IMRT) for whole-breast irradiation. Seventy-eight (36 right-, 42 left-) breast patients were randomly selected. Hybrid IMRT was performed by direct aperture optimization. A semiautomated method for planning hybrid IMRT was implemented using Pinnacle scripts. A plan optimization volume (POV), defined as the portion of the planning target volume covered by the open beams, was used as the target objective during inverse planning. Treatment goals were to prescribe a minimum dose of 47.5 Gy to greater than 90% of the POV and to minimize the POV and/or normal tissue receiving a dose greater than 107%. When treatment goals were not achieved by using a 4-field technique (2 conventional open plus 2 IMRT tangents), a 6-field technique was applied, adding 2 non tangential (anterior-oblique) IMRT beams. Using scripts, manual procedures were minimized (choice of optimal beam angle, setting monitor units for open tangentials, and POV definition). Treatment goals were achieved by using the 4-field technique in 61 of 78 (78%) patients. The 6-field technique was applied in the remaining 17 of 78 (22%) patients, allowing for significantly better achievement of goals, at the expense of an increase of low-dose (∼5 Gy) distribution in the contralateral tissue, heart, and lungs but with no significant increase of higher doses (∼20 Gy) in heart and lungs. The mean monitor unit contribution to IMRT beams was significantly greater (18.7% vs 9.9%) in the group of patients who required 6-field procedure. Because hybrid IMRT can be performed semiautomatically, it can be planned for a large number of patients with little impact on human or departmental resources, promoting it as the standard practice for whole-breast irradiation. Copyright © 2012 Elsevier Inc. All rights reserved.

Intestinal microbiota in infants at high risk for allergy: Effects of prebiotics and role in eczema development.

PubMed

Wopereis, Harm; Sim, Kathleen; Shaw, Alexander; Warner, John O; Knol, Jan; Kroll, J Simon

2018-04-01

Development of the gut microbiota in infancy is important in maturation of the immune system. Deviations in colonization patterns have been associated with allergic manifestations such as eczema, but exact microbiome dysfunctions underlying allergies remain unclear. We studied the gut microbiota of 138 infants at increased risk of allergy, participating in a clinical trial investigating the effectiveness of a partially hydrolyzed protein formula supplemented with nondigestible oligosaccharides on the prevention of eczema. The effects of interventions and breast-feeding on fecal microbiota were investigated. Additionally, we aimed to identify microbial patterns associated with the onset of eczema. Bacterial taxonomic compositions in the first 26 weeks of life were analyzed by using 16S rRNA gene sequencing. Additionally, fecal pH and microbial metabolite levels were measured. Fecal microbial composition, metabolites, and pH of infants receiving partially hydrolyzed protein formula supplemented with nondigestible oligosaccharides was closer to that of breast-fed infants than that of infants receiving standard cow's milk formula. Infants with eczema by 18 months showed discordant development of bacterial genera of Enterobacteriaceae and Parabacteroides species in the first 26 weeks, as well as decreased acquisition of lactate-utilizing bacteria producing butyrate, namely Eubacterium and Anaerostipes species, supported by increased lactate and decreased butyrate levels. We showed that a partially hydrolyzed protein infant formula with specific prebiotics modulated the gut microbiota closer to that of breast-fed infants. Additionally, we identified a potential link between microbial activity and onset of eczema, which might reflect a suboptimal implementation of gut microbiota at specific developmental stages in infants at high risk for allergy. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

SU-E-T-79: A Study of the Effect of Clinical Tumor Volume Displacement On the Dosage of Post Modified Radical Mastectomy Intensity-Modulated Radiation Therapy Plans for Left-Sided Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhang, W; Ma, C; Li, D

Purpose: To explore the effect of clinical tumor volume (CTV) displacement on the dosage of intensity-modulated radiation therapy (IMRT) plans for left-sided breast cancer after modified radical mastectomy. Methods: We created 2 sets of IMRT plans based on PTV0.5 and PTV0.7 (with CTV displacement of 0.5cm and 0.7cm respectively) for each of the ten consecutive left-sided breast cancer patients after modified radical mastectomy, and compared the difference in PTV coverage and organ at risk (OAR) sparing between the two groups. And then, we compared the difference in PTV coverage in IMRT plans based on PTV0.5 between the group with properlymore » estimated CTV displacement (presuming the actual CTV displacement was 0.5cm) and the one with underestimated CTV displacement (presuming the actual CTV displacement was 0.7cm). The difference in results between the corresponding two groups was compared using paired-sample t-test. P values less than 0.05 were considered statistically significant. Results: IMRT plans derived from PTV0.5 had more homogenous PTV coverage, and less heart, left lung, right breast, right lung, left humeral head and B-P radiation exposure, as well as less total Mu as compared with the ones stemmed from PTV0.7 (all p<0.05). IMRT plans with appropriate estimation of CTV displacement had better PTV coverage compared with the ones with underestimated CTV displacement (all p<0.01). Conclusion: The IMRT plans with smaller CTV displacement in post modified radical mastectomy radiotherapy for left-sided breast cancer has dosimetrical advantages over the ones with larger CTV displacement. Underestimation of CTV displacement can lead to significant reduction of PTV coverage. Individually quantifying and minimizing CTV displacement can significantly improve PTV coverage and OAR (including heart and left lung) sparing. This work was supported by the Medical Scientific Research Foundation of Guangdong Procvince (A2014455 to Changchun Ma)« less

Impact of healthy eating practices and physical activity on quality of life among breast cancer survivors.

PubMed

Mohammadi, Shooka; Sulaiman, Suhaina; Koon, Poh Bee; Amani, Reza; Hosseini, Seyed Mohammad

2013-01-01

Following breast cancer diagnosis, women often attempt to modify their lifestyles to improve their health and prevent recurrence. These behavioral changes typically involve diet and physical activity modification. The aim of this study was to determine association between healthy eating habits and physical activity with quality of life among Iranian breast cancer survivors. A total of 100 Iranian women, aged between 32 to 61 years were recruited to participate in this cross-sectional study. Eating practices were evaluated by a validated questionnaire modified from the Women's Healthy Eating and Living (WHEL) study. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). A standardized questionnaire by the European Organization of Research and Treatment of Cancer Quality of Life and its breast cancer module (EORTC QLQ-C30/+BR-23) were applied to determine quality of life. Approximately 29% of the cancer survivors were categorized as having healthy eating practices, 34% had moderate eating practices and 37% had poor eating practices based on nutrition guidelines. The study found positive changes in the decreased intake of fast foods (90%), red meat (70%) and increased intake of fruits (85%) and vegetables (78%). Generally, breast cancer survivors with healthy eating practices had better global quality of life, social, emotional, cognitive and role functions. Result showed that only 12 women (12%) met the criteria for regular vigorous exercise, 22% had regular moderate-intensity exercise while the majority (65%) had low-intensity physical activity. Breast cancer survivors with higher level of physical activity had better emotional and cognitive functions. Healthy eating practices and physical activity can improve quality of life of cancer survivors. Health care professionals should promote good dietary habits and physical activity to improve survivors' health and quality of life.

Ultrasound-Based Guidance for Partial Breast Irradiation Therapy

DTIC Science & Technology

2011-01-01

and also are inexpensive. b. Collect US data from patient before the PBI treatment at the same time that CT is collected (months 2-14). We...introduces minimal divergence from the original workflow of PBI treatment. We have an approved institutional review board (IRB) protocol to obtain B...irradiation of only the in- volved area of the breast, partial breast irradiation ( PBI ), is as effective as whole breast irradiation [1]. Benefits of PBI

MicroRNA miR-30 family regulates non-attachment growth of breast cancer cells

PubMed Central

2013-01-01

Background A subset of breast cancer cells displays increased ability to self-renew and reproduce breast cancer heterogeneity. The characterization of these so-called putative breast tumor-initiating cells (BT-ICs) may open the road for novel therapeutic strategies. As microRNAs (miRNAs) control developmental programs in stem cells, BT-ICs may also rely on specific miRNA profiles for their sustained activity. To explore the notion that miRNAs may have a role in sustaining BT-ICs, we performed a comprehensive profiling of miRNA expression in a model of putative BT-ICs enriched by non-attachment growth conditions. Results We found breast cancer cells grown under non-attachment conditions display a unique pattern of miRNA expression, highlighted by a marked low expression of miR-30 family members relative to parental cells. We further show that miR-30a regulates non-attachment growth. A target screening revealed that miR-30 family redundantly modulates the expression of apoptosis and proliferation-related genes. At least one of these targets, the anti-apoptotic protein AVEN, was able to partially revert the effect of miR-30a overexpression. Finally, overexpression of miR-30a in vivo was associated with reduced breast tumor progression. Conclusions miR30-family regulates the growth of breast cancer cells in non-attachment conditions. This is the first analysis of target prediction in a whole family of microRNAs potentially involved in survival of putative BT-ICs. PMID:23445407

Breast-feeding in relation to weight retention up to 36 months postpartum in the Norwegian Mother and Child Cohort Study: modification by socio-economic status?

PubMed

Brandhagen, Martin; Lissner, Lauren; Brantsaeter, Anne Lise; Meltzer, Helle Margrete; Häggkvist, Anna-Pia; Haugen, Margaretha; Winkvist, Anna

2014-07-01

We investigated the association between full breast-feeding up to 6 months as well as partial breast-feeding after 6 months and maternal weight retention at 6, 18 and 36 months after delivery in the Norwegian Mother and Child Cohort Study (MoBa), conducted by the Norwegian Institute of Public Health. Cohort study. Information on exposure and outcome was collected by questionnaire. Norway. Women at 6 months (n 49 676), 18 months (n 27 187) and 36 months (n 17 343) postpartum. Longer duration of full breast-feeding as well as partial breast-feeding was significantly related to lower weight retention at 6 months. At 18 months full breast-feeding (0-6 months) and partial breast-feeding for 12-18 months were significantly related to lower weight retention. At 36 months only full breast-feeding (0-6 months) was significantly related to lower weight retention. For each additional month of full breast-feeding, maternal weight was lowered by 0·50 kg/month at 6 months, 0·10 kg/month at 18 months and 0·14 kg/month at 36 months (adjusted for pre-pregnant BMI, pregnancy weight gain, age and parity). Partial breast-feeding resulted in 0·25 kg/month lower maternal weight at 6 months. Interactions were found between household income and full breast-feeding in relation to weight retention at 6, 18 and 36 months, indicating most benefit among women with low income. The present study supports the hypothesis that full breast-feeding contributes to lower postpartum weight retention and shows that the effect is maintained for as long as 3 years postpartum.

Model-based approach for quantitative estimates of skin, heart, and lung toxicity risk for left-side photon and proton irradiation after breast-conserving surgery.

PubMed

Tommasino, Francesco; Durante, Marco; D'Avino, Vittoria; Liuzzi, Raffaele; Conson, Manuel; Farace, Paolo; Palma, Giuseppe; Schwarz, Marco; Cella, Laura; Pacelli, Roberto

2017-05-01

Proton beam therapy represents a promising modality for left-side breast cancer (BC) treatment, but concerns have been raised about skin toxicity and poor cosmesis. The aim of this study is to apply skin normal tissue complication probability (NTCP) model for intensity modulated proton therapy (IMPT) optimization in left-side BC. Ten left-side BC patients undergoing photon irradiation after breast-conserving surgery were randomly selected from our clinical database. Intensity modulated photon (IMRT) and IMPT plans were calculated with iso-tumor-coverage criteria and according to RTOG 1005 guidelines. Proton plans were computed with and without skin optimization. Published NTCP models were employed to estimate the risk of different toxicity endpoints for skin, lung, heart and its substructures. Acute skin NTCP evaluation suggests a lower toxicity level with IMPT compared to IMRT when the skin is included in proton optimization strategy (0.1% versus 1.7%, p < 0.001). Dosimetric results show that, with the same level of tumor coverage, IMPT attains significant heart and lung dose sparing compared with IMRT. By NTCP model-based analysis, an overall reduction in the cardiopulmonary toxicity risk prediction can be observed for all IMPT compared to IMRT plans: the relative risk reduction from protons varies between 0.1 and 0.7 depending on the considered toxicity endpoint. Our analysis suggests that IMPT might be safely applied without increasing the risk of severe acute radiation induced skin toxicity. The quantitative risk estimates also support the potential clinical benefits of IMPT for left-side BC irradiation due to lower risk of cardiac and pulmonary morbidity. The applied approach might be relevant on the long term for the setup of cost-effectiveness evaluation strategies based on NTCP predictions.

Partial breast radiation therapy - external beam

MedlinePlus

APBI is used to prevent breast cancer from coming back. When radiation therapy is given after breast- ... breast conservation therapy reduces the risk of cancer coming back, and possibly even death from breast cancer.

Breast Cancer Recognition Using a Novel Hybrid Intelligent Method

PubMed Central

Addeh, Jalil; Ebrahimzadeh, Ata

2012-01-01

Breast cancer is the second largest cause of cancer deaths among women. At the same time, it is also among the most curable cancer types if it can be diagnosed early. This paper presents a novel hybrid intelligent method for recognition of breast cancer tumors. The proposed method includes three main modules: the feature extraction module, the classifier module, and the optimization module. In the feature extraction module, fuzzy features are proposed as the efficient characteristic of the patterns. In the classifier module, because of the promising generalization capability of support vector machines (SVM), a SVM-based classifier is proposed. In support vector machine training, the hyperparameters have very important roles for its recognition accuracy. Therefore, in the optimization module, the bees algorithm (BA) is proposed for selecting appropriate parameters of the classifier. The proposed system is tested on Wisconsin Breast Cancer database and simulation results show that the recommended system has a high accuracy. PMID:23626945

Assessment of female breast dose for thoracic cone-beam CT using MOSFET dosimeters

PubMed Central

Qiu, Bo; Liang, Jian; Xie, Weihao; Deng, Xiaowu; Qi, Zhenyu

2017-01-01

Objective: To assess the breast dose during a routine thoracic cone-beam CT (CBCT) check with the efforts to explore the possible dose reduction strategy. Materials and Methods: Metal oxide semiconductor field-effect transistor (MOSFET) dosimeters were used to measure breast surface doses during a thorax kV CBCT scan in an anthropomorphic phantom. Breast doses for different scanning protocols and breast sizes were compared. Dose reduction was attempted by using partial arc CBCT scan with bowtie filter. The impact of this dose reduction strategy on image registration accuracy was investigated. Results: The average breast surface doses were 20.02 mGy and 11.65 mGy for thoracic CBCT without filtration and with filtration, respectively. This indicates a dose reduction of 41.8% by use of bowtie filter. It was found 220° partial arc scanning significantly reduced the dose to contralateral breast (44.4% lower than ipsilateral breast), while the image registration accuracy was not compromised. Conclusions: Breast dose reduction can be achieved by using ipsilateral 220° partial arc scan with bowtie filter. This strategy also provides sufficient image quality for thorax image registration in daily patient positioning verification. PMID:28423624

Rational use of intensity-modulated radiation therapy: the importance of clinical outcome.

PubMed

De Neve, Wilfried; De Gersem, Werner; Madani, Indira

2012-01-01

During the last 2 decades, intensity-modulated radiation therapy (IMRT) became a standard technique despite its drawbacks of volume delineation, planning, robustness of delivery, challenging quality assurance, and cost as compared with non-IMRT. The theoretic advantages of IMRT dose distributions are generally accepted, but the clinical advantages remain debatable because of the lack of clinical assessment of the effort that is required to overshadow the disadvantages. Rational IMRT use requires a positive advantage/drawback balance. Only 5 randomized clinical trials (RCTs), 3 in the breast and 2 in the head and neck, which compare IMRT with non-IMRT (2-dimensional technique in four fifths of the trials), have been published (as of March 2011), and all had toxicity as the primary endpoint. More than 50 clinical trials compared results of IMRT-treated patients with a non-IMRT group, mostly historical controls. RCTs systematically showed a lower toxicity in IMRT-treated patients, and the non-RCTs confirmed these findings. Toxicity reduction, counterbalancing the drawbacks of IMRT, was convincing for breast and head and neck IMRT. For other tumor sites, the arguments favoring IMRT are weaker because of the inability to control bias outside the randomized setting. For anticancer efficacy endpoints, like survival, disease-specific survival, or locoregional control, the balance between advantages and drawbacks is fraught with uncertainties because of the absence of robust clinical data. Copyright © 2012 Elsevier Inc. All rights reserved.

Ubiquitin specific protease 2 acts as a key modulator for the regulation of cell cycle by adiponectin and leptin in cancer cells.

PubMed

Nepal, Saroj; Shrestha, Anup; Park, Pil-Hoon

2015-09-05

Adiponectin and leptin, both produced from adipose tissue, cause cell cycle arrest and progression, respectively in cancer cells. Ubiquitin specific protease-2 (USP-2), a deubiquitinating enzyme, is known to impair proteasome-induced degradation of cyclin D1, a critical cell cycle regulator. Herein, we investigated the effects of these adipokines on USP-2 expression and its potential role in the modulation of cell cycle. Treatment with globular adiponectin (gAcrp) decreased, whereas leptin increased USP-2 expression both in human hepatoma and breast cancer cells. In addition, overexpression or gene silencing of USP-2 affected cyclin D1 expression and cell cycle progression/arrest by adipokines. Adiponectin and leptin also modulated in vitro proteasomal activity, which was partially dependent on USP-2 expression. Taken together, our results reveal that modulation of USP-2 expression plays a crucial role in cell cycle regulation by adipokines. Thus, USP-2 would be a promising therapeutic target for the modulation of cancer cell growth by adipokines. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Dosimetric advantages of generalised equivalent uniform dose-based optimisation on dose–volume objectives in intensity-modulated radiotherapy planning for bilateral breast cancer

PubMed Central

Lee, T-F; Ting, H-M; Chao, P-J; Wang, H-Y; Shieh, C-S; Horng, M-F; Wu, J-M; Yeh, S-A; Cho, M-Y; Huang, E-Y; Huang, Y-J; Chen, H-C; Fang, F-M

2012-01-01

Objective We compared and evaluated the differences between two models for treating bilateral breast cancer (BBC): (i) dose–volume-based intensity-modulated radiation treatment (DV plan), and (ii) dose–volume-based intensity-modulated radiotherapy with generalised equivalent uniform dose-based optimisation (DV-gEUD plan). Methods The quality and performance of the DV plan and DV-gEUD plan using the Pinnacle3® system (Philips, Fitchburg, WI) were evaluated and compared in 10 patients with stage T2–T4 BBC. The plans were delivered on a Varian 21EX linear accelerator (Varian Medical Systems, Milpitas, CA) equipped with a Millennium 120 leaf multileaf collimator (Varian Medical Systems). The parameters analysed included the conformity index, homogeneity index, tumour control probability of the planning target volume (PTV), the volumes V20 Gy and V30 Gy of the organs at risk (OAR, including the heart and lungs), mean dose and the normal tissue complication probability. Results Both plans met the requirements for the coverage of PTV with similar conformity and homogeneity indices. However, the DV-gEUD plan had the advantage of dose sparing for OAR: the mean doses of the heart and lungs, lung V20 Gy, and heart V30 Gy in the DV-gEUD plan were lower than those in the DV plan (p<0.05). Conclusions A better result can be obtained by starting with a DV-generated plan and then improving it by adding gEUD-based improvements to reduce the number of iterations and to improve the optimum dose distribution. Advances to knowledge The DV-gEUD plan provided superior dosimetric results for treating BBC in terms of PTV coverage and OAR sparing than the DV plan, without sacrificing the homogeneity of dose distribution in the PTV. PMID:23091290

Early microbial contact, the breast milk microbiome and child health.

PubMed

Rautava, S

2016-02-01

The significance of contact with microbes in early life for subsequent health has been the subject of intense research during the last 2 decades. Disturbances in the establishment of the indigenous intestinal microbiome caused by cesarean section delivery or antibiotic exposure in early life have been linked to the risk of immune-mediated and inflammatory conditions such as atopic disorders, inflammatory bowel disease and obesity later in life. Distinct microbial populations have recently been discovered at maternal sites including the amniotic cavity and breast milk, as well as meconium, which have previously been thought to be sterile. Our understanding of the impact of fetal microbial contact on health outcomes is still rudimentary. Breast milk is known to modulate immune and metabolic programming. The breast milk microbiome is hypothesized to guide infant gut colonization and is affected by maternal health status and mode of delivery. Immunomodulatory factors in breast milk interact with the maternal and infant gut microbiome and may mediate some of the health benefits associated with breastfeeding. The intimate connection between the mother and the fetus or the infant is a potential target for microbial therapeutic interventions aiming to support healthy microbial contact and protect against disease.

Cardiac autonomic modulation impairments in advanced breast cancer patients.

PubMed

Arab, Claudia; Vanderlei, Luiz Carlos Marques; da Silva Paiva, Laércio; Fulghum, Kyle Levi; Fristachi, Carlos Elias; Nazario, Afonso Celso Pinto; Elias, Simone; Gebrim, Luiz Henrique; Ferreira Filho, Celso; Gidron, Yori; Ferreira, Celso

2018-05-02

To compare cardiac autonomic modulation in early- versus advanced-stage breast cancer patients before any type of cancer treatment and investigate associated factors. This cross-sectional study included women (30-69 years old) with primary diagnosis of breast cancer and women with benign breast tumors. We evaluated cardiac modulation by heart rate variability and assessed factors of anxiety, depression, physical activity, and other relevant medical variables. Patients were divided into three groups based on TNM staging of cancer severity: early-stage cancer (n = 42), advanced-stage cancer (n = 37), or benign breast tumors to serve as a control (n = 37). We analyzed heart rate variability in time and frequency domains. The advanced-stage cancer group had lower vagal modulation than early-stage and benign groups; also, the advance-stage group had lower overall heart rate variability when compared to benign conditions. Heart rate variability was influenced by age, menopausal status, and BMI. Heart rate variability seems to be a promising, non-invasive tool for early diagnosis of autonomic dysfunction in breast cancer and detection of cardiovascular impairments at cancer diagnosis. Cardiac autonomic modulation is inversely associated with breast cancer staging.

Effects of a phytoestrogen-containing soy extract on the growth-inhibitory activity of ICI 182 780 in an experimental model of estrogen-dependent breast cancer.

PubMed

Gallo, Daniela; Mantuano, Elisabetta; Fabrizi, Manuela; Ferlini, Cristiano; Mozzetti, Simona; De Stefano, Ilaria; Scambia, Giovanni

2007-06-01

The study reported here was designed to determine whether a phytoestrogen-containing soy extract (SSE) could negate/overwhelm the inhibitory effects of ICI 182 780 on the growth of estrogen-sustained human breast cancer xenografts (MCF-7), in ovariectomized athymic mice. As expected, estradiol-supplemented tumors did not grow over the study period in ICI 182 780-treated females; concomitant administration of 50 mg/kg per day SSE slightly potentiated the inhibitory activity of the drug, while at 100 mg/kg per day, SSE partially negated ICI 182 780 activity. In keeping with these in vivo outcomes, we observed that the level of cyclin D1 (and progesterone receptor) in MCF-7 xenografts was considerably reduced by ICI 182 780, an effect enhanced by concomitant treatment with 50 SSE, but reduced by the higher dosage (i.e. 100 mg/kg per day). Thrombospondin-1 (TSP-1) and kallikrein 6 (KLK6) levels were also reduced following ICI 182 780, although to a lesser degree; again, combined anti-estrogen and SSE produced a dose-dependent regulation in TSP-1 and KLK6 tumor level, with a further reduction in the mRNA gene expression at 50 SSE (compared with ICI 182 780) and a partial reversion of the drug-induced down-regulation at 100 mg/kg per day. No modulation was detected in the serum concentration of IGF-1 (a potent mitogen for estrogen receptor-positive breast cancer cell lines) either upon treatment with ICI 182 780 or concomitant administration of the anti-estrogen with SSE. In conclusion, results from this study raise concerns about the consumption of isoflavone supplements in conjunction with ICI 182 780 therapy, in postmenopausal women with estrogen-dependent breast cancer.

Three-year outcomes of a once daily fractionation scheme for accelerated partial breast irradiation (APBI) using 3-D conformal radiotherapy (3D-CRT)

PubMed Central

Goyal, Sharad; Daroui, Parima; Khan, Atif J; Kearney, Thomas; Kirstein, Laurie; Haffty, Bruce G

2013-01-01

The aim of this study was to report 3-year outcomes of toxicity, cosmesis, and local control using a once daily fractionation scheme (49.95 Gy in 3.33 Gy once daily fractions) for accelerated partial breast irradiation (APBI) using three-dimensional conformal radiotherapy (3D-CRT). Between July 2008 and August 2010, women aged ≥40 years with ductal carcinoma in situ or node-negative invasive breast cancer ≤3 cm in diameter, treated with breast-conserving surgery achieving negative margins, were accrued to a prospective study. Women were treated with APBI using 3–5 photon beams, delivering 49.95 Gy over 15 once daily fractions over 3 weeks. Patients were assessed for toxicities, cosmesis, and local control rates before APBI and at specified time points. Thirty-four patients (mean age 60 years) with Tis 0 (n = 9) and T1N0 (n = 25) breast cancer were treated and followed up for an average of 39 months. Only 3% (1/34) patients experienced a grade 3 subcutaneous fibrosis and breast edema and 97% of the patients had good/excellent cosmetic outcome at 3 years. The 3-year rate of ipsilateral breast tumor recurrence (IBTR) was 0% while the rate of contralateral breast events was 6%. The 3-year disease-free survival (DFS), overall survival (OS), and breast cancer-specific survival (BCSS) was 94%, 100%, and 100%, respectively. Our novel accelerated partial breast fractionation scheme of 15 once daily fractions of 3.33 Gy (49.95 Gy total) is a remarkably well-tolerated regimen of 3D-CRT-based APBI. A larger cohort of patients is needed to further ascertain the toxicity of this accelerated partial breast regimen. PMID:24403270

Left-sided breast cancer irradiation using rotational and fixed-field radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qi, X. Sharon, E-mail: xqi@mednet.ucla.edu; Liu, Tian X.; Liu, Arthur K.

2014-10-01

The 3-dimensional conformal radiotherapy (3DCRT) technique is the standard for breast cancer radiotherapy. During treatment planning, not only the coverage of the planning target volume (PTV) but also the minimization of the dose to critical structures, such as the lung, heart, and contralateral breast tissue, need to be considered. Because of the complexity and variations of patient anatomy, more advanced radiotherapy techniques are sometimes desired to better meet the planning goals. In this study, we evaluated external-beam radiation treatment techniques for left breast cancer using various delivery platforms: fixed-field including TomoDirect (TD), static intensity-modulated radiotherapy (sIMRT), and rotational radiotherapy includingmore » Elekta volumetric-modulated arc therapy (VMAT) and tomotherapy helical (TH). A total of 10 patients with left-sided breast cancer who did or did not have positive lymph nodes and were previously treated with 3DCRT/sIMRT to the entire breast were selected, their treatment was planned with Monaco VMAT, TD, and TH. Dosimetric parameters including PTV coverage, organ-at-risk (OAR) sparing, dose-volume histograms, and target minimum/maximum/mean doses were evaluated. It is found that for plans providing comparable PTV coverage, the Elekta VMAT plans were generally more inhomogeneous than the TH and TD plans. For the cases with regional node involvement, the average mean doses administered to the heart were 9.2 (± 5.2) and 8.8 (± 3.0) Gy in the VMAT and TH plans compared with 11.9 (± 6.4) and 11.8 (± 9.2) Gy for the 3DCRT and TD plans, respectively, with slightly higher doses given to the contralateral lung or breast or both. On average, the total monitor units for VMAT plans are 11.6% of those TH plans. Our studies have shown that VMAT and TH plans offer certain dosimetric advantages over fixed-field IMRT plans for advanced breast cancer requiring regional nodal treatment. However, for early-stage breast cancer fixed-field radiotherapy is potentially more beneficial in terms of OAR sparing.« less

Left-sided breast cancer irradiation using rotational and fixed-field radiotherapy.

PubMed

Qi, X Sharon; Liu, Tian X; Liu, Arthur K; Newman, Francis; Rabinovitch, Rachel; Kavanagh, Brian; Hu, Y Angie

2014-01-01

The 3-dimensional conformal radiotherapy (3DCRT) technique is the standard for breast cancer radiotherapy. During treatment planning, not only the coverage of the planning target volume (PTV) but also the minimization of the dose to critical structures, such as the lung, heart, and contralateral breast tissue, need to be considered. Because of the complexity and variations of patient anatomy, more advanced radiotherapy techniques are sometimes desired to better meet the planning goals. In this study, we evaluated external-beam radiation treatment techniques for left breast cancer using various delivery platforms: fixed-field including TomoDirect (TD), static intensity-modulated radiotherapy (sIMRT), and rotational radiotherapy including Elekta volumetric-modulated arc therapy (VMAT) and tomotherapy helical (TH). A total of 10 patients with left-sided breast cancer who did or did not have positive lymph nodes and were previously treated with 3DCRT/sIMRT to the entire breast were selected, their treatment was planned with Monaco VMAT, TD, and TH. Dosimetric parameters including PTV coverage, organ-at-risk (OAR) sparing, dose-volume histograms, and target minimum/maximum/mean doses were evaluated. It is found that for plans providing comparable PTV coverage, the Elekta VMAT plans were generally more inhomogeneous than the TH and TD plans. For the cases with regional node involvement, the average mean doses administered to the heart were 9.2 (± 5.2) and 8.8 (± 3.0)Gy in the VMAT and TH plans compared with 11.9 (± 6.4) and 11.8 (± 9.2)Gy for the 3DCRT and TD plans, respectively, with slightly higher doses given to the contralateral lung or breast or both. On average, the total monitor units for VMAT plans are 11.6% of those TH plans. Our studies have shown that VMAT and TH plans offer certain dosimetric advantages over fixed-field IMRT plans for advanced breast cancer requiring regional nodal treatment. However, for early-stage breast cancer fixed-field radiotherapy is potentially more beneficial in terms of OAR sparing. Copyright © 2014 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Calculations of the Sound Scattering of Hyperbolic Frequency Modulated Chirped Pulses from Fluid-filled Spherical Shell Sonar Targets

DTIC Science & Technology

2010-02-01

calculated the target strength of the most intense partial wave, a quantity termed the “effective target strength” by Kaduchak and Loeffler (1998...ed., United States Naval Institute, Annapolis, 417 pp. Kaduchak, G. and Loeffler , C.M. (1998). “Relationship between material parameters and

Two nursing mothers treated with zonisamide: Should breast-feeding be avoided?

PubMed

Ando, Hitoshi; Matsubara, Shigeki; Oi, Asako; Usui, Rie; Suzuki, Mitsuaki; Fujimura, Akio

2014-01-01

Zonisamide, an antiepileptic drug, is excreted into breast milk, but information regarding the safety of breast-feeding while using this drug is limited. We present the cases of two nursing mothers, taking 300 and 100 mg/day zonisamide. At 5 days after delivery, the milk concentrations and relative infant doses of the drug were 18.0 and 5.1 μg/mL, and 44 and 36%, respectively. In the first case, the mother fed colostrum and continued partial breast-feeding thus reducing the relative infant dose to 8%. The neonatal serum concentration of zonisamide declined to below the limit of detection at day 34 after birth. In the second case, the mother breast-fed partially until 2 weeks postpartum. No adverse effect was observed in the infants. These findings suggest that mothers taking zonisamide should not breast-feed exclusively, but may not have to avoid partial breast-feeding, with significant caution regarding adverse effects in infants. © 2013 The Authors. Journal of Obstetrics and Gynaecology Research © 2013 Japan Society of Obstetrics and Gynecology.

Reduced Mortality With Partial-Breast Irradiation for Early Breast Cancer: A Meta-Analysis of Randomized Trials

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vaidya, Jayant S., E-mail: jayant.vaidya@ucl.ac.uk; Department of Surgery, Royal Free Hospital, London; Department of Surgery, Whittington Health, London

Purpose: With earlier detection and more effective treatment, mortality from breast cancer continues to fall and it has become increasingly important to reduce the toxicity of treatments. Partial-breast radiation therapy, which focuses radiation to the tumor bed, may achieve this aim. We analyzed mortality differences in randomized trials of partial-breast irradiation (PBI). Methods and Materials: We included data from published randomized trials of PBI (alone or as part of a risk-adapted approach) versus whole-breast irradiation (WBI) for invasive breast cancer suitable for breast-conserving therapy. We identified trials using PubMed and Google searches with the terms “partial breast irradiation” OR “intraoperativemore » radiotherapy” OR “IMRT” OR (“accelerated” AND “radiation”) AND “randomised/randomized,” as well as through discussion with colleagues in the field. We calculated the proportion of patients who had events in each randomized arm at 5 years' follow-up and created a forest plot using Stata, version 14.1. Results: We identified 9 randomized trials of PBI versus WBI in invasive breast cancer; 5-year outcomes were available for non–breast cancer mortality in 5 trials (n=4489) and for breast cancer mortality in 4 trials (n=4231). The overall mortality was 4.9%. There was no detectable heterogeneity between the trials for any of the outcomes. There was no difference in the proportion of patients dying of breast cancer (difference, 0.000% [95% confidence interval (CI), −0.7 to +0.7]; P=.999). Non–breast cancer mortality with PBI was lower than with WBI (difference, 1.1% [95% CI, −2.1% to −0.2%]; P=.023). Total mortality with PBI was also lower than with WBI (difference, 1.3% [95% CI, −2.5% to 0.0%]; P=.05). Conclusions: Use of PBI instead of WBI in selected patients results in a lower 5-year non–breast cancer and overall mortality, amounting to a 25% reduction in relative terms. This information should be included when breast-conserving therapy is proposed to a patient.« less

Quantifying Solar Cell Cracks in Photovoltaic Modules by Electroluminescence Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Spataru, Sergiu; Hacke, Peter; Sera, Dezso

2015-06-14

This article proposes a method for quantifying the percentage of partially and totally disconnected solar cell cracks by analyzing electroluminescence images of the photovoltaic module taken under high- and low-current forward bias. The method is based on the analysis of the module's electroluminescence intensity distribution, applied at module and cell level. These concepts are demonstrated on a crystalline silicon photovoltaic module that was subjected to several rounds of mechanical loading and humidity-freeze cycling, causing increasing levels of solar cell cracks. The proposed method can be used as a diagnostic tool to rate cell damage or quality of modules after transportation.more » Moreover, the method can be automated and used in quality control for module manufacturers, installers, or as a diagnostic tool by plant operators and diagnostic service providers.« less

Partial lower axillary dissection for patients with clinically node-negative breast cancer.

PubMed

Kodama, H; Mise, K; Kan, N

2012-01-01

To evaluate retrospectively the outcomes of partial lower axillary lymph node dissection caudal to the intercostobrachial nerve in patients with clinically node-negative (N(0)) breast cancer. Numbers of dissected and metastatic nodes, overall and disease-free survival rates, postoperative complication rates, and axillary recurrence were compared between patients who underwent breast cancer surgery with partial axillary node dissection (n = 1043) and historical controls who underwent conventional dissection (n = 1084). The 5-year overall and disease-free survival rates were 95.6% and 89.7%, and 94.9% and 88.4%, respectively, in the partial dissection and conventional dissection groups; the differences were not significant. Mean duration of surgery (41.6 min versus 60.9 min), intraoperative blood loss (28.0 ml versus 51.3 ml), volume of lymphatic drainage at 2 weeks postoperatively (488 ml versus 836 ml), and persistent arm lymphoedema (0.0% versus 11.8%) were significantly different between the partial and conventional dissection groups, respectively. Partial axillary lymph node dissection was associated with similar survival rates (but lower postoperative complication rates) compared with conventional axillary dissection and is recommended in patients with N(0) breast cancer.

Mother's Milk: A Purposeful Contribution to the Development of the Infant Microbiota and Immunity.

PubMed

Le Doare, Kirsty; Holder, Beth; Bassett, Aisha; Pannaraj, Pia S

2018-01-01

Breast milk is the perfect nutrition for infants, a result of millions of years of evolution. In addition to providing a source of nutrition, breast milk contains a diverse array of microbiota and myriad biologically active components that are thought to guide the infant's developing mucosal immune system. It is believed that bacteria from the mother's intestine may translocate to breast milk and dynamically transfer to the infant. Such interplay between mother and her infant is a key to establishing a healthy infant intestinal microbiome. These intestinal bacteria protect against many respiratory and diarrheal illnesses, but are subject to environmental stresses such as antibiotic use. Orchestrating the development of the microbiota are the human milk oligosaccharides (HMOs), the synthesis of which are partially determined by the maternal genotype. HMOs are thought to play a role in preventing pathogenic bacterial adhesion though multiple mechanisms, while also providing nutrition for the microbiome. Extracellular vesicles (EVs), including exosomes, carry a diverse cargo, including mRNA, miRNA, and cytosolic and membrane-bound proteins, and are readily detectable in human breast milk. Strongly implicated in cell-cell signaling, EVs could therefore may play a further role in the development of the infant microbiome. This review considers the emerging role of breast milk microbiota, bioactive HMOs, and EVs in the establishment of the neonatal microbiome and the consequent potential for modulation of neonatal immune system development.

Energy- and Intensity-Modulated Electron Beam for Breast Cancer Treatment

DTIC Science & Technology

1999-10-01

calculations," in Teletherapy: Present and Future, Ed. By T.R. Mackie and J.R. Palta (Advanced Medical Publishing, Madison WI) Mackie TR, Reckwerdt PJ...edited by T. R. Mackie and J. R. Palta from 10% to 20% (or a 5-20 mm shift in the isodose lines) (Advanced Medical Publishing, Madison, WI, 1996). to...Ayyangar K, Palta J R, Sweet J W and Suntharalingam N 1993 Experimental verification of a three-dimensional dose calculation algorithm using a specially

Three Dimensional Reconstruction Algorithm for Imaging Pathophysiological Signals Within Breast Tissue Using Near Infrared Light

DTIC Science & Technology

2006-07-01

of water, gelatin (G2625, Sigma Inc.), India ink (for absorption), and titanium dioxide powder (for scatter) (TiO2, Sigma Inc.) is poured into a mold...R. C., Ference, R. J, Refractive index of some mammalian tissue using a fiber optic cladding method. Applied Optics, 1989. 28(12): p. 2297-2303. 3...scans. The NIR system utilizes six optical wavelengths from 660 to 850 nm using intensity modulated diode lasers nominally working at 100 MHz

Curcumin: the spicy modulator of breast carcinogenesis.

PubMed

Banik, Urmila; Parasuraman, Subramani; Adhikary, Arun Kumar; Othman, Nor Hayati

2017-07-19

Worldwide breast cancer is the most common cancer in women. For many years clinicians and the researchers are examining and exploring various therapeutic modalities for breast cancer. Yet the disease has remained unconquered and the quest for cure is still going on. Present-day strategy of breast cancer therapy and prevention is either combination of a number of drugs or a drug that modulates multiple targets. In this regard natural products are now becoming significant options. Curcumin exemplifies a promising natural anticancer agent for this purpose. This review primarily underscores the modulatory effect of curcumin on the cancer hallmarks. The focus is its anticancer effect in the complex pathways of breast carcinogenesis. Curcumin modulates breast carcinogenesis through its effect on cell cycle and proliferation, apoptosis, senescence, cancer spread and angiogenesis. Largely the NFkB, PI3K/Akt/mTOR, MAPK and JAK/STAT are the key signaling pathways involved. The review also highlights the curcumin mediated modulation of tumor microenvironment, cancer immunity, breast cancer stem cells and cancer related miRNAs. Using curcumin as a therapeutic and preventive agent in breast cancer is perplexed by its diverse biological activity, much of which remains inexplicable. The information reviewed here should point toward potential scope of future curcumin research in breast cancer.

Mammographic density estimation with automated volumetric breast density measurement.

PubMed

Ko, Su Yeon; Kim, Eun-Kyung; Kim, Min Jung; Moon, Hee Jung

2014-01-01

To compare automated volumetric breast density measurement (VBDM) with radiologists' evaluations based on the Breast Imaging Reporting and Data System (BI-RADS), and to identify the factors associated with technical failure of VBDM. In this study, 1129 women aged 19-82 years who underwent mammography from December 2011 to January 2012 were included. Breast density evaluations by radiologists based on BI-RADS and by VBDM (Volpara Version 1.5.1) were compared. The agreement in interpreting breast density between radiologists and VBDM was determined based on four density grades (D1, D2, D3, and D4) and a binary classification of fatty (D1-2) vs. dense (D3-4) breast using kappa statistics. The association between technical failure of VBDM and patient age, total breast volume, fibroglandular tissue volume, history of partial mastectomy, the frequency of mass > 3 cm, and breast density was analyzed. The agreement between breast density evaluations by radiologists and VBDM was fair (k value = 0.26) when the four density grades (D1/D2/D3/D4) were used and moderate (k value = 0.47) for the binary classification (D1-2/D3-4). Twenty-seven women (2.4%) showed failure of VBDM. Small total breast volume, history of partial mastectomy, and high breast density were significantly associated with technical failure of VBDM (p = 0.001 to 0.015). There is fair or moderate agreement in breast density evaluation between radiologists and VBDM. Technical failure of VBDM may be related to small total breast volume, a history of partial mastectomy, and high breast density.

SU-F-T-650: The Comparison of Robotic Partial Breast Stereotactic Irradiation Using MLC Vs. Iris Cone

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ding, C; Timmerman, R; Jiang, S

Purpose: To evaluate the dosimetric impact on treatment planning for partial breast stereotactic irradiation using Cyberknife with MLC versus Iris Cone. Methods: Ten patients whom underwent lumpectomy for DCIS or stage I invasive non-lobular epithelial breast cancer were included in this study. All patients were previously treated on the Cyberknife using Iris cone with the prescription dose of 37.5Gy in 5 fractions covering at least 95% of PTV on our phase I SBRT 5 fraction partial breast irradiation trial. Retrospectively, treatment planning was performed and compared using the new Cyberknife M6 MLC system for each patient. Using the same contoursmore » and critical organ constraints for both MLC and Iris cone plans, the dose on target and critical organs were analyzed accordingly. Results: Dose to critical organs such as ipsilateral lung, contralateral lung, heart, skin, ipsilateral breast, and rib were analyzed, as well as conformity index and high dose spillage of the target area. In 9 of 10 patients, the MLC plans had less total ipsilateral breast volume encompassing the 50% prescription isodose (mean:22.3±8.2% MLC vs. 31.6±8.0 Iris, p=0.00014) .The MLC plans mean estimated treatment delivery time was significantly less than the Iris plans (51±3.9min vs. 56.2±9min, p=0.03) Both MLC and Iris cone plans were able to meet all dose constraints and there was no statistical difference between those dose constraints. Conclusion: Both MLC and Iris Cone can deliver conformal dose to a partial breast target and satisfy the dose constraints of critical organs. The new Cyberknife with MLC can deliver a more conformal dose in the lower dose region and spare more ipsilateral breast tissue to the 50% prescription isodose. The treatment time for partial breast SBRT plans was also reduced using MLC. Project receives research support from Accuray Inc.« less

COMPARISON OF THE PERIPHERAL DOSES FROM DIFFERENT IMRT TECHNIQUES FOR PEDIATRIC HEAD AND NECK RADIATION THERAPY.

PubMed

Toyota, Masahiko; Saigo, Yasumasa; Higuchi, Kenta; Fujimura, Takuya; Koriyama, Chihaya; Yoshiura, Takashi; Akiba, Suminori

2017-11-01

Intensity-modulated radiation therapy (IMRT) can deliver high and homogeneous doses to the target area while limiting doses to organs at risk. We used a pediatric phantom to simulate the treatment of a head and neck tumor in a child. The peripheral doses were examined for three different IMRT techniques [dynamic multileaf collimator (DMLC), segmental multileaf collimator (SMLC) and volumetric modulated arc therapy (VMAT)]. Peripheral doses were evaluated taking thyroid, breast, ovary and testis as the points of interest. Doses were determined using a radio-photoluminescence glass dosemeter, and the COMPASS system was used for three-dimensional dose evaluation. VMAT achieved the lowest peripheral doses because it had the highest monitor unit efficiency. However, doses in the vicinity of the irradiated field, i.e. the thyroid, could be relatively high, depending on the VMAT collimator angle. DMLC and SMLC had a large area of relatively high peripheral doses in the breast region. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Assessment of the potential activity of major dietary compounds as selective estrogen receptor modulators in two distinct cell models for proliferation and differentiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lecomte, Sylvain; Lelong, Marie; Bourgine, Gaëlle

Estrogen receptors (ERs) α and β are distributed in most tissues of women and men. ERs are bound by estradiol (E2), a natural hormone, and mediate the pleiotropic and tissue-specific effects of E2, such as proliferation of breast epithelial cells or protection and differentiation of neuronal cells. Numerous environmental molecules, called endocrine disrupting compounds, also interact with ERs. Phytoestrogens belong to this large family and are considered potent therapeutic molecules that act through their selective estrogen receptor modulator (SERM) activity. Using breast cancer cell lines as a model of estrogen-dependent proliferation and a stably ER-expressing PC12 cell line as amore » model of neuronal differentiating cells, we studied the SERM activity of major dietary compounds, such as apigenin, liquiritigenin, daidzein, genistein, coumestrol, resveratrol and zearalenone. The ability of these compounds to induce ER-transactivation and breast cancer cell proliferation and enhance Nerve Growth Factor (NGF) -induced neuritogenesis was assessed. Surprisingly, although all compounds were able to activate the ER through an estrogen responsive element reporter gene, they showed differential activity toward proliferation or differentiation. Apigenin and resveratrol showed a partial or no proliferative effect on breast cancer cells but fully contributed to the neuritogenesis effect of NGF. However, daidzein and zearalenone showed full effects on cellular proliferation but did not induce cellular differentiation. In summary, our results suggest that the therapeutic potential of phytoestrogens can diverge depending on the molecule and the phenotype considered. Hence, apigenin and resveratrol might be used in the development of therapeutics for breast cancer and brain diseases. - Highlights: • SERM activity of dietary compounds on proliferation and differentiation is studied. • All the dietary compounds tested transactivate estrogen receptors. • Apigenin and resveratrol could be good candidates for future therapeutics. • Daidzein and zearalenone are to be avoided to maintain human health.« less

System and method that suppresses intensity fluctuations for free space high-speed optical communication

DOEpatents

Berman, Gennady P [Los Alamos, NM; Bishop, Alan R [Los Alamos, NM; Nguyen, Dinh C [Los Alamos, NM; Chernobrod, Boris M [Santa Fe, NM; Gorshkov, Vacheslav N [Kiev, UA

2009-10-13

A high-speed (Gbps), free space optical communication system is based on spectral encoding of radiation from a wide band light source, such as a laser. By using partially coherent laser beams in combination with a relatively slow photosensor, scintillations can be suppressed by orders of magnitude for distances of more than 10 km. To suppress the intensity fluctuations due to atmospheric turbulence, a source with partial transverse coherence in combination with slow response time photodetector is used. Information is encoded in the spectral domain of a wideband optical source by modulation of spectral amplitudes. A non-coherent light source with wide spectrum (an LED, for example) may be used for high-speed communication over short (less than about a mile) distances.

Immediate Partial Breast Reconstruction with Endoscopic Latissimus Dorsi Muscle Flap Harvest

PubMed Central

Yang, Chae Eun; Roh, Tai Suk; Yun, In Sik; Lew, Dae Hyun

2014-01-01

Background Currently, breast conservation therapy is commonly performed for the treatment of early breast cancer. Depending on the volume excised, patients may require volume replacement, even in cases of partial mastectomy. The use of the latissimus dorsi muscle is the standard method, but this procedure leaves an unfavorable scar on the donor site. We used an endoscope for latissimus dorsi harvesting to minimize the incision, thus reducing postoperative scars. Methods Ten patients who underwent partial mastectomy and immediate partial breast reconstruction with endoscopic latissimus dorsi muscle flap harvest were reviewed retrospectively. The total operation time, hospital stay, and complications were reviewed. Postoperative scarring, overall shape of the reconstructed breast, and donor site deformity were assessed using a 10-point scale. Results In the mean follow-up of 11 weeks, no tumor recurrence was reported. The mean operation time was 294.5 (±38.2) minutes. The postoperative hospital stay was 11.4 days. Donor site seroma was reported in four cases and managed by office aspiration and compressive dressing. Postoperative scarring, donor site deformity, and the overall shape of the neobreast were acceptable, scoring above 7. Conclusions Replacement of 20% to 40% of breast volume in the upper and the lower outer quadrants with a latissimus dorsi muscle flap by using endoscopic harvesting is a good alternative reconstruction technique after partial mastectomy. Short incision benefits from a very acceptable postoperative scar, less pain, and early upper extremity movement. PMID:25276643

The effects of partial defeathering on energy metabolism in the laying fowl.

PubMed

Tullett, S G; MacLeod, M G; Jewitt, T R

1980-05-01

1. The effects of a complete removal of feathers from the neck and/or breast on the energy metabolism of laying hens were measured by indirect calorimetry. 2. The daily heat production of fed birds was significantly increased if feathers were removed from the entire neck plus breast region but not if the neck only or breast only were denuded. 3. Removal of feathers from neck plus breast led to a 10% increase in food consumption. 4. The partially-defeathered birds laid more eggs.

Dosimetric comparison of four different external beams for breast irradiation

NASA Astrophysics Data System (ADS)

Lee, Yoon Hee; Chung, Weon Kuu; Kim, Dong Wook; Kwon, Oh Young

2017-02-01

An intensity-modulated radiation-therapy (IMRT)-based technique, blocked single iso-centric IMRT (IMRT), is compared to multi-center IMRT (MIRT) and other conventional techniques such as three dimensional conformal radiation therapy (3D-CRT) and volumetric modulated arc therapy (VMAT) for the treatment of breast cancer patients. Four different plans were devised and compared for 15 breast cancer patients, all of whom had early stage disease and had undergone breast conserving surgery. A total dose of 50.4 Gy in 28 fractions was prescribed as the planning target volume in all treatment plans. The doses to the ipsilateral lung, heart, and opposite breast were compared using a dose-volume histogram. The conformity index (CI), homogeneity index (HI), and coverage index (CoVI) were evaluated and compared among the four treatment techniques. The lifetime attributable risk (LAR) associated with each of the four techniques from age at exposure of 30 to 100 years was measured for the organs at risk. We found that MIRT had a better CoVI (1.02 ± 0.13 and 1.01 ± 0.04, respectively) and IMRT had a better CI (0.88 ± 0.04, and 0.87 ± 0.02, respectively) compared to the other three modalities. All four techniques had similar HIs. Moreover, we found that IMRT and MIRT were less likely to cause radiation induced-pneumonitis, 3D-CRT had the lowest LAR, IMRT and MIRT had similar LARs and VMAT had the highest LAR. In study we found that compared to the VMAT, MIRT and IMRT provided adequate the planning target volume (PTV) coverage and reduced the risk of secondary cancers in most of the organs at risk (OARs), while 3D-CRT had the lowest secondary-cancer risks. Therefore, 3D-CRT is still a reasonable choice for whole breast RT except for patients with complex PTV shapes, in which cases IMRT and MIRT may provide better target coverage.

Estimate of the risk of radiation-induced cancers after linear-accelerator-based breast-cancer radiotherapy

NASA Astrophysics Data System (ADS)

Koh, Eui Kwan; Seo, Jungju; Baek, Tae Seong; Chung, Eun Ji; Yoon, Myonggeun; Lee, Hyun-ho

2013-07-01

The aim of this study is to assess and compare the excess absolute risks (EARs) of radiation-induced cancers following conformal (3D-CRT), fixed-field intensity-modulated (IMRT) and volumetric modulated arc (RapidArc) radiation therapy in patients with breast cancer. 3D-CRT, IMRT and RapidArc were planned for 10 breast cancer patients. The organ-specific EAR for cancer induction was estimated using the organ equivalent dose (OED) based on computed dose volume histograms (DVHs) and the secondary doses measured at various points from the field edge. The average secondary dose per Gy treatment dose from 3D-CRT, measured 10 to 50 cm from the field edge, ranged from 8.27 to 1.04 mGy. The secondary doses per Gy from IMRT and RapidArc, however, ranged between 5.86 and 0.54 mGy, indicating that IMRT and RapidArc are associated with smaller doses of secondary radiation than 3D-CRT. The organ specific EARs for out-of-field organs, such as the thyroid, liver and colon, were higher with 3D-CRT than with IMRT or RapidArc. In contrast, EARs for in-field organs were much lower with 3D-CRT than with IMRT or RapidArc. The overall estimate of EAR indicated that the radiation-induced cancer risk was 1.8-2.0 times lower with 3D-CRT than with IMRT or RapidArc. Comparisons of EARs during breast irradiation suggested that the predicted risk of secondary cancers was lower with 3D-CRT than with IMRT or RapidArc.

Mammographic Density Estimation with Automated Volumetric Breast Density Measurement

PubMed Central

Ko, Su Yeon; Kim, Eun-Kyung; Kim, Min Jung

2014-01-01

Objective To compare automated volumetric breast density measurement (VBDM) with radiologists' evaluations based on the Breast Imaging Reporting and Data System (BI-RADS), and to identify the factors associated with technical failure of VBDM. Materials and Methods In this study, 1129 women aged 19-82 years who underwent mammography from December 2011 to January 2012 were included. Breast density evaluations by radiologists based on BI-RADS and by VBDM (Volpara Version 1.5.1) were compared. The agreement in interpreting breast density between radiologists and VBDM was determined based on four density grades (D1, D2, D3, and D4) and a binary classification of fatty (D1-2) vs. dense (D3-4) breast using kappa statistics. The association between technical failure of VBDM and patient age, total breast volume, fibroglandular tissue volume, history of partial mastectomy, the frequency of mass > 3 cm, and breast density was analyzed. Results The agreement between breast density evaluations by radiologists and VBDM was fair (k value = 0.26) when the four density grades (D1/D2/D3/D4) were used and moderate (k value = 0.47) for the binary classification (D1-2/D3-4). Twenty-seven women (2.4%) showed failure of VBDM. Small total breast volume, history of partial mastectomy, and high breast density were significantly associated with technical failure of VBDM (p = 0.001 to 0.015). Conclusion There is fair or moderate agreement in breast density evaluation between radiologists and VBDM. Technical failure of VBDM may be related to small total breast volume, a history of partial mastectomy, and high breast density. PMID:24843235

Breast-feeding problems after epidural analgesia for labour: a retrospective cohort study of pain, obstetrical procedures and breast-feeding practices.

PubMed

Volmanen, P; Valanne, J; Alahuhta, S

2004-01-01

Various clinical practices have been found to be associated with breast-feeding problems. However, little is known about the effect of pain, obstetrical procedures and analgesia on breast-feeding behaviour. We designed a retrospective study with a questionnaire concerning pain, obstetrical procedures and breast-feeding practices mailed to 164 primiparae in Lapland. Altogether 99 mothers (60%) returned completed questionnaires that could be included in the analysis, which was carried out in two steps. Firstly, all accepted questionnaires were grouped according to the success or failure to breast-feed fully during the first 12 weeks of life. Secondly, an ad hoc cohort study was performed on the sub-sample of 64 mothers delivered vaginally. As many as 44% of the 99 mothers reported partial breast feeding or formula feeding during the first 12 weeks. Older age of the mother, use of epidural analgesia and the problem of "not having enough milk" were associated with the failure to breast-feed fully. Caesarean section, other methods of labour analgesia and other breast-feeding problems were not associated with partial breast feeding or formula feeding. In the sub-sample, 67% of the mothers who had laboured with epidural analgesia and 29% of the mothers who laboured without epidural analgesia reported partial breast feeding or formula feeding (P = 0.003). The problem of "not having enough milk" was more often reported by those who had had epidural analgesia. Further studies conducted prospectively are needed to establish whether a causal relationship exists between epidural analgesia and breast-feeding problems.

Is it possible for knowledge-based planning to improve intensity modulated radiation therapy plan quality for planners with different planning experiences in left-sided breast cancer patients?

PubMed

Wang, Juanqi; Hu, Weigang; Yang, Zhaozhi; Chen, Xiaohui; Wu, Zhiqiang; Yu, Xiaoli; Guo, Xiaomao; Lu, Saiquan; Li, Kaixuan; Yu, Gongyi

2017-05-22

Knowledge-based planning (KBP) is a promising technique that can improve plan quality and increase planning efficiency. However, no attempts have been made to extend the domain of KBP for planners with different planning experiences so far. The purpose of this study was to quantify the potential gains for planners with different planning experiences after implementing KBP in intensity modulated radiation therapy (IMRT) plans for left-sided breast cancer patients. The model libraries were populated with 80 expert clinical plans from treated patients who previously received left-sided breast-conserving surgery and IMRT with simultaneously integrated boost. The libraries were created on the RapidPlan TM . 6 planners with different planning experiences (2 beginner planners, 2 junior planners and 2 senior planners) generated manual and KBP optimized plans for additional 10 patients, similar to those included in the model libraries. The plan qualities were compared between manual and KBP plans. All plans were capable of achieving the prescription requirement. There were almost no statistically significant differences in terms of the planning target volume (PTV) coverage and dose conformality. It was demonstrated that the doses for most of organs-at-risk (OARs) were on average lower or equal in KBP plans compared to manual plans except for the senior planners, where the very small differences were not statistically significant. KBP data showed a systematic trend to have superior dose sparing at most parameters for the heart and ipsilateral lung. The observed decrease in the doses to these OARs could be achieved, particularly for the beginner and junior planners. Many differences were statistically significant. It is feasible to generate acceptable IMRT plans after implementing KBP for left-sided breast cancer. KBP helps to effectively improve the quality of IMRT plans against the benchmark of manual plans for less experienced planners without any manual intervention. KBP showed promise for homogenizing the plan quality by transferring planning expertise from more experienced to less experienced planners.

Detection of partial-thickness tears in ligaments and tendons by Stokes-polarimetry imaging

NASA Astrophysics Data System (ADS)

Kim, Jihoon; John, Raheel; Walsh, Joseph T.

2008-02-01

A Stokes polarimetry imaging (SPI) system utilizes an algorithm developed to construct degree of polarization (DoP) image maps from linearly polarized light illumination. Partial-thickness tears of turkey tendons were imaged by the SPI system in order to examine the feasibility of the system to detect partial-thickness rotator cuff tear or general tendon pathology. The rotating incident polarization angle (IPA) for the linearly polarized light provides a way to analyze different tissue types which may be sensitive to IPA variations. Degree of linear polarization (DoLP) images revealed collagen fiber structure, related to partial-thickness tears, better than standard intensity images. DoLP images also revealed structural changes in tears that are related to the tendon load. DoLP images with red-wavelength-filtered incident light may show tears and related organization of collagen fiber structure at a greater depth from the tendon surface. Degree of circular polarization (DoCP) images exhibited well the horizontal fiber orientation that is not parallel to the vertically aligned collagen fibers of the tendon. The SPI system's DOLP images reveal alterations in tendons and ligaments, which have a tissue matrix consisting largely of collagen, better than intensity images. All polarized images showed modulated intensity as the IPA was varied. The optimal detection of the partial-thickness tendon tears at a certain IPA was observed. The SPI system with varying IPA and spectral information can improve the detection of partial-thickness rotator cuff tears by higher visibility of fiber orientations and thereby improve diagnosis and treatment of tendon related injuries.

NRG Oncology-Radiation Therapy Oncology Group Study 1014: 1-Year Toxicity Report From a Phase 2 Study of Repeat Breast-Preserving Surgery and 3-Dimensional Conformal Partial-Breast Reirradiation for In-Breast Recurrence.

PubMed

Arthur, Douglas W; Winter, Kathryn A; Kuerer, Henry M; Haffty, Bruce G; Cuttino, Laurie W; Todor, Dorin A; Simone, Nicole L; Hayes, Shelly B; Woodward, Wendy A; McCormick, Beryl; Cohen, Randi J; Sahijdak, Walter M; Canaday, Daniel J; Brown, Doris R; Currey, Adam D; Fisher, Christine M; Jagsi, Reshma; White, Julia

2017-08-01

To determine the associated toxicity, tolerance, and safety of partial-breast reirradiation. Eligibility criteria included in-breast recurrence occurring >1 year after whole-breast irradiation, <3 cm, unifocal, and resected with negative margins. Partial-breast reirradiation was targeted to the surgical cavity plus 1.5 cm; a prescription dose of 45 Gy in 1.5 Gy twice daily for 30 treatments was used. The primary objective was to evaluate the rate of grade ≥3 treatment-related skin, fibrosis, and/or breast pain adverse events (AEs), occurring ≤1 year from re-treatment completion. A rate of ≥13% for these AEs in a cohort of 55 patients was determined to be unacceptable (86% power, 1-sided α = 0.07). Between 2010 and 2013, 65 patients were accrued, and the first 55 eligible and with 1 year follow-up were analyzed. Median age was 68 years. Twenty-two patients had ductal carcinoma in situ, and 33 had invasive disease: 19 ≤1 cm, 13 >1 to ≤2 cm, and 1 >2 cm. All patients were clinically node negative. Systemic therapy was delivered in 51%. All treatment plans underwent quality review for contouring accuracy and dosimetric compliance. All treatment plans scored acceptable for tumor volume contouring and tumor volume dose-volume analysis. Only 4 (7%) scored unacceptable for organs at risk contouring and organs at risk dose-volume analysis. Treatment-related skin, fibrosis, and/or breast pain AEs were recorded as grade 1 in 64% and grade 2 in 7%, with only 1 (<2%) grade ≥3 and identified as grade 3 fibrosis of deep connective tissue. Partial-breast reirradiation with 3-dimensional conformal radiation therapy after second lumpectomy for patients experiencing in-breast failures after whole-breast irradiation is safe and feasible, with acceptable treatment quality achieved. Skin, fibrosis, and breast pain toxicity was acceptable, and grade 3 toxicity was rare. Copyright © 2017 Elsevier Inc. All rights reserved.

Study for reducing lung dose of upper thoracic esophageal cancer radiotherapy by auto-planning: volumetric-modulated arc therapy vs intensity-modulated radiation therapy.

PubMed

Chen, Hua; Wang, Hao; Gu, Hengle; Shao, Yan; Cai, Xuwei; Fu, Xiaolong; Xu, Zhiyong

2017-10-27

This study aimed to investigate the dosimetric differences and lung sparing between volumetric-modulated arc therapy (VMAT) and intensity-modulated radiation therapy (IMRT) in the treatment of upper thoracic esophageal cancer with T3N0M0 for preoperative radiotherapy by auto-planning (AP). Sixteen patient cases diagnosed with upper thoracic esophageal cancer T3N0M0 for preoperative radiotherapy were retrospectively studied, and 3 plans were generated for each patient: full arc VMAT AP plan with double arcs, partial arc VMAT AP plan with 6 partial arcs, and conventional IMRT AP plan. A simultaneous integrated boost with 2 levels was planned in all patients. Target coverage, organ at risk sparing, treatment parameters including monitor units and treatment time (TT) were evaluated. Wilcoxon signed-rank test was used to check for significant differences (p < 0.05) between datasets. VMAT plans (pVMAT and fVMAT) significantly reduced total lung volume treated above 20 Gy (V 20 ), 25 Gy (V 25 ), 30 Gy (V 30 ), 35 Gy (V 35 ), 40 Gy (V 40 ), and without increasing the value of V 10 , V 13 , and V 15 . For V 5 of total lung value, pVMAT was similar to aIMRT, and it was better than fVMAT. Both pVMAT and fVMAT improved the target dose coverage and significantly decreased maximum dose for the spinal cord, monitor unit, and TT. No significant difference was observed with respect to V 10 and V 15 of body. VMAT AP plan was a good option for treating upper thoracic esophageal cancer with T3N0M0, especially partial arc VMAT AP plan. It had the potential to effectively reduce lung dose in a shorter TT and with superior target coverage and dose homogeneity. Copyright © 2017 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

Breast-feeding protects infantile diarrhea caused by intestinal protozoan infections.

PubMed

Abdel-Hafeez, Ekhlas Hamed; Belal, Usama Salah; Abdellatif, Manal Zaki Mohamed; Naoi, Koji; Norose, Kazumi

2013-10-01

This study investigated the effect of breast-feeding in protection against protozoan infection in infants with persistent diarrhea. Infants were classified into 2 groups; 161 breast-fed infants and the same number of non-breast-fed infants. Microscopic examinations of stool were done for detection of parasites and measuring the intensity of infection. Moreover, serum levels of IgE and TNF-α were measured by ELISA. Cryptosporidium spp., Entamoeba histolytica/Entamoeba dispar, Giardia lamblia, and Blastocystis sp. were demonstrated in infants with persistent diarrhea. The percentage of protozoan infections was significantly lower in breast-fed infants than that in the non-breast-fed infants. The levels of IgE and TNF-α were significantly lower in the breast-fed group than in the non-breast-fed group. There were significant positive associations between the serum levels of IgE and TNF-α and the intensity of parasite infection in the breast-fed group. It is suggested that breast-feeding has an attenuating effect on the rate and intensity of parasite infection.

Association of Physical and Technical Activities With Partial Match Status in a Soccer Professional Team.

PubMed

Moalla, Wassim; Fessi, Mohamed Saieffedin; Makni, Emna; Dellal, Alexandre; Filetti, Cristoforo; Di Salvo, Valter; Chamari, Karim

2018-06-01

Moalla, W, Fessi, MS, Makni, E, Dellal, A, Filetti, C, Di Salvo, V, and Chamari, K. Association of physical and technical activities with partial match status in a soccer professional team. J Strength Cond Res 32(6): 1708-1714, 2018-The purpose of this study was to examine the association between physical and technical activities and partial match status (winning, drawing, or losing) in a professional soccer team over 2 seasons. Physical and technical activities of 52 official matches were collected and analyzed at each 15-minute interval, for each half (45 minutes), and full match (90 minutes) using a multiple-camera computerized tracking system. The results indicated that according to full match outcome: winning status was characterized by players covering more total distance (p ≤ 0.05) and low-intensity running (<14.4 km·h) (p ≤ 0.05), whereas, losing status induced more sprinting (≥25.2 km·h) (p < 0.01) and high-intensity running (≥19.8 km·h) (p ≤ 0.05). However, according to partial match status (i.e., 15 minutes and half time), players covered more distance for all running intensities while winning (p < 0.01). Technical match performance scores were not influenced by match status. In conclusion, the present study showed that the physical activities including high-intensity running and total distance covered were related to the match status, whereas technical activities were not. The overall outcome shows that higher physical activity was associated with winning partial match periods. This approach highlights the importance of physical fitness in soccer and may help coaches to better modulate players' roles and team tactical organization throughout the match.

High resolution PET breast imager with improved detection efficiency

DOEpatents

Majewski, Stanislaw

2010-06-08

A highly efficient PET breast imager for detecting lesions in the entire breast including those located close to the patient's chest wall. The breast imager includes a ring of imaging modules surrounding the imaged breast. Each imaging module includes a slant imaging light guide inserted between a gamma radiation sensor and a photodetector. The slant light guide permits the gamma radiation sensors to be placed in close proximity to the skin of the chest wall thereby extending the sensitive region of the imager to the base of the breast. Several types of photodetectors are proposed for use in the detector modules, with compact silicon photomultipliers as the preferred choice, due to its high compactness. The geometry of the detector heads and the arrangement of the detector ring significantly reduce dead regions thereby improving detection efficiency for lesions located close to the chest wall.

Insights into significant pathways and gene interaction networks underlying breast cancer cell line MCF-7 treated with 17β-estradiol (E2).

PubMed

Huan, Jinliang; Wang, Lishan; Xing, Li; Qin, Xianju; Feng, Lingbin; Pan, Xiaofeng; Zhu, Ling

2014-01-01

Estrogens are known to regulate the proliferation of breast cancer cells and to alter their cytoarchitectural and phenotypic properties, but the gene networks and pathways by which estrogenic hormones regulate these events are only partially understood. We used global gene expression profiling by Affymetrix GeneChip microarray analysis, with KEGG pathway enrichment, PPI network construction, module analysis and text mining methods to identify patterns and time courses of genes that are either stimulated or inhibited by estradiol (E2) in estrogen receptor (ER)-positive MCF-7 human breast cancer cells. Of the genes queried on the Affymetrix Human Genome U133 plus 2.0 microarray, we identified 628 (12h), 852 (24h) and 880 (48 h) differentially expressed genes (DEGs) that showed a robust pattern of regulation by E2. From pathway enrichment analysis, we found out the changes of metabolic pathways of E2 treated samples at each time point. At 12h time point, the changes of metabolic pathways were mainly focused on pathways in cancer, focal adhesion, and chemokine signaling pathway. At 24h time point, the changes were mainly enriched in neuroactive ligand-receptor interaction, cytokine-cytokine receptor interaction and calcium signaling pathway. At 48 h time point, the significant pathways were pathways in cancer, regulation of actin cytoskeleton, cell adhesion molecules (CAMs), axon guidance and ErbB signaling pathway. Of interest, our PPI network analysis and module analysis found that E2 treatment induced enhancement of PRSS23 at the three time points and PRSS23 was in the central position of each module. Text mining results showed that the important genes of DEGs have relationship with signal pathways, such as ERbB pathway (AREG), Wnt pathway (NDP), MAPK pathway (NTRK3, TH), IP3 pathway (TRA@) and some transcript factors (TCF4, MAF). Our studies highlight the diverse gene networks and metabolic and cell regulatory pathways through which E2 operates to achieve its widespread effects on breast cancer cells. © 2013 Elsevier B.V. All rights reserved.

Can Reproductive Hormones Modulate Host Immunity to Breast Cancer Antigens

DTIC Science & Technology

2005-07-01

AD Award Number: W81XWH-04-1-0668 TITLE: Can Reproductive Hormones Modulate Host Immunity to Breast Cancer Antigens PRINCIPAL INVESTIGATOR: Richard T...AND SUBTITLE 5a. CONTRACT NUMBER Can Reproductive Hormones Modulate Host Immunity to Breast Cancer Antigens 5b. GRANT NUMBER W81XWH-04-!1-0668 5c...neu-N mice can be readily applied to clinical trial development. The goal of the present work is to test the hypothesis that reproductive hormones can

Histopathology of breast cancer after magnetic resonance-guided high-intensity focused ultrasound and radiofrequency ablation.

PubMed

Knuttel, Floortje M; Waaijer, Laurien; Merckel, Laura G; van den Bosch, Maurice A A J; Witkamp, Arjen J; Deckers, Roel; van Diest, Paul J

2016-08-01

Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) ablation and radiofrequency ablation (RFA) are being researched as possible substitutes for surgery in breast cancer patients. The histopathological appearance of ablated tissue has not been studied in great detail. This study aimed to compare histopathological features of breast cancer after MR-HIFU ablation and RFA. MR-HIFU ablation and RFA were performed in- and ex-vivo. Tumours in six mastectomy specimens were partially ablated with RFA or MR-HIFU. In-vivo MR-HIFU ablation was performed 3-6 days before excision; RFA was performed in the operation room. Tissue was fixed in formalin and processed to haematoxylin and eosin (H&E) and cytokeratin-8 (CK-8)-stained slides. Morphology and cell viability were assessed. Ex-vivo ablation resulted in clear morphological changes after RFA versus subtle differences after MR-HIFU. CK-8 staining was decreased or absent. H&E tended to underestimate the size of thermal damage. In-vivo MR-HIFU resulted in necrotic-like changes. Surprisingly, some ablated lesions were CK-8-positive. Histopathology after in-vivo RFA resembled ex-vivo RFA, with hyper-eosinophilic stroma and elongated nuclei. Lesion borders were sharp after MR-HIFU and indistinct after RFA. Histopathological differences between MR-HIFU-ablated tissue and RF-ablated tissue were demonstrated. CK-8 was more reliable for cell viability assessment than H&E when used directly after ablation, while H&E was more reliable in ablated tissue left in situ for a few days. Our results contribute to improved understanding of histopathological features in breast cancer lesions treated with minimally invasive ablative techniques. © 2016 John Wiley & Sons Ltd.

Volumetric modulated arc therapy: a review of current literature and clinical use in practice

PubMed Central

Teoh, M; Clark, C H; Wood, K; Whitaker, S; Nisbet, A

2011-01-01

Volumetric modulated arc therapy (VMAT) is a novel radiation technique, which can achieve highly conformal dose distributions with improved target volume coverage and sparing of normal tissues compared with conventional radiotherapy techniques. VMAT also has the potential to offer additional advantages, such as reduced treatment delivery time compared with conventional static field intensity modulated radiotherapy (IMRT). The clinical worldwide use of VMAT is increasing significantly. Currently the majority of published data on VMAT are limited to planning and feasibility studies, although there is emerging clinical outcome data in several tumour sites. This article aims to discuss the current use of VMAT techniques in practice and review the available data from planning and clinical outcome studies in various tumour sites including prostate, pelvis (lower gastrointestinal, gynaecological), head and neck, thoracic, central nervous system, breast and other tumour sites. PMID:22011829

The 3 M's of breast-feeding the preterm infant.

PubMed

Hurst, Nancy M

2007-01-01

Mother's own milk is considered best for preterm infants. Given the often protracted period between birth and breast-feeding for most preterm newborns, a number of challenges exist for mothers and neonatal intensive care unit nurses in establishing lactation, providing mother's own milk, and achieving breast-feeding. This article conceptualizes breast-feeding the preterm infant in the context of the neonatal intensive care unit as a 3-phase process, the 3 M's of breast-feeding: medication, mother's milk feedings, and the mechanics of breast-feeding.

Fat Necrosis After Partial-Breast Irradiation With Brachytherapy or Electron Irradiation Versus Standard Whole-Breast Radiotherapy-4-Year Results of a Randomized Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Loevey, Katalin; Fodor, Janos; Major, Tibor

Purpose: To examine the incidence and clinical relevance of fat necrosis after accelerated partial-breast irradiation (PBI) using interstitial high-dose-rate brachytherapy (HDR-BT) in comparison with partial-breast electron irradiation (ELE) and whole-breast irradiation (WBI). Methods and Materials: Between 1998 and 2004, 258 early-stage breast cancer patients were randomized to receive 50 Gy WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 x 5.2 Gy HDR-BT (n = 88) or 50 Gy ELE (n = 40). The incidence of fat necrosis, its impact on cosmetic outcome, accompanying radiologic features, and clinical symptoms were evaluated. Results: The 4-yearmore » actuarial rate of fat necrosis was 31.1% for all patients, and 31.9%, 36.5%, and 17.7% after WBI, HDR-BT and ELE, respectively (p{sub WBI/HDR-BT} = 0.26; p{sub WBI/ELE} = 0.11; p{sub ELE/HDR-BT} = 0.025). The respective rate of asymptomatic fat necrosis was 20.2%, 25.3%, and 10% of patients. The incidence of symptomatic fat necrosis was not significantly different after WBI (8.5%), HDR-BT (11.4%), and ELE (7.5%). Symptomatic fat necrosis was significantly associated with a worse cosmetic outcome, whereas asymptomatic fat necrosis was not. Fat necrosis was detectable with mammography and/or ultrasound in each case. Additional imaging examinations were required in 21% of cases and aspiration cytology in 42%. Conclusions: Asymptomatic fat necrosis is a common adverse event of breast-conserving therapy, having no significant clinical relevance in the majority of the cases. The incidence of both symptomatic and asymptomatic fat necrosis is similar after conventional WBI and accelerated partial-breast HDR-BT.« less

Differential gene expression pattern in human mammary epithelial cells induced by realistic organochlorine mixtures described in healthy women and in women diagnosed with breast cancer.

PubMed

Rivero, Javier; Henríquez-Hernández, Luis Alberto; Luzardo, Octavio P; Pestano, José; Zumbado, Manuel; Boada, Luis D; Valerón, Pilar F

2016-03-30

Organochlorine pesticides (OCs) have been associated with breast cancer development and progression, but the mechanisms underlying this phenomenon are not well known. In this work, we evaluated the effects exerted on normal human mammary epithelial cells (HMEC) by the OC mixtures most frequently detected in healthy women (H-mixture) and in women diagnosed with breast cancer (BC-mixture), as identified in a previous case-control study developed in Spain. Cytotoxicity and gene expression profile of human kinases (n=68) and non-kinases (n=26) were tested at concentrations similar to those described in the serum of those cases and controls. Although both mixtures caused a down-regulation of genes involved in the ATP binding process, our results clearly indicate that both mixtures may exert a very different effect on the gene expression profile of HMEC. Thus, while BC-mixture up-regulated the expression of oncogenes associated to breast cancer (GFRA1 and BHLHB8), the H-mixture down-regulated the expression of tumor suppressor genes (EPHA4 and EPHB2). Our results indicate that the composition of the OC mixture could play a role in the initiation processes of breast cancer. In addition, the present results suggest that subtle changes in the composition and levels of pollutants involved in environmentally relevant mixtures might induce very different biological effects, which explain, at least partially, why some mixtures seem to be more carcinogenic than others. Nonetheless, our findings confirm that environmentally relevant pollutants may modulate the expression of genes closely related to carcinogenic processes in the breast, reinforcing the role exerted by environment in the regulation of genes involved in breast carcinogenesis. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

CT reconstruction from portal images acquired during volumetric-modulated arc therapy

NASA Astrophysics Data System (ADS)

Poludniowski, G.; Thomas, M. D. R.; Evans, P. M.; Webb, S.

2010-10-01

Volumetric-modulated arc therapy (VMAT), a form of intensity-modulated arc therapy (IMAT), has become a topic of research and clinical activity in recent years. As a form of arc therapy, portal images acquired during the treatment fraction form a (partial) Radon transform of the patient. We show that these portal images, when used in a modified global cone-beam filtered backprojection (FBP) algorithm, allow a surprisingly recognizable CT-volume to be reconstructed. The possibility of distinguishing anatomy in such VMAT-CT reconstructions suggests that this could prove to be a valuable treatment position-verification tool. Further, some potential for local-tomography techniques to improve image quality is shown.

In vivo dosimetry with optically stimulated luminescent dosimeters for conformal and intensity-modulated radiation therapy: A 2-year multicenter cohort study.

PubMed

Riegel, Adam C; Chen, Yu; Kapur, Ajay; Apicello, Laura; Kuruvilla, Abraham; Rea, Anthony J; Jamshidi, Abolghassem; Potters, Louis

Optically stimulated luminescent dosimeters (OSLDs) are utilized for in vivo dosimetry (IVD) of modern radiation therapy techniques such as intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). Dosimetric precision achieved with conventional techniques may not be attainable. In this work, we measured accuracy and precision for a large sample of clinical OSLD-based IVD measurements. Weekly IVD measurements were collected from 4 linear accelerators for 2 years and were expressed as percent differences from planned doses. After outlier analysis, 10,224 measurements were grouped in the following way: overall, modality (photons, electrons), treatment technique (3-dimensional [3D] conformal, field-in-field intensity modulation, inverse-planned IMRT, and VMAT), placement location (gantry angle, cardinality, and central axis positioning), and anatomical site (prostate, breast, head and neck, pelvis, lung, rectum and anus, brain, abdomen, esophagus, and bladder). Distributions were modeled via a Gaussian function. Fitting was performed with least squares, and goodness-of-fit was assessed with the coefficient of determination. Model means (μ) and standard deviations (σ) were calculated. Sample means and variances were compared for statistical significance by analysis of variance and the Levene tests (α = 0.05). Overall, μ ± σ was 0.3 ± 10.3%. Precision for electron measurements (6.9%) was significantly better than for photons (10.5%). Precision varied significantly among treatment techniques (P < .0001) with field-in-field lowest (σ = 7.2%) and IMRT and VMAT highest (σ = 11.9% and 13.4%, respectively). Treatment site models with goodness-of-fit greater than 0.90 (6 of 10) yielded accuracy within ±3%, except for head and neck (μ = -3.7%). Precision varied with treatment site (range, 7.3%-13.0%), with breast and head and neck yielding the best and worst precision, respectively. Placement on the central axis of cardinal gantry angles yielded more precise results (σ = 8.5%) compared with other locations (range, 10.5%-11.4%). Accuracy of ±3% was achievable. Precision ranged from 6.9% to 13.4% depending on modality, technique, and treatment site. Simple, standardized locations may improve IVD precision. These findings may aid development of patient-specific tolerances for OSLD-based IVD. Copyright © 2016 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Taking a look at the calibration of a CCD detector with a fiber-optic taper

PubMed Central

Alkire, R. W.; Rotella, F. J.; Duke, N. E. C.; Otwinowski, Zbyszek; Borek, Dominika

2016-01-01

At the Structural Biology Center beamline 19BM, located at the Advanced Photon Source, the operational characteristics of the equipment are routinely checked to ensure they are in proper working order. After performing a partial flat-field calibration for the ADSC Quantum 210r CCD detector, it was confirmed that the detector operates within specifications. However, as a secondary check it was decided to scan a single reflection across one-half of a detector module to validate the accuracy of the calibration. The intensities from this single reflection varied by more than 30% from the module center to the corner of the module. Redistribution of light within bent fibers of the fiber-optic taper was identified to be a source of this variation. The degree to which the diffraction intensities are corrected to account for characteristics of the fiber-optic tapers depends primarily upon the experimental strategy of data collection, approximations made by the data processing software during scaling, and crystal symmetry. PMID:27047303

Mother’s Milk: A Purposeful Contribution to the Development of the Infant Microbiota and Immunity

PubMed Central

Le Doare, Kirsty; Holder, Beth; Bassett, Aisha; Pannaraj, Pia S.

2018-01-01

Breast milk is the perfect nutrition for infants, a result of millions of years of evolution. In addition to providing a source of nutrition, breast milk contains a diverse array of microbiota and myriad biologically active components that are thought to guide the infant’s developing mucosal immune system. It is believed that bacteria from the mother’s intestine may translocate to breast milk and dynamically transfer to the infant. Such interplay between mother and her infant is a key to establishing a healthy infant intestinal microbiome. These intestinal bacteria protect against many respiratory and diarrheal illnesses, but are subject to environmental stresses such as antibiotic use. Orchestrating the development of the microbiota are the human milk oligosaccharides (HMOs), the synthesis of which are partially determined by the maternal genotype. HMOs are thought to play a role in preventing pathogenic bacterial adhesion though multiple mechanisms, while also providing nutrition for the microbiome. Extracellular vesicles (EVs), including exosomes, carry a diverse cargo, including mRNA, miRNA, and cytosolic and membrane-bound proteins, and are readily detectable in human breast milk. Strongly implicated in cell–cell signaling, EVs could therefore may play a further role in the development of the infant microbiome. This review considers the emerging role of breast milk microbiota, bioactive HMOs, and EVs in the establishment of the neonatal microbiome and the consequent potential for modulation of neonatal immune system development. PMID:29599768

Human Milk and Allergic Diseases: An Unsolved Puzzle

PubMed Central

Peroni, Diego G.; Boix-Amorós, Alba; Hsu, Peter S.; Van’t Land, Belinda; Skevaki, Chrysanthi; Collado, Maria Carmen; Garssen, Johan; Geddes, Donna T.; Nanan, Ralph; Slupsky, Carolyn; Wegienka, Ganesa; Kozyrskyj, Anita L.; Warner, John O.

2017-01-01

There is conflicting evidence on the protective role of breastfeeding in relation to the development of allergic sensitisation and allergic disease. Studies vary in methodology and definition of outcomes, which lead to considerable heterogeneity. Human milk composition varies both within and between individuals, which may partially explain conflicting data. It is known that human milk composition is very complex and contains variable levels of immune active molecules, oligosaccharides, metabolites, vitamins and other nutrients and microbial content. Existing evidence suggests that modulation of human breast milk composition has potential for preventing allergic diseases in early life. In this review, we discuss associations between breastfeeding/human milk composition and allergy development. PMID:28817095

Human Milk and Allergic Diseases: An Unsolved Puzzle.

PubMed

Munblit, Daniel; Peroni, Diego G; Boix-Amorós, Alba; Hsu, Peter S; Van't Land, Belinda; Gay, Melvin C L; Kolotilina, Anastasia; Skevaki, Chrysanthi; Boyle, Robert J; Collado, Maria Carmen; Garssen, Johan; Geddes, Donna T; Nanan, Ralph; Slupsky, Carolyn; Wegienka, Ganesa; Kozyrskyj, Anita L; Warner, John O

2017-08-17

There is conflicting evidence on the protective role of breastfeeding in relation to the development of allergic sensitisation and allergic disease. Studies vary in methodology and definition of outcomes, which lead to considerable heterogeneity. Human milk composition varies both within and between individuals, which may partially explain conflicting data. It is known that human milk composition is very complex and contains variable levels of immune active molecules, oligosaccharides, metabolites, vitamins and other nutrients and microbial content. Existing evidence suggests that modulation of human breast milk composition has potential for preventing allergic diseases in early life. In this review, we discuss associations between breastfeeding/human milk composition and allergy development.

[Assessment of breast feeding rates during compulsory vaccination: preliminary outcomes].

PubMed

Candriella, M; Uga, E; Perino, A; Angilella, G; Alloni, V; Trada, M; Grossi, L; Tripaldi, C; Bagnasco, G; Silano, V; Olmo, L M; Allen, M; Provera, S

2009-02-01

In consideration of the World Health Organization (WHO) recommendations on promoting and supporting breast feeding, a measurement of breast feeding rates was planned within Vercelli's Province (ASL 11, Piedmont, Italy) in order to compare the local situation to the national and international one, and to promote ideas and strategies for increasing the practice of breast feeding up to six months or beyond. During Diptheria Tetanus whole cell Pertussis vaccination (DTP) vaccination a questionnaire about their children's feeding was handed out to all mothers. Preliminary outcomes were elaborated after a follow-up of six months. So far 1591 questionnaires have been collected. During the first DTP immunizations 31.63% of the children were exclusively breastfed and 15.81% were partially breastfed. At the second vaccination, 11.14% and 37.68% of infants were completely and partially breastfed, respectively. A 36.11% of partially breast feeding still emerged during the third DTP vaccination. The outcomes of this study are inferior compared to WHO expectation and to national statistics. Increasing breast feeding rates should consequently become a priority aim, pursuing it through the health workers training, the support of mothers who encounter difficulties during their hospital stay or at home, and making the public aware of breast feeding practices.

Modulation of spectral intensity, polarization and coherence of a stochastic electromagnetic beam.

PubMed

Wu, Gaofeng; Cai, Yangjian

2011-04-25

Analytical formula for the cross-spectral density matrix of a stochastic electromagnetic Gaussian Schell-model (EGSM) beam truncated by a circular phase aperture propagating in free space is derived with the help of a tensor method, which provides a reliable and fast way for studying the propagation and transformation of a truncated EGSM beam. Statistics properties, such as the spectral intensity, the degree of coherence, the degree of polarization and the polarization ellipse of a truncated EGSM beam in free space are studied numerically. The propagation factor of a truncated EGSM beam is also analyzed. Our numerical results show that we can modulate the spectral intensity, the polarization, the coherence and the propagation factor of an EGSM beam by a circular phase aperture. It is found that the phase aperture can be used to shape the beam profile of an EGSM beam and generate electromagnetic partially coherent dark hollow or flat-topped beam, which is useful in some applications, such as optical trapping, material processing, free-space optical communications.

Analysis of electric field distribution in GaAs metal-semiconductor field effect transistor with a field-modulating plate

NASA Astrophysics Data System (ADS)

Hori, Yasuko; Kuzuhara, Masaaki; Ando, Yuji; Mizuta, Masashi

2000-04-01

Electric field distribution in the channel of a field effect transistor (FET) with a field-modulating plate (FP) has been theoretically investigated using a two-dimensional ensemble Monte Carlo simulation. This analysis revealed that the introduction of FP is effective in canceling the influence of surface traps under forward bias conditions and in reducing the electric field intensity at the drain side of the gate edge under pinch-off bias conditions. This study also found that a partial overlap of the high-field region under the gate and that at the FP electrode is important for reducing the electric field intensity. The optimized metal-semiconductor FET with FP (FPFET) (LGF˜0.2 μm) exhibited a much lower peak electric field intensity than a conventional metal-semiconductor FET. Based on these numerically calculated results, we have proposed a design procedure to optimize the power FPFET structure with extremely high breakdown voltages while maintaining reasonable gain performance.

Does warming the breasts affect the amount of breastmilk production?

PubMed

Yiğit, Feride; Çiğdem, Zerrin; Temizsoy, Ebru; Cingi, Melek Ersoy; Korel, Özlem; Yıldırım, Egemen; Ovalı, Fahri

2012-12-01

Increasing the amount of breastmilk is vital for both the nursing mother and child. Warming up breasts before using electrical pumps to pump out breastmilk may help to increase the amount of breastmilk, especially in the mothers of babies who are being nursed in the neonatal intensive care unit. Thirty-nine mothers whose babies had been admitted to the neonatal intensive care unit were analyzed. A breast compress that was warmed up in a microwave oven for 1 minute at 180 W was applied to one of the breasts for 20 minutes, and both breasts were sucked by an electrical breast pump for 15 minutes. The amount of breastmilk after each procedure was recorded. The amount of breastmilk that was obtained from warmed breasts was significantly higher than that obtained from nonwarmed breasts (maximum, 47.02 ± 23.01 mL vs. 33.15 ± 19.98 mL) (p=0.000). Warming up breasts by a breast compress is easy and affordable, and this procedure increases the amount of breastmilk, thus facilitating infant nutrition and recovery especially in the neonatal intensive care unit.

Defining the Molecular Actions of Dietary Fatty Acids in Breast Cancer: Selective Modulation of Peroxisome Proliferator-Activated Receptor Gamma

DTIC Science & Technology

2005-05-01

Maximum 200 Words) Stark differences in the actions of lenoleic acid (LAA), an omega-6 fatty acid , and eicosapentaenoic acid (EPA), an omega-3 fatty acid ...AD_ Award Number: W81XWH-04-1-0532 TITLE: Defining the Molecular Actions of Dietary Fatty acids in Breast Cancer: Selective Modulation of Peroxisome...TITLE AND SUBTITLE 5. FUNDING NUMBERS Defining the Molecular Actions of Dietary Fatty acids in W81XWH-04-1-0532 Breast Cancer: Selective Modulation of

Potentials of radial partially coherent beams in free-space optical communication: a numerical investigation.

PubMed

Wang, Minghao; Yuan, Xiuhua; Ma, Donglin

2017-04-01

Nonuniformly correlated partially coherent beams (PCBs) have extraordinary propagation properties, making it possible to further improve the performance of free-space optical communications. In this paper, a series of PCBs with varying degrees of coherence in the radial direction, academically called radial partially coherent beams (RPCBs), are considered. RPCBs with arbitrary coherence distributions can be created by adjusting the amplitude profile of a spatial modulation function imposed on a uniformly correlated phase screen. Since RPCBs cannot be well characterized by the coherence length, a modulation depth factor is introduced as an indicator of the overall distribution of coherence. By wave optics simulation, free-space and atmospheric propagation properties of RPCBs with (inverse) Gaussian and super-Gaussian coherence distributions are examined in comparison with conventional Gaussian Schell-model beams. Furthermore, the impacts of varying central coherent areas are studied. Simulation results reveal that under comparable overall coherence, beams with a highly coherent core and a less coherent margin exhibit a smaller beam spread and greater on-axis intensity, which is mainly due to the self-focusing phenomenon right after the beam exits the transmitter. Particularly, those RPCBs with super-Gaussian coherence distributions will repeatedly focus during propagation, resulting in even greater intensities. Additionally, RPCBs also have a considerable ability to reduce scintillation. And it is demonstrated that those properties have made RPCBs very effective in improving the mean signal-to-noise ratio of small optical receivers, especially in relatively short, weakly fluctuating links.

Effects of online cone-beam computed tomography with active breath control in determining planning target volume during accelerated partial breast irradiation.

PubMed

Li, Y; Zhong, R; Wang, X; Ai, P; Henderson, F; Chen, N; Luo, F

2017-04-01

To test if active breath control during cone-beam computed tomography (CBCT) could improve planning target volume during accelerated partial breast radiotherapy for breast cancer. Patients who were more than 40 years old, underwent breast-conserving dissection and planned for accelerated partial breast irradiation, and with postoperative staging limited to T1-2 N0 M0, or postoperative staging T2 lesion no larger than 3cm with a negative surgical margin greater than 2mm were enrolled. Patients with lobular carcinoma or extensive ductal carcinoma in situ were excluded. CBCT images were obtained pre-correction, post-correction and post-treatment. Set-up errors were recorded at left-right, anterior-posterior and superior-inferior directions. The differences between these CBCT images, as well as calculated radiation doses, were compared between patients with active breath control or free breathing. Forty patients were enrolled, among them 25 had active breath control. A total of 836 CBCT images were obtained for analysis. CBCT significantly reduced planning target volume. However, active breath control did not show significant benefit in decreasing planning target volume margin and the doses of organ-at-risk when compared to free breathing. CBCT, but not active breath control, could reduce planning target volume during accelerated partial breast irradiation. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Dosimetric considerations and early clinical experience of accelerated partial breast irradiation using multi-lumen applicators in the setting of breast augmentation.

PubMed

Akhtari, Mani; Pino, Ramiro; Scarboro, Sarah B; Bass, Barbara L; Miltenburg, Darlene M; Butler, E Brian; Teh, Bin S

2015-12-01

Accelerated partial breast irradiation (APBI) is an accepted treatment option in breast-conserving therapy for early stage breast cancer. However, data regarding outcomes of patients treated with multi-lumen catheter systems who have existing breast implants is limited. The purpose of this study was to report treatment parameters, outcomes, and possible dosimetric correlation with cosmetic outcome for this population of patients at our institution. We report the treatment and outcome of seven consecutive patients with existing breast implants and early stage breast cancer who were treated between 2009 and 2013 using APBI following lumpectomy. All patients were treated twice per day for five days to a total dose of 34 Gy using a high-dose-rate (192)Ir source. Cosmetic outcomes were evaluated using the Harvard breast cosmesis scale, and late toxicities were reported using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity schema. After a mean follow-up of 32 months, all patients have remained cancer free. Six out of seven patients had an excellent or good cosmetic outcome. There were no grade 3 or 4 late toxicities. The average total breast implant volume was 279.3 cc, received an average mean dose of 12.1 Gy, and a maximum dose of 234.1 Gy. The average percentage of breast implant volume receiving 50%, 75%, 100%, 150%, and 200% of the prescribed dose was 15.6%, 7.03%, 4.6%, 1.58%, and 0.46%, respectively. Absolute volume of breast implants receiving more than 50% of prescribed dose correlated with worse cosmetic outcomes. Accelerated partial breast irradiation using a multi-lumen applicator in patients with existing breast implants can safely be performed with promising early clinical results. The presence of the implant did not compromise the ability to achieve dosimetric criteria; however, dose to the implant and the irradiated implant volume may be related with worse cosmetic outcomes.

Dosimetric considerations and early clinical experience of accelerated partial breast irradiation using multi-lumen applicators in the setting of breast augmentation

PubMed Central

Akhtari, Mani; Pino, Ramiro; Scarboro, Sarah B.; Bass, Barbara L.; Miltenburg, Darlene M.; Butler, E. Brian

2015-01-01

Purpose Accelerated partial breast irradiation (APBI) is an accepted treatment option in breast-conserving therapy for early stage breast cancer. However, data regarding outcomes of patients treated with multi-lumen catheter systems who have existing breast implants is limited. The purpose of this study was to report treatment parameters, outcomes, and possible dosimetric correlation with cosmetic outcome for this population of patients at our institution. Material and methods We report the treatment and outcome of seven consecutive patients with existing breast implants and early stage breast cancer who were treated between 2009 and 2013 using APBI following lumpectomy. All patients were treated twice per day for five days to a total dose of 34 Gy using a high-dose-rate 192Ir source. Cosmetic outcomes were evaluated using the Harvard breast cosmesis scale, and late toxicities were reported using the Radiation Therapy Oncology Group (RTOG) late radiation morbidity schema. Results After a mean follow-up of 32 months, all patients have remained cancer free. Six out of seven patients had an excellent or good cosmetic outcome. There were no grade 3 or 4 late toxicities. The average total breast implant volume was 279.3 cc, received an average mean dose of 12.1 Gy, and a maximum dose of 234.1 Gy. The average percentage of breast implant volume receiving 50%, 75%, 100%, 150%, and 200% of the prescribed dose was 15.6%, 7.03%, 4.6%, 1.58%, and 0.46%, respectively. Absolute volume of breast implants receiving more than 50% of prescribed dose correlated with worse cosmetic outcomes. Conclusions Accelerated partial breast irradiation using a multi-lumen applicator in patients with existing breast implants can safely be performed with promising early clinical results. The presence of the implant did not compromise the ability to achieve dosimetric criteria; however, dose to the implant and the irradiated implant volume may be related with worse cosmetic outcomes. PMID:26816499

Normative Data for Interpreting the BREAST-Q: Augmentation

PubMed Central

Mundy, Lily R.; Homa, Karen; Klassen, Anne F.; Pusic, Andrea L.; Kerrigan, Carolyn L.

2016-01-01

Background The BREAST-Q is a rigorously developed, well-validated, patient-reported outcome (PRO) instrument with a module designed for evaluating breast augmentation outcomes. However, there are no published normative BREAST-Q scores, limiting interpretation. Methods Normative data were generated for the BREAST-Q Augmentation Module via the Army of Women (AOW), an online community of women (with and without breast cancer) engaged in breast-cancer related research. Members were recruited via email, with women 18 years or older without a history of breast cancer or breast surgery invited to participate. Descriptive statistics and a linear multivariate regression were performed. A separate analysis compared normative scores to findings from previously published BREAST-Q augmentation studies. Results The preoperative BREAST-Q Augmentation Module was completed by 1,211 women. Mean age was 54 ±24 years, mean body mass index (BMI) was 27 ±6, and 39% (n=467) had a bra cup size ≥D. Mean scores were Satisfaction with Breasts (54 ±19), Psychosocial Well-being (66 ±20), Sexual Well-being (49 ±20), and Physical Well-being (86 ±15). Women with a BMI of 30 or greater and bra cup size D or greater had lower scores. In comparison to AOW scores, published BREAST-Q augmentation scores were lower before and higher after surgery for all scales except Physical Well-being. Conclusions The AOW normative data represent breast-related satisfaction and well-being in woman not actively seeking breast augmentation. This data may be used as normative comparison values for those seeking and undergoing surgery as we did, demonstrating the value of breast augmentation in this patient population. PMID:28350657

Intensive follow-up for women with breast cancer: review of clinical, economic and patient's preference domains through evidence to decision framework.

PubMed

Lafranconi, Alessandra; Pylkkänen, Liisa; Deandrea, Silvia; Bramesfeld, Anke; Lerda, Donata; Neamțiu, Luciana; Saz-Parkinson, Zuleika; Posso, Margarita; Rigau, David; Sola, Ivan; Alonso-Coello, Pablo; Martinez-Zapata, Maria José

2017-10-19

Women treated for breast cancer are followed-up for monitoring of treatment effectiveness and for detecting recurrences at an early stage. The type of follow-up received may affect women's reassurance and impact on their quality of life. Anxiety and depression among women with breast cancer has been described, but little is known about how the intensity of the follow-up can affect women's psychological status. This study was undertaken to evaluate the effects of intensive vs. less-intensive follow-up on different health outcomes, to determine what are women's preferences and values regarding the follow-up received, and also assess the costs of these different types of follow-up. A systematic review following standard Cochrane Collaboration methods was carried out to assess the efficacy of intensive follow-up versus non-intensive follow-up in breast cancer patients. Two additional reviews on women's preferences and economic evidence were also carried out. The search was performed up to January 2016 in: MEDLINE, EMBASE, PDQ, McMaster Health Systems Evidence, CENTRAL, and NHS EED (through The Cochrane Library). The quality of evidence was assessed by GRADE (for quantitative studies) and CerQUAL (for qualitative studies). Several outcomes including mortality, breast cancer recurrences, quality of life, and patient satisfaction were evaluated. Six randomised trials (corresponding to 3534 women) were included for the evaluation of health outcomes; three studies were included for women's values and preferences and four for an economic assessment. There is moderate certainty of evidence showing that intensive follow-up, including more frequent diagnostic tests or visits, does not have effects on 5- or 10-year overall mortality and recurrences in women with breast cancer, compared with less intensive follow-up. Regarding women's preferences and values, there was important variability among studies and within studies (low confidence due to risk of bias and inconsistency). Furthermore, intensive follow-up, as opposed to less intensive follow-up, is not likely to be cost-effective. Less intensive follow-up appears to be justified and can be recommended over intensive follow-up. Resources could thus be mobilised to other aspects of breast cancer care, or other areas of healthcare.

Efficiency and prognosis of whole brain irradiation combined with precise radiotherapy on triple-negative breast cancer.

PubMed

Wu, Xinhong; Luo, Bo; Wei, Shaozhong; Luo, Yan; Feng, Yaojun; Xu, Juan; Wei, Wei

2013-11-01

To investigate the treatment efficiency of whole brain irradiation combined with precise radiotherapy on triple-negative (TN) phenotype breast cancer patients with brain metastases and their survival times. A total of 112 metastatic breast cancer patients treated with whole brain irradiation and intensity modulated radiotherapy (IMRT) or 3D conformal radiotherapy (3DCRT) were analyzed. Thirty-seven patients were of TN phenotype. Objective response rates were compared. Survival times were estimated by using the Kaplan-Meier method. Log-rank test was used to compare the survival time difference between the TN and non-TN groups. Potential prognostic factors were determined by using a Cox proportional hazard regression model. The efficiency of radiotherapy treatment on TN and non-TN phenotypes was 96.2% and 97%, respectively. TN phenotype was associated with worse survival times than non-TN phenotype after radiotherapy (6.9 months vs. 17 months) (P < 0.01). On multivariate analysis, good prognosis was associated with non-TN status, lower graded prognosis assessment class, and nonexistence of active extracranial metastases. After whole brain irradiation followed by IMRT or 3DCRT treatment, TN phenotype breast cancer patients with intracranial metastasis had high objective response rates but shorter survival time. With respect to survival in breast cancer patients with intracranial metastasis, the TN phenotype represents a significant adverse prognostic factor.

Breast-feeding: A commentary by the ESPGHAN Committee on Nutrition.

PubMed

Agostoni, Carlo; Braegger, Christian; Decsi, Tamas; Kolacek, Sanja; Koletzko, Berthold; Michaelsen, Kim Fleischer; Mihatsch, Walter; Moreno, Luis A; Puntis, John; Shamir, Raanan; Szajewska, Hania; Turck, Dominique; van Goudoever, Johannes

2009-07-01

This medical position article by the European Society for Paediatric Gastroenterology, Hepatology, and Nutrition summarises the current status of breast-feeding practice, the present knowledge on the composition of human milk, advisable duration of exclusive and partial breast-feeding, growth of the breast-fed infant, health benefits associated with breast-feeding, nutritional supplementation for breast-fed infants, and contraindications to breast-feeding. This article emphasises the important role of paediatricians in the implementation of health policies devised to promote breast-feeding.The European Society for Paediatric Gastroenterology, Hepatology, and Nutrition Committee on Nutrition recognises breast-feeding as the natural and advisable way of supporting the healthy growth and development of young children. This article delineates the health benefits of breast-feeding, reduced risk of infectious diarrhoea and acute otitis media being the best documented. Exclusive breast-feeding for around 6 months is a desirable goal, but partial breast-feeding as well as breast-feeding for shorter periods of time are also valuable. Continuation of breast-feeding after the introduction of complementary feeding is encouraged as long as mutually desired by mother and child.The role of health care workers, including paediatricians, is to protect, promote, and support breast-feeding. Health care workers should be trained in breast-feeding issues and counselling, and they should encourage practices that do not undermine breast-feeding. Societal standards and legal regulations that facilitate breast-feeding should be promoted, such as providing maternity leave for at least 6 months and protecting working mothers.

Non-thermal High-intensity Focused Ultrasound for Breast Cancer Therapy

DTIC Science & Technology

2012-07-01

AD ________________ Award Number: W81XWH-11-1-0341 TITLE: Non-thermal high-intensity focused ultrasound for breast cancer therapy PRINCIPAL...30 Jun 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Non-thermal high-intensity focused ultrasound for breast cancer therapy 5b. GRANT NUMBER W81XWH...the in vivo animal experiments. However, the tasks planned for the animal studies were not completed due to the delayed approval of the animal

Hypofractionated whole breast radiation and partial breast radiation for early-stage breast cancers: an update on progress.

PubMed

McCormick, Beryl

2012-09-01

This article provides an update of recent progress using partial breast irradiation (PBI) for the treatment of early-stage breast cancer, rather than whole breast radiotherapy (WBRT), which is the standard of care. Several large, prospective, randomized trials are nearing target accrual or have been completed, including the NSABP/RTOG trial, the Milan-based intraoperative radiation trial, and the international TARGIT trial, and the status of each is discussed. The American Society for Radiation Oncology has also published a consensus statement to guide the use of PBI until some of the phase III trials are more mature. Finally, several articles have appeared recently, reporting unexpected adverse effects of PBI in small series, and this information is reviewed. Several recent prospective trials of WBRT are also discussed, with the theme of comparing the standard 25 fractions to a shortened, hypofractionated trial arm delivering equivalent doses of WBRT in approximately 15 treatments, another radiation strategy for a shortened course of treatment after breast-conserving surgery.

Sensitivity of Breast Tumors to Oncolytic Viruses

DTIC Science & Technology

2005-08-01

reproductions will be in black and white. 14. ABSTRACT The goal of this project is to develop novel therapies for breast cancer based on the oncolytic...effect than breast cancer cells. However, in syngeneic breast cancer system in vivo, rM51R-M virus is only partially effective at killing breast tumors...aggressive tumors that are resistant to more conventional therapies. 15. SUBJECT TERMS Vesicular stomatitis virus, interleukin 12, breast cancer

Validation of the electronic version of the BREAST-Q in the army of women study.

PubMed

Fuzesi, Sarah; Cano, Stefan J; Klassen, Anne F; Atisha, Dunya; Pusic, Andrea L

2017-06-01

Women undergoing surgery for primary breast cancer can choose between breast conserving therapy and mastectomy (with or without breast reconstruction). Patients often turn to outcomes data to help guide the decision-making process. The BREAST-Q is a validated breast surgery-specific patient-reported outcome measure that evaluates satisfaction, quality of life, and patient experience. It was originally developed for paper-and-pencil administration. However, the BREAST-Q has increasingly been administered electronically. Therefore, the aim of this study was to evaluate the psychometric properties of an electronic version of the BREAST-Q in a large online survey. Women with a history of breast cancer surgery recruited from the Love/AVON Army of Women program completed an electronic version of the BREAST-Q in addition to the Impact of Cancer Survey and PTSD Checklist. Traditional psychometric analyses were performed on the collected data. BREAST-Q data were collected from 6748 women (3497 Breast Conserving Therapy module, 1295 Mastectomy module, 1956 Breast Reconstruction module). Acceptability was supported by a high response rate (82%), low frequency of missing data (<5%), and maximum endorsement frequencies (<80%) in all but 17 items. Scale reliability was supported by high Cronbach's α coefficients (≥0.78) and item-total correlations (range of means, 0.65-0.91). Validity was supported by interscale correlations, convergent and divergent hypotheses as well as clinical hypotheses. The electronically administered BREAST-Q yields highly reliable, clinically meaningful data for use in clinical outcomes research. The BREAST-Q can be used in the clinical setting, whether administered electronically or using paper-and-pencil, at the choice of the patient and surgeon. Copyright © 2017 Elsevier Ltd. All rights reserved.

TH-AB-BRB-01: Trajectory Modulated Arc Therapy: Application to Partial Breast Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hristov, D.

2016-06-15

Current state-of-the art digital C-arm medical linear accelerators are capable of delivering radiation treatments with high level of automation, which affords coordinated motions of gantry, couch, and multileaf collimator (MLC) with dose rate modulations. The new machine capacity has shown the potential to bring substantially improved radiation dosimetry and/or delivery efficiency to many challenging diseases. Combining an integrated beam orientation optimization algorithm with automated machine navigation, markedly improved dose conformity has been achieved using 4ρ therapy. Trajectory modulated radiation therapy (TMAT) can be used to deliver highly conformal dose to partial breast or to carve complex dose distribution for therapymore » involving extended volumes such as total marrow and total lymph node treatment. Dynamic electron arc radiotherapy (DEAR) not only overcomes the deficiencies of conventional electron therapy in dose conformity and homogeneity but also achieves so without patient-specific shields. The combination of MLC and couch tracking provides improved motion management of thoracic and abdominal tumors. A substantial body of work has been done in these technological advances for clinical translation. The proposed symposium will provide a timely review of these exciting opportunities. Learning Objectives: Recognize the potential of using digitally controlled linacs for clinically significant improvements in delivered dose distributions for various treatment sites. Identify existing approaches to treatment planning, optimization and delivery for treatment techniques utilizing the advanced functions of digital linacs and venues for further development and improvement. Understand methods for testing and validating delivery system performance. Identify tools available on current delivery systems for implementation and control for such treatments. Obtain the update in clinical applications, trials and regulatory approval. K. Sheng, NIH U19AI067769, NIH R43CA183390, NIH R01CA188300, Varian Medical Systems V. Yu, Varian Medical Systems, AAPM Summer Undergraduate Fellowship, NSF graduate fellowship S. Nill, Elekta AB. Cancer Research UK under Programme C33589/A19727, NIHR Biomedical Research Centre at The Royal Marsden and The Institute of Cancer Research.« less

MO-A-BRD-01: An Investigation of the Dynamic Response of a Novel Acousto-Optic Liquid Crystal Detector for Full-Field Transmission Ultrasound Breast Imaging

DOE Office of Scientific and Technical Information (OSTI.GOV)

Rosenfield, J.R.; La Riviere, P.J.; Sandhu, J.S.

Purpose: To characterize the dynamic response of a novel acousto-optic (AO) liquid crystal detector for high-resolution transmission ultrasound breast imaging. Transient and steady-state lesion contrast were investigated to identify optimal transducer settings for our prototype imaging system consistent with the FDA limits of 1 W/cm{sup 2} and 50 J/cm{sup 2} on the incident acoustic intensity and the transmitted acoustic energy flux density. Methods: We have developed a full-field transmission ultrasound breast imaging system that uses monochromatic plane-wave illumination to acquire projection images of the compressed breast. The acoustic intensity transmitted through the breast is converted into a visual image bymore » a proprietary liquid crystal detector operating on the basis of the AO effect. The dynamic response of the AO detector in the absence of an imaged breast was recorded by a CCD camera as a function of the acoustic field intensity and the detector exposure time. Additionally, a stereotactic needle biopsy breast phantom was used to investigate the change in opaque lesion contrast with increasing exposure time for a range of incident acoustic field intensities. Results: Using transducer voltages between 0.3 V and 0.8 V and exposure times of 3 minutes, a unique one-to-one mapping of incident acoustic intensity to steady-state optical brightness in the AO detector was observed. A transfer curve mapping acoustic intensity to steady-state optical brightness shows a high-contrast region analogous to the linear portion of the Hurter-Driffield curves of radiography. Using transducer voltages between 1 V and 1.75 V and exposure times of 90 s, the lesion contrast study demonstrated increasing lesion contrast with increasing breast exposure time and acoustic field intensity. Lesion-to-background contrast on the order of 0.80 was observed. Conclusion: Maximal lesion contrast in our prototype system can be obtained using the highest acoustic field intensity and the longest breast exposure time allowable under FDA standards. Department of Defense (DOD) Breast Cancer Research Program IDEA Award W81XWH-11-1-0332; National Institutes of Health (NIH) Grant T32 EB002103-21 from the National Institute of Biomedical Imaging and Bioengineering (NIBIB)« less

Contralateral Breast Dose After Whole-Breast Irradiation: An Analysis by Treatment Technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Williams, Terence M.; Moran, Jean M., E-mail: jmmoran@med.umich.edu; Hsu, Shu-Hui

2012-04-01

Purpose: To investigate the contralateral breast dose (CBD) across a continuum of breast-conservation therapy techniques. Methods and Materials: An anthropomorphic phantom was CT-simulated, and six treatment plans were generated: open tangents, tangents with an external wedge on the lateral beam, tangents with lateral and medial external wedges, a simple segment plan (three segments per tangent), a complex segmental intensity-modulated radiotherapy (IMRT) plan (five segments per tangent), and a beamlet IMRT plan (>100 segments). For all techniques, the breast on the phantom was irradiated to 5000 cGy. Contralateral breast dose was measured at a uniform depth at the center and eachmore » quadrant using thermoluminescent detectors. Results: Contralateral breast dose varied with position and was 50 {+-} 7.3 cGy in the inner half, 24 {+-} 4.1 cGy at the center, and 16 {+-} 2.2 cGy in the outer half for the open tangential plan. Compared with an average dose of 31 cGy across all points for the open field, the average doses were simple segment 32 cGy (range, 99-105% compared with open technique), complex segment 34 cGy (range, 103-117% compared with open technique), beamlet IMRT 34 cGy (range, 103-124% compared with open technique), lateral wedge only 46 cGy (range, 133-175% compared with open technique), and medial and lateral wedge 96 cGy (range, 282-370% compared with open technique). Conclusions: Single or dual wedge techniques resulted in the highest CBD increases compared with open tangents. To obtain the desired homogeneity to the treated breast while minimizing CBD, segmental and IMRT techniques should be encouraged over external physical compensators.« less

Digital tomosynthesis mammography using a parallel maximum-likelihood reconstruction method

NASA Astrophysics Data System (ADS)

Wu, Tao; Zhang, Juemin; Moore, Richard; Rafferty, Elizabeth; Kopans, Daniel; Meleis, Waleed; Kaeli, David

2004-05-01

A parallel reconstruction method, based on an iterative maximum likelihood (ML) algorithm, is developed to provide fast reconstruction for digital tomosynthesis mammography. Tomosynthesis mammography acquires 11 low-dose projections of a breast by moving an x-ray tube over a 50° angular range. In parallel reconstruction, each projection is divided into multiple segments along the chest-to-nipple direction. Using the 11 projections, segments located at the same distance from the chest wall are combined to compute a partial reconstruction of the total breast volume. The shape of the partial reconstruction forms a thin slab, angled toward the x-ray source at a projection angle 0°. The reconstruction of the total breast volume is obtained by merging the partial reconstructions. The overlap region between neighboring partial reconstructions and neighboring projection segments is utilized to compensate for the incomplete data at the boundary locations present in the partial reconstructions. A serial execution of the reconstruction is compared to a parallel implementation, using clinical data. The serial code was run on a PC with a single PentiumIV 2.2GHz CPU. The parallel implementation was developed using MPI and run on a 64-node Linux cluster using 800MHz Itanium CPUs. The serial reconstruction for a medium-sized breast (5cm thickness, 11cm chest-to-nipple distance) takes 115 minutes, while a parallel implementation takes only 3.5 minutes. The reconstruction time for a larger breast using a serial implementation takes 187 minutes, while a parallel implementation takes 6.5 minutes. No significant differences were observed between the reconstructions produced by the serial and parallel implementations.

Candidate mechanisms accounting for effects of physical activity on breast carcinogenesis.

PubMed

Thompson, Henry J; Jiang, Weiqin; Zhu, Zongjian

2009-09-01

Evidence is strong that a reduction in risk for breast cancer is associated with moderate to vigorous physical activity (PA); however, there is limited understanding of the role of type, intensity, duration, and frequency of PA and their mechanisms in accounting for this health benefit. The objective of this review is to stimulate investigations of candidate mechanisms that may account for the effects of the intensity and duration of aerobic PA on breast cancer risk and tumor burden. Three hypotheses are considered: 1) the mTOR network hypothesis: PA inhibits carcinogenesis by suppressing the activation of the mTOR signaling network in mammary carcinomas; 2) the hormesis hypothesis: the carcinogenic response to PA is nonlinear and accounted for by a physiological cellular stress response; and 3) the metabolic reprogramming hypothesis: PA limits the amount of glucose and glutamine available to mammary carcinomas thereby inducing apoptosis because tumor-associated metabolic programming is reversed. To link these hypotheses to systemic effects of PA, it is recommended that consideration be given to determining: 1) what contracting muscle releases into circulation or removes from circulation that would directly modulate the carcinogenic process in epithelial cells; 2) whether the effects of muscle contraction on epithelial cell carcinogenesis are exerted in an endocrine, paracrine, autocrine, or intracrine manner; and 3) if the effects of muscle contraction on malignant cells differ from effects on normal or premalignant cells that do not manifest the hallmarks of malignancy. (c) 2009 IUBMB

ERβ Expression and Breast Cancer Risk Prediction for Women with Atypias

PubMed Central

Hieken, Tina J; Carter, Jodi M; Hawse, John R; Hoskin, Tanya L; Bois, Melanie; Frost, Marlene; Hartmann, Lynn C; Radisky, Derek C; Visscher, Daniel W; Degnim, Amy C

2015-01-01

Estrogen receptor beta (ERβ) is highly expressed in normal breast epithelium and a putative tumor suppressor. Atypical hyperplasia substantially increases breast cancer risk, but identification of biomarkers to further improve risk stratification is needed. We evaluated ERβ expression in breast tissues from women with atypical hyperplasia and association with subsequent breast cancer risk. ERβ expression was examined by immunohistochemistry in a well-characterized 171 women cohort with atypical hyperplasia diagnosed 1967–1991. Nuclear ERβ percent and intensity was scored in the atypia and adjacent normal lobules. An ERβ sum score (percent + intensity) was calculated and grouped as low, moderate or high. Competing risks regression was used to assess associations of ERβ expression with breast cancer risk. After 15 years median follow-up, 36 women developed breast cancer. ERβ expression was lower in atypia lobules than normal lobules, by percent staining and intensity (both p<0.001). Higher ERβ expression in the atypia or normal lobules, evaluated by percent staining, intensity or sum score, decreased the risk of subsequent breast cancer by 2 (p=0.04) and 2.5-fold (p=0.006). High normal lobule ERβ expression conferred the strongest protective effect in pre-menopausal women: the 20-year cumulative incidence of breast cancer was 0% for women

Partial breast brachytherapy

MedlinePlus

... 11, 2016. www.cancer.gov/types/breast/hp/breast-treatment-pdq . Accessed September 13, 2016. National Cancer Institute. Radiation therapy and you: support for people who have cancer. Cancer.gov Web site. www.cancer.gov/publications/patient-education/radiation-therapy-and-you . Accessed September 13, ...

High-intensity focused ultrasound for the treatment of solid tumor: Chinese clinical experience

NASA Astrophysics Data System (ADS)

Takeuchi, Akira; Zhang, Hong; Sun, Kun; Hasumura, Hiromi; Liu, Botao; Fu, Yurui; Yang, Zaocheng

2006-05-01

As a non-invasive modality, high-intensity focused ultrasound (HIFU) therapy has been received an interest for the treatment of solid tumor. There are some makers of HIFU for the equipment in China. The Sonic CZ901 is developed from the Mianyang stream that has a great advantage for guiding by color Doppler ultrasound imaging. For the research about possibility of this equipment, we evaluate the clinical usefulness to the solid tumor of HIFU treatment at Wujing general hospital in Beijing. We elucidate the result in 28 cases with benign and malignant tumor (Uterine myoma:16, Benign prostatic hypertrophy:5, Benign breast tumor:2, Breast cancer:1, Retroperitoneal tumor:1, Pheochromocytoma:1, Liver cancer: 2) . After 14˜90days, all cases show the reduction of tumor size (Max.3.2cm, Min.1.6cm, :Mean 2.2cm reduced), and the blood flow of tumor completely reduced in 7/23, partially reduced in16/23. Clinical symptoms disappeared in 7, clearly improved in 14, improved in 7. All treatments had no adverse event except for two cases of liver cancer. They felt an abdominal pain that controllable by medicine and it improved within 6hours. It is concluded that HIFU with guide by ultrasound imaging is very safe, painless and effective as the anti-tumor treatment.

Frequency Domain Fluorescent Molecular Tomography and Molecular Probes for Small Animal Imaging

NASA Astrophysics Data System (ADS)

Kujala, Naresh Gandhi

Fluorescent molecular tomography (FMT) is a noninvasive biomedical optical imaging that enables 3-dimensional quantitative determination of fluorochromes distributed in biological tissues. There are three methods for imaging large volume tissues based on different light sources: (a) using a light source of constant intensity, through a continuous or constant wave, (b) using a light source that is intensity modulated with a radio frequency (RF), and (c) using ultrafast pulses in the femtosecond range. In this study, we have developed a frequency domain fluorescent molecular tomographic system based on the heterodyne technique, using a single source and detector pair that can be used for small animal imaging. In our system, the intensity of the laser source is modulated with a RF frequency to produce a diffuse photon density wave in the tissue. The phase of the diffuse photon density wave is measured by comparing the reference signal with the signal from the tissue using a phasemeter. The data acquisition was performed by using a Labview program. The results suggest that we can measure the phase change from the heterogeneous inside tissue. Combined with fiber optics and filter sets, the system can be used to sensitively image the targeted fluorescent molecular probes, allowing the detection of cancer at an early stage. We used the system to detect the tumor-targeting molecular probe Alexa Fluor 680 and Alexa Fluor 750 bombesin peptide conjugates in phantoms as well as mouse tissues. We also developed and evaluated fluorescent Bombesin (BBN) probes to target gastrin-releasing peptide (GRP) receptors for optical molecular imaging. GRP receptors are over-expressed in several types of human cancer cells, including breast, prostate, small cell lung, and pancreatic cancers. BBN is a 14 amino acid peptide that is an analogue to human gastrin-releasing peptide that binds specifically to GRPr receptors. BBN conjugates are significant in cancer detection and therapy. The optical molecular probe AF750 BBN peptide exhibits optimal pharmacokinetic properties for targeting GRPr in mice. Fluorescent microscopic imaging of the molecular probe in PC-3 prostate and T-47D breast cancer cell lines indicated specific uptake, internalization, and receptor blocking of these probes. In vivo investigations in severely compromised immunodeficient (SCID) mice bearing xenografted PC-3 prostate and T47-D breast cancer lesions demonstrated the ability of this new molecular probe to specifically target tumor tissue with high selectively and affinity.

Polyacrylamide gel injections for breast augmentation: management of complications in 106 patients, a multicenter study.

PubMed

Unukovych, Dmytro; Khrapach, Vasyl; Wickman, Marie; Liljegren, Annelie; Mishalov, Volodymyr; Patlazhan, Gennadiy; Sandelin, Kerstin

2012-04-01

Polyacrylamide gel (PAAG) was first manufactured in Ukraine in the late 1980s and introduced as a biomaterial for "breast augmentation without surgery." Since it is prohibited in most countries, PAAG injections are rare nowadays, but their consequences and long-term complications can be crucial. We identified 106 patients consecutively operated on for PAAG complications at three teaching Ukrainian hospitals between 1998 and 2009. All relevant sociodemographic, clinical, and treatment characteristics were collected. Forty-five (42%) patients were available for clinical follow-up. The majority (88%) had had bilateral PAAG injections. The mean volume of injected PAAG was 230 ml/breast (range = 50-400). Mean age at injection was 29 years (range = 17-49) and the mean time from the injection to complications was 6.1 years (SD = 4.1). Symptoms preceding debridement were pain in 85 patients (80%), breast hardening in 79 (74%), breast deformity in 77 (73%), lumps in 57 (54%), gel migration in 39 (37%), fistulas in 17 (16%), and gel leakage in 12 (11%). The surgical interventions in 199 breasts included gel evacuation alone in 107 (54%) or in combination with partial mastectomy in 65 (33%), partial mastectomy and partial pectoralis muscle resection in 12 (6%), or subcutaneous mastectomy in 15 (7%). Of the 199 operated breasts, 86 (43%) immediate and 58 (29%) delayed implant-based breast reconstructions were performed. Injections of PAAG can cause irreversible damage to the breast necessitating complex debridement procedures, even mastectomy and breast reconstruction. Despite numerous surgical interventions, gel remnants are still found on subsequent breast imaging. Although PAAG is prohibited in many countries, different types of injections with unknown long-term effects are currently being used. Making the public aware of the problems of injectables for breast augmentation is warranted.

Breast Tumors with Elevated Expression of 1q Candidate Genes Confer Poor Clinical Outcome and Sensitivity to Ras/PI3K Inhibition

PubMed Central

Viveka Thangaraj, Soundara; Periasamy, Jayaprakash; Bhaskar Rao, Divya; Barnabas, Georgina D.; Raghavan, Swetha; Ganesan, Kumaresan

2013-01-01

Genomic aberrations are common in cancers and the long arm of chromosome 1 is known for its frequent amplifications in breast cancer. However, the key candidate genes of 1q, and their contribution in breast cancer pathogenesis remain unexplored. We have analyzed the gene expression profiles of 1635 breast tumor samples using meta-analysis based approach and identified clinically significant candidates from chromosome 1q. Seven candidate genes including exonuclease 1 (EXO1) are consistently over expressed in breast tumors, specifically in high grade and aggressive breast tumors with poor clinical outcome. We derived a EXO1 co-expression module from the mRNA profiles of breast tumors which comprises 1q candidate genes and their co-expressed genes. By integrative functional genomics investigation, we identified the involvement of EGFR, RAS, PI3K / AKT, MYC, E2F signaling in the regulation of these selected 1q genes in breast tumors and breast cancer cell lines. Expression of EXO1 module was found as indicative of elevated cell proliferation, genomic instability, activated RAS/AKT/MYC/E2F1 signaling pathways and loss of p53 activity in breast tumors. mRNA–drug connectivity analysis indicates inhibition of RAS/PI3K as a possible targeted therapeutic approach for the patients with activated EXO1 module in breast tumors. Thus, we identified seven 1q candidate genes strongly associated with the poor survival of breast cancer patients and identified the possibility of targeting them with EGFR/RAS/PI3K inhibitors. PMID:24147022

Activity and safety of the antiestrogen EM-800, the orally active precursor of acolbifene, in tamoxifen-resistant breast cancer.

PubMed

Labrie, Fernand; Champagne, Pierre; Labrie, Claude; Roy, Jean; Laverdière, Jacques; Provencher, Louise; Potvin, Martin; Drolet, Yvan; Pollak, Michael; Panasci, Lawrence; L'Espérance, Bernard; Dufresne, Jean; Latreille, Jean; Robert, Jean; Samson, Benoît; Jolivet, Jacques; Yelle, Louise; Cusan, Lionel; Diamond, Pierre; Candas, Bernard

2004-03-01

To determine the efficacy and safety of EM-800 (SCH-57050), the precursor of acolbifene, a new, highly potent, orally active, pure antiestrogen in the mammary gland and endometrium, for the treatment of tamoxifen-resistant breast cancer. Forty-three post menopausal/ovariectomized women with breast cancer who had received tamoxifen, either for metastatic disease or as adjuvant to surgery for > or = 1 year, and had relapsed were treated in a prospective, multicenter, phase II study with EM-800 (20 mg/d [n = 21] or 40 mg/d [n = 22] orally). Results Thirty-seven patients had estrogen receptor (ER)-positive tumors (>10 fmol/mg; mean, 146 fmol/mg cytosolic protein), three patients had ER-negative/progesterone receptor-positive tumors, and three patients had undetermined ER status. The objective response rate to EM-800 was 12%, with one complete response and four partial responses. Ten patients (23%) had stable disease for > or = 3 months, and 7 patients (16%) had stable disease for > or = 6 months. With a median follow-up of 29 months, median duration of response was 8 months (range, 7 to 71+ months). Treatment with EM-800 was well tolerated. No significant adverse events related to the study drug were observed clinically or biochemically. EM-800 produced responses in a significant proportion of patients with tamoxifen-resistant breast cancer, thus showing that this highly potent, selective estrogen receptor modulator, which lacks estrogenic activity in the mammary gland and endometrium, has incomplete cross-resistance with tamoxifen, thus suggesting additional benefits in the treatment of breast cancer.

Quality of Life of Nepalese Women Post Mastectomy

PubMed

Maharjan, Muna; Thapa, Niresh; Adhikari, Raj Devi; Petrini, Marcia A; Amatya, Kapendra Shekhar

2018-04-25

Introduction: Worldwide breast cancer is the common invasive cancer among the females. The quality of life of women after treatment, which is often a mastectomy, is frequently decreased. Objective: To determine the life quality of Nepalese women post mastectomy. Materials and Methods: One hundred seven women after a mastectomy were selected and interviewed by using the European Organization for Research and Treatment of Cancer-Quality of Life Questionnaire and its Breast Specific Module to assess women’s quality of life. Result: The study findings revealed a good score on global health status/quality of life. The respondents performed well on functional and symptom scales. In the Breast Specific Module, all respondents performed poor regarding sexual function and sexual enjoyment. Global Health Status was found useful among the women involved in service/business/agriculture and the survivors using breast prosthesis. In Breast Specific Module, systemic therapy side effects showed strong statistical associations with age, marital status, occupation, education, use of breast prosthesis and co-morbidity. Body image was highly significant with age, occupation, education, use of breast prosthesis and co-morbidity. Conclusion: Based on the study findings, counseling, and a structured educational programme is recommended to improve the QOL of women after a mastectomy. Creative Commons Attribution License

MDA-MB-231 breast cancer cell viability, motility and matrix adhesion are regulated by a complex interplay of heparan sulfate, chondroitin-/dermatan sulfate and hyaluronan biosynthesis.

PubMed

Viola, Manuela; Brüggemann, Kathrin; Karousou, Evgenia; Caon, Ilaria; Caravà, Elena; Vigetti, Davide; Greve, Burkhard; Stock, Christian; De Luca, Giancarlo; Passi, Alberto; Götte, Martin

2017-06-01

Proteoglycans and glycosaminoglycans modulate numerous cellular processes relevant to tumour progression, including cell proliferation, cell-matrix interactions, cell motility and invasive growth. Among the glycosaminoglycans with a well-documented role in tumour progression are heparan sulphate, chondroitin/dermatan sulphate and hyaluronic acid/hyaluronan. While the mode of biosynthesis differs for sulphated glycosaminoglycans, which are synthesised in the ER and Golgi compartments, and hyaluronan, which is synthesized at the plasma membrane, these polysaccharides partially compete for common substrates. In this study, we employed a siRNA knockdown approach for heparan sulphate (EXT1) and heparan/chondroitin/dermatan sulphate-biosynthetic enzymes (β4GalT7) in the aggressive human breast cancer cell line MDA-MB-231 to study the impact on cell behaviour and hyaluronan biosynthesis. Knockdown of β4GalT7 expression resulted in a decrease in cell viability, motility and adhesion to fibronectin, while these parameters were unchanged in EXT1-silenced cells. Importantly, these changes were associated with a decreased expression of syndecan-1, decreased signalling response to HGF and an increase in the synthesis of hyaluronan, due to an upregulation of the hyaluronan synthases HAS2 and HAS3. Interestingly, EXT1-depleted cells showed a downregulation of the UDP-sugar transporter SLC35D1, whereas SLC35D2 was downregulated in β4GalT7-depleted cells, indicating an intricate regulatory network that connects all glycosaminoglycans synthesis. The results of our in vitro study suggest that a modulation of breast cancer cell behaviour via interference with heparan sulphate biosynthesis may result in a compensatory upregulation of hyaluronan biosynthesis. These findings have important implications for the development of glycosaminoglycan-targeted therapeutic approaches for malignant diseases.

Prediction of initiation and duration of breast-feeding for neonates admitted to the neonatal intensive care unit.

PubMed

Lessen, Rachelle; Crivelli-Kovach, Andrea

2007-01-01

Women who desire to breast-feed their sick newborns often encounter obstacles, including insufficient support and education as well as unsupportive hospital practices. The purpose of this study was to describe maternal, neonatal, and outside influences associated with the intention, initiation, and duration of breast-feeding for women whose newborns were admitted to the neonatal intensive care unit. One hundred mothers were interviewed. Most mothers (67%) intended to breast-feed exclusively and this was significantly related to maternal characteristics such as age, education, parity, smoking and marital status, pre-breast-feeding experience, and the influences of the neonate's father and prenatal education. Seventy-eight mothers initiated pumping. Initiation was significantly related to maternal education, smoking, parity, previous breast-feeding experience, the neonate's physician, the neonate's father, and postpartum breast-feeding education. Fifty-four mothers were followed up by telephone after discharge until weaning. Thirty percent were exclusively breast-feeding at 2 weeks after discharge, and 15% were breast-feeding at 1 year. Duration of breast-feeding was significantly associated with education, marital status, ethnicity, income, assistance from nurses and lactation consultants, and feeding method along with milk type and milk volume at discharge. Increased family support, timely breast-feeding information, and a supportive neonatal intensive care unit environment are needed for women to succeed in breast-feeding their hospitalized newborns.

Reduction of conditioned pain modulation in humans by naltrexone: an exploratory study of the effects of pain catastrophizing

PubMed Central

Goodin, Burel; Kindler, Lindsay L.; Caudle, Robert M.; Edwards, Robert R.; Gravenstein, Nikolaus; Riley, Joseph L.; Fillingim, Roger B.

2013-01-01

The current study tested the hypothesis that conditioned pain modulation is mediated by the release of endogenous opioids with a placebo-controlled (sugar pill) study of naltrexone (50 mg) in 33 healthy volunteers over two counter-balanced sessions. Pain modulation consisted of rating of heat pain (palm) during concurrent cold water immersion (foot). Compared to baseline heat pain ratings, concurrent foot immersion lowered pain intensity ratings, which suggests an inhibitory effect, was reduced with naltrexone, suggesting at least partial dependence of inhibition on endogenous opioids. An exploratory analysis revealed that individual differences in catastrophizing moderated the effects of naltrexone; endogenous opioid blockade abolished modulation in subjects lower in catastrophizing while modulation was unaffected by naltrexone among high catastrophizers. The results suggest a role of endogenous opioids in endogenous analgesia, but hint that multiple systems might contribute to conditioned pain modulation, and that these systems might be differentially activated as a function of individual differences in responses to pain. PMID:22534819

Taking a look at the calibration of a CCD detector with a fiber-optic taper

DOE PAGES

Alkire, R. W.; Rotella, F. J.; Duke, Norma E. C.; ...

2016-02-16

At the Structural Biology Center beamline 19BM, located at the Advanced Photon Source, the operational characteristics of the equipment are routinely checked to ensure they are in proper working order. After performing a partial flat-field calibration for the ADSC Quantum 210r CCD detector, it was confirmed that the detector operates within specifications. However, as a secondary check it was decided to scan a single reflection across one-half of a detector module to validate the accuracy of the calibration. The intensities from this single reflection varied by more than 30% from the module center to the corner of the module. Redistributionmore » of light within bent fibers of the fiber-optic taper was identified to be a source of this variation. As a result, the degree to which the diffraction intensities are corrected to account for characteristics of the fiber-optic tapers depends primarily upon the experimental strategy of data collection, approximations made by the data processing software during scaling, and crystal symmetry.« less

Differential network analysis reveals the genome-wide landscape of estrogen receptor modulation in hormonal cancers

PubMed Central

Hsiao, Tzu-Hung; Chiu, Yu-Chiao; Hsu, Pei-Yin; Lu, Tzu-Pin; Lai, Liang-Chuan; Tsai, Mong-Hsun; Huang, Tim H.-M.; Chuang, Eric Y.; Chen, Yidong

2016-01-01

Several mutual information (MI)-based algorithms have been developed to identify dynamic gene-gene and function-function interactions governed by key modulators (genes, proteins, etc.). Due to intensive computation, however, these methods rely heavily on prior knowledge and are limited in genome-wide analysis. We present the modulated gene/gene set interaction (MAGIC) analysis to systematically identify genome-wide modulation of interaction networks. Based on a novel statistical test employing conjugate Fisher transformations of correlation coefficients, MAGIC features fast computation and adaption to variations of clinical cohorts. In simulated datasets MAGIC achieved greatly improved computation efficiency and overall superior performance than the MI-based method. We applied MAGIC to construct the estrogen receptor (ER) modulated gene and gene set (representing biological function) interaction networks in breast cancer. Several novel interaction hubs and functional interactions were discovered. ER+ dependent interaction between TGFβ and NFκB was further shown to be associated with patient survival. The findings were verified in independent datasets. Using MAGIC, we also assessed the essential roles of ER modulation in another hormonal cancer, ovarian cancer. Overall, MAGIC is a systematic framework for comprehensively identifying and constructing the modulated interaction networks in a whole-genome landscape. MATLAB implementation of MAGIC is available for academic uses at https://github.com/chiuyc/MAGIC. PMID:26972162

Accelerated hyperfractionated intensity-modulated radiotherapy for recurrent/unresectable rectal cancer in patients with previous pelvic irradiation: results of a phase II study.

PubMed

Cai, Gang; Zhu, Ji; Hu, Weigang; Zhang, Zhen

2014-12-11

This study was conducted to investigate the local effects and toxicity of accelerated hyperfractionated intensity-modulated radiotherapy for recurrent/unresectable rectal cancer in patients with previous pelvic irradiation. Twenty-two patients with recurrent/unresectable rectal cancer who previously received pelvic irradiation were enrolled in our single-center trial between January 2007 and August 2012. Reirradiation was scheduled for up to 39 Gy in 30 fractions using intensity-modulated radiotherapy plans. The dose was delivered via a hyperfractionation schedule of 1.3 Gy twice daily. Patient follow-up was performed by clinical examination, CT/MRI, or PET/CT every 3 months for the first 2 years and every 6 months thereafter. Tumor response was evaluated 1 month after reirradiation by CT/MRI based on the RECIST criteria. Adverse events were assessed using the National Cancer Institute (NCI) common toxicity criteria (version 3.0). The median time from the end of the initial radiation therapy to reirradiation was 30 months (range, 18-93 months). Overall local responses were observed in 9 patients (40.9%). None of the patients achieved a complete response (CR), and 9 patients (40.9%) had a partial response (PR). Thirteen patients failed to achieve a clinical response: 12 (54.5%) presented with stable disease (SD) and 1 (4.5%) with progressive disease (PD). Among all the patients who underwent reirradiation, partial or complete symptomatic relief was achieved in 6 patients (27.3%) and 13 patients (59.1%), respectively. Grade 4 acute toxicity and treatment-related deaths were not observed. The following grade 3 acute toxicities were observed: diarrhea (2 patients, 9.1%), cystitis (1 patient, 4.5%), dermatitis (1 patient, 4.5%), and intestinal obstruction (1 patient, 4.5%). Late toxicity was infrequent. Chronic severe diarrhea, small bowel obstruction, and dysuria were observed in 2 (9.1%), 1 (4.5%) and 2 (9.1%) of the patients, respectively. This study showed that accelerated hyperfractionated intensity-modulated radiotherapy significantly relieved local symptoms and led to a promising local response with an acceptable toxicity profile in patients with recurrent/unresectable rectal cancer and previous pelvic irradiation. Innovative treatment regimens should be evaluated in future studies to improve the clinical outcome while avoiding excessive toxicity in patients with recurrent rectal cancer and previous pelvic irradiation.

Image Guidance in External Beam Accelerated Partial Breast Irradiation: Comparison of Surrogates for the Lumpectomy Cavity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hasan, Yasmin; Kim, Leonard; Martinez, Alvaro

Purpose: To compare localization of the lumpectomy cavity by using breast surface matching vs. clips for image-guided external beam accelerated partial breast irradiation. Methods and Materials: Twenty-seven patients with breast cancer with two computed tomography (CT) scans each had three CT registrations performed: (1) to bony anatomy, (2) to the center of mass (COM) of surgical clips, and (3) to the breast surface. The cavity COM was defined in both the initial and second CT scans after each type of registration, and distances between COMs ({delta}COM{sub Bone}, {delta}COM{sub Clips}, and {delta}COM{sub Surface}) were determined. Smaller {delta}COMs were interpreted as bettermore » localizations. Correlation coefficients were calculated for {delta}COM vs. several variables. Results: The {delta}COM{sub Bone} (mean, 7 {+-} 2 [SD] mm) increased with breast volume (r = 0.4; p = 0.02) and distance from the chest wall (r = 0.5; p = 0.003). Relative to bony registration, clip registration provided better localization ({delta}COM{sub Clips} < {delta}COM{sub Bone}) in 25 of 27 cases. Breast surface matching improved cavity localization ({delta}COM{sub Surface} < {delta}COM{sub Bone}) in 19 of 27 cases. Mean improvements ({delta}COM{sub Bone} - {delta}COM{sub ClipsorSurface}) were 4 {+-} 3 and 2 {+-} 4 mm, respectively. In terms of percentage of improvement ([{delta}COM{sub Bone} - {delta}COM{sub ClipsorSurface}]/{delta}COM{sub Bone}), only surface matching showed a correlation with breast volume. Clip localization outperformed surface registration for cavities located superior to the breast COM. Conclusions: Use of either breast surface or surgical clips as surrogates for the cavity results in improved localization in most patients compared with bony registration and may allow smaller planning target volume margins for external beam accelerated partial breast irradiation. Compared with surface registration, clip registration may be less sensitive to anatomic characteristics and therefore more broadly applicable.« less

Benchtop and animal validation of a portable fluorescence microscopic imaging system for potential use in cholecystectomy

NASA Astrophysics Data System (ADS)

Ye, Jian; Liu, Guanghui; Liu, Peng; Zhang, Shiwu; Shao, Pengfei; Smith, Zachary J.; Liu, Chenhai; Xu, Ronald X.

2018-02-01

We propose a portable fluorescence microscopic imaging system (PFMS) for intraoperative display of biliary structure and prevention of iatrogenic injuries during cholecystectomy. The system consists of a light source module, a camera module, and a Raspberry Pi computer with an LCD. Indocyanine green (ICG) is used as a fluorescent contrast agent for experimental validation of the system. Fluorescence intensities of the ICG aqueous solution at different concentration levels are acquired by our PFMS and compared with those of a commercial Xenogen IVIS system. We study the fluorescence detection depth by superposing different thicknesses of chicken breast on an ICG-loaded agar phantom. We verify the technical feasibility for identifying potential iatrogenic injury in cholecystectomy using a rat model in vivo. The proposed PFMS system is portable, inexpensive, and suitable for deployment in resource-limited settings.

Modulating laser intensity profile ellipticity for microstructural control during metal additive manufacturing

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roehling, Tien T.; Wu, Sheldon S. Q.; Khairallah, Saad A.

Additively manufactured (AM) metals are often highly textured, containing large columnar grains that initiate epitaxially under steep temperature gradients and rapid solidification conditions. These unique microstructures partially account for the massive property disparity existing between AM and conventionally processed alloys. Although equiaxed grains are desirable for isotropic mechanical behavior, the columnar-to-equiaxed transition remains difficult to predict for conventional solidification processes, and much more so for AM. In this study, the effects of laser intensity profile ellipticity on melt track macrostructures and microstructures were studied in 316L stainless steel. Experimental results were supported by temperature gradients and melt velocities simulated usingmore » the ALE3D multi-physics code. As a general trend, columnar grains preferentially formed with increasing laser power and scan speed for all beam profiles. However, when conduction mode laser heating occurs, scan parameters that result in coarse columnar microstructures using Gaussian profiles produce equiaxed or mixed equiaxed-columnar microstructures using elliptical profiles. Furthermore, by modulating spatial laser intensity profiles on the fly, site-specific microstructures and properties can be directly engineered into additively manufactured parts.« less

Modulating laser intensity profile ellipticity for microstructural control during metal additive manufacturing

DOE PAGES

Roehling, Tien T.; Wu, Sheldon S. Q.; Khairallah, Saad A.; ...

2017-02-12

Additively manufactured (AM) metals are often highly textured, containing large columnar grains that initiate epitaxially under steep temperature gradients and rapid solidification conditions. These unique microstructures partially account for the massive property disparity existing between AM and conventionally processed alloys. Although equiaxed grains are desirable for isotropic mechanical behavior, the columnar-to-equiaxed transition remains difficult to predict for conventional solidification processes, and much more so for AM. In this study, the effects of laser intensity profile ellipticity on melt track macrostructures and microstructures were studied in 316L stainless steel. Experimental results were supported by temperature gradients and melt velocities simulated usingmore » the ALE3D multi-physics code. As a general trend, columnar grains preferentially formed with increasing laser power and scan speed for all beam profiles. However, when conduction mode laser heating occurs, scan parameters that result in coarse columnar microstructures using Gaussian profiles produce equiaxed or mixed equiaxed-columnar microstructures using elliptical profiles. Furthermore, by modulating spatial laser intensity profiles on the fly, site-specific microstructures and properties can be directly engineered into additively manufactured parts.« less

Early life factors associated with the exclusivity and duration of breast feeding in an Irish birth cohort study.

PubMed

Smith, Hazel Ann; O'B Hourihane, Jonathan; Kenny, Louise C; Kiely, Mairead; Murray, Deirdre M; Leahy-Warren, Patricia

2015-09-01

to investigate the influence of parental and infant characteristics on exclusive breast feeding from birth to six months of age and breast feeding rates at two, six and 12 months of age in Ireland. secondary data analysis from the Cork BASELINE Birth Cohort Study (http://www.baselinestudy.net/). Infants were seen at birth and two, six, and 12 months of age. Maternal and paternal history, neonatal course and feeding data were collected at birth and using parental questionnaires at each time point. 1094 singleton infants of primiparous women recruited at 20 weeks' gestation who were breastfeeding on discharge from the maternity hospital. at discharge from the maternity hospital and at two months, neonatal intensive-care unit admission had the strongest influence on exclusive breast feeding status (adjusted OR 0.17, 95% CI 0.07-0.41 at discharge) and at two months (adjusted OR=0.20, 95% CI 0.05-0.83). A shorter duration of breast feeding was significantly associated with younger maternal age, non-tertiary education, Irish nationality and neonatal intensive-care unit admission. There was a significant difference in the duration of any breast feeding between infants who were and were not admitted to the neonatal intensive-care unit, 28(10.50, 32) weeks versus 32(27, 40) weeks. Mothers whose maternity leave was between seven and 12 months (adjusted OR=2.76, 95% CI 1.51-5.05) breast fed for a longer duration compared to mothers who had less than six months of maternity leave. admission to the neonatal intensive care unit negatively influenced both exclusivity and duration of breast feeding. Length of maternity leave, and not employment status, was significantly associated with duration of breast feeding. additional support may be required to ensure continued breast feeding in infants admitted to the neonatal intensive-care unit. Length of maternity leave is a modifiable influence on breast feeding and offers the opportunity for intervention to improve our rates of breast feeding. Copyright © 2015 Elsevier Ltd. All rights reserved.

Partial breast radiation for early-stage breast cancer.

PubMed

McCormick, Beryl

2012-02-01

This review is to provide an update on the current status of partial breast irradiation (PBI) for women presenting with early-stage breast cancer, as an alternate radiation technique to fractionated, whole breast radiation, following conservation surgery. As more women are asking for and receiving this treatment, both on and off protocols, understanding recent additions to the literature is important to physicians caring for this patient population. Newly published retrospective studies, with follow-up times out to 10 years and the status of both recently completed and still open large prospective phase III trials will be covered, with emphasis on unexpected side effects reported, and some hypothesis-generating radiobiology observations. A recent consensus treatment guideline for PBI use is also discussed. Selected retrospective studies continue to report outcomes matching those achieved with whole breast radiation; however, results from large prospective randomized trials comparing PBI to whole breast radiation have been reported only with short follow-up times, or in two studies, are still pending. A recent consensus guideline is useful at present in selecting patients for discussion of this treatment.

Accelerated Partial Breast Irradiation Using Only Intraoperative Electron Radiation Therapy in Early Stage Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maluta, Sergio; Dall'Oglio, Stefano, E-mail: stefano.dalloglio@ospedaleuniverona.it; Marciai, Nadia

2012-10-01

Background: We report the results of a single-institution, phase II trial of accelerated partial breast irradiation (APBI) using a single dose of intraoperative electron radiation therapy (IOERT) in patients with low-risk early stage breast cancer. Methods and Materials: A cohort of 226 patients with low-risk, early stage breast cancer were treated with local excision and axillary management (sentinel node biopsy with or without axillary node dissection). After the surgeon temporarily reapproximated the excision cavity, a dose of 21 Gy using IOERT was delivered to the tumor bed, with a margin of 2 cm laterally. Results: With a mean follow-up ofmore » 46 months (range, 28-63 months), only 1 case of local recurrence was reported. The observed toxicity was considered acceptable. Conclusions: APBI using a single dose of IOERT can be delivered safely in women with early, low-risk breast cancer in carefully selected patients. A longer follow-up is needed to ascertain its efficacy compared to that of the current standard treatment of whole-breast irradiation.« less

Id-1 gene and gene products as therapeutic targets for treatment of breast cancer and other types of carcinoma

DOEpatents

Desprez, Pierre-Yves; Campisi, Judith

2014-08-19

A method for treatment of breast cancer and other types of cancer. The method comprises targeting and modulating Id-1 gene expression, if any, for the Id-1 gene, or gene products in breast or other epithelial cancers in a patient by delivering products that modulate Id-1 gene expression. When expressed, Id-1 gene is a prognostic indicator that cancer cells are invasive and metastatic.

Quality of Life in Women Undergoing Breast Irradiation in a Randomized, Controlled Clinical Trial Evaluating Different Tumor Bed Boost Fractionations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Finkel, Morgan A.; Cooper, Benjamin T.; Li, Xiaochun

Purpose: To identify differences in breast cancer patient-reported quality of life (QOL) between 2 radiation tumor bed boost dose regimens. Methods and Materials: Four hundred patients with stage 0, I, or II breast cancer who underwent segmental mastectomy with sentinel node biopsy and/or axillary node dissection were treated with either a daily or weekly boost. Patients were treated prone to 40.5 Gy/15 fractions to the whole breast, 5 days per week. Patients were randomized to a concomitant daily boost to the tumor bed of 0.5 Gy, or a weekly boost of 2 Gy on Friday. Patients completed 6 validated QOL survey instruments at baseline,more » last week of treatment (3 weeks), 45-60 days from the completion of radiation treatment, and at 2-year follow-up. Results: There were no statistically significance differences in responses to the 6 QOL instruments between the daily and weekly radiation boost regimens, even after adjustment for important covariates. However, several changes in responses over time occurred in both arms, including worsening functional status, cosmetic status, and breast-specific pain at the end of treatment as compared with before and 45 to 60 days after the conclusion of treatment. Conclusions: Whole-breast, prone intensity modulated radiation has similar outcomes in QOL measures whether given with a daily or weekly boost. This trial has generated the foundation for a current study of weekly versus daily radiation boost in women with early breast cancer in which 3-dimensional conformal radiation is allowed as a prospective stratification factor.« less

Multi-probe-based resonance-frequency electrical impedance spectroscopy for detection of suspicious breast lesions: improving performance using partial ROC optimization

NASA Astrophysics Data System (ADS)

Lederman, Dror; Zheng, Bin; Wang, Xingwei; Wang, Xiao Hui; Gur, David

2011-03-01

We have developed a multi-probe resonance-frequency electrical impedance spectroscope (REIS) system to detect breast abnormalities. Based on assessing asymmetry in REIS signals acquired between left and right breasts, we developed several machine learning classifiers to classify younger women (i.e., under 50YO) into two groups of having high and low risk for developing breast cancer. In this study, we investigated a new method to optimize performance based on the area under a selected partial receiver operating characteristic (ROC) curve when optimizing an artificial neural network (ANN), and tested whether it could improve classification performance. From an ongoing prospective study, we selected a dataset of 174 cases for whom we have both REIS signals and diagnostic status verification. The dataset includes 66 "positive" cases recommended for biopsy due to detection of highly suspicious breast lesions and 108 "negative" cases determined by imaging based examinations. A set of REIS-based feature differences, extracted from the two breasts using a mirror-matched approach, was computed and constituted an initial feature pool. Using a leave-one-case-out cross-validation method, we applied a genetic algorithm (GA) to train the ANN with an optimal subset of features. Two optimization criteria were separately used in GA optimization, namely the area under the entire ROC curve (AUC) and the partial area under the ROC curve, up to a predetermined threshold (i.e., 90% specificity). The results showed that although the ANN optimized using the entire AUC yielded higher overall performance (AUC = 0.83 versus 0.76), the ANN optimized using the partial ROC area criterion achieved substantially higher operational performance (i.e., increasing sensitivity level from 28% to 48% at 95% specificity and/ or from 48% to 58% at 90% specificity).

Surface-enhanced Raman spectroscopy of saliva proteins for the noninvasive differentiation of benign and malignant breast tumors

PubMed Central

Feng, Shangyuan; Huang, Shaohua; Lin, Duo; Chen, Guannan; Xu, Yuanji; Li, Yongzeng; Huang, Zufang; Pan, Jianji; Chen, Rong; Zeng, Haishan

2015-01-01

The capability of saliva protein analysis, based on membrane protein purification and surface-enhanced Raman spectroscopy (SERS), for detecting benign and malignant breast tumors is presented in this paper. A total of 97 SERS spectra from purified saliva proteins were acquired from samples obtained from three groups: 33 healthy subjects; 33 patients with benign breast tumors; and 31 patients with malignant breast tumors. Subtle but discernible changes in the mean SERS spectra of the three groups were observed. Tentative assignments of the saliva protein SERS spectra demonstrated that benign and malignant breast tumors led to several specific biomolecular changes of the saliva proteins. Multiclass partial least squares–discriminant analysis was utilized to analyze and classify the saliva protein SERS spectra from healthy subjects, benign breast tumor patients, and malignant breast tumor patients, yielding diagnostic sensitivities of 75.75%, 72.73%, and 74.19%, as well as specificities of 93.75%, 81.25%, and 86.36%, respectively. The results from this exploratory work demonstrate that saliva protein SERS analysis combined with partial least squares–discriminant analysis diagnostic algorithms has great potential for the noninvasive and label-free detection of breast cancer. PMID:25609959

Treatment outcomes and feasibility of partial neck irradiation for patients with nasopharyngeal carcinoma with only retropharyngeal lymph node metastasis after intensity-modulated radiotherapy.

PubMed

Chen, Mo; Tang, Ling-Long; Sun, Ying; Mao, Yan-Ping; Li, Wen-Fei; Guo, Rui; Liu, Li-Zhi; Li, Li; Lin, Ai-Hua; Ma, Jun

2014-04-01

The purpose of this study was to summarize the treatment outcomes and evaluate the feasibility of partial neck irradiation in patients with nasopharyngeal carcinoma (NPC) with only retropharyngeal lymph nodes (RLNs) metastasis. Between January 2003 and December 2007, 54 patients with NPC who received partial neck irradiation to levels II, III, and VA and 100 patients who received whole neck irradiation were reviewed. The 5-year disease free survival (DFS), disease metastasis-free survival, (DMFS) local relapse-free survival (LRFS), and regional relapse-free survival (RRFS) rates were 81.8%, 87.7%, 94.8%, and 98.1%, respectively. The 5-year RRFS and DFS rates for the partial neck irradiation group and whole neck irradiation group were 98.1% versus 98.0% (p = .882), 87.0% vs 77.0% (p = .117), respectively. Partial neck irradiation was not considered a significant prognostic factor for any endpoint in univariate and multivariate analyses. Partial irradiation of neck levels II, III, and VA might be acceptable for patients with NPC with only RLN metastasis. Copyright © 2013 Wiley Periodicals, Inc.

CT breast dose reduction with the use of breast positioning and organ-based tube current modulation.

PubMed

Fu, Wanyi; Tian, Xiaoyu; Sturgeon, Gregory M; Agasthya, Greeshma; Segars, William Paul; Goodsitt, Mitchell M; Kazerooni, Ella A; Samei, Ehsan

2017-02-01

This study aimed to investigate the breast dose reduction potential of a breast-positioning (BP) technique for thoracic CT examinations with organ-based tube current modulation (OTCM). This study included 13 female anthropomorphic computational phantoms (XCAT, age range: 27-65 y.o., weight range: 52-105.8 kg). Each phantom was modified to simulate three breast sizes in standard supine geometry. The modeled breasts were then morphed to emulate BP that constrained the majority of the breast tissue inside the 120° anterior tube current (mA) reduction zone. The OTCM mA value was modeled using a ray-tracing program, which reduced the mA to 20% in the anterior region with a corresponding increase to the posterior region. The organ doses were estimated by a validated Monte Carlo program for a typical clinical CT system (SOMATOM Definition Flash, Siemens Healthcare). The simulated organ doses and organ doses normalized by CTDI vol were used to compare three CT protocols: attenuation-based tube current modulation (ATCM), OTCM, and OTCM with BP (OTCM BP ). On average, compared to ATCM, OTCM reduced breast dose by 19.3 ± 4.5%, whereas OTCM BP reduced breast dose by 38.6 ± 8.1% (an additional 23.8 ± 9.4%). The dose saving of OTCM BP was more significant for larger breasts (on average 33, 38, and 44% reduction for 0.5, 1, and 2 kg breasts, respectively). Compared to ATCM, OTCM BP also reduced thymus and heart dose by 15.1 ± 7.4% and 15.9 ± 6.2% respectively. In thoracic CT examinations, OTCM with a breast-positioning technique can markedly reduce unnecessary exposure to radiosensitive organs in anterior chest wall, specifically breast tissue. The breast dose reduction is more notable for women with larger breasts. © 2016 American Association of Physicists in Medicine.

Thyroid Hormone Differentially Modulates Warburg Phenotype in Breast Cancer Cells

PubMed Central

Suhane, Sonal; Ramanujan, V Krishnan

2011-01-01

Sustenance of cancer cells in vivo critically depends on a variety of genetic and metabolic adaptations. Aerobic glycolysis or Warburg effect has been a defining biochemical hallmark of transformed cells for more than five decades although a clear molecular basis of this observation is emerging only in recent years. In this study, we present our findings that thyroid hormone exerts its non-genomic and genomic actions in two model human breast cancer cell lines differentially. By laying a clear foundation for experimentally monitoring the Warburg phenotype in living cancer cells, we demonstrate that thyroid hormone-induced modulation of bioenergetic profiles in these two model cell lines depends on the degree of Warburg phenotype that they display. Further we also show that thyroid hormone can sensitize mitochondria in aggressive, triple-negative breast cancer cells favorably to increase the chemotherapeutic efficacy in these cells. Even though the role of thyroid hormone in modulating mitochondrial metabolism has been known, the current study accentuates the critical role it plays in modulating Warburg phenotype in breast cancer cells. The clinical significance of this finding is the possibility to devise strategies for metabolically modulating aggressive triple-negative tumors so as to enhance their chemosensitivity in vivo. PMID:21945435

Coherent radiation characteristics of modulated electron bunch formed in stack of two plates

NASA Astrophysics Data System (ADS)

Gevorgyan, H. L.; Gevorgian, L. A.

2017-07-01

The present article is devoted to the radiation from the electron bunch with modulated density passes through the stack consisting of two plates with different thicknesses and electrodynamic properties. The new elegant expression for the frequency-angular distribution of transition radiation is obtained. Using the existence of resonant frequency at which the longitudinal form-factor of bunch not suppresses radiation coherence and choosing parameters for the stack of plates, one can also avoid suppression of the radiation coherence by transverse form-factor of bunch. The radiation from a bunch with modulated density in the process SASE (self-amplified spontaneous emission) FEL can be partially coherent at a resonant frequency. Then the intense sub monochromatic beam of X-ray photons is formed. On the other hand one can define an important parameter of the bunch density modulation depth which is unknown to this day.

Postoperative radiotherapy following mastectomy for patients with left-sided breast cancer: A comparative dosimetric study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Jiahao, E-mail: mashenglin@medmail.com.cn; Li, Xiadong; Deng, Qinghua

2015-10-01

The purposes of this article were to compare the biophysical dosimetry for postmastectomy left-sided breast cancer using 4 different radiotherapy (RT) techniques. In total, 30 patients with left-sided breast cancer were randomly selected for this treatment planning study. They were planned using 4 RT techniques, including the following: (1) 3-dimensional conventional tangential fields (TFs), (2) tangential intensity-modulated therapy (T-IMRT), (3) 4 fields IMRT (4F-IMRT), and (4) single arc volumetric-modulated arc therapy (S-VMAT). The planning target volume (PTV) dose was prescribed 50 Gy, the comparison of target dose distribution, conformity index, homogeneity index, dose to organs at risk (OARs), tumor controlmore » probability (TCP), normal tissue complication probability (NTCP), and number of monitor units (MUs) between 4 plans were investigated for their biophysical dosimetric difference. The target conformity and homogeneity of S-VMAT were better than the other 3 kinds of plans, but increased the volume of OARs receiving low dose (V{sub 5}). TCP of PTV and NTCP of the left lung showed no statistically significant difference in 4 plans. 4F-IMRT plan was superior in terms of target coverage and protection of OARs and demonstrated significant advantages in decreasing the NTCP of heart by 0.07, 0.03, and 0.05 compared with TFs, T-IMRT, and S-VMAT plan. Compared with other 3 plans, TFs reduced the average number of MUs. Of the 4 techniques studied, this analysis supports 4F-IMRT as the most appropriate balance of target coverage and normal tissue sparing.« less

Is there competition between breast-feeding and maternal employment?

PubMed

Roe, B; Whittington, L A; Fein, S B; Teisl, M F

1999-05-01

Theory suggests that the decision to return to employment after childbirth and the decision to breast-feed may be jointly determined. We estimate models of simultaneous equations for two different aspects of the relationship between maternal employment and breast-feeding using 1993-1994 data from the U.S. Food and Drug Administration's Infant Feeding Practices Study. We first explore the simultaneous duration of breast-feeding and work leave following childbirth. We find that the duration of leave from work significantly affects the duration of breast-feeding, but the effect of breast-feeding on work leave is insignificant. We also estimate models of the daily hours of work and breast-feedings at infant ages 3 months and 6 months postpartum. At both times, the intensity of work effort significantly affects the intensity of breast-feeding, but the reverse is generally not found. Competition clearly exists between work and breast-feeding for many women in our sample.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Aznar, Marianne C., E-mail: marianne.camille.aznar@regionh.dk; Faculty of Sciences, Niels Bohr Institute, and Faculty of Health Sciences, University of Copenhagen, Copenhagen; Maraldo, Maja V.

Purpose: Hodgkin lymphoma (HL) survivors have an increased risk of cardiovascular disease (CD), lung cancer, and breast cancer. We investigated the risk for the development of CD and secondary lung, breast, and thyroid cancer after radiation therapy (RT) delivered with deep inspiration breath-hold (DIBH) compared with free-breathing (FB) using 3-dimensional conformal RT (3DCRT) and intensity modulated RT (IMRT). The aim of this study was to determine which treatment modality best reduced the combined risk of life-threatening late effects in patients with mediastinal HL. Methods and Materials: Twenty-two patients with early-stage mediastinal HL were eligible for the study. Treatment plans weremore » calculated with both 3DCRT and IMRT on both DIBH and FB planning computed tomographic scans. We reported the estimated dose to the heart, lung, female breasts, and thyroid and calculated the estimated life years lost attributable to CD and to lung, breast, and thyroid cancer. Results: DIBH lowered the estimated dose to heart and lung regardless of delivery technique (P<.001). There was no significant difference between IMRT-FB and 3DCRT-DIBH in mean heart dose, heart V20Gy, and lung V20Gy. The mean breast dose was increased with IMRT regardless of breathing technique. Life years lost was lowest with DIBH and highest with FB. Conclusions: In this cohort, 3DCRT-DIBH resulted in lower estimated doses and lower lifetime excess risks than did IMRT-FB. Combining IMRT and DIBH could be beneficial for a subgroup of patients.« less

SU-E-T-217: Comprehensive Dosimetric Evaluation On 3D-CRT, IMRT and Non-Coplanar Arc Treatment for Prone Accelerated Partial Breast Irradiation (APBI)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiu, T; Yan, Y; Ramirez, E

2015-06-15

Purpose: Accelerated partial breast irradiation (APBI) is an effective treatment for early stage breast-cancer. Irradiation in a prone position can mitigate breast motion and spare heart and lung. In this study, a comprehensive study is performed to evaluate various treatment techniques for prone APBI treatment including: 3D-CRT, IMRT, co-planar and non-coplanar partial arcs treatment. Methods: In this treatment planning study, a left breast patient treated in prone position in our clinic was imported into Varian Eclipse TPS. Six beams tangential to chest wall were used in both 3D-CRT and IMRT plans. These six beams were coplanar in a transactional planemore » achieved by both gantry and couch rotation. A 60-beam IMRT plan was also created to explore the maximum benefit of co-planar IMRT. Within deliverable couch rotation range (±30°), partial arc treatment plans with one and up to ten couch positions were generated for comparison. For each plan, 30Gy in 6 fractions was prescribed to 95% PTV volume. Critical dosimetric parameters, such as conformity index, mean, maximum, and volume dose of organ at risk, are evaluated. Results: The conformity indexes (CI) are 3.53, 3.17, 2.21 and 1.08 respectively to 3D-CRT, 6-beam IMRT, 60-beam IMRT, and two-partial-arcs coplanar plans. However, arc plans increase heart dose. CI for non-coplanar arc plans decreases from 1.19 to 1.10 when increases couch positions. Maximum dose in ipsilateral lung (1.98 to 1.13 Gy), and heart (0.62 to 0.43 Gy) are steadily decreased with the increased number of non-coplanar arcs. Conclusions: The dosimetric evaluation results show that partial arc plans have improved CIs compared to conventional 3D-CRT and IMRT plans. Increasing number of partial arcs decreases lung and heart dose. The dosimetric benefit obtained from non-coplanar arcs should be considered with treatment delivery time.« less

Synchronous of breast and vulvar Paget's disease: a case report.

PubMed

Cooper, J C; Hew, K E; Audlin, K M; Im, D D; Matsuo, K

2012-01-01

Synchronous Paget's disease of breast and vulva is extremely rare and has only been reported in the literature in one other case. A 58-year-old postmenopausal woman was found to have crusting, bleeding, and discharge from left nipple, as well as vulvar pruritis at the same time. Biopsy of breast lesion demonstrated Paget's disease with an underlying foci of ductal carcinoma in-situ that required total mastectomy of left breast with sentinel node biopsy and breast reconstruction. For vulvar symptoms, the patient was initially diagnosed with dermatitis and topical ointment was prescribed. However, her symptoms persisted for the next several months, and she underwent vulvar biopsy that demonstrated Paget's disease. She underwent partial vulvectomy. Multiple episodes of recurrent vulvar Paget's disease were noted in the postoperative course that medical therapy with Imiquimod and a second partial vulvectomy was performed. Synchronous of breast and vulvar Paget's disease is presented. There was a delay in diagnosing vulvar Paget's disease in this experienced case. While coincidence of breast and vulvar Paget's disease is likely, ectopic mammary tissue in vulvar as well as secondary metastasis from a focal lesion of breast Paget's disease needs to be carefully evaluated whenever the patient complains of vulvar symptoms in the setting of breast Paget's disease.

38 CFR 4.116 - Schedule of ratings-gynecological conditions and disorders of the breast.

Code of Federal Regulations, 2014 CFR

2014-07-01

... removal of the entire breast, underlying pectoral muscles, and regional lymph nodes up to the... nodes (in continuity with the breast). Pectoral muscles are left intact. (3) Simple (or total... lymph nodes and muscles are left intact. (4) Wide local excision (including partial mastectomy...

38 CFR 4.116 - Schedule of ratings-gynecological conditions and disorders of the breast.

Code of Federal Regulations, 2013 CFR

2013-07-01

... removal of the entire breast, underlying pectoral muscles, and regional lymph nodes up to the... nodes (in continuity with the breast). Pectoral muscles are left intact. (3) Simple (or total... lymph nodes and muscles are left intact. (4) Wide local excision (including partial mastectomy...

38 CFR 4.116 - Schedule of ratings-gynecological conditions and disorders of the breast.

Code of Federal Regulations, 2012 CFR

2012-07-01

... removal of the entire breast, underlying pectoral muscles, and regional lymph nodes up to the... nodes (in continuity with the breast). Pectoral muscles are left intact. (3) Simple (or total... lymph nodes and muscles are left intact. (4) Wide local excision (including partial mastectomy...

Visible/near-infrared spectroscopy to predict water holding capacity in broiler breast meat

USDA-ARS?s Scientific Manuscript database

Visible/Near-infrared spectroscopy (Vis/NIRS) was examined as a tool for rapidly determining water holding capacity (WHC) in broiler breast meat. Both partial least squares (PLS) and principal component analysis (PCA) models were developed to relate Vis/NIRS spectra of 85 broiler breast meat sample...

MO-E-BRD-02: Accelerated Partial Breast Irradiation in Brachytherapy: Is Shorter Better?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Todor, D.

2015-06-15

Is Non-invasive Image-Guided Breast Brachytherapy Good? – Jess Hiatt, MS Non-invasive Image-Guided Breast Brachytherapy (NIBB) is an emerging therapy for breast boost treatments as well as Accelerated Partial Breast Irradiation (APBI) using HDR surface breast brachytherapy. NIBB allows for smaller treatment volumes while maintaining optimal target coverage. Considering the real-time image-guidance and immobilization provided by the NIBB modality, minimal margins around the target tissue are necessary. Accelerated Partial Breast Irradiation in brachytherapy: is shorter better? - Dorin Todor, PhD VCU A review of balloon and strut devices will be provided together with the origins of APBI: the interstitial multi-catheter implant.more » A dosimetric and radiobiological perspective will help point out the evolution in breast brachytherapy, both in terms of devices and the protocols/clinical trials under which these devices are used. Improvements in imaging, delivery modalities and convenience are among the factors driving the ultrashort fractionation schedules but our understanding of both local control and toxicities associated with various treatments is lagging. A comparison between various schedules, from a radiobiological perspective, will be given together with a critical analysis of the issues. to review and understand the evolution and development of APBI using brachytherapy methods to understand the basis and limitations of radio-biological ‘equivalence’ between fractionation schedules to review commonly used and proposed fractionation schedules Intra-operative breast brachytherapy: Is one stop shopping best?- Bruce Libby, PhD. University of Virginia A review of intraoperative breast brachytherapy will be presented, including the Targit-A and other trials that have used electronic brachytherapy. More modern approaches, in which the lumpectomy procedure is integrated into an APBI workflow, will also be discussed. Learning Objectives: To review past and current clinical trials for IORT To discuss lumpectomy-scan-plan-treat workflow for IORT.« less

Long-term outcome of accelerated partial breast irradiation using a multilumen balloon applicator in a patient with existing breast implants.

PubMed

Akhtari, Mani; Nitsch, Paige L; Bass, Barbara L; Teh, Bin S

2015-01-01

Accelerated partial breast irradiation is now an accepted component of breast-conserving therapy. However, data regarding long-term outcomes of patients treated with multilumen catheter systems who have existing breast implants are limited. We report the treatment and outcome of our patient who had existing bilateral silicone subpectoral implants at the time of presentation. Ultrasound-guided core needle biopsy of the right breast showed infiltrating mucinous carcinoma. Right breast lumpectomy revealed an 8 mm area of infiltrating ductal carcinoma with mucinous features and nuclear grade 1. A 4-5 cm Contura (Bard Biopsy Systems, Tempe, AZ) device was placed, and she was treated over the course of 5 days twice daily to a dose of 34 Gy using a high-dose-rate iridium-192 source. The planning target volume for evaluation was 73.9 cc. The percentage of the planning target volume for evaluation receiving 90%, 95%, and 100% of the prescribed dose was 99.9%, 99.3%, and 97.8%, respectively. The total implant volume was 234.5 cc and received a mean dose of 15.4 Gy and a maximum dose of 72.8 Gy. The percentage of implant volume receiving 50%, 75%, 100%, and 200% of the prescribed dose was 31.1%, 16.5%, 8.6%, 2.0%, and 0%, respectively. Maximum skin dose was 97% of the prescribed dose. With a followup of nearly 5 years, she continues to be cancer free with minimal late toxicities and good to excellent cosmetic outcome. Accelerated partial breast irradiation using a multilumen balloon applicator in patients with existing breast implants can safely be performed with excellent long-term cosmetic outcome. Further studies are needed to establish the absolute dosimetric tolerance of breast implants. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.

Objectively measured physical activity and sedentary time of breast cancer survivors, and associations with adiposity: findings from NHANES (2003-2006).

PubMed

Lynch, Brigid M; Dunstan, David W; Healy, Genevieve N; Winkler, Elisabeth; Eakin, Elizabeth; Owen, Neville

2010-02-01

Obesity and physical inactivity are poor prognostic indicators for breast cancer. Studies to date have relied on self-report measures of physical activity, which tend mainly to assess moderate-to-vigorous intensity leisure-time physical activity. We report the cross-sectional associations of objectively assessed physical activity and sedentary time with adiposity in a sample of breast cancer survivors from the United States. One hundred and eleven women from the National Health and Nutrition Examination Survey (NHANES) 2003-2004 and 2005-2006 reported a history of breast cancer. Participants wore an accelerometer for 7 days, and activity levels were summarized as moderate-to-vigorous intensity (accelerometer counts/min > or =1,952), light intensity (counts/min 100-1,951), and sedentary time (counts/min <100). Anthropometric measures were taken by study staff at examination centers. Participants spent the majority of their day in sedentary time (66%) or in light intensity activities (33%). Log moderate-to-vigorous intensity physical activity was negatively associated with adiposity (waist circumference beta = -9.805 [95% CI: -15.836, -3.775]; BMI beta = -3.576 [95% CI: -6.687, -0.464]). Light intensity physical activity was negatively associated with adiposity; however, the fully adjusted models did not retain statistical significance. Similarly, sedentary time was positively associated with adiposity, but the fully adjusted models were not statistically significant. This is the first study to describe the objectively assessed physical activity and sedentary time of breast cancer survivors. Increasing moderate-to-vigorous and light intensity physical activity, and decreasing sedentary time, may assist with weight management and improve other metabolic health outcomes for breast cancer survivors.

Shikonin, an ingredient of Lithospermum erythrorhizon, down-regulates the expression of steroid sulfatase genes in breast cancer cells.

PubMed

Zhang, Yi; Qian, Rui-Qin; Li, Ping-Ping

2009-10-18

Steroid sulfatase (STS) has an important role in regulating the biosynthesis of estrogen within breast tumors. We aimed to investigate whether shikonin, an ingredient of Lithospermum erythrorhizon, could modulate STS expression in breast cancer cells. By MTT assay, shikonin inhibited the cell proliferation of breast cancer cells MCF-7 and SK-BR-3. Moreover, by semi-quantitative/quantitative reverse transcription polymerase chain reaction and dual-luciferase reporter based bioluminescent measurements, the mRNA and enzymatic activity levels of STS were decreased after shikonin treatment. Concluding, shikonin could act as a selective estrogen enzyme modulator by down-regulating the STS expression.

Prospective Multicenter Trial Evaluating Balloon-Catheter Partial-Breast Irradiation for Ductal Carcinoma in Situ

DOE Office of Scientific and Technical Information (OSTI.GOV)

Abbott, Andrea M.; Portschy, Pamela R.; Lee, Chung

2013-11-01

Purpose: To determine outcomes of accelerated partial-breast irradiation (APBI) with MammoSite in the treatment of ductal carcinoma in situ (DCIS) after breast-conserving surgery. Methods and Materials: We conducted a prospective, multicenter trial between 2003 and 2009. Inclusion criteria included age >18 years, core needle biopsy diagnosis of DCIS, and no prior breast cancer history. Patients underwent breast-conserving surgery plus MammoSite placement. Radiation was given twice daily for 5 days for a total of 34 Gy. Patients were evaluated for development of toxicities, cosmetic outcome, and ipsilateral breast tumor recurrence (IBTR). Results: A total of 41 patients (42 breasts) completed treatmentmore » in the study, with a median follow up of 5.3 years. Overall, 28 patients (68.3%) experienced an adverse event. Skin changes and pain were the most common adverse events. Cosmetic outcome at 6 months was judged excellent/good by 100% of physicians and by 96.8% of patients. At 12 months, 86.7% of physicians and 92.3% of patients rated the cosmetic outcome as excellent/good. Overall, 4 patients (9.8%) developed an IBTR (all DCIS), with a 5-year actuarial rate of 11.3%. All IBTRs were outside the treatment field. Among patients with IBTRs, the mean time to recurrence was 3.2 years. Conclusions: Accelerated partial-breast irradiation using MammoSite seems to provide a safe and cosmetically acceptable outcome; however, the 9.8% IBTR rate with median follow-up of 5.3 years is concerning. Prospective randomized trials are necessary before routine use of APBI for DCIS can be recommended.« less

Non-Thermal High-Intensity Focused Ultrasound for Breast Cancer Therapy

DTIC Science & Technology

2013-07-01

ultrasound for breast cancer therapy PRINCIPAL INVESTIGATOR: Chang Ming (Charlie) Ma, Ph.D...TITLE AND SUBTITLE 5a. CONTRACT NUMBER Non-thermal high-intensity focused ultrasound for breast cancer therapy 5b. GRANT NUMBER W81XWH-11-1-0341...treatment systems for small animal models. Advanced imaging systems will be required to determine the gross tumor volume, to plan the HIFU treatment, to

Evaluation of a mixed beam therapy for post-mastectomy breast cancer patients: bolus electron conformal therapy combined with intensity modulated photon radiotherapy and volumetric modulated photon arc therapy.

PubMed

Zhang, Rui; Heins, David; Sanders, Mary; Guo, Beibei; Hogstrom, Kenneth

2018-05-10

The purpose of this study was to assess the potential benefits and limitations of a mixed beam therapy, which combined bolus electron conformal therapy (BECT) with intensity modulated photon radiotherapy (IMRT) and volumetric modulated photon arc therapy (VMAT), for left-sided post-mastectomy breast cancer patients. Mixed beam treatment plans were produced for nine post-mastectomy radiotherapy (PMRT) patients previously treated at our clinic with VMAT alone. The mixed beam plans consisted of 40 Gy to the chest wall area using BECT, 40 Gy to the supraclavicular area using parallel opposed IMRT, and 10 Gy to the total planning target volume (PTV) by optimizing VMAT on top of the BECT+IMRT dose distribution. The treatment plans were created in a commercial treatment planning system (TPS), and all plans were evaluated based on PTV coverage, dose homogeneity index (DHI), conformity index (CI), dose to organs at risk (OARs), normal tissue complication probability (NTCP), and secondary cancer complication probability (SCCP). The standard VMAT alone planning technique was used as the reference for comparison. Both techniques produced clinically acceptable PMRT plans but with a few significant differences: VMAT showed significantly better CI (0.70 vs. 0.53, p < 0.001) and DHI (0.12 vs. 0.20, p < 0.001) over mixed beam therapy. For normal tissues, mixed beam therapy showed better OAR sparing and significantly reduced NTCP for cardiac mortality (0.23% vs. 0.80%, p = 0.01) and SCCP for contralateral breast (1.7% vs. 3.1% based on linear model, and 1.2% vs. 1.9% based on linear-exponential model, p < 0.001 in both cases), but showed significantly higher mean (50.8 Gy vs. 49.3 Gy, p < 0.001) and maximum skin doses (59.7 Gy vs. 53.3 Gy, p < 0.001) compared with VMAT. Patients with more tissue (minimum distance between the distal PTV surface and lung approximately > 0.5 cm and volume of tissue between the distal PTV surface and heart or lung approximately > 250 cm 3 ) between distal PTV surface and lung may benefit the most from mixed beam therapy. This work has demonstrated that mixed beam therapy (BECT+IMRT : VMAT = 4 : 1) produces clinically acceptable plans having reduced OAR doses and risks of side effects compared with VMAT. Even though VMAT alone produces more homogenous and conformal dose distributions, mixed beam therapy remains as a viable option for treating post-mastectomy patients, possibly leading to reduced normal tissue complications. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Partial dependence of breast tumor malignancy on ultrasound image features derived from boosted trees

NASA Astrophysics Data System (ADS)

Yang, Wei; Zhang, Su; Li, Wenying; Chen, Yaqing; Lu, Hongtao; Chen, Wufan; Chen, Yazhu

2010-04-01

Various computerized features extracted from breast ultrasound images are useful in assessing the malignancy of breast tumors. However, the underlying relationship between the computerized features and tumor malignancy may not be linear in nature. We use the decision tree ensemble trained by the cost-sensitive boosting algorithm to approximate the target function for malignancy assessment and to reflect this relationship qualitatively. Partial dependence plots are employed to explore and visualize the effect of features on the output of the decision tree ensemble. In the experiments, 31 image features are extracted to quantify the sonographic characteristics of breast tumors. Patient age is used as an external feature because of its high clinical importance. The area under the receiver-operating characteristic curve of the tree ensembles can reach 0.95 with sensitivity of 0.95 (61/64) at the associated specificity 0.74 (77/104). The partial dependence plots of the four most important features are demonstrated to show the influence of the features on malignancy, and they are in accord with the empirical observations. The results can provide visual and qualitative references on the computerized image features for physicians, and can be useful for enhancing the interpretability of computer-aided diagnosis systems for breast ultrasound.

A Functional and Regulatory Network Associated with PIP Expression in Human Breast Cancer

PubMed Central

Debily, Marie-Anne; Marhomy, Sandrine El; Boulanger, Virginie; Eveno, Eric; Mariage-Samson, Régine; Camarca, Alessandra; Auffray, Charles; Piatier-Tonneau, Dominique; Imbeaud, Sandrine

2009-01-01

Background The PIP (prolactin-inducible protein) gene has been shown to be expressed in breast cancers, with contradictory results concerning its implication. As both the physiological role and the molecular pathways in which PIP is involved are poorly understood, we conducted combined gene expression profiling and network analysis studies on selected breast cancer cell lines presenting distinct PIP expression levels and hormonal receptor status, to explore the functional and regulatory network of PIP co-modulated genes. Principal Findings Microarray analysis allowed identification of genes co-modulated with PIP independently of modulations resulting from hormonal treatment or cell line heterogeneity. Relevant clusters of genes that can discriminate between [PIP+] and [PIP−] cells were identified. Functional and regulatory network analyses based on a knowledge database revealed a master network of PIP co-modulated genes, including many interconnecting oncogenes and tumor suppressor genes, half of which were detected as differentially expressed through high-precision measurements. The network identified appears associated with an inhibition of proliferation coupled with an increase of apoptosis and an enhancement of cell adhesion in breast cancer cell lines, and contains many genes with a STAT5 regulatory motif in their promoters. Conclusions Our global exploratory approach identified biological pathways modulated along with PIP expression, providing further support for its good prognostic value of disease-free survival in breast cancer. Moreover, our data pointed to the importance of a regulatory subnetwork associated with PIP expression in which STAT5 appears as a potential transcriptional regulator. PMID:19262752

[Diagnostic efficiency of decline rate of signal intensity and apparent diffusion coefficient with different b values for differentiating benign and malignant breast lesions on diffusion-weighted 3.0T magnetic resonance imaging].

PubMed

Jiang, Jing; Liu, Wanhua; Ye, Yuanyuan; Wang, Rui; Li, Fengfang; Peng, Chengyu

2014-06-17

To investigate the diagnostic efficiency of decline rate of signal intensity and apparent diffusion coefficient with different b values for differentiating benign and malignant breast lesions on diffusion-weighted 3.0 T magnetic resonance imaging. A total of 152 patients with 162 confirmed histopathologically breast lesions (85 malignant and 77 benign) underwent 3.0 T diffusion-weighted magnetic resonance imaging. Four b values (0, 400, 800 and 1 000 s/mm²) were used. The signal intensity and ADC values of breast lesions were measured respectively. The signal intensity decline rate (SIDR) and apparent diffusion coefficient decline rate (ADCDR) were calculated respectively. SIDR = (signal intensity of lesions with low b value-signal intensity of lesions with high b value)/signal intensity of lesions with low b value, ADCDR = (ADC value of lesions with low b value-ADC value of lesions with high b value) /ADC value of lesions with low b value. The independent sample t-test was employed for statistical analyses and the receiver operating characteristic (ROC) curve for evaluating the diagnosis efficiency of SIDR and ADCDR values. Significant differences were observed in SIDR between benign and malignant breast lesions with b values of 0-400, 400-800 and 800-1 000 s/mm². The sensitivities of SIDR for differentiating benign and malignant breast lesions were 61.2%, 68.2% and 67.1%, the specificities 74.0%, 85.7% and 67.5%, the diagnosis accordance rates 67.3%, 76.5% and 67.3%, the positive predictive values 72.2%, 84.1% and 69.5% and the negative predictive values 63.3%, 71.0% and 65.0% respectively. Significant differences were observed in ADCDR between benign and malignant breast lesions with b values of 400-800 s/mm² and 800-1 000 s/mm². The sensitivities of SDR for differentiating benign and malignant breast lesions were 80.0% and 65.9%, the specificities 72.7% and 65.0%, the diagnostic accordance rates 76.5% and 65.4%, the positive predictive values 76.4% and 67.5% and the negative predictive values 76.7% and 63.3% respectively. The decline rate of signal intensity and apparent diffusion coefficient with different b values may be used for differentiating benign and malignant breast lesions. And the diagnostic efficiency with b values of 400-800 s/mm² is optimal.

Favorable modulation of benign breast tissue and serum risk biomarkers is associated with > 10 % weight loss in postmenopausal women.

PubMed

Fabian, Carol J; Kimler, Bruce F; Donnelly, Joseph E; Sullivan, Debra K; Klemp, Jennifer R; Petroff, Brian K; Phillips, Teresa A; Metheny, Trina; Aversman, Sonya; Yeh, Hung-Wen; Zalles, Carola M; Mills, Gordon B; Hursting, Stephen D

2013-11-01

We conducted a phase II feasibility study of a 6-month behavioral weight loss intervention in postmenopausal overweight and obese women at increased risk for breast cancer and the effects of weight loss on anthropomorphic, blood, and benign breast tissue biomarkers. 67 women were screened by random peri-areolar fine-needle aspiration, 27 were registered and 24 participated in the interventional phase. The 24 biomarker evaluable women had a median baseline BMI of 34.2 kg/m(2) and lost a median of 11 % of their initial weight. Significant tissue biomarker modulation after the 6-month intervention was noted for Ki-67 (if restricted to the 15 women with any Ki-67 at baseline, p = 0.041), adiponectin to leptin ratio (p = 0.003); and cyclin B1 (p = 0.001), phosphorylated retinoblastoma (p = 0.005), and ribosomal S6 (p = 0.004) proteins. Favorable modulation for serum markers was observed for sex hormone-binding globulin (p < 0.001), bioavailable estradiol (p < 0.001), bioavailable testosterone (p = 0.033), insulin (p = 0.018), adiponectin (p = 0.001), leptin (p < 0.001), the adiponectin to leptin ratio (p < 0.001), C-reactive protein (p = 0.002), and hepatocyte growth factor (p = 0.011). When subdivided by <10 or >10 % weight loss, change in percent total body and android (visceral) fat, physical activity, and the majority of the serum and tissue biomarkers were significantly modulated only for women with >10 % weight loss from baseline. Some factors such as serum PAI-1 and breast tissue pS2 (estrogen-inducible gene) mRNA were not significantly modulated overall but were when considering only those with >10 % weight loss. In conclusion, a median weight loss of 11 % over 6 months resulted in favorable modulation of a number of anthropomorphic, breast tissue and serum risk and mechanistic markers. Weight loss of 10 % or more should likely be the goal for breast cancer risk reduction studies in obese women.

Pentasaccharide resin glycosides from Ipomoea pes-caprae.

PubMed

Yu, Bang-Wei; Luo, Jian-Guang; Wang, Jun-Song; Zhang, Dong-Ming; Yu, Shi-Shan; Kong, Ling-Yi

2011-04-25

Pescapreins XXI-XXX (1-10), pentasaccharide resin glycosides, together with the known pescapreins I-IV and stoloniferin III were isolated from the aerial parts of Ipomoea pes-caprae (beach morning-glory). The pescapreins are macrolactones of simonic acid B, partially esterified with different fatty acids. The lactonization site of the aglycone, jalapinolic acid, was located at C-2 or C-3 of the second saccharide moiety. Their structures were established by a combination of spectroscopic and chemical methods. Compounds 1-10 were evaluated for their potential to modulate multidrug resistance in the human breast cancer cell line MCF-7/ADR. The combined use of these new compounds at a concentration of 5 μg/mL increased the cytotoxicity of doxorubicin by 1.5-3.7-fold.

Coma and respiratory failure in a child with severe vitamin B(12) deficiency.

PubMed

Codazzi, Daniela; Sala, Francesca; Parini, Rossella; Langer, Martin

2005-07-01

Psychofunctional follow-up of severe vitamin B(12) deficit. Case report. Pediatric intensive care unit. Ten-month-old boy. Follow-up at 3 yrs. A 10-month-old boy was admitted to the pediatric intensive care unit with respiratory failure, muscular hypotonia, and involuntary movements. Although a central nervous system infection was excluded, computed tomography scan showed a diffuse cortical-subcortical atrophy. Vitamin B(12) deficiency was suspected because of a red-cell count of 1,350,000/mm(3) and a hemoglobin value 5.9 g/dL (MCV 116). The baby had been exclusively breast-fed, but his mother had been a strict vegan for 10 yrs. Chronic dietary vitamin B(12) deprivation was confirmed by blood and urinary samples. Treatment with vitamin B(12) led in 2 wks to rapid and complete hematological improvement and to partial regression of neurologic symptoms. During the following 3 yrs the boy had normal vitamin intake and underwent intensive rehabilitative treatment. The brain atrophy regressed, but linguistic and psychomotor delay persisted. Rapid clinical improvement after vitamin supply does not correlate with a complete recovery.

Accelerated partial breast irradiation: Past, present, and future

PubMed Central

Tann, Anne W; Hatch, Sandra S; Joyner, Melissa M; Wiederhold, Lee R; Swanson, Todd A

2016-01-01

Accelerated partial breast irradiation (APBI) focuses higher doses of radiation during a shorter interval to the lumpectomy cavity, in the setting of breast conserving therapy for early stage breast cancer. The utilization of APBI has increased in the past decade because of the shorter treatment schedule and a growing body of outcome data showing positive cosmetic outcomes and high local control rates in selected patients undergoing breast conserving therapy. Technological advances in various APBI modalities, including intracavitary and interstitial brachytherapy, intraoperative radiation therapy, and external beam radiation therapy, have made APBI more accessible in the community. Results of early APBI trials served as the basis for the current consensus guidelines, and multiple prospective randomized clinical trials are currently ongoing. The pending long term results of these trials will help us identify optimal candidates that can benefit from ABPI. Here we provide an overview of the clinical and cosmetic outcomes of various APBI techniques and review the current guidelines for selecting suitable breast cancer patients. We also discuss the impact of APBI on the economics of cancer care and patient reported quality of life. PMID:27777879

Benchtop and animal validation of a portable fluorescence microscopic imaging system for potential use in cholecystectomy.

PubMed

Ye, Jian; Liu, Guanghui; Liu, Peng; Zhang, Shiwu; Shao, Pengfei; Smith, Zachary J; Liu, Chenhai; Xu, Ronald X

2018-02-01

We propose a portable fluorescence microscopic imaging system (PFMS) for intraoperative display of biliary structure and prevention of iatrogenic injuries during cholecystectomy. The system consists of a light source module, a camera module, and a Raspberry Pi computer with an LCD. Indocyanine green (ICG) is used as a fluorescent contrast agent for experimental validation of the system. Fluorescence intensities of the ICG aqueous solution at different concentration levels are acquired by our PFMS and compared with those of a commercial Xenogen IVIS system. We study the fluorescence detection depth by superposing different thicknesses of chicken breast on an ICG-loaded agar phantom. We verify the technical feasibility for identifying potential iatrogenic injury in cholecystectomy using a rat model in vivo. The proposed PFMS system is portable, inexpensive, and suitable for deployment in resource-limited settings. (2018) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

Monte Carlo simulations to assess the effects of tube current modulation on breast dose for multidetector CT

NASA Astrophysics Data System (ADS)

Angel, Erin; Yaghmai, Nazanin; Matilda Jude, Cecilia; DeMarco, John J.; Cagnon, Christopher H.; Goldin, Jonathan G.; Primak, Andrew N.; Stevens, Donna M.; Cody, Dianna D.; McCollough, Cynthia H.; McNitt-Gray, Michael F.

2009-02-01

Tube current modulation was designed to reduce radiation dose in CT imaging while maintaining overall image quality. This study aims to develop a method for evaluating the effects of tube current modulation (TCM) on organ dose in CT exams of actual patient anatomy. This method was validated by simulating a TCM and a fixed tube current chest CT exam on 30 voxelized patient models and estimating the radiation dose to each patient's glandular breast tissue. This new method for estimating organ dose was compared with other conventional estimates of dose reduction. Thirty detailed voxelized models of patient anatomy were created based on image data from female patients who had previously undergone clinically indicated CT scans including the chest area. As an indicator of patient size, the perimeter of the patient was measured on the image containing at least one nipple using a semi-automated technique. The breasts were contoured on each image set by a radiologist and glandular tissue was semi-automatically segmented from this region. Previously validated Monte Carlo models of two multidetector CT scanners were used, taking into account details about the source spectra, filtration, collimation and geometry of the scanner. TCM data were obtained from each patient's clinical scan and factored into the model to simulate the effects of TCM. For each patient model, two exams were simulated: a fixed tube current chest CT and a tube current modulated chest CT. X-ray photons were transported through the anatomy of the voxelized patient models, and radiation dose was tallied in the glandular breast tissue. The resulting doses from the tube current modulated simulations were compared to the results obtained from simulations performed using a fixed mA value. The average radiation dose to the glandular breast tissue from a fixed tube current scan across all patient models was 19 mGy. The average reduction in breast dose using the tube current modulated scan was 17%. Results were size dependent with smaller patients getting better dose reduction (up to 64% reduction) and larger patients getting a smaller reduction, and in some cases the dose actually increased when using tube current modulation (up to 41% increase). The results indicate that radiation dose to glandular breast tissue generally decreases with the use of tube current modulated CT acquisition, but that patient size (and in some cases patient positioning) may affect dose reduction.

The role of heparins and nano-heparins as therapeutic tool in breast cancer.

PubMed

Afratis, Nikos A; Karamanou, Konstantina; Piperigkou, Zoi; Vynios, Demitrios H; Theocharis, Achilleas D

2017-06-01

Glycosaminoglycans are integral part of the dynamic extracellular matrix (ECM) network that control crucial biochemical and biomechanical signals required for tissue morphogenesis, differentiation, homeostasis and cancer development. Breast cancer cells communicate with stromal ones to modulate ECM mainly through release of soluble effectors during cancer progression. The intracellular cross-talk between cell surface receptors and estrogen receptors is important for the regulation of breast cancer cell properties and production of ECM molecules. In turn, reorganized ECM-cell surface interface modulates signaling cascades, which regulate almost all aspects of breast cell behavior. Heparan sulfate chains present on cell surface and matrix proteoglycans are involved in regulation of breast cancer functions since they are capable of binding numerous matrix molecules, growth factors and inflammatory mediators thus modulating their signaling. In addition to its anticoagulant activity, there is accumulating evidence highlighting various anticancer activities of heparin and nano-heparin derivatives in numerous types of cancer. Importantly, heparin derivatives significantly reduce breast cancer cell proliferation and metastasis in vitro and in vivo models as well as regulates the expression profile of major ECM macromolecules, providing strong evidence for therapeutic targeting. Nano-formulations of the glycosaminoglycan heparin are possibly novel tools for targeting tumor microenvironment. In this review, the role of heparan sulfate/heparin and its nano-formulations in breast cancer biology are presented and discussed in terms of future pharmacological targeting.

Toxicity and cosmesis following partial breast irradiation consisting of 40 Gy in 10 daily fractions.

PubMed

Trovo, Marco; Roncadin, Mario; Polesel, Jerry; Piccoli, Erica; Mileto, Mario; Micheli, Elvia; Perin, Tiziana; Carbone, Antonino; Massarut, Samuele; Trovo, Mauro G

2013-10-01

To assess the toxicity and cosmetic results in breast cancer patients undergoing adjuvant partial breast irradiation (PBI) to a total dose of 40 Gy in 10 daily fractions (4 Gy/fraction). Patients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old and treated with breast conservative surgery for early stage (pT1-T2 pN0-N1a) invasive ductal carcinoma. 77 patients were enrolled. Median follow-up was 18 months. The proposed schedule was well tolerated. One patient reported Grade 3 pain at the site of irradiation. Four (5%) patients experience Grade 2 erythema. Late Grade 2 and 1 fibrosis was observed in 3 (4%) and 14 (18%) patients, respectively. Cosmesis was judged "good/excellent" and "poor" in 75 (97%) and in 2 (3%) patients, respectively. 40 Gy in 10 daily fractions, 4 Gy/fraction, is a well tolerated regimen to deliver PBI. Copyright © 2013 Elsevier Ltd. All rights reserved.

Contrast-enhanced spectral mammography (CESM) versus breast magnetic resonance imaging (MRI): A retrospective comparison in 66 breast lesions.

PubMed

Li, L; Roth, R; Germaine, P; Ren, S; Lee, M; Hunter, K; Tinney, E; Liao, L

2017-02-01

The purpose of this study was to retrospectively compare the diagnostic performance of contrast-enhanced spectral mammography (CESM) with that of breast magnetic resonance imaging (BMRI) in breast cancer detection using parameters, including sensitivity, positive predictive value (PPV), lesion size, morphology, lesion and background enhancement, and examination time. A total of 48 women (mean age, 56years±10.6 [SD]) with breast lesions detected between October 2012 and March 2014 were included. Both CESM and BMRI were performed for each patient within 30 days. The enhancement intensity of lesions and breast background parenchyma was subjectively assessed for both modalities and was quantified for comparison. Statistical significance was analyzed using paired t-test for mean size of index lesions in all malignant breasts (an index lesion defined as the largest lesion in each breast), and a mean score of enhancement intensity for index lesions and breast background. PPV, sensitivity, and accuracy were calculated for both CESM and BMRI. The average duration time of CESM and MRI examinations was also compared. A total of 66 lesions were identified, including 62 malignant and 4 benign lesions. Both CESM and BMRI demonstrated a sensitivity of 100% for detection of breast cancer. There was no statistically significant difference between the mean size of index lesions (P=0.108). The enhancement intensity of breast background was significantly lower for CESM than for BMRI (P<0.01). The mean score of enhancement intensity of index lesions on CESM was significantly less than that for BMRI (P<0.01). The smallest lesion that was detected by both modalities measured 4mm. CESM had a higher PPV than BMRI (P>0.05). The average examination time for CESM was significantly shorter than that of BMRI (P<0.01). CESM has similar sensitivity than BMRI in breast cancer detection, with higher PPV and less background enhancement. CESM is associate with significantly shorter exam time thus a more accessible alternative to BMRI, and has the potential to play an important tool in breast cancer detection and staging. Copyright © 2016 Éditions françaises de radiologie. Published by Elsevier Masson SAS. All rights reserved.

Assessment of juiciness intensity of cooked chicken pectoralis major

USDA-ARS?s Scientific Manuscript database

The objectives were to assess sensory descriptive juiciness of cooked chicken breast meat (pectoralis major) during the entire process of consumption and to determine the relationship between sensory juiciness intensity scores during eating and raw meat characteristics. Chicken breast fillets were c...

Modulation of estrogen and epidermal growth factor receptors by rosemary extract in breast cancer cells.

PubMed

González-Vallinas, Margarita; Molina, Susana; Vicente, Gonzalo; Sánchez-Martínez, Ruth; Vargas, Teodoro; García-Risco, Mónica R; Fornari, Tiziana; Reglero, Guillermo; Ramírez de Molina, Ana

2014-06-01

Breast cancer is the leading cause of cancer-related mortality among females worldwide, and therefore the development of new therapeutic approaches is still needed. Rosemary (Rosmarinus officinalis L.) extract possesses antitumor properties against tumor cells from several organs, including breast. However, in order to apply it as a complementary therapeutic agent in breast cancer, more information is needed regarding the sensitivity of the different breast tumor subtypes and its effect in combination with the currently used chemotherapy. Here, we analyzed the antitumor activities of a supercritical fluid rosemary extract (SFRE) in different breast cancer cells, and used a genomic approach to explore its effect on the modulation of ER-α and HER2 signaling pathways, the most important mitogen pathways related to breast cancer progression. We found that SFRE exerts antitumor activity against breast cancer cells from different tumor subtypes and the downregulation of ER-α and HER2 receptors by SFRE might be involved in its antitumor effect against estrogen-dependent (ER+) and HER2 overexpressing (HER2+) breast cancer subtypes. Moreover, SFRE significantly enhanced the effect of breast cancer chemotherapy (tamoxifen, trastuzumab, and paclitaxel). Overall, our results support the potential utility of SFRE as a complementary approach in breast cancer therapy. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Quantification of mammary organoid toxicant response and mammary tissue motility using OCT fluctuation spectroscopy (Conference Presentation)

NASA Astrophysics Data System (ADS)

Yu, Xiao; Blackmon, Richard L.; Carabas-Hernendez, Patricia; Fuller, Ashley; Troester, Melissa A.; Oldenburg, Amy L.

2016-03-01

Mammary epithelial cell (MEC) organoids in 3D culture recapitulate features of breast ducts in vivo. OCT has the ability to monitor the evolution of MEC organoids non-invasively and longitudinally. The anti-cancer drug Doxorubicin (Dox) is able to inhibit proliferation of cancer cells and has been widely used for chemotherapy of breast cancers; while environmental toxins implicated in breast cancer such as estrogen regulates mammary tumor growth and stimulates the proliferation and metastatic potential of breast cancers. Here we propose a quantitative method for measuring motility of breast cells in 3D cultures based upon OCT speckle fluctuation spectroscopy. The metrics of the inverse power-law exponent (α) and fractional modulation amplitude (M) were extracted from speckle fluctuation spectra. These were used to quantify the responses of MEC organoids to Dox, and estrogen. We investigated MEC organoids comprised of two different MEC lines: MCF10DCIS.com exposed to Dox, and MCF7 exposed to estrogen. We found an increase (p<0.001) in α of MEC along time (t=0, 1 hour, 24 hours, 48 hours and 6 days) at each dose of Dox (0, 1 μM and 10 μM), indicating lower fluctuation intensity at higher frequencies. We also observed a decrease (p<0.001) in M for increasing time. However, both α and M of MCF7 treated with estrogen (0, 1 nM and 10 nM) exhibited the opposite trend along time. This novel technology provides rapid and non-invasive measurements of the effects of toxicants on MEC motility for understanding breast cancer development and assessing anti-cancer drugs.

Cardiac Dose Reduction with Deep-Inspiratory Breath Hold Technique of Radiotherapy for Left-Sided Breast Cancer.

PubMed

Sripathi, Lalitha Kameshwari; Ahlawat, Parveen; Simson, David K; Khadanga, Chira Ranjan; Kamarsu, Lakshmipathi; Surana, Shital Kumar; Arasu, Kavi; Singh, Harpreet

2017-01-01

Different techniques of radiation therapy have been studied to reduce the cardiac dose in left breast cancer. In this prospective dosimetric study, the doses to heart as well as other organs at risk (OAR) were compared between free-breathing (FB) and deep inspiratory breath hold (DIBH) techniques in intensity modulated radiotherapy (IMRT) and opposed-tangent three-dimensional radiotherapy (3DCRT) plans. Fifteen patients with left-sided breast cancer underwent computed tomography simulation and images were obtained in both FB and DIBH. Radiotherapy plans were generated with 3DCRT and IMRT techniques in FB and DIBH images in each patient. Target coverage, conformity index, homogeneity index, and mean dose to heart (Heart D mean ), left lung, left anterior descending artery (LAD) and right breast were compared between the four plans using the Wilcoxon signed rank test. Target coverage was adequate with both 3DCRT and IMRT plans, but IMRT plans showed better conformity and homogeneity. A statistically significant dose reduction of all OARs was found with DIBH. 3DCRT DIBH decreased the Heart D mean by 53.5% (7.1 vs. 3.3 Gy) and mean dose to LAD by 28% compared to 3DCRT FB . IMRT further lowered mean LAD dose by 18%. Heart D mean was lower with 3DCRT DIBH over IMRT DIBH (3.3 vs. 10.2 Gy). Mean dose to the contralateral breast was also lower with 3DCRT over IMRT (0.32 vs. 3.35 Gy). Mean dose and the V 20 of ipsilateral lung were lower with 3DCRT DIBH over IMRT DIBH (13.78 vs. 18.9 Gy) and (25.16 vs. 32.95%), respectively. 3DCRT DIBH provided excellent dosimetric results in patients with left-sided breast cancer without the need for IMRT.

Cardiac Dose Reduction with Deep-Inspiratory Breath Hold Technique of Radiotherapy for Left-Sided Breast Cancer

PubMed Central

Sripathi, Lalitha Kameshwari; Ahlawat, Parveen; Simson, David K; Khadanga, Chira Ranjan; Kamarsu, Lakshmipathi; Surana, Shital Kumar; Arasu, Kavi; Singh, Harpreet

2017-01-01

Introduction: Different techniques of radiation therapy have been studied to reduce the cardiac dose in left breast cancer. Aim: In this prospective dosimetric study, the doses to heart as well as other organs at risk (OAR) were compared between free-breathing (FB) and deep inspiratory breath hold (DIBH) techniques in intensity modulated radiotherapy (IMRT) and opposed-tangent three-dimensional radiotherapy (3DCRT) plans. Materials and Methods: Fifteen patients with left-sided breast cancer underwent computed tomography simulation and images were obtained in both FB and DIBH. Radiotherapy plans were generated with 3DCRT and IMRT techniques in FB and DIBH images in each patient. Target coverage, conformity index, homogeneity index, and mean dose to heart (Heart Dmean), left lung, left anterior descending artery (LAD) and right breast were compared between the four plans using the Wilcoxon signed rank test. Results: Target coverage was adequate with both 3DCRT and IMRT plans, but IMRT plans showed better conformity and homogeneity. A statistically significant dose reduction of all OARs was found with DIBH. 3DCRTDIBH decreased the Heart Dmean by 53.5% (7.1 vs. 3.3 Gy) and mean dose to LAD by 28% compared to 3DCRTFB. IMRT further lowered mean LAD dose by 18%. Heart Dmean was lower with 3DCRTDIBH over IMRTDIBH (3.3 vs. 10.2 Gy). Mean dose to the contralateral breast was also lower with 3DCRT over IMRT (0.32 vs. 3.35 Gy). Mean dose and the V20 of ipsilateral lung were lower with 3DCRTDIBH over IMRTDIBH (13.78 vs. 18.9 Gy) and (25.16 vs. 32.95%), respectively. Conclusions: 3DCRTDIBH provided excellent dosimetric results in patients with left-sided breast cancer without the need for IMRT. PMID:28974856

Simultaneous integrated boost (SIB) radiation therapy of right sided breast cancer with and without flattening filter - A treatment planning study.

PubMed

Maier, Johannes; Knott, Bernadette; Maerz, Manuel; Loeschel, Rainer; Koelbl, Oliver; Dobler, Barbara

2016-08-31

The aim of the study was to compare the two irradiation modes with (FF) and without flattening filter (FFF) for three different treatment techniques for simultaneous integrated boost radiation therapy of patients with right sided breast cancer. An Elekta Synergy linac with Agility collimating device is used to simulate the treatment of 10 patients. Six plans were generated in Monaco 5.0 for each patient treating the whole breast and a simultaneous integrated boost (SIB) volume: intensity modulated radiation therapy (IMRT), volumetric modulated arc therapy (VMAT) and a tangential arc VMAT (tVMAT), each with and without flattening filter. Plan quality was assessed considering target coverage, sparing of the contralateral breast, the lungs, the heart and the normal tissue. All plans were verified by a 2D-ionisation-chamber-array and delivery times were measured and compared. The Wilcoxon test was used for statistical analysis with a significance level of 0.05. Significantly best target coverage and homogeneity was achieved using VMAT FFF with V95% = (98.7 ± 0.8) % and HI = (8.2 ± 0.9) % for the SIB and V95% = (98.3 ± 0.7) % for the PTV, whereas tVMAT showed significantly lowest doses to the contralateral organs at risk with a Dmean of (0.7 ± 0.1) Gy for the contralateral lung, (1.0 ± 0.2) Gy for the contralateral breast and (1.4 ± 0.2) Gy for the heart. All plans passed the gamma evaluation with a mean passing rate of (99.2 ± 0.8) %. Delivery times were significantly reduced for VMAT and tVMAT but increased for IMRT, when FFF was used. Lowest delivery times were observed for tVMAT FFF with (1:20 ± 0:07) min. Balancing target coverage, OAR sparing and delivery time, VMAT FFF and tVMAT FFF are considered the preferable of the investigated treatment options in simultaneous integrated boost irradiation of right sided breast cancer for the combination of an Elekta Synergy linac with Agility and the treatment planning system Monaco 5.0.

Targeting Metabolic Plasticity in Breast Cancer Cells via Mitochondrial Complex I Modulation

PubMed Central

Xu, Qijin; Biener-Ramanujan, Eva; Yang, Wei; Ramanujan, V Krishnan

2016-01-01

Purpose Heterogeneity commonly observed in clinical tumors stems both from the genetic diversity as well as from the differential metabolic adaptation of multiple cancer types during their struggle to maintain uncontrolled proliferation and invasion in vivo. This study aims to identify a potential metabolic window of such adaptation in aggressive human breast cancer cell lines. Methods With a multidisciplinary approach using high resolution imaging, cell metabolism assays, proteomic profiling and animal models of human tumor xenografts and via clinically-relevant, pharmacological approach for modulating mitochondrial complex I function in human breast cancer cell lines, we report a novel route to target metabolic plasticity in human breast cancer cells. Results By a systematic modulation of mitochondrial function and by mitigating metabolic switch phenotype in aggressive human breast cancer cells, we demonstrate that the resulting metabolic adaptation signatures can predictably decrease tumorigenic potential in vivo. Proteomic profiling of the metabolic adaptation in these cells further revealed novel protein-pathway interactograms highlighting the importance of antioxidant machinery in the observed metabolic adaptation. Conclusions Improved metabolic adaptation potential in aggressive human breast cancer cells contribute to improving mitochondrial function and reducing metabolic switch phenotype –which may be vital for targeting primary tumor growth in vivo. PMID:25677747

WE-AB-204-10: Evaluation of a Novel Dedicated Breast PET System (Mammi-PET)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Long, Z; Swanson, T; O’Connor, M

2015-06-15

Purpose: To evaluate the performance characteristics of a novel dedicated breast PET system (Mammi-PET, Oncovision). The system has 2 detector rings giving axial/transaxial field of view of 8/17 cm. Each ring consists of 12 monolithic LYSO modules coupled to PSPMTs. Methods: Uniformity, sensitivity, energy and spatial resolution were measured according to NEMA standards. Count rate performance was investigated using a source of F-18 (1384uCi) decayed over 5 half-lives. A prototype PET phantom was imaged for 20 min to evaluate image quality, recovery coefficients and partial volume effects. Under an IRB-approved protocol, 11 patients who just underwent whole body PET/CT examsmore » were imaged prone with the breast pendulant at 5–10 minutes/breast. Image quality was assessed with and without scatter/attenuation correction and using different reconstruction algorithms. Results: Integral/differential uniformity were 9.8%/6.0% respectively. System sensitivity was 2.3% on axis, 2.2% and 2.8% at 3.8 cm and 7.8 cm off-axis. Mean energy resolution of all modules was 23.3%. Spatial resolution (FWHM) was 1.82 mm and 2.90 mm on axis and 5.8 cm off axis. Three cylinders (14 mm diameter) in the PET phantom were filled with activity concentration ratios of 4:1, 3:1, and 2:1 relative to the background. Measured cylinder to background ratios were 2.6, 1.8 and 1.5 (without corrections) and 3.6, 2.3 and 1.5 (with attenuation/scatter correction). Five cylinders (14, 10, 6, 4 and 2 mm diameter) each with an activity ratio of 4:1 were measured and showed recovery coefficients of 1, 0.66, 0.45, 0.18 and 0.18 (without corrections), and 1, 0.53, 0.30, 0.13 and 0 (with attenuation/scatter correction). Optimal phantom image quality was obtained with 3D MLEM algorithm, >20 iterations and without attenuation/scatter correction. Conclusion: The MAMMI system demonstrated good performance characteristics. Further work is needed to determine the optimal reconstruction parameters for qualitative and quantitative applications.« less

Treatment of Breast Tumors using Pulsed HIFU for Delivery and Activation of Sonosensitizers

DTIC Science & Technology

2009-08-01

ABSTRACT High intensity focused ultrasound ( HIFU ) has been combined with a Rose Bengal derivative (RB2) to provide a synergistic cytotoxicity requiring the...by high intensity focused ultrasound ( HIFU ). Applying HIFU in pulsed mode (to avoid overheating) has shown promise in improving the penetration of...ablation for breast cancer treatment. 15. SUBJECT TERMS high intensity focused ultrasound , sonodynamic, cavitation, free radicals, chemotherapy

CDDO-Me protects normal lung and breast epithelial cells but not cancer cells from radiation.

PubMed

El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E; Shay, Jerry W

2014-01-01

Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients.

CDDO-Me Protects Normal Lung and Breast Epithelial Cells but Not Cancer Cells from Radiation

PubMed Central

El-Ashmawy, Mariam; Delgado, Oliver; Cardentey, Agnelio; Wright, Woodring E.; Shay, Jerry W.

2014-01-01

Although radiation therapy is commonly used for treatment for many human diseases including cancer, ionizing radiation produces reactive oxygen species that can damage both cancer and healthy cells. Synthetic triterpenoids, including CDDO-Me, act as anti-inflammatory and antioxidant modulators primarily by inducing the transcription factor Nrf2 to activate downstream genes containing antioxidant response elements (AREs). In the present series of experiments, we determined if CDDO-Me can be used as a radioprotector in normal non-cancerous human lung and breast epithelial cells, in comparison to lung and breast cancer cell lines. A panel of normal non-cancerous, partially cancer progressed, and cancer cell lines from both lung and breast tissue was exposed to gamma radiation with and without pre-treatment with CDDO-Me. CDDO-Me was an effective radioprotector when given ∼18 hours before radiation in epithelial cells (average dose modifying factor (DMF) = 1.3), and Nrf2 function was necessary for CDDO-Me to exert these radioprotective effects. CDDO-Me did not protect cancer lines tested from radiation-induced cytotoxicity, nor did it protect experimentally transformed human bronchial epithelial cells (HBECs) with progressive oncogenic manipulations. CDDO-Me also protected human lymphocytes against radiation-induced DNA damage. A therapeutic window exists in which CDDO-Me protects normal cells from radiation by activating the Nrf2 pathway, but does not protect experimentally transformed or cancer cell lines. This suggests that use of this oral available, non-toxic class of drug can protect non-cancerous healthy cells during radiotherapy, resulting in better outcomes and less toxicity for patients. PMID:25536195

A planning comparison of 7 irradiation options allowed in RTOG 1005 for early-stage breast cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chen, Guang-Pei, E-mail: gpchen@mcw.edu; Liu, Feng; White, Julia

2015-04-01

This study compared the 7 treatment plan options in achieving the dose-volume criteria required by the Radiation Therapy Oncology Group (RTOG) 1005 protocol. Dosimetry plans were generated for 15 representative patients with early-stage breast cancer (ESBC) based on the protocol-required dose-volume criteria for each of the following 7 treatment options: 3D conformal radiotherapy (3DCRT), whole-breast irradiation (WBI) plus 3DCRT lumpectomy boost, 3DCRT WBI plus electron boost, 3DCRT WBI plus intensity-modulated radiation therapy (IMRT) boost, IMRT WBI plus 3DCRT boost, IMRT WBI plus electron boost, IMRT WBI plus IMRT boost, and simultaneous integrated boost (SIB) with IMRT. A variety of dose-volumemore » parameters, including target dose conformity and uniformity and normal tissue sparing, were compared for these plans. For the patients studied, all plans met the required acceptable dose-volume criteria, with most of them meeting the ideal criteria. When averaged over patients, most dose-volume goals for all plan options can be achieved with a positive gap of at least a few tenths of standard deviations. The plans for all 7 options are generally comparable. The dose-volume goals required by the protocol can in general be easily achieved. IMRT WBI provides better whole-breast dose uniformity than 3DCRT WBI does, but it causes no significant difference for the dose conformity. All plan options are comparable for lumpectomy dose uniformity and conformity. Patient anatomy is always an important factor when whole-breast dose uniformity and conformity and lumpectomy dose conformity are considered.« less

Use of tomotherapy in treatment of synchronous bilateral breast cancer: dosimetric comparison study

PubMed Central

Wadasadawala, T; Sarin, R; Upreti, R R; Paul, S; Phurailatpam, R

2015-01-01

Objective: Synchronous malignancy in both breasts is a rare incidence. The present study aims at dosimetric comparison of conventional bitangential radiotherapy (RT) technique with conventional [field-in-field (FIF)] and rotational [Helical TomoTherapy® and TomoDirect™ (TD); Accuray Inc., Sunnyvale, CA] intensity-modulated RT for patients with synchronous bilateral breast cancer (SBBC). Methods: CT data sets of 10 patients with SBBC were selected for the present study. RT was planned for all patients on both sides to whole breast and/or chest wall using the above-mentioned techniques. Six females with breast conservation on at least one side also had a composite plan along with tumour bed (TB) boost using sequential electrons for bitangential and FIF techniques or sequential helical tomotherapy (HT) boost (for TD) or simultaneous integrated boost (SIB) for HT. Results: All techniques produced acceptable target coverage. The hotspot was significantly lower with FIF technique and HT but higher with TD. For the organs at risk doses, HT resulted in significant reduction of the higher dose volumes. Similarly, TD resulted in significant reduction of the mean dose to the heart and total lung by reducing the lower dose volumes. All techniques of delivering boost to the TB were comparable in terms of target coverage. HT-SIB markedly reduced mean doses to the total lung and heart by specifically lowering the higher dose volumes. Conclusion: This study demonstrates the cardiac and pulmonary sparing ability of tomotherapy in the setting of SBBC. Advances in knowledge: This is the first study demonstrating feasibility of treatment of SBBC using tomotherapy. PMID:25605345

Delta and theta power spectra of night sleep EEG are higher in breast-feeding mothers than in non-pregnant women.

PubMed

Nishihara, Kyoko; Horiuchi, Shigeko; Eto, Hiromi; Uchida, Sunao; Honda, Makoto

2004-09-23

The power spectra of night sleep EEGs of 12 breast-feeding 9-13 week postpartum mothers were analyzed and compared with those of 12 non-pregnant women. The power spectra in the delta and theta frequency range during NREM sleep for breast-feeding mothers were significantly higher than those for non-pregnant women. In addition, the all-night sleep patterns of the mothers were classified into two groups - interrupted sleep due to taking care of their infants and non-interrupted sleep - in order to observe the influence of partial sleep deprivation. The power spectra in the delta and theta frequency range were not significantly different between them. This result suggests that increased delta and theta power spectra during postpartum sleep do not result from partial sleep deprivation. The role of prolactin in breast-feeding mothers' sleep is also discussed.

Is anxiety associated with hot flashes in women with breast cancer?

PubMed

Guimond, Anne-Josée; Massicotte, Elsa; Savard, Marie-Hélène; Charron-Drolet, Jade; Ruel, Sophie; Ivers, Hans; Savard, Josée

2015-08-01

Women with breast cancer are at higher risk for experiencing hot flashes (HFs), which is attributable, in large part, to systemic cancer treatments and their effects on estrogen levels. However, other factors, such as anxiety, could also play a role. This study aimed to assess the cross-sectional and temporal relationships between anxiety and HFs among women treated for breast cancer and to clarify the direction of these relationships. Fifty-six women recently treated for breast cancer were assessed prospectively using a 14-day Hot Flashes and Anxiety Diary (HFAD). Anxiety and HFs were also assessed using the Hospital Anxiety and Depression Scale-anxiety subscale and the Menopause-Specific Quality of Life Questionnaire-vasomotor subscale. In addition, HFs were objectively recorded for a continuous 24-hour period using home-based sternal skin conductance. No cross-sectional relationship was found between anxiety and subjectively assessed HFs, or between anxiety and the frequency and intensity of objectively assessed HFs. However, a greater anxiety level on the HFAD was significantly associated with a shorter time to reach the HF peak, as assessed with sternal skin conductance (partial Spearman correlation coefficient rsp = -0.44). Moreover, greater anxiety predicted more severe self-reported HFs on the following night, both assessed with the HFAD (rsp = 0.13). Conversely, self-reported diurnal and nocturnal HFs on the HFAD did not predict next-day anxiety level. This study reveals a significant relationship between anxiety and faster-developing objectively measured HFs. Furthermore, anxiety has been found to significantly predict subsequent increases in self-reported HFs, suggesting that strategies that target anxiety could potentially have a beneficial effect on HFs in women with breast cancer.

Radiation Therapy Versus No Radiation Therapy to the Neo-breast Following Skin-Sparing Mastectomy and Immediate Autologous Free Flap Reconstruction for Breast Cancer: Patient-Reported and Surgical Outcomes at 1 Year-A Mastectomy Reconstruction Outcomes Consortium (MROC) Substudy.

PubMed

Cooke, Andrew L; Diaz-Abele, Julian; Hayakawa, Tom; Buchel, Ed; Dalke, Kimberly; Lambert, Pascal

2017-09-01

To determine whether adjuvant radiation therapy (RT) is associated with adverse patient-reported outcomes and surgical complications 1 year after skin-sparing mastectomy and immediate autologous free flap reconstruction for breast cancer. We compared 24 domains of patient-reported outcome measures 1 year after autologous reconstruction between patients who received adjuvant RT and those who did not. A total of 125 patients who underwent surgery between 2012 and 2015 at our institution were included from the Mastectomy Reconstruction Outcomes Consortium study database. Adjusted multivariate models were created incorporating RT technical data, age, cancer stage, estrogen receptor, chemotherapy, breast size, body mass index, and income to determine whether RT was associated with outcomes. At 1 year after surgery, European Organisation for Research and Treatment of Cancer (EORTC) Breast Cancer-Specific Quality of Life Questionnaire breast symptoms were significantly greater in 64 patients who received RT (8-point difference on 100-point ordinal scale, P<.0001) versus 61 who did not receive RT in univariate and multivariate models. EORTC arm symptoms (20-point difference on 100-point ordinal scale, P=.0200) differed on univariate analysis but not on multivariate analysis. All other outcomes-including Numerical Pain Rating Scale, BREAST-Q (Post-operative Reconstruction Module), Patient-Report Outcomes Measurement Information System Profile 29, McGill Pain Questionnaire-Short Form (MPQ-SF) score, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire-were not statistically different between groups. Surgical complications were uncommon and did not differ by treatment. RT to the neo-breast compared with no RT following immediate autologous free flap reconstruction for breast cancer is well tolerated at 1 year following surgery despite patients undergoing RT also having a higher cancer stage and more intensive surgical and systemic treatment. Neo-breast symptoms are more common in patients receiving RT by the EORTC Breast Cancer-Specific Quality of Life Questionnaire but not by the BREAST-Q. Patient-reported results at 1 year after surgery suggest RT following immediate autologous free flap breast reconstruction is well tolerated. Copyright © 2017 Elsevier Inc. All rights reserved.

Persistent breast pain among women with histories of breast conserving surgery for breast cancer compared to women without histories of breast surgery or cancer

PubMed Central

Edmond, Sara N.; Shelby, Rebecca A.; Keefe, Francis J.; Fisher, Hannah M.; Schmidt, John; Soo, Mary Scott; Skinner, Celette Sugg; Ahrendt, Gretchen M.; Manculich, Jessica; Sumkin, Jules H.; Zuley, Margarita L.; Bovbjerg, Dana H.

2016-01-01

Objectives This study compared persistent breast pain among women who received breast-conserving surgery for breast cancer and women without a history of breast cancer. Methods Breast cancer survivors (n=200) were recruited at their first post-surgical surveillance mammogram (6-15 months post-surgery). Women without a breast cancer history (n=150) were recruited at the time of a routine screening mammogram. All women completed measures of breast pain, pain interference with daily activities and intimacy, worry about breast pain, anxiety symptoms, and depression symptoms. Demographic and medical information were also collected. Results Persistent breast pain (duration ≥ 6 months) was reported by 46.5% of breast cancer survivors and 12.7% of women without a breast cancer history (p<0.05). Breast cancer survivors also had significantly higher rates of clinically significant persistent breast pain (pain intensity score ≥3/10), as well as higher average breast pain intensity and unpleasantness scores. Breast cancer survivors with persistent breast pain had significantly higher levels of depressive symptoms, as well as pain worry and interference, compared to survivors without persistent breast pain or women without a breast cancer history. Anxiety symptoms were significantly higher in breast cancer survivors with persistent breast pain compared to women without a breast cancer history. Discussion Results indicate that persistent breast pain negatively impacts women with a history of breast conserving cancer surgery compared to women without that history. Strategies to ameliorate persistent breast pain and to improve adjustment among women with persistent breast pain should be explored for incorporation into standard care for breast cancer survivors. PMID:27922843

Decision to adopt medical technology: case study of breast cancer radiotherapy techniques.

PubMed

Gold, Heather Taffet; Pitrelli, Kimberly; Hayes, Mary Katherine; Murphy, Madhuvanti Mahadeo

2014-11-01

To understand decision making concerning adoption and nonadoption of accelerated partial breast radiotherapy (RT) prior to long-term randomized trial evidence. A total of 36 radiation oncologists and surgeons were recruited through purposive and snowball sampling strategies from September 2010 through January 2013. Semistructured phone interviews were conducted and audio-recorded and lasted 20-45 minutes. Qualitative analysis was conducted using a framework approach, iteratively exploring key concepts and emerging issues raised by subjects. Interviews were transcribed and imported into Atlas.ti v6. Transcripts were independently coded by 3 researchers shortly after each interview, followed by consensus development on each coded transcript. Barriers and facilitators of adoption, practice patterns, and informational/educational sources concerning accelerated partial breast RT were all assessed to determine major themes. Nearly half of physicians were surgeons (47%), and half were radiation oncologists (53%), with 61% overall in urban settings. Twenty-nine of the 36 physicians interviewed used brachytherapy-based partial breast RT. Five major factors were involved in physicians' decisions to adopt accelerated partial breast RT: facilitators encouraging adoption (e.g., enthusiastic colleagues and patient convenience), financial and prestige incentives, pressures to adopt (e.g., potential declines in referrals), judgment concerning acceptable level of scientific evidence, and barriers (e.g., not having appropriate machinery or referral mechanism in place). If technology was adopted, clinical guideline adherence varied. Technology adoption is based on financial and social pressures, along with often-limited scientific evidence and what seems "best" for patients. For technology adoption and diffusion to be rational and evidence-based, we must encourage appropriate financial payment models to curb use outside of research studies and promote development of additional treatment registries until sufficient evidence is gathered. © The Author(s) 2014.

A Targeted RNAi Screen of the Breast Cancer Genome Identifies KIF14 and TLN1 as Genes That Modulate Docetaxel Chemosensitivity in Triple-Negative Breast Cancer

PubMed Central

Singel, Stina Mui; Cornelius, Crystal; Batten, Kimberly; Fasciani, Gail; Wright, Woodring E.; Lum, Lawrence; Shay, Jerry W.

2015-01-01

Purpose To identify biomarkers within the breast cancer genome that may predict chemosensitivity in breast cancer. Experimental Design We conducted an RNA interference (RNAi) screen within the breast cancer genome for genes whose loss-of-function enhanced docetaxel chemosensitivity in an estrogen receptor–negative, progesterone receptor–negative, and Her2-negative (ER−, PR−, and Her2−, respectively) breast cancer cell line, MDA-MB-231. Top candidates were tested for their ability to modulate chemosensitivity in 8 breast cancer cell lines and to show in vivo chemosensitivity in a mouse xenograft model. Results From ranking chemosensitivity of 328 short hairpin RNA (shRNA) MDA-MB-231 cell lines (targeting 133 genes with known somatic mutations in breast cancer), we focused on the top two genes, kinesin family member 14 (KIF14) and talin 1 (TLN1). KIF14 and TLN1 loss-of-function significantly enhanced chemosensitivity in four triple-negative breast cancer (TNBC) cell lines (MDA-MB-231, HCC38, HCC1937, and Hs478T) but not in three hormone receptor–positive cell lines (MCF7, T47D, and HCC1428) or normal human mammary epithelial cells (HMEC). Decreased expression of KIF14, but not TLN1, also enhanced docetaxel sensitivity in a Her2-amplified breast cancer cell line, SUM190PT. Higher KIF14 and TLN1 expressions are found in TNBCs compared with the other clinical subtypes. Mammary fat pad xenografts of KIF14- and TLN1-deficient MDA-MB-231 cells revealed reduced tumor mass compared with control MDA-MB-231 cells after chemotherapy. KIF14 expression is also prognostic of relapse-free and overall survival in representative breast cancer expression arrays. Conclusion KIF14 and TLN1 are modulators of response to docetaxel and potential therapeutic targets in TNBC. PMID:23479679

Physical Activity and Weight Loss Reduce the Risk of Breast Cancer: A Meta-analysis of 139 Prospective and Retrospective Studies.

PubMed

Hardefeldt, Prue J; Penninkilampi, Ross; Edirimanne, Senarath; Eslick, Guy D

2017-10-17

Physical activity and weight loss have been shown to reduce breast cancer incidence in numerous observational studies. The aim of this meta-analysis was to assess the effect of both physical activity and weight loss on breast cancer incidence. Specifically, we aimed to complete subgroup analyses by the intensity of physical activity and menopausal status at breast cancer diagnosis to further elucidate the relationship between physical activity, weight loss, and breast cancer incidence. Studies were obtained from a database search of MEDLINE, EMBASE, PubMed, Current Contents Connect, and Google Scholar through November 5, 2017. A random-effects model was used for pooled data. There were 139 studies included in the meta-analysis, including 236,955 cases and 3,963,367 controls. Physical activity significantly reduced the risk of breast cancer (odds ratio [OR], 0.78; 95% confidence interval [CI], 0.76-0.81; P < .001), with high-intensity physical activity being slightly more protective (OR, 0.73; 95% CI, 0.65-0.81; P < .001) than low-intensity exercise (OR, 0.79; 95% CI, 0.72-0.86; P < .001). The effect size for general exercise was similar in both premenopausal (OR, 0.79; 95% CI, 0.73-0.87; P < .001) and postmenopausal (OR, 0.82; 95% CI, 0.78-0.86; P < .001) women. Additionally, weight loss reduced the risk of breast cancer incidence (OR, 0.82; 95% CI, 0.67-0.97). Physical activity and weight loss significantly reduce the risk of breast cancer, irrespective of the timing and intensity of the exercise. Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Cytotoxic Effect of Nano-SiO2 in Human Breast Cancer Cells via Modulation of EGFR Signaling Cascades.

PubMed

Jeon, Donghwan; Kim, Hyungjoo; Nam, Keesoo; Oh, Sunhwa; Son, Seog-Ho; Shin, Incheol

2017-11-01

Silica nanoparticles (nano-SiO 2 ) are widely used in many industrial areas and there is much controversy surrounding cytotoxic effects of such nanoparticles. In order to determine the toxicity and possible molecular mechanisms involved, we conducted several tests with two breast cancer cell lines, MDA-MB-231 and Hs578T. After exposure to nano-SiO 2 , growth, apoptosis, motility of breast cancer cells were monitored. In addition, modulation of signal transduction induced by nano-SiO 2 was detected through western blot analysis. Treatment of nano-SiO 2 repressed the growth of breast cancer cell lines. It also increased apoptosis and reduced cell motility. Moreover, exposure to nano-SiO 2 significantly disturbed the dimerization of epidermal growth factor receptor (EGFR), followed by down-regulation of its downstream cellular sarcoma kinase (c-SRC) and signal transducer and activator of transcription 3 (STAT3) signaling cascades. Nano-SiO 2 has a cytotoxic effect on MDA-MB-231 and Hs578T breast cancer cells via modulation of EGFR signaling cascades. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Accelerated Partial Breast Irradiation Consensus Statement From the American Society for Radiation Oncology (ASTRO)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Smith, Benjamin D.; Department of Radiation Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX; Arthur, Douglas W.

2009-07-15

Purpose: To present guidance for patients and physicians regarding the use of accelerated partial-breast irradiation (APBI), based on current published evidence complemented by expert opinion. Methods and Materials: A systematic search of the National Library of Medicine's PubMed database yielded 645 candidate original research articles potentially applicable to APBI. Of these, 4 randomized trials and 38 prospective single-arm studies were identified. A Task Force composed of all authors synthesized the published evidence and, through a series of meetings, reached consensus regarding the recommendations contained herein. Results: The Task Force proposed three patient groups: (1) a 'suitable' group, for whom APBImore » outside of a clinical trial is acceptable, (2) a 'cautionary' group, for whom caution and concern should be applied when considering APBI outside of a clinical trial, and (3) an 'unsuitable' group, for whom APBI outside of a clinical trial is not generally considered warranted. Patients who choose treatment with APBI should be informed that whole-breast irradiation (WBI) is an established treatment with a much longer track record that has documented long-term effectiveness and safety. Conclusion: Accelerated partial-breast irradiation is a new technology that may ultimately demonstrate long-term effectiveness and safety comparable to that of WBI for selected patients with early breast cancer. This consensus statement is intended to provide guidance regarding the use of APBI outside of a clinical trial and to serve as a framework to promote additional clinical investigations into the optimal role of APBI in the treatment of breast cancer.« less

Prospective association between red and processed meat intakes and breast cancer risk: modulation by an antioxidant supplementation in the SU.VI.MAX randomized controlled trial.

PubMed

Pouchieu, Camille; Deschasaux, Mélanie; Hercberg, Serge; Druesne-Pecollo, Nathalie; Latino-Martel, Paule; Touvier, Mathilde

2014-10-01

The level of evidence regarding the association between red and processed meat intakes and breast cancer risk is still low, due to insufficient prospective studies. Moreover, mechanistic data suggest that some antioxidants may modulate this relationship but epidemiological evidence is lacking. Our objectives were to investigate relationships between red and processed meat intakes and breast cancer risk, and to study whether an antioxidant supplementation modulates these associations, which, to our knowledge, has never been investigated before. The SU.VI.MAX study was a randomized, double-blind, placebo-controlled trial in which participants received a combination of low-dose antioxidants or a placebo from 1994 to 2002. This observational prospective analysis included 4684 women among whom 190 developed a first incident breast cancer between 1994 and 2007 [mean (range) follow-up=11.3 (0-13)years]. Baseline dietary data were assessed by repeated dietary records in 1994-1995. Associations between quartiles of red and processed meat intakes and breast cancer risk were characterized by multivariate Cox proportional hazards models. Breast cancer risk was directly associated with processed meat intake [hazard ratio (HR)Q4vsQ1=1.45 (0.92-2.27), Ptrend=0.03] and this association was stronger when excluding cooked ham [HRQ4vsQ1=1.90 (1.18-3.05), Ptrend=0.005]. In stratified analyses, processed meat intake was directly associated with breast cancer risk in the placebo group only [HRQ4vsQ1=2.46 (1.28-4.72), Ptrend=0.001], but not in the supplemented group [HRQ4vsQ1=0.86 (0.45-1.63), Ptrend=0.7]. Processed meat intake was prospectively associated with increased breast cancer risk. This study also suggests that antioxidants may modulate this association by counteracting the potential pro-carcinogenic effects of processed meat on breast cancer. © The Author 2014; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.

Sirtuin 1-dependent resveratrol cytotoxicity and pro-differentiation activity on breast cancer cells.

PubMed

Deus, Cláudia M; Serafim, Teresa L; Magalhães-Novais, Silvia; Vilaça, Andreia; Moreira, Ana C; Sardão, Vilma A; Cardoso, Susana M; Oliveira, Paulo J

2017-03-01

Sirtuins regulate several processes associated with tumor development. Resveratrol was shown to stimulate sirtuin 1 and 3 (SIRT1/3) activities and to result in cytotoxicity for some tumor types. The relationship between modulation of sirtuin activities, cellular metabolic remodeling and resveratrol cytotoxicity mechanism on breast cancer cells is still an open question. Here, we evaluated whether sirtuin 1 and 3 are involved in resveratrol toxicity and whether resveratrol leads to a metabolic remodeling and cell differentiation. Results using the Extracellular Flux Analyzer indicated that resveratrol inhibits mitochondrial respiration in breast cancer cells. We also demonstrated here for the first time that resveratrol cytotoxic effects on breast cancer cells were modulated by SIRT1 and also involved mitochondrial complex I inhibition. Importantly, we also demonstrated that resveratrol reduced the pool of breast cancer cells with stemness markers through a SIRT1-dependent mechanism. Our data highlights the role of SIRT1 in regulating resveratrol induced differentiation and/or toxicity in breast cancer cells.

Estimation of breast dose reduction potential for organ-based tube current modulated CT with wide dose reduction arc

NASA Astrophysics Data System (ADS)

Fu, Wanyi; Sturgeon, Gregory M.; Agasthya, Greeshma; Segars, W. Paul; Kapadia, Anuj J.; Samei, Ehsan

2017-03-01

This study aimed to estimate the organ dose reduction potential for organ-dose-based tube current modulated (ODM) thoracic CT with wide dose reduction arc. Twenty-one computational anthropomorphic phantoms (XCAT, age range: 27- 75 years, weight range: 52.0-105.8 kg) were used to create a virtual patient population with clinical anatomic variations. For each phantom, two breast tissue compositions were simulated: 50/50 and 20/80 (glandular-to-adipose ratio). A validated Monte Carlo program was used to estimate the organ dose for standard tube current modulation (TCM) (SmartmA, GE Healthcare) and ODM (GE Healthcare) for a commercial CT scanner (Revolution, GE Healthcare) with explicitly modeled tube current modulation profile, scanner geometry, bowtie filtration, and source spectrum. Organ dose was determined using a typical clinical thoracic CT protocol. Both organ dose and CTDIvol-to-organ dose conversion coefficients (h factors) were compared between TCM and ODM. ODM significantly reduced all radiosensitive organ doses (p<0.01). The breast dose was reduced by 30+/-2%. For h factors, organs in the anterior region (e.g. thyroid, stomach) exhibited substantial decreases, and the medial, distributed, and posterior region either saw an increase or no significant change. The organ-dose-based tube current modulation significantly reduced organ doses especially for radiosensitive superficial anterior organs such as the breasts.

Patient Preferences and Physician Practice Patterns Regarding Breast Radiotherapy

DTIC Science & Technology

2011-01-01

breast irradiation (HF-WBI) 62%, partial breast irradiation ( PBI ) 28%, and conventionally fractionated whole breast irradiation (CF-WBI) 10%. By...comparison, 82% of physicians use CF-WBI for more than 2/3 of women and 56% never use HF-WBI. With respect to PBI , 62% of women preferred three...dimensional (3D)- PBI and 38% favor brachytherapy- PBI , whereas 36% of physicians offer 3D- PBI and 66% offer brachytherapy- PBI . 70% of women prefer once-daily

Patient-reported outcomes of catheter-based accelerated partial breast brachytherapy and whole breast irradiation, a single institution experience.

PubMed

Jethwa, Krishan R; Kahila, Mohamed M; Mara, Kristin C; Harmsen, William S; Routman, David M; Pumper, Geralyn M; Corbin, Kimberly S; Sloan, Jeff A; Ruddy, Kathryn J; Hieken, Tina J; Park, Sean S; Mutter, Robert W

2018-05-01

Accelerated partial breast irradiation (APBI) and whole breast irradiation (WBI) are treatment options for early-stage breast cancer. The purpose of this study was to compare patient-reported-outcomes (PRO) between patients receiving multi-channel intra-cavitary brachytherapy APBI or WBI. Between 2012 and 2015, 131 patients with ductal carcinoma in situ (DCIS) or early stage invasive breast cancer were treated with adjuvant APBI (64) or WBI (67) and participated in a PRO questionnaire. The linear analog scale assessment (LASA), harvard breast cosmesis scale (HBCS), PRO-common terminology criteria for adverse events- PRO (PRO-CTCAE), and breast cancer treatment outcome scale (BCTOS) were used to assess quality of life (QoL), pain, fatigue, aesthetic and functional status, and breast cosmesis. Comparisons of PROs were performed using t-tests, Wilcoxon rank-sum, Chi square, Fisher exact test, and regression methods. Median follow-up from completion of radiotherapy and questionnaire completion was 13.3 months. There was no significant difference in QoL, pain, or fatigue severity, as assessed by the LASA, between treatment groups (p > 0.05). No factors were found to be predictive of overall QoL on regression analysis. BCTOS health-related QoL scores were similar between treatment groups (p = 0.52).The majority of APBI and WBI patients reported excellent/good breast cosmesis, 88.5% versus 93.7% (p = 0.37). Skin color change (p = 0.011) and breast elevation (p = 0.01) relative to baseline were more common in the group receiving WBI. APBI and WBI were both associated with favorable patient-reported outcomes in early follow-up. APBI resulted in a lesser degree of patient-reported skin color change and breast elevation relative to baseline.

Five-Year Analysis of Treatment Efficacy and Cosmesis by the American Society of Breast Surgeons MammoSite Breast Brachytherapy Registry Trial in Patients Treated With Accelerated Partial Breast Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vicini, Frank, E-mail: fvicini@beaumont.ed; Beitsch, Peter; Quiet, Coral

2011-03-01

Purpose: To present 5-year data on treatment efficacy, cosmetic results, and toxicities for patients enrolled on the American Society of Breast Surgeons MammoSite breast brachytherapy registry trial. Methods and Materials: A total of 1440 patients (1449 cases) with early-stage breast cancer receiving breast-conserving therapy were treated with the MammoSite device to deliver accelerated partial-breast irradiation (APBI) (34 Gy in 3.4-Gy fractions). Of 1449 cases, 1255 (87%) had invasive breast cancer (IBC) (median size, 10 mm) and 194 (13%) had ductal carcinoma in situ (DCIS) (median size, 8 mm). Median follow-up was 54 months. Results: Thirty-seven cases (2.6%) developed an ipsilateralmore » breast tumor recurrence (IBTR), for a 5-year actuarial rate of 3.80% (3.86% for IBC and 3.39% for DCIS). Negative estrogen receptor status (p = 0.0011) was the only clinical, pathologic, or treatment-related variable associated with IBTR for patients with IBC and young age (<50 years; p = 0.0096) and positive margin status (p = 0.0126) in those with DCIS. The percentage of breasts with good/excellent cosmetic results at 60 months (n = 371) was 90.6%. Symptomatic breast seromas were reported in 13.0% of cases, and 2.3% developed fat necrosis. A subset analysis of the first 400 consecutive cases enrolled was performed (352 with IBC, 48 DCIS). With a median follow-up of 60.5 months, the 5-year actuarial rate of IBTR was 3.04%. Conclusion: Treatment efficacy, cosmesis, and toxicity 5 years after treatment with APBI using the MammoSite device are good and similar to those reported with other forms of APBI with similar follow-up.« less

Validation of a measurement tool to assess awareness of breast cancer.

PubMed

Linsell, Louise; Forbes, Lindsay J L; Burgess, Caroline; Kapari, Marcia; Thurnham, Angela; Ramirez, Amanda J

2010-05-01

Until now, there has been no universally accepted and validated measure of breast cancer awareness. This study aimed to validate the new Breast Cancer Awareness Measure (BCAM) which assesses, using a self-complete questionnaire, knowledge of breast cancer symptoms and age-related risk, and frequency of breast checking. We measured the psychometric properties of the BCAM in 1035 women attending the NHS Breast Screening Programme: acceptability was assessed using a feedback questionnaire (n=292); sensitivity to change after an intervention promoting breast cancer awareness (n=576), and test-retest reliability (n=167). We also assessed readability, and construct validity using the 'known-groups' method. The readability of the BCAM was high. Over 90% of women found it acceptable. The BCAM was sensitive to change: there was an increase in the proportion of women obtaining the full score for breast cancer awareness one month after receiving the intervention promoting breast cancer awareness; this was greater among those who received a more intensive version (less intensive version (booklet): 9.3%, 95% confidence interval (CI): 4.5-14.1%; more intensive version (interaction with health professional plus booklet): 30%, 95% CI: 23.4-36.6%). Test-retest reliability of the BCAM was moderate to good for most items. Cancer experts had higher levels of cancer awareness than non-medical academics (50% versus 6%, p=0.001), indicating good construct validity. The BCAM is a valid and robust measure of breast cancer awareness suitable for use in surveys of breast cancer awareness in the general population and to evaluate the impact of awareness-raising interventions. Copyright (c) 2010 Elsevier Ltd. All rights reserved.

Structural Insights into Drug Processing by Human Carboxylesterase 1: Tamoxifen, Mevastatin, and Inhibition by Benzil

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fleming, Christopher D.; Bencharit, Sompop; Edwards, Carol C.

2010-07-19

Human carboxylesterase 1 (hCE1) exhibits broad substrate specificity and is involved in xenobiotic processing and endobiotic metabolism. We present and analyze crystal structures of hCE1 in complexes with the cholesterol-lowering drug mevastatin, the breast cancer drug tamoxifen, the fatty acyl ethyl ester (FAEE) analogue ethyl acetate, and the novel hCE1 inhibitor benzil. We find that mevastatin does not appear to be a substrate for hCE1, and instead acts as a partially non-competitive inhibitor of the enzyme. Similarly, we show that tamoxifen is a low micromolar, partially non-competitive inhibitor of hCE1. Further, we describe the structural basis for the inhibition ofmore » hCE1 by the nanomolar-affinity dione benzil, which acts by forming both covalent and non-covalent complexes with the enzyme. Our results provide detailed insights into the catalytic and non-catalytic processing of small molecules by hCE1, and suggest that the efficacy of clinical drugs may be modulated by targeted hCE1 inhibitors.« less

Structural insights into drug processing by human carboxylesterase 1: tamoxifen, mevastatin, and inhibition by benzil.

PubMed

Fleming, Christopher D; Bencharit, Sompop; Edwards, Carol C; Hyatt, Janice L; Tsurkan, Lyudmila; Bai, Feng; Fraga, Charles; Morton, Christopher L; Howard-Williams, Escher L; Potter, Philip M; Redinbo, Matthew R

2005-09-09

Human carboxylesterase 1 (hCE1) exhibits broad substrate specificity and is involved in xenobiotic processing and endobiotic metabolism. We present and analyze crystal structures of hCE1 in complexes with the cholesterol-lowering drug mevastatin, the breast cancer drug tamoxifen, the fatty acyl ethyl ester (FAEE) analogue ethyl acetate, and the novel hCE1 inhibitor benzil. We find that mevastatin does not appear to be a substrate for hCE1, and instead acts as a partially non-competitive inhibitor of the enzyme. Similarly, we show that tamoxifen is a low micromolar, partially non-competitive inhibitor of hCE1. Further, we describe the structural basis for the inhibition of hCE1 by the nanomolar-affinity dione benzil, which acts by forming both covalent and non-covalent complexes with the enzyme. Our results provide detailed insights into the catalytic and non-catalytic processing of small molecules by hCE1, and suggest that the efficacy of clinical drugs may be modulated by targeted hCE1 inhibitors.

Clinical impact of IMPORT HIGH trial (CRUK/06/003) on breast radiotherapy practices in the United Kingdom

PubMed Central

Ciurlionis, Laura; Kirby, Anna M; Locke, Imogen; Venables, Karen; Yarnold, John R; Titley, Jenny; Bliss, Judith; Coles, Charlotte E

2015-01-01

Objective: IMPORT HIGH is a multicentre randomized UK trial testing dose-escalated intensity-modulated radiotherapy (IMRT) after tumour excision in females with early breast cancer and higher than average local recurrence risk. A survey was carried out to investigate the impact of this trial on the adoption of advanced breast radiotherapy (RT) techniques in the UK. Methods: A questionnaire was sent to all 26 IMPORT HIGH recruiting RT centres to determine whether the trial has influenced non-trial breast RT techniques in terms of volume delineation, dosimetry, treatment delivery and verification. In order to compare the clinical practice of breast RT between IMPORT HIGH and non–IMPORT HIGH centres, parts of the Royal College of Radiologists (RCR) breast RT audit result were used in this study. Results: 26/26 participating centres completed the questionnaire. After joining the trial, the number of centres routinely using tumour bed clips to guide whole-breast RT rose from 5 (19%) to 21 (81%). 20/26 (77%) centres now contour target volumes and organs at risk (OARs) in some or all patients compared with 14 (54%) before the trial. 14/26 (54%) centres offer inverse-planned IMRT for selected non-trial patients with breast cancer, and 10/14 (71%) have adopted the IMPORT HIGH trial protocol for target volume and OARs dose constraints. Only 2/26 (8%) centres used clip information routinely for breast treatment verification prior to IMPORT HIGH, a minority that has since risen to 7/26 (27%). Data on 1386 patients was included from the RCR audit. This suggested that more cases from IMPORT HIGH centres had surgical clips implanted (83 vs 67%), were treated using CT guided planning with full three-dimensional dose compensation (100 vs 75%), and were treated with photon boost RT (30 vs 8%). Conclusion: The study suggests that participation in the IMPORT HIGH trial has played an important part in providing the guidance and support networks needed for the safe integration of advanced RT techniques, where appropriate, as a standard of care for breast cancer patients treated at participating cancer centres. Advances in knowledge: We investigated the impact of the IMPORT HIGH trial on the adoption of advanced breast RT techniques in the UK and the trial has influenced non-trial breast RT techniques in terms of volume delineation, dosimetry, treatment delivery and verification. PMID:26492402

Clinical impact of IMPORT HIGH trial (CRUK/06/003) on breast radiotherapy practices in the United Kingdom.

PubMed

Tsang, Yat; Ciurlionis, Laura; Kirby, Anna M; Locke, Imogen; Venables, Karen; Yarnold, John R; Titley, Jenny; Bliss, Judith; Coles, Charlotte E

2015-01-01

IMPORT HIGH is a multicentre randomized UK trial testing dose-escalated intensity-modulated radiotherapy (IMRT) after tumour excision in females with early breast cancer and higher than average local recurrence risk. A survey was carried out to investigate the impact of this trial on the adoption of advanced breast radiotherapy (RT) techniques in the UK. A questionnaire was sent to all 26 IMPORT HIGH recruiting RT centres to determine whether the trial has influenced non-trial breast RT techniques in terms of volume delineation, dosimetry, treatment delivery and verification. In order to compare the clinical practice of breast RT between IMPORT HIGH and non-IMPORT HIGH centres, parts of the Royal College of Radiologists (RCR) breast RT audit result were used in this study. 26/26 participating centres completed the questionnaire. After joining the trial, the number of centres routinely using tumour bed clips to guide whole-breast RT rose from 5 (19%) to 21 (81%). 20/26 (77%) centres now contour target volumes and organs at risk (OARs) in some or all patients compared with 14 (54%) before the trial. 14/26 (54%) centres offer inverse-planned IMRT for selected non-trial patients with breast cancer, and 10/14 (71%) have adopted the IMPORT HIGH trial protocol for target volume and OARs dose constraints. Only 2/26 (8%) centres used clip information routinely for breast treatment verification prior to IMPORT HIGH, a minority that has since risen to 7/26 (27%). Data on 1386 patients was included from the RCR audit. This suggested that more cases from IMPORT HIGH centres had surgical clips implanted (83 vs 67%), were treated using CT guided planning with full three-dimensional dose compensation (100 vs 75%), and were treated with photon boost RT (30 vs 8%). The study suggests that participation in the IMPORT HIGH trial has played an important part in providing the guidance and support networks needed for the safe integration of advanced RT techniques, where appropriate, as a standard of care for breast cancer patients treated at participating cancer centres. We investigated the impact of the IMPORT HIGH trial on the adoption of advanced breast RT techniques in the UK and the trial has influenced non-trial breast RT techniques in terms of volume delineation, dosimetry, treatment delivery and verification.

Network-based approach to identify prognostic biomarkers for estrogen receptor-positive breast cancer treatment with tamoxifen.

PubMed

Liu, Rong; Guo, Cheng-Xian; Zhou, Hong-Hao

2015-01-01

This study aims to identify effective gene networks and prognostic biomarkers associated with estrogen receptor positive (ER+) breast cancer using human mRNA studies. Weighted gene coexpression network analysis was performed with a complex ER+ breast cancer transcriptome to investigate the function of networks and key genes in the prognosis of breast cancer. We found a significant correlation of an expression module with distant metastasis-free survival (HR = 2.25; 95% CI .21.03-4.88 in discovery set; HR = 1.78; 95% CI = 1.07-2.93 in validation set). This module contained genes enriched in the biological process of the M phase. From this module, we further identified and validated 5 hub genes (CDK1, DLGAP5, MELK, NUSAP1, and RRM2), the expression levels of which were strongly associated with poor survival. Highly expressed MELK indicated poor survival in luminal A and luminal B breast cancer molecular subtypes. This gene was also found to be associated with tamoxifen resistance. Results indicated that a network-based approach may facilitate the discovery of biomarkers for the prognosis of ER+ breast cancer and may also be used as a basis for establishing personalized therapies. Nevertheless, before the application of this approach in clinical settings, in vivo and in vitro experiments and multi-center randomized controlled clinical trials are still needed.

Dose profiles for lung and breast regions at prospective and retrospective CT coronary angiography using optically stimulated luminescence dosimeters on a 64-detector CT scanner.

PubMed

Funama, Yoshinori; Taguchi, Katsuyuki; Utsunomiya, Daisuke; Oda, Seitaro; Murasaki, Hiroo; Yamashita, Yasuyuki; Awai, Kazuo

2012-01-01

The purpose of our study was to acquire dose profiles at critical organs of lung and breast regions using optically stimulated luminescence (OSL) dosimeters; assess the actual radiation dose delivered at retrospective and prospective computed tomography coronary angiography (CTCA). Using a chest CT phantom we applied a prospectively-gated step-and-shoot- and a retrospectively-gated helical mode on a 64-detector row CT scanner. Retrospective scan mode was used with and without electrocardiogram (ECG) based tube current modulation. OSL dosimeters were used to measure dose profiles. In the both scan modes we acquired dose profiles and determined the mean and maximum dose in left lung and in left breast regions. In prospective mode, the mean dose was 21.53 mGy in left lung- and 23.59 mGy in left breast region. With respect to the retrospective mode, the mean dose with tube current modulation was 38.63 mGy for left lung- and 46.02 mGy for left breast region, i.e. 0.56 and 0.55 times lower than the mean dose without modulation. The OSL dosimeter is useful for measurement of the actual radiation dose along z-axis at lung and breast regions in the prospective and the retrospective CTCA. Copyright © 2011 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

Nested Nanotherapeutics for Drug Synergy Enhancement in Breast Cancer Therapy

DTIC Science & Technology

2014-09-01

completion of the proposed aims has resulted in the development of a truly innovative nanoparticle platform for synergistic enhancement in breast cancer ...of nested nanoparticles and intracellular release in MCF-7 breast cancer cells. a. Confocal microscopy of MCF-7 breast cancer cells at... nanoparticle accumulation over time in MCF-7 breast cancer cells. d. Mean fluorescence intensity over time in MCF-7 breast cancer cells as determined by

MR-guided high-intensity focused ultrasound ablation of breast cancer with a dedicated breast platform.

PubMed

Merckel, Laura G; Bartels, Lambertus W; Köhler, Max O; van den Bongard, H J G Desirée; Deckers, Roel; Mali, Willem P Th M; Binkert, Christoph A; Moonen, Chrit T; Gilhuijs, Kenneth G A; van den Bosch, Maurice A A J

2013-04-01

Optimizing the treatment of breast cancer remains a major topic of interest. In current clinical practice, breast-conserving therapy is the standard of care for patients with localized breast cancer. Technological developments have fueled interest in less invasive breast cancer treatment. Magnetic resonance-guided high-intensity focused ultrasound (MR-HIFU) is a completely noninvasive ablation technique. Focused beams of ultrasound are used for ablation of the target lesion without disrupting the skin and subcutaneous tissues in the beam path. MRI is an excellent imaging method for tumor targeting, treatment monitoring, and evaluation of treatment results. The combination of HIFU and MR imaging offers an opportunity for image-guided ablation of breast cancer. Previous studies of MR-HIFU in breast cancer patients reported a limited efficacy, which hampered the clinical translation of this technique. These prior studies were performed without an MR-HIFU system specifically developed for breast cancer treatment. In this article, a novel and dedicated MR-HIFU breast platform is presented. This system has been designed for safe and effective MR-HIFU ablation of breast cancer. Furthermore, both clinical and technical challenges are discussed, which have to be solved before MR-HIFU ablation of breast cancer can be implemented in routine clinical practice.

Monitoring of hemodynamic changes induced in the healthy breast through inspired gas stimuli with MR-guided diffuse optical imaging

PubMed Central

Carpenter, C. M.; Rakow-Penner, R.; Jiang, S.; Pogue, B. W.; Glover, G. H.; Paulsen, K. D.

2010-01-01

Purpose: The modulation of tissue hemodynamics has important clinical value in medicine for both tumor diagnosis and therapy. As an oncological tool, increasing tissue oxygenation via modulation of inspired gas has been proposed as a method to improve cancer therapy and determine radiation sensitivity. As a radiological tool, inducing changes in tissue total hemoglobin may provide a means to detect and characterize malignant tumors by providing information about tissue vascular function. The ability to change and measure tissue hemoglobin and oxygenation concentrations in the healthy breast during administration of three different types of modulated gas stimuli (oxygen∕carbogen, air∕carbogen, and air∕oxygen) was investigated. Methods: Subjects breathed combinations of gases which were modulated in time. MR-guided diffuse optical tomography measured total hemoglobin and oxygen saturation in the breast every 30 s during the 16 min breathing stimulus. Metrics of maximum correlation and phase lag were calculated by cross correlating the measured hemodynamics with the stimulus. These results were compared to an air∕air control to determine the hemodynamic changes compared to the baseline physiology. Results: This study demonstrated that a gas stimulus consisting of alternating oxygen∕carbogen induced the largest and most robust hemodynamic response in healthy breast parenchyma relative to the changes that occurred during the breathing of room air. This stimulus caused increases in total hemoglobin and oxygen saturation during the carbogen phase of gas inhalation, and decreases during the oxygen phase. These findings are consistent with the theory that oxygen acts as a vasoconstrictor, while carbogen acts as a vasodilator. However, difficulties in inducing a consistent change in tissue hemoglobin and oxygenation were observed because of variability in intersubject physiology, especially during the air∕oxygen or air∕carbogen modulated breathing protocols. Conclusions: MR-guided diffuse optical imaging is a unique tool that can measure tissue hemodynamics in the breast during modulated breathing. This technique may have utility in determining the therapeutic potential of pretreatment tissue oxygenation or in investigating vascular function. Future gas modulation studies in the breast should use a combination of oxygen and carbogen as the functional stimulus. Additionally, control measures of subject physiology during air breathing are critical for robust measurements. PMID:20443485

Optimism and depression: a new look at social support as a mediator among women at risk for breast cancer.

PubMed

Garner, Melissa J; McGregor, Bonnie A; Murphy, Karly M; Koenig, Alex L; Dolan, Emily D; Albano, Denise

2015-12-01

Breast cancer risk is a chronic stressor associated with depression. Optimism is associated with lower levels of depression among breast cancer survivors. However, to our knowledge, no studies have explored the relationship between optimism and depression among women at risk for breast cancer. We hypothesized that women at risk for breast cancer who have higher levels of optimism would report lower levels of depression and that social support would mediate this relationship. Participants (N = 199) with elevated distress were recruited from the community and completed self-report measures of depression, optimism, and social support. Participants were grouped based on their family history of breast cancer. Path analysis was used to examine the cross-sectional relationship between optimism, social support, and depressive symptoms in each group. Results indicated that the variance in depressive symptoms was partially explained through direct paths from optimism and social support among women with a family history of breast cancer. The indirect path from optimism to depressive symptoms via social support was significant (β = -.053; 90% CI = -.099 to -.011, p = .037) in this group. However, among individuals without a family history of breast cancer, the indirect path from optimism to depressive symptoms via social support was not significant. These results suggest that social support partially mediates the relationship between optimism and depression among women at risk for breast cancer. Social support may be an important intervention target to reduce depression among women at risk for breast cancer. Copyright © 2015 John Wiley & Sons, Ltd.

Pain and uterine contractions during breast feeding in the immediate post-partum period increase with parity.

PubMed

Holdcroft, Anita; Snidvongs, Saowarat; Cason, Angie; Doré, Caroline J; Berkley, Karen J

2003-08-01

Previous research has shown that post-partum abdominal pain is greater in multiparous than primiparous women (Murray and Holdcroft, 1989). Although breast feeding in the immediate post-partum period induces uterine contractions and abdominal pain, it is unknown how parity influences the contractions. Here, a structured questionnaire that included the McGill Pain Questionnaire (total pain intensity index, TPI) and visual analog scales (VAS) was used to evaluate the intensity, location, referred tenderness (hyperalgesia), descriptor, and temporal characteristics of pain during breast feeding up to three days after uncomplicated vaginal delivery. Three groups of women were studied: primiparous (n=25); low parity (1-2 prior births; n=14); high parity (3-5 prior births; n=11). Uterine contractions during breast feeding were recorded using tocodynamometry in some women from each group (n=17, 6, 7, respectively). For comparison, an identical questionnaire was used to evaluate pains the women remembered experiencing during menstruation in the year immediately preceding the current pregnancy. During breast feeding, nearly all women (96%) reported deep pain primarily at three sites: lower abdomen, low back, and breast, with associated referred hyperalgesia in 62% of them. The intensity of these pains increased significantly with parity (P<0.001), along with an increase in the number of pain sites (P=0.03), mainly in lower abdomen and back, but not breast. Similarly, both the mean duration and number of uterine contractions increased significantly with parity (P<0.001). Furthermore, the mean duration of contractions correlated significantly with the pain scores (P=0.03 [VAS] and P=0.006 [TPI]). In contrast with pain during breast feeding, the intensity of pain during menstruation did not change with parity. These results demonstrate that pain, referred pain, and uterine contractions during breast feeding in the immediate post-partum period increase with parity, suggesting that childbirth can induce central neural changes that increase predisposition for pain during the post-partum period.

Giant fibroadenoma presenting like fungating breast cancer in a Nigerian teenager.

PubMed

Arowolo, O A; Akinkuolie, A A; Adisa, A O; Obonna, G C; Olasode, B J

2013-03-01

Giant fibroadenoma of the breast is a rare benign breast tumour which seldom grows to a giant size, it is even rarer for this benign tumour to grow rapidly, ulcerate spontaneously and present like a fungating breast tumour in a way mimicking breast cancer. This is a presentation of a 14 year old premenarchal girl with a massive ulcerating and fungating left breast mass that was initially thought to be a fungating locally advanced breast carcinoma on clinical examination. Further examination of the morphology of the resected surgical specimen and histological examination confirmed it to be giant fibroadenoma of the breast. It was successfully managed by partial mastectomy and breast reconstruction with an excellent result and a high degree of patient satisfaction was achieved. Though a rare clinical entity benign breast tumour can present like a fungating breast cancer and this must be bore in mind especially in young adolescent patients presenting with ulcerating breast tumour.

Role of MicroRNA Regulation in Obesity-Associated Breast Cancer: Nutritional Perspectives.

PubMed

Kasiappan, Ravi; Rajarajan, Dheeran

2017-11-01

Breast cancer is the most common malignancy diagnosed in women, and the incidence of breast cancer is increasing every year. Obesity has been identified as one of the major risk factors for breast cancer progression. The mechanisms by which obesity contributes to breast cancer development is not yet understood; however, there are a few mechanisms counted as potential producers of breast cancer in obesity, including insulin resistance, chronic inflammation and inflammatory cytokines, adipokines, and sex hormones. Recent emerging evidence suggests that alterations in microRNA (miRNA) expressions are found in several diseases, including breast cancer and obesity; however, miRNA roles in obesity-linked breast cancer are beginning to unravel. miRNAs are thought to be potential noninvasive biomarkers for diagnosis and prognosis of cancer patients with comorbid conditions of obesity as well as therapeutic targets. Recent studies have evidenced that nutrients and other dietary factors protect against cancer and obesity through modulation of miRNA expressions. Herein, we summarize a comprehensive overview of up-to-date information related to miRNAs and their molecular targets involved in obesity-associated breast cancer. We also address the mechanisms by which dietary factors modulate miRNA expression and its protective roles in obesity-associated breast cancer. It is hoped that this review would provide new therapeutic strategies for the treatment of obesity-associated breast cancer to reduce the burden of breast cancer. © 2017 American Society for Nutrition.

Involvement of Tyrosine Phosphatses in Insulin Signaling and Apoptosis in Breast Cancer

DTIC Science & Technology

2003-06-01

a role in both diseases and investigated the role of a tyrosine phosphatase, PTP1B , previously reported to be a regulator of both insulin signaling...and breast cancer. We noted that calcium flux into breast cancer cells suppressed tyrosine phosphorylation and induced partial proteolysis of PTP1B ...resulting in liberation of PTP1B from its membranous anchor. To investigate the role of the cytoplasmic form of PTP1B (tPTP1B) in breast cancer cells

Single-cycle high-intensity electromagnetic pulse generation in the interaction of a plasma wakefield with regular nonlinear structures.

PubMed

Bulanov, S S; Esirkepov, T Zh; Kamenets, F F; Pegoraro, F

2006-03-01

The interaction of regular nonlinear structures (such as subcycle solitons, electron vortices, and wake Langmuir waves) with a strong wake wave in a collisionless plasma can be exploited in order to produce ultrashort electromagnetic pulses. The electromagnetic field of the nonlinear structure is partially reflected by the electron density modulations of the incident wake wave and a single-cycle high-intensity electromagnetic pulse is formed. Due to the Doppler effect the length of this pulse is much shorter than that of the nonlinear structure. This process is illustrated with two-dimensional particle-in-cell simulations. The considered laser-plasma interaction regimes can be achieved in present day experiments and can be used for plasma diagnostics.

Energy modulated electron therapy using a few leaf electron collimator in combination with IMRT and 3D-CRT: Monte Carlo-based planning and dosimetric evaluation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Al-Yahya, Khalid; Schwartz, Matthew; Shenouda, George

2005-09-15

Energy modulated electron therapy (EMET) based on Monte Carlo dose calculation is a promising technique that enhances the treatment planning and delivery of superficially located tumors. This study investigated the application of EMET using a novel few-leaf electron collimator (FLEC) in head and neck and breast sites in comparison with three-dimensional conventional radiation therapy (3D-CRT) and intensity modulated radiation therapy (IMRT) techniques. Treatment planning was performed for two parotid cases and one breast case. Four plans were compared for each case: 3D-CRT, IMRT, 3D-CRT in conjunction with EMET (EMET-CRT), and IMRT in conjunction with EMET (EMET-IMRT), all of which weremore » performed and calculated with Monte Carlo techniques. For all patients, dose volume histograms (DVHs) were obtained for all organs of interest and the DVHs were used as a means of comparing the plans. Homogeneity and conformity of dose distributions were calculated, as well as a sparing index that compares the effect of the low isodose lines. In addition, the whole-body dose equivalent (WBDE) was estimated for each plan. Adding EMET delivered with the FLEC to 3D-CRT improves sparing of normal tissues. For the two head and neck cases, the mean dose to the contralateral parotid and brain stem was reduced relative to IMRT by 43% and 84%, and by 57% and 71%, respectively. Improved normal tissue sparing was quantified as an increase in sparing index of 47% and 30% for the head and neck and the breast cases, respectively. Adding EMET to either 3D-CRT or IMRT results in preservation of target conformity and dose homogeneity. When adding EMET to the treatment plan, the WBDE was reduced by between 6% and 19% for 3D-CRT and by between 21% and 33% for IMRT, while WBDE for EMET-CRT was reduced by up to 72% when compared with IMRT. FLEC offers a practical means of delivering modulated electron therapy. Although adding EMET delivered using the FLEC results in perturbation of target conformity when compared to IMRT, it significantly improves normal tissue sparing while offering enhanced target conformity to the 3D-CRT planning. The addition of EMET systematically leads to a reduction in WBDE especially when compared with IMRT.« less

Diaper dermatitis care of newborns human breast milk or barrier cream.

PubMed

Gozen, Duygu; Caglar, Seda; Bayraktar, Sema; Atici, Funda

2014-02-01

To establish the effectiveness of human breast milk and barrier cream (40% zinc oxide with cod liver oil formulation) applied for the skincare of newborns in the neonatal intensive care unit on the healing process of diaper dermatitis. Diaper dermatitis is the most common dermatological condition in newborns who are cared for in the neonatal intensive care unit. Recently, there are several kinds of complementary skincare methods suggested for newborns, such as sunflower oil, human breast milk, etc. Also, some chemical formulations are still being used in many neonatal intensive care units. Randomised controlled, prospective, experimental. This study was carried out with a population including term and preterm newborns who developed diaper rash while being treated in the neonatal intensive care unit of a university hospital in Istanbul between February-October 2010. On completion of the research, a total of 63 newborns from human breast milk (n = 30) and barrier cream (n = 33) groups were contacted. Genders, mean gestation weeks, feeding method, antibiotic use, diaper area cleansing methods, diaper brands and prelesion scores of newborns in both groups were found to be comparable (p > 0·05). There was no statistically significant difference (p = 0.294) between the groups in terms of mean number of clinical improvement days, but postlesion score of the barrier cream group was statistically significantly lower (p = 0·002) than the human breast milk group. Barrier cream delivers more effective results than treatment with human breast milk, particularly in the treatment of newborns with moderate to severe dermatitis in the result of the study. This study will shed light on nursing care of skin for newborns who are treated in neonatal intensive care unit. © 2013 Blackwell Publishing Ltd.

Energy intake from human milk covers the requirement of 6-month-old Senegalese exclusively breast-fed infants.

PubMed

Agne-Djigo, Anta; Kwadjode, Komlan M; Idohou-Dossou, Nicole; Diouf, Adama; Guiro, Amadou T; Wade, Salimata

2013-11-01

Exclusive breast-feeding until 6 months is advised by the WHO as the best practice to feed infants. Yet, some studies have suggested a gap between energy requirements and the energy provided by human milk for many infants at 6 months. In order to assess the adequacy of WHO recommendations in 6-month-old Senegalese lactating infants, a comprehensive study was designed to measure human milk intake by the dose-to-the mother 2H2O turnover method. Infants’ energy intakes were calculated using daily breast milk intake and the energy content of milk was estimated on the basis of creamatocrit. Of the fifty-nine mother–infant pairs enrolled, fifteen infants were exclusively breast-fed (Ex) while forty-four were partially breast-fed (Part). Infants’ breast milk intake was significantly higher in the Ex group (993 (SD 135) g/d, n 15) compared with the Part group (828 (SD 222) g/d, n 44, P¼0·009). Breast milk energy content as well as infants' growth was comparable in both groups. However, infants’ energy intake from human milk was significantly higher (364 (SD 50) kJ/kg per d (2586 (SD 448) kJ/d)) in the Ex group than in the Part group (289 (SD 66) kJ/kg per d (2150 (SD 552) kJ/d), P,0·01). Compared with WHO recommendations, the results demonstrate that energy intake from breast milk was low in partially breast-fed infants while exclusively breast-fed 6-month-old Senegalese infants received adequate energy from human milk alone, the most complete food for infants. Therefore, advocacy of exclusive breast-feeding until 6 months should be strengthened.

Using molecular functional networks to manifest connections between obesity and obesity-related diseases

PubMed Central

Yang, Jialiang; Qiu, Jing; Wang, Kejing; Zhu, Lijuan; Fan, Jingjing; Zheng, Deyin; Meng, Xiaodi; Yang, Jiasheng; Peng, Lihong; Fu, Yu; Zhang, Dahan; Peng, Shouneng; Huang, Haiyun; Zhang, Yi

2017-01-01

Obesity is a primary risk factor for many diseases such as certain cancers. In this study, we have developed three algorithms including a random-walk based method OBNet, a shortest-path based method OBsp and a direct-overlap method OBoverlap, to reveal obesity-disease connections at protein-interaction subnetworks corresponding to thousands of biological functions and pathways. Through literature mining, we also curated an obesity-associated disease list, by which we compared the methods. As a result, OBNet outperforms other two methods. OBNet can predict whether a disease is obesity-related based on its associated genes. Meanwhile, OBNet identifies extensive connections between obesity genes and genes associated with a few diseases at various functional modules and pathways. Using breast cancer and Type 2 diabetes as two examples, OBNet identifies meaningful genes that may play key roles in connecting obesity and the two diseases. For example, TGFB1 and VEGFA are inferred to be the top two key genes mediating obesity-breast cancer connection in modules associated with brain development. Finally, the top modules identified by OBNet in breast cancer significantly overlap with modules identified from TCGA breast cancer gene expression study, revealing the power of OBNet in identifying biological processes involved in the disease. PMID:29156709

Breast-feeding Duration: Early Weaning-Do We Sufficiently Consider the Risk Factors?

PubMed

Karall, Daniela; Ndayisaba, Jean-Pierre; Heichlinger, Angelika; Kiechl-Kohlendorfer, Ursula; Stojakovic, Sarah; Leitner, Hermann; Scholl-Bürgi, Sabine

2015-11-01

Breast-feeding is the recommended form of nutrition for the first 6 months. This target is unmet, however, in most industrialized regions. We evaluated aspects of breast-feeding in a cohort of mother-baby dyads. Breast-feeding practices in 555 mother-baby dyads were prospectively studied for 24 months (personal interview at birth and 7 structured telephone interviews). Of the babies, 71.3% were fully breast-fed on discharge from maternity hospitals and 11.9% were partially breast-feed. Median breast-feeding duration was 6.93 (interquartile range 2.57-11.00) months; for full (exclusive) breast-feeding 5.62 (interquartile range 3.12-7.77) months; 61.7% received supplemental feedings during the first days of life. Breast-feeding duration in babies receiving supplemental feedings was significantly shorter (median 5.06 months versus 8.21 months, P < 0.001). At 6 months, 9.4% of the mothers were exclusively and 39.5% partially breast-feeding. Risk factors for early weaning were early supplemental feedings (odds ratio [OR] 2.87, 95% CI 1.65-4.98), perceived milk insufficiency (OR 7.35, 95% CI 3.59-15.07), low breast-feeding self-efficacy (a mother's self-confidence in her ability to adequately feed her baby) (OR 3.42, 95% CI 1.48-7.94), lower maternal age (OR 3.89, 95% CI 1.45-10.46), and lower education level of the mother (OR 7.30, 95% CI 2.93-18.20). The recommended full breast-feeding duration of the first 6 months of life was not reached. Sociodemographic variables and factors directly related to breast-feeding practices play an important role on breast-feeding duration/weaning in our region. Understanding risk factors will provide insights to give better support to mothers and prevent short- and long-term morbidity following early weaning.

Detection and modulation of capsaicin perception in the human oral cavity.

PubMed

Smutzer, Gregory; Jacob, Jeswin C; Tran, Joseph T; Shah, Darshan I; Gambhir, Shilpa; Devassy, Roni K; Tran, Eric B; Hoang, Brian T; McCune, Joseph F

2018-05-09

Capsaicin causes a burning or spicy sensation when this vanilloid compound comes in contact with trigeminal neurons of the tongue. This compound has low solubility in water, which presents difficulties in examining the psychophysical properties of capsaicin by standard aqueous chemosensory tests. This report describes a new approach that utilizes edible strips for delivering precise amounts of capsaicin to the human oral cavity for examining threshold and suprathreshold amounts of this irritant. When incorporated into pullulan-based edible strips, recognition thresholds for capsaicin occurred over a narrow range, with a mean value near 1 nmol. When incorporated into edible strips at suprathreshold amounts, capsaicin yielded robust intensity values that were readily measured in our subject population. Maximal capsaicin intensity was observed 20 s after strips dissolved on the tongue surface, and then decreased in intensity. Suprathreshold studies showed that complete blockage of nasal airflow diminished capsaicin perception in the oral cavity. Oral rinses with vanillin-linoleic acid emulsions decreased mean intensity values for capsaicin by approximately 75%, but only modestly affected recognition threshold values. Also, oral rinses with isointense amounts of aqueous sucrose and sucralose solutions decreased mean intensity values for capsaicin by approximately 50%. In addition, this decrease in capsaicin intensity following an oral rinse with sucrose was partially reversed by the sweet taste inhibitor lactisole. These results suggest that blockage of nasal airflow, vanillin, sucrose, and sucralose modulate capsaicin perception in the human oral cavity. The results further suggest a chemosensory link between receptor cells that detect sweet taste stimuli and trigeminal neurons that detect capsaicin. Copyright © 2018 Elsevier Inc. All rights reserved.

Feasibility and effects of a combined adjuvant high-intensity interval/strength training in breast cancer patients: a single-center pilot study.

PubMed

Schulz, Sebastian Viktor Waldemar; Laszlo, Roman; Otto, Stephanie; Prokopchuk, Dmytro; Schumann, Uwe; Ebner, Florian; Huober, Jens; Steinacker, Jürgen Michael

2018-06-01

To evaluate feasibility of an exercise intervention consisting of high-intensity interval endurance and strength training in breast cancer patients. Twenty-six women with nonmetastatic breast cancer were consecutively assigned to the exercise intervention- (n= 15, mean age 51.9 ± 9.8 years) and the control group (n = 11, mean age 56.9 ± 7.0 years). Cardiopulmonary exercise testing that included lactate sampling, one-repetition maximum tests and a HADS-D questionnaire were used to monitor patients both before and after a supervised six weeks period of either combined high-intensity interval endurance and strength training (intervention group, twice a week) or leisure training (control group). Contrarily to the control group, endurance (mean change of VO 2 , peak 12.0 ± 13.0%) and strength performance (mean change of cumulative load 25.9 ± 11.2%) and quality of life increased in the intervention group. No training-related adverse events were observed. Our guided exercise intervention could be used effectively for initiation and improvement of performance capacity and quality of life in breast cancer patients in a relatively short time. This might be especially attractive during medical treatment. Long-term effects have to be evaluated in randomized controlled studies also with a longer follow-up. Implications for Rehabilitation High-intensity interval training allows improvement of aerobic capacity within a comparable short time. Standard leisure training in breast cancer patients is rather suitable for the maintenance of performance capacity and quality of life. Guided high-intensity interval training combined with strength training can be used effectively for the improvement of endurance and strength capacity and also quality of life. After exclusion of contraindications, guided adjuvant high-intensity interval training combined with strength training can be safely used in breast cancer patients.

Tumor response ratio predicts overall survival in breast cancer patients treated with neoadjuvant chemotherapy.

PubMed

Miller, Marian; Ottesen, Rebecca A; Niland, Joyce C; Kruper, Laura; Chen, Steven L; Vito, Courtney

2014-10-01

Neoadjuvant chemotherapy (NAC) is commonly used to treat locally advanced breast cancer. Pathologic complete response (pCR) predicts improved overall survival (OS); however, prognosis of patients with partial response remains unclear. We evaluated whether tumor response ratio (TRR) is a better predictor of OS than current staging methods. Using the National Comprehensive Cancer Network Breast Cancer Outcomes Database, we identified patients with stage I-III breast cancer who had NAC and pretreatment imaging at City of Hope (1997-2010). Patient demographics, tumor characteristics, and OS were analyzed. TRR was calculated as residual in-breast disease divided by size on pre-NAC imaging. Four TRR groups were stratified; TRR 0 (pCR), TRR > 0-0.4 (strong partial response, SPR), TRR > 0.4-1.0 (weak partial response, WPR), or TRR > 1.0 (tumor growth, TG). OS was estimated by the Kaplan-Meier method and tested by the log-rank test. Cox regression was performed to evaluate associations between OS and TRR in a multivariable analysis while controlling for potential confounders. There were 218 eligible patients identified; 59 (27 %) had pCR, 61 (28 %) SPR, 72 (33 %) WPR, and 26 (12 %) TG. Five-year OS decreased continuously with increasing TRR:pCR (90 %), SPR (79 %), WPR (66 %), and TG (60 %). TRR was the only measure that significantly predicted OS (p = 0.0035); pathologic stage (p = 0.23) and pre-NAC clinical tumor stage (cT) (p = 0.87) were not significant. TRR continued to be statistically significant by multivariable analysis (p = 0.016). TRR takes into account both pretreatment and residual disease and more accurately predicts OS than pathologic stage and pre-NAC cT. TRR may be useful to more accurately assess prognosis and OS in breast cancer patients undergoing NAC.

Exposure to a specific time-varying electromagnetic field inhibits cell proliferation via cAMP and ERK signaling in cancer cells.

PubMed

Buckner, Carly A; Buckner, Alison L; Koren, Stan A; Persinger, Michael A; Lafrenie, Robert M

2018-04-01

Exposure to specific electromagnetic field (EMF) patterns can affect a variety of biological systems. We have shown that exposure to Thomas-EMF, a low-intensity, frequency-modulated (25-6 Hz) EMF pattern, inhibited growth and altered cell signaling in malignant cells. Exposure to Thomas-EMF for 1 h/day inhibited the growth of malignant cells including B16-BL6 mouse melanoma cells, MDA-MB-231, MDA-MB-468, BT-20, and MCF-7 human breast cancer and HeLa cervical cancer cells but did not affect non-malignant cells. The Thomas-EMF-dependent changes in cell proliferation were mediated by adenosine 3',5'-cyclic monophosphate (cAMP) and extracellular-signal-regulated kinase (ERK) signaling pathways. Exposure of malignant cells to Thomas-EMF transiently changed the level of cellular cAMP and promoted ERK phosphorylation. Pharmacologic inhibitors (SQ22536) and activators (forskolin) of cAMP production both blocked the ability of Thomas-EMF to inhibit cell proliferation, and an inhibitor of the MAP kinase pathway (PD98059) was able to partially block Thomas-EMF-dependent inhibition of cell proliferation. Genetic modulation of protein kinase A (PKA) in B16-BL6 cells also altered the effect of Thomas-EMF on cell proliferation. Cells transfected with the constitutively active form of PKA (PKA-CA), which interfered with ERK phosphorylation, also interfered with the Thomas-EMF effect on cell proliferation. The non-malignant cells did not show any EMF-dependent changes in cAMP levels, ERK phosphorylation, or cell growth. These data indicate that exposure to the specific Thomas-EMF pattern can inhibit the growth of malignant cells in a manner dependent on contributions from the cAMP and MAP kinase pathways. Bioelectromagnetics. 39;217-230, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Engineering Breast Cancer Microenvironments and 3D Bioprinting

PubMed Central

Belgodere, Jorge A.; King, Connor T.; Bursavich, Jacob B.; Burow, Matthew E.; Martin, Elizabeth C.; Jung, Jangwook P.

2018-01-01

The extracellular matrix (ECM) is a critical cue to direct tumorigenesis and metastasis. Although two-dimensional (2D) culture models have been widely employed to understand breast cancer microenvironments over the past several decades, the 2D models still exhibit limited success. Overwhelming evidence supports that three dimensional (3D), physiologically relevant culture models are required to better understand cancer progression and develop more effective treatment. Such platforms should include cancer-specific architectures, relevant physicochemical signals, stromal–cancer cell interactions, immune components, vascular components, and cell-ECM interactions found in patient tumors. This review briefly summarizes how cancer microenvironments (stromal component, cell-ECM interactions, and molecular modulators) are defined and what emerging technologies (perfusable scaffold, tumor stiffness, supporting cells within tumors and complex patterning) can be utilized to better mimic native-like breast cancer microenvironments. Furthermore, this review emphasizes biophysical properties that differ between primary tumor ECM and tissue sites of metastatic lesions with a focus on matrix modulation of cancer stem cells, providing a rationale for investigation of underexplored ECM proteins that could alter patient prognosis. To engineer breast cancer microenvironments, we categorized technologies into two groups: (1) biochemical factors modulating breast cancer cell-ECM interactions and (2) 3D bioprinting methods and its applications to model breast cancer microenvironments. Biochemical factors include matrix-associated proteins, soluble factors, ECMs, and synthetic biomaterials. For the application of 3D bioprinting, we discuss the transition of 2D patterning to 3D scaffolding with various bioprinting technologies to implement biophysical cues to model breast cancer microenvironments. PMID:29881724

Hispolon inhibits the growth of estrogen receptor positive human breast cancer cells through modulation of estrogen receptor alpha

DOE Office of Scientific and Technical Information (OSTI.GOV)

Jang, Eun Hyang; Jang, Soon Young; Cho, In-Hye

Human estrogen receptor α (ERα) is a nuclear transcription factor that is a major therapeutic target in breast cancer. The transcriptional activity of ERα is regulated by certain estrogen-receptor modulators. Hispolon, isolated from Phellinus linteus, a traditional medicinal mushroom called Sanghwang in Korea, has been used to treat various pathologies, such as inflammation, gastroenteric disorders, lymphatic diseases, and cancers. In this latter context, Hispolon has been reported to exhibit therapeutic efficacy against various cancer cells, including melanoma, leukemia, hepatocarcinoma, bladder cancer, and gastric cancer cells. However, ERα regulation by Hispolon has not been reported. In this study, we investigated themore » effects of Hispolon on the growth of breast cancer cells. We found that Hispolon decreased expression of ERα at both mRNA and the protein levels in MCF7 and T47D human breast cancer cells. Luciferase reporter assays showed that Hispolon decreased the transcriptional activity of ERα. Hispolon treatment also inhibited expression of the ERα target gene pS2. We propose that Hispolon, an anticancer drug extracted from natural sources, inhibits cell growth through modulation of ERα in estrogen-positive breast cancer cells and is a candidate for use in human breast cancer chemotherapy. - Highlights: • Hispolon decreased ERα expression at both mRNA and protein levels. • Hispolon decreased ERα transcriptional activity. • Hispolon treatment inhibited expression of ERα target gene pS2. • Shikonin is a candidate chemotherapeutic target in the treatment of human breast cancer.« less

Strut-adjusted volume implant (SAVI) brachytherapy-based accelerated partial breast irradiation (APBI) in African American women.

PubMed

Isbell, Amir; Dunmore-Griffith, Jacquelyn; Abayomi, Olubunmi

2017-02-01

To examine the clinical outcomes of postmenopausal African American (AA) women treated with strut-adjusted volume implant brachytherapy-based accelerated partial breast irradiation for early-stage node-negative breast cancer. From January 2011 through April 2015, a total of 50 AA patients, meeting criteria to receive APBI as defined by the National Surgical Adjuvant Breast and Bowel Project B-39 (NASBP B-39), completed treatment with the SAVI breast brachytherapy device at Howard University Hospital. 4% ipsilateral breast tumor recurrence and 2% breast cancer-specific mortality was observed. Median follow-up has been 3.8 years with a range of 0.29-4.69 years. Dosimetry parameters yielded a median V90 of 96.22% (range 77.86-105.00%), a median V150 of 31.27 cm 3 (range 23.30-49.15 mL), and a median V200 of 14.53 cm 3 (range 5.92-19.38 mL). Cosmesis was excellent. There were no infections, persistent seromas, fat necrosis, or telangiectasias observed to date. This study is the first study to describe the use of SAVI as APBI in an exclusively AA population. This study has demonstrated excellent local control in appropriately selected patients, similar clinical outcomes to the general population, and good to excellent cosmesis in AA women to date.

A planning comparison of 7 irradiation options allowed in RTOG 1005 for early-stage breast cancer.

PubMed

Chen, Guang-Pei; Liu, Feng; White, Julia; Vicini, Frank A; Freedman, Gary M; Arthur, Douglas W; Li, X Allen

2015-01-01

This study compared the 7 treatment plan options in achieving the dose-volume criteria required by the Radiation Therapy Oncology Group (RTOG) 1005 protocol. Dosimetry plans were generated for 15 representative patients with early-stage breast cancer (ESBC) based on the protocol-required dose-volume criteria for each of the following 7 treatment options: 3D conformal radiotherapy (3DCRT), whole-breast irradiation (WBI) plus 3DCRT lumpectomy boost, 3DCRT WBI plus electron boost, 3DCRT WBI plus intensity-modulated radiation therapy (IMRT) boost, IMRT WBI plus 3DCRT boost, IMRT WBI plus electron boost, IMRT WBI plus IMRT boost, and simultaneous integrated boost (SIB) with IMRT. A variety of dose-volume parameters, including target dose conformity and uniformity and normal tissue sparing, were compared for these plans. For the patients studied, all plans met the required acceptable dose-volume criteria, with most of them meeting the ideal criteria. When averaged over patients, most dose-volume goals for all plan options can be achieved with a positive gap of at least a few tenths of standard deviations. The plans for all 7 options are generally comparable. The dose-volume goals required by the protocol can in general be easily achieved. IMRT WBI provides better whole-breast dose uniformity than 3DCRT WBI does, but it causes no significant difference for the dose conformity. All plan options are comparable for lumpectomy dose uniformity and conformity. Patient anatomy is always an important factor when whole-breast dose uniformity and conformity and lumpectomy dose conformity are considered. Copyright © 2015 American Association of Medical Dosimetrists. Published by Elsevier Inc. All rights reserved.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Elyn H.; Mougalian, Sarah S.; Yale Cancer Center, New Haven, Connecticut

Purpose: Intensity modulated radiation therapy (IMRT) is a newer method of radiation therapy (RT) that has been increasingly adopted as an adjuvant treatment after breast-conserving surgery (BCS). IMRT may result in improved cosmesis compared to standard RT, although at greater expense. To investigate the adoption of IMRT, we examined trends and factors associated with IMRT in women under the age of 65 with early stage breast cancer. Methods and Materials: We performed a retrospective study of early stage breast cancer patients treated with BCS followed by whole-breast irradiation (WBI) who were ≤65 years old in the National Cancer Data Base frommore » 2004 to 2011. We used logistic regression to identify factors associated with receipt of IMRT (vs standard RT). Results: We identified 11,089 women with early breast cancer (9.6%) who were treated with IMRT and 104,448 (90.4%) who were treated with standard RT, after BCS. The proportion of WBI patients receiving IMRT increased yearly from 2004 to 2009, with 5.3% of WBI patients receiving IMRT in 2004 and 11.6% receiving IMRT in 2009. Further use of IMRT declined afterward, with the proportion remaining steady at 11.0% and 10.7% in 2010 and 2011, respectively. Patients treated in nonacademic community centers were more likely to receive IMRT (odds ratio [OR], 1.36; 95% confidence interval [CI], 1.30-1.43 for nonacademic vs academic center). Compared to privately insured patients, the uninsured patients (OR, 0.81; 95% CI, 0.70-0.95) and those with Medicaid insurance (OR, 0.87; 95% CI, 0.79-0.95) were less likely to receive IMRT. Conclusions: The use of IMRT rose from 2004 to 2009 and then stabilized. Important nonclinical factors associated with IMRT use included facility type and insurance status.« less

Contrast features of breast cancer in frequency-domain laser scanning mammography

NASA Astrophysics Data System (ADS)

Moesta, K. Thomas; Fantini, Sergio; Jess, Helge; Totkas, Susan; Franceschini, Maria-Angela; Kaschke, Michael; Schlag, Peter M.

1998-04-01

Frequency-domain optical mammography has been advocated to improve contrast and thus cancer detectability in breast transillumination. To the best of our knowledge, this report provides the first systematic clinical results of a frequency-domain laser scanning mammograph (FLM). The instrument provides monochromatic light at 690 and 810 nm, whose intensity is modulated at 110.0008 MHz, respectively. The breast is scanned by stepwise positioning of source and detector, and amplitude and phase for both wavelengths are measured by a photomultiplier tube using heterodyne detection. Images are formed representing amplitude or phase data on linear gray scales. Furthermore, various algorithms carrying on more than one signal were essayed. Twenty visible cancers out of 25 cancers in the first 59 investigations were analyzed for their quantitative contrast with respect to the whole breast or to defined reference areas. Contrast definitions refer to the signal itself, to the signal noise, or were based on nonparametric comparison. The amplitude signal provides better contrast than the phase signal. Ratio images between red and IR amplitudes gave variable results; in some cases the tumor contrast was canceled. The algorithms to determine (mu) a and (mu) sPRM from amplitude and phase data did not significantly improve upon objective contrast. The N algorithm, using the phase signal to flatten the amplitude signal did significantly improve upon contrast according to contrast definitions 1 and 2, however, did not improve upon nonparametric contrast. Thus, with the current instrumentation, the phase signal is helpful to correct for the complex and variable geometry of the breast. However, an independent informational content for tumor differentiation could not be determined. The flat field algorithm did greatly enhance optical contrast in comparison with amplitude or amplitude ratio images. Further evaluation of FLM will have to be based on the N-algorithm images.

Role of differential physical properties in the collective mechanics and dynamics of tissues

NASA Astrophysics Data System (ADS)

Das, Moumita

Living cells and tissues are highly mechanically sensitive and active. Mechanical stimuli influence the shape, motility, and functions of cells, modulate the behavior of tissues, and play a key role in several diseases. In this talk I will discuss how collective biophysical properties of tissues emerge from the interplay between differential mechanical properties and statistical physics of underlying components, focusing on two complementary tissue types whose properties are primarily determined by (1) the extracellular matrix (ECM), and (2) individual and collective cell properties. I will start with the structure-mechanics-function relationships in articular cartilage (AC), a soft tissue that has very few cells, and its mechanical response is primarily due to its ECM. AC is a remarkable tissue: it can support loads exceeding ten times our body weight and bear 60+ years of daily mechanical loading despite having minimal regenerative capacity. I will discuss the biophysical principles underlying this exceptional mechanical response using the framework of rigidity percolation theory, and compare our predictions with experiments done by our collaborators. Next I will discuss ongoing theoretical work on how the differences in cell mechanics, motility, adhesion, and proliferation in a co-culture of breast cancer cells and healthy breast epithelial cells may modulate experimentally observed differential migration and segregation. Our results may provide insights into the mechanobiology of tissues with cell populations with different physical properties present together such as during the formation of embryos or the initiation of tumors. This work was partially supported by a Cottrell College Science Award.

Toward a planning scheme for emission guided radiation therapy (EGRT): FDG based tumor tracking in a metastatic breast cancer patient

PubMed Central

Fan, Qiyong; Nanduri, Akshay; Yang, Jaewon; Yamamoto, Tokihiro; Loo, Billy; Graves, Edward; Zhu, Lei; Mazin, Samuel

2013-01-01

Purpose: Emission guided radiation therapy (EGRT) is a new modality that uses PET emissions in real-time for direct tumor tracking during radiation delivery. Radiation beamlets are delivered along positron emission tomography (PET) lines of response (LORs) by a fast rotating ring therapy unit consisting of a linear accelerator (Linac) and PET detectors. The feasibility of tumor tracking and a primitive modulation method to compensate for attenuation have been demonstrated using a 4D digital phantom in our prior work. However, the essential capability of achieving dose modulation as in conventional intensity modulated radiation therapy (IMRT) treatments remains absent. In this work, the authors develop a planning scheme for EGRT to accomplish sophisticated intensity modulation based on an IMRT plan while preserving tumor tracking. Methods: The planning scheme utilizes a precomputed LOR response probability distribution to achieve desired IMRT planning modulation with effects of inhomogeneous attenuation and nonuniform background activity distribution accounted for. Evaluation studies are performed on a 4D digital patient with a simulated lung tumor and a clinical patient who has a moving breast cancer metastasis in the lung. The Linac dose delivery is simulated using a voxel-based Monte Carlo algorithm. The IMRT plan is optimized for a planning target volume (PTV) that encompasses the tumor motion using the MOSEK package and a Pinnacle3™ workstation (Philips Healthcare, Fitchburg, WI) for digital and clinical patients, respectively. To obtain the emission data for both patients, the Geant4 application for tomographic emission (GATE) package and a commercial PET scanner are used. As a comparison, 3D and helical IMRT treatments covering the same PTV based on the same IMRT plan are simulated. Results: 3D and helical IMRT treatments show similar dose distribution. In the digital patient case, compared with the 3D IMRT treatment, EGRT achieves a 15.1% relative increase in dose to 95% of the gross tumor volume (GTV) and a 31.8% increase to 50% of the GTV. In the patient case, EGRT yields a 15.2% relative increase in dose to 95% of the GTV and a 20.7% increase to 50% of the GTV. The organs at risk (OARs) doses are kept similar or lower for EGRT in both cases. Tumor tracking is observed in the presence of planning modulation in all EGRT treatments. Conclusions: As compared to conventional IMRT treatments, the proposed EGRT planning scheme allows an escalated target dose while keeping dose to the OARs within the same planning limits. With the capabilities of incorporating planning modulation and accurate tumor tracking, EGRT has the potential to greatly improve targeting in radiation therapy and enable a practical and effective implementation of 4D radiation therapy for planning and delivery. PMID:23927305

Minimizing donor-site morbidity following bilateral pedicled TRAM breast reconstruction with the double mesh fold over technique.

PubMed

Bharti, Gaurav; Groves, Leslie; Sanger, Claire; Thompson, James; David, Lisa; Marks, Malcolm

2013-05-01

Transverse rectus abdominus muscle flaps (TRAM) can result in significant abdominal wall donor-site morbidity. We present our experience with bilateral pedicle TRAM breast reconstruction using a double-layered polypropylene mesh fold over technique to repair the rectus fascia. A retrospective study was performed that included patients with bilateral pedicle TRAM breast reconstruction and abdominal reconstruction using a double-layered polypropylene mesh fold over technique. Thirty-five patients met the study criteria with a mean age of 49 years old and mean follow-up of 7.4 years. There were no instances of abdominal hernia and only 2 cases (5.7%) of abdominal bulge. Other abdominal complications included partial umbilical necrosis (14.3%), seroma (11.4%), partial wound dehiscence (8.6%), abdominal weakness (5.7%), abdominal laxity (2.9%), and hematoma (2.9%). The TRAM flap is a reliable option for bilateral autologous breast reconstruction. Using the double mesh repair of the abdominal wall can reduce instances of an abdominal bulge and hernia.

Intensity of recreational physical activity in different life periods in relation to breast cancer among women in the region of Western Pomerania

PubMed Central

2013-01-01

Background Recreational physical activity has been consistently associated with lower breast cancer risk, but there is a need to study the intensity and duration of activity that are critical to reduce the risk. The aim of this study was to examine the influence of moderate and vigorous intensity of recreational physical activity performed at different age periods on breast cancer risk. Material and methods The case-control study included 858 women with histological confirmation of invasive breast cancer and 1085 women free of any cancer diagnosis, residents of the region of Western Pomerania, aged 28–79 years. The frequency, duration and intensity of lifetime household, occupational and recreational physical activity, sociodemographic characteristics, reproductive factors, family history of breast cancer, current weight and height, and lifestyle habits were measured using a self-administered questionnaire. Unconditional logistic regression analyses were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs). The risk estimates were controlled for potential risk factors and lifetime household and occupational activities. Results We found a risk reduction for recreational activity done early in life (age periods 14–20, 21–34, 35–50 years), particularly at ages 14–20 and 21–34 years, regardless of intensity. Active women engaging in more than 4.5 hours per week of moderate activity during ages 14–20 years had, on average, a 36% lower risk (OR = 0.64, 95% CI: 0.45–0.89) than women who were never or rarely active. For the women who reported 4.5 hours per week of vigorous activity during this period we found about 64% risk reduction (OR = 0.36, 95% CI: 0.26–0.51). For the period after 50 years of age, recreational activity of moderate or vigorous intensity was not significantly associated with the risk. Conclusions Recreational physical activity of moderate or vigorous intensity done during adolescence, early and middle adulthood, particularly at ages 14–20 and 21–34 years, is associated with significantly decreased breast cancer risk. PMID:23788947

Severe menopausal symptoms are widespread among survivors of breast cancer treatment regardless of time since diagnosis.

PubMed

Mortimer, Joanne; Behrendt, Carolyn E

2013-09-01

The intensity and persistence of treatment-related symptoms among breast cancer survivors is incompletely understood. The objective of the study was to estimate prevalence of severe symptoms well after initial treatment for breast cancer, to test whether symptom intensity diminishes with time or varies by treatment received. This was a cross-sectional survey of female survivors of stage I-III invasive breast cancer, seen for routine follow-up a year or more after diagnosis. Data was derived from three validated questionnaires indicating physical and emotional domains. Symptoms rated in the top two levels of four- or five-item Likert scales were "severe." Associations with symptom intensity were tested using multivariate linear regression. Survey response was 68.5% (50/73). Respondents were age 55.4 (±9.1) years, median 2.2 (1.0-13.1) years since diagnosis; 64% were receiving endocrine therapy. Severe levels of hot flashes (42% of respondents), weight gain (32%), low libido (32%), and joint pain (30%) were common; (36%) of respondents rated sleep "fairly poor" or "very bad;" 30% were fatigued at least half the day. For 34%, health typically limited vigorous activities "a lot." Most (84%) respondents were experiencing at least one severe symptom. Symptom intensity did not vary with time since diagnosis. Of seven symptoms, three (hot flashes, weight gain, low libido) were more intense when systemic treatment had included endocrine therapy. Time in past month feeling down, nervous, or worn out increased with intensity of physical symptoms. Given their severity, persistence, and association with emotional burden, treatment-related symptoms among breast cancer survivors (BCS) merit greater attention toward clinical management, patient education, and longitudinal study.

The impact of different dose response parameters on biologically optimized IMRT in breast cancer

NASA Astrophysics Data System (ADS)

Costa Ferreira, Brigida; Mavroidis, Panayiotis; Adamus-Górka, Magdalena; Svensson, Roger; Lind, Bengt K.

2008-05-01

The full potential of biologically optimized radiation therapy can only be maximized with the prediction of individual patient radiosensitivity prior to treatment. Unfortunately, the available biological parameters, derived from clinical trials, reflect an average radiosensitivity of the examined populations. In the present study, a breast cancer patient of stage I II with positive lymph nodes was chosen in order to analyse the effect of the variation of individual radiosensitivity on the optimal dose distribution. Thus, deviations from the average biological parameters, describing tumour, heart and lung response, were introduced covering the range of patient radiosensitivity reported in the literature. Two treatment configurations of three and seven biologically optimized intensity-modulated beams were employed. The different dose distributions were analysed using biological and physical parameters such as the complication-free tumour control probability (P+), the biologically effective uniform dose (\\bar{\\bar{D}} ), dose volume histograms, mean doses, standard deviations, maximum and minimum doses. In the three-beam plan, the difference in P+ between the optimal dose distribution (when the individual patient radiosensitivity is known) and the reference dose distribution, which is optimal for the average patient biology, ranges up to 13.9% when varying the radiosensitivity of the target volume, up to 0.9% when varying the radiosensitivity of the heart and up to 1.3% when varying the radiosensitivity of the lung. Similarly, in the seven-beam plan, the differences in P+ are up to 13.1% for the target, up to 1.6% for the heart and up to 0.9% for the left lung. When the radiosensitivity of the most important tissues in breast cancer radiation therapy was simultaneously changed, the maximum gain in outcome was as high as 7.7%. The impact of the dose response uncertainties on the treatment outcome was clinically insignificant for the majority of the simulated patients. However, the jump from generalized to individualized radiation therapy may significantly increase the therapeutic window for patients with extreme radio sensitivity or radioresistance, provided that these are identified. Even for radiosensitive patients a simple treatment technique is sufficient to maximize the outcome, since no significant benefits were obtained with a more complex technique using seven intensity-modulated beams portals.

Molecular Mechanisms and Metabolomics of Natural Polyphenols Interfering with Breast Cancer Metastasis.

PubMed

Ci, Yingqian; Qiao, Jinping; Han, Mei

2016-12-17

Metastatic cancers are the main cause of cancer-related death. In breast primary cancer, the five-year survival rate is close to 100%; however, for metastatic breast cancer, that rate drops to a mere 25%, due in part to the paucity of effective therapeutic options for treating metastases. Several in vitro and in vivo studies have indicated that consumption of natural polyphenols significantly reduces the risk of cancer metastasis. Therefore, this review summarizes the research findings involving the molecular mechanisms and metabolomics of natural polyphenols and how they may be blocking breast cancer metastasis. Most natural polyphenols are thought to impair breast cancer metastasis through downregulation of MMPs expression, interference with the VEGF signaling pathway, modulation of EMT regulator, inhibition of NF-κB and mTOR expression, and other related mechanisms. Intake of natural polyphenols has been shown to impact endogenous metabolites and complex biological metabolic pathways in vivo. Breast cancer metastasis is a complicated process in which each step is modulated by a complex network of signaling pathways. We hope that by detailing the reported interactions between breast cancer metastasis and natural polyphenols, more attention will be directed to these promising candidates as effective adjunct therapies against metastatic breast cancer in the clinic.

Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling

PubMed Central

Feys, Lynn; Descamps, Benedicte; Vanhove, Christian; Vral, Anne; Veldeman, Liv; Vermeulen, Stefan; De Wagter, Carlos; Bracke, Marc; De Wever, Olivier

2015-01-01

Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model. Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells. PMID:26396176

Radiation-induced lung damage promotes breast cancer lung-metastasis through CXCR4 signaling.

PubMed

Feys, Lynn; Descamps, Benedicte; Vanhove, Christian; Vral, Anne; Veldeman, Liv; Vermeulen, Stefan; De Wagter, Carlos; Bracke, Marc; De Wever, Olivier

2015-09-29

Radiotherapy is a mainstay in the postoperative treatment of breast cancer as it reduces the risks of local recurrence and mortality after both conservative surgery and mastectomy. Despite recent efforts to decrease irradiation volumes through accelerated partial irradiation techniques, late cardiac and pulmonary toxicity still occurs after breast irradiation. The importance of this pulmonary injury towards lung metastasis is unclear. Preirradiation of lung epithelial cells induces DNA damage, p53 activation and a secretome enriched in the chemokines SDF-1/CXCL12 and MIF. Irradiated lung epithelial cells stimulate adhesion, spreading, growth, and (transendothelial) migration of human MDA-MB-231 and murine 4T1 breast cancer cells. These metastasis-associated cellular activities were largely mimicked by recombinant CXCL12 and MIF. Moreover, an allosteric inhibitor of the CXCR4 receptor prevented the metastasis-associated cellular activities stimulated by the secretome of irradiated lung epithelial cells. Furthermore, partial (10%) irradiation of the right lung significantly stimulated breast cancer lung-specific metastasis in the syngeneic, orthotopic 4T1 breast cancer model.Our results warrant further investigation of the potential pro-metastatic effects of radiation and indicate the need to develop efficient drugs that will be successful in combination with radiotherapy to prevent therapy-induced spread of cancer cells.

Comparison of Chest Wall and Lymphatic Radiotherapy Techniques in Patients with Left Breast Carcinoma.

PubMed

Gültekin, Melis; Karabuğa, Mehmet; Yıldız, Ferah; Özyiğit, Gökhan; Cengiz, Mustafa; Zorlu, Faruk; Akyol, Fadıl; Gürkaynak, Murat

2014-04-01

The aim of this study was to find the most appropriate technique for postmastectomy chest wall (CW) and lymphatic irradiation. Partially wide tangent, 30/70 photon/electron mix, 20/80 photon/electron mix and CW and internal mammary en face electron field, were studied on computerized tomography (CT) scans of 10 left breast carcinoma patients and dosimetric calculations have been studied. Dose volume histograms (DVH) obtained from treatment planning system (TPS) were used for minimal, maximal and mean doses received by the clinical target volumes and critical structures. Partially wide tangent field resulted in the most homogeneous dose distribution for the CW and a significantly lower lung and heart doses compared with all other techniques. However, right breast dose was significantly higher for partially wide tangent technique than that each of the other techniques. Approximately 0.6-7.9% differences were found between thermoluminescent dosimeter (TLD) and treatment planning system (TPS). The daily surface doses calculating using Gafchromic® external beam therapy (EBT) dosimetry films were 161.8±2.7 cGy for the naked, 241.0±1.5 cGy when 0.5 cm bolus was used and 255.3±2.7 cGy when 1 cm bolus was used. As a result of this study, partially wide tangent field was found to be the most appropriate technique in terms of the dose distribution, treatment planning and set-up procedure. The main disadvantage of this technique was the higher dose to the contralateral breast comparing the other techniques.

An Optimized Online Verification Imaging Procedure for External Beam Partial Breast Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Willis, David J., E-mail: David.Willis@petermac.or; Royal Melbourne Institute of Technology University, Melbourne, Victoria; Kron, Tomas

2011-07-01

The purpose of this study was to evaluate the capabilities of a kilovoltage (kV) on-board imager (OBI)-equipped linear accelerator in the setting of on-line verification imaging for external-beam partial breast irradiation. Available imaging techniques were optimized and assessed for image quality using a modified anthropomorphic phantom. Imaging dose was also assessed. Imaging techniques were assessed for physical clearance between patient and treatment machine using a volunteer. Nonorthogonal kV image pairs were identified as optimal in terms of image quality, clearance, and dose. After institutional review board approval, this approach was used for 17 patients receiving accelerated partial breast irradiation. Imagingmore » was performed before every fraction verification with online correction of setup deviations >5 mm (total image sessions = 170). Treatment staff rated risk of collision and visibility of tumor bed surgical clips where present. Image session duration and detected setup deviations were recorded. For all cases, both image projections (n = 34) had low collision risk. Surgical clips were rated as well as visualized in all cases where they were present (n = 5). The average imaging session time was 6 min, 16 sec, and a reduction in duration was observed as staff became familiar with the technique. Setup deviations of up to 1.3 cm were detected before treatment and subsequently confirmed offline. Nonorthogonal kV image pairs allowed effective and efficient online verification for partial breast irradiation. It has yet to be tested in a multicenter study to determine whether it is dependent on skilled treatment staff.« less

Signal enhancement ratio (SER) quantified from breast DCE-MRI and breast cancer risk

NASA Astrophysics Data System (ADS)

Wu, Shandong; Kurland, Brenda F.; Berg, Wendie A.; Zuley, Margarita L.; Jankowitz, Rachel C.; Sumkin, Jules; Gur, David

2015-03-01

Breast magnetic resonance imaging (MRI) is recommended as an adjunct to mammography for women who are considered at elevated risk of developing breast cancer. As a key component of breast MRI, dynamic contrast-enhanced MRI (DCE-MRI) uses a contrast agent to provide high intensity contrast between breast tissues, making it sensitive to tissue composition and vascularity. Breast DCE-MRI characterizes certain physiologic properties of breast tissue that are potentially related to breast cancer risk. Studies have shown that increased background parenchymal enhancement (BPE), which is the contrast enhancement occurring in normal cancer-unaffected breast tissues in post-contrast sequences, predicts increased breast cancer risk. Signal enhancement ratio (SER) computed from pre-contrast and post-contrast sequences in DCE-MRI measures change in signal intensity due to contrast uptake over time and is a measure of contrast enhancement kinetics. SER quantified in breast tumor has been shown potential as a biomarker for characterizing tumor response to treatments. In this work we investigated the relationship between quantitative measures of SER and breast cancer risk. A pilot retrospective case-control study was performed using a cohort of 102 women, consisting of 51 women who had diagnosed with unilateral breast cancer and 51 matched controls (by age and MRI date) with a unilateral biopsy-proven benign lesion. SER was quantified using fully-automated computerized algorithms and three SER-derived quantitative volume measures were compared between the cancer cases and controls using logistic regression analysis. Our preliminary results showed that SER is associated with breast cancer risk, after adjustment for the Breast Imaging Reporting and Data System (BI-RADS)-based mammographic breast density measures. This pilot study indicated that SER has potential for use as a risk factor for breast cancer risk assessment in women at elevated risk of developing breast cancer.

Leptin and Adiponectin Modulate the Self-renewal of Normal Human Breast Epithelial Stem Cells.

PubMed

Esper, Raymond M; Dame, Michael; McClintock, Shannon; Holt, Peter R; Dannenberg, Andrew J; Wicha, Max S; Brenner, Dean E

2015-12-01

Multiple mechanisms are likely to account for the link between obesity and increased risk of postmenopausal breast cancer. Two adipokines, leptin and adiponectin, are of particular interest due to their opposing biologic functions and associations with breast cancer risk. In the current study, we investigated the effects of leptin and adiponectin on normal breast epithelial stem cells. Levels of leptin in human adipose explant-derived conditioned media positively correlated with the size of the normal breast stem cell pool. In contrast, an inverse relationship was found for adiponectin. Moreover, a strong linear relationship was observed between the leptin/adiponectin ratio in adipose conditioned media and breast stem cell self-renewal. Consistent with these findings, exogenous leptin stimulated whereas adiponectin suppressed breast stem cell self-renewal. In addition to local in-breast effects, circulating factors, including leptin and adiponectin, may contribute to the link between obesity and breast cancer. Increased levels of leptin and reduced amounts of adiponectin were found in serum from obese compared with age-matched lean postmenopausal women. Interestingly, serum from obese women increased stem cell self-renewal by 30% compared with only 7% for lean control serum. Taken together, these data suggest a plausible explanation for the obesity-driven increase in postmenopausal breast cancer risk. Leptin and adiponectin may function as both endocrine and paracrine/juxtacrine factors to modulate the size of the normal stem cell pool. Interventions that disrupt this axis and thereby normalize breast stem cell self-renewal could reduce the risk of breast cancer. ©2015 American Association for Cancer Research.

The selective estrogen receptor modulators in breast cancer prevention.

PubMed

Li, Fangxuan; Dou, Jinli; Wei, Lijuan; Li, Shixia; Liu, Juntian

2016-05-01

Persistently increased blood levels of estrogens are associated with an increased risk of breast cancer. Selective estrogen receptor modulators (SERMs) are a class of compounds that act on the estrogen receptor (ER). Several clinical trials have demonstrated the effectiveness of its prophylactic administration. Incidence of invasive ER-positive breast cancer was reduced by SERMs treatment, especially for those women with high risk of developing breast cancer. In this study, we reviewed the clinical application of SERMs in breast cancer prevention. To date, four prospective randomized clinical trials had been performed to test the efficacy of tamoxifen for this purpose. Concerning on the benefit and cost of tamoxifen, various studies from different countries demonstrated that chemoprevention with tamoxifen seemed to be cost-effective for women with a high risk of invasive breast cancer. Based above, tamoxifen was approved for breast cancer prevention by the US Food and Drug Administration in 1998. Raloxifene was also approved for postmenopausal women in 2007 for breast cancer prevention which reduces the risk of invasive breast cancer with a lower risk of unwanted stimulation of endometrium. Thus, raloxifene is considered to have a better clinical possesses as prophylactic agent. Several other agents, such as arzoxifene and lasofoxifene, are currently being investigated in clinic. The American Society of Clinical Oncology and National Comprehensive Cancer Network had published guidelines on breast cancer chemoprevention by SERMs. However, use of tamoxifen and raloxifene for primary breast cancer prevention was still low. A broader educational effort is needed to alert women and primary care physicians that SERMs are available to reduce breast cancer risk.

Importance of exercise immunology in health promotion.

PubMed

Neto, J C Rosa; Lira, F S; de Mello, M T; Santos, Ronaldo Vagner T

2011-11-01

Chronic physical exercise with adequate intensity and volume associated with sufficient recovery promotes adaptations in several physiological systems. While intense and exhaustive exercise is considered an important immunosuppressor agent and increases the incidence of upper respiratory tract infections (URTI), moderate regular exercise has been associated with significant disease protection and is a complementary treatment of many chronic diseases. The effects of chronic exercise occur because physical training can induce several physiological, biochemical and psychological adaptations. More recently, the effect of acute exercise and training on the immunological system has been discussed, and many studies suggest the importance of the immune system in prevention and partial recovery in pathophysiological situations. Currently, there are two important hypotheses that may explain the effects of exercise and training on the immune system. These hypotheses including (1) the effect of exercise upon hormones and cytokines (2) because exercise can modulate glutamine concentration. In this review, we discuss the hypothesis that exercise may modulate immune functions and the importance of exercise immunology in respect to chronic illnesses, chronic heart failure, malnutrition and inflammation.

Correction for Eddy Current-Induced Echo-Shifting Effect in Partial-Fourier Diffusion Tensor Imaging.

PubMed

Truong, Trong-Kha; Song, Allen W; Chen, Nan-Kuei

2015-01-01

In most diffusion tensor imaging (DTI) studies, images are acquired with either a partial-Fourier or a parallel partial-Fourier echo-planar imaging (EPI) sequence, in order to shorten the echo time and increase the signal-to-noise ratio (SNR). However, eddy currents induced by the diffusion-sensitizing gradients can often lead to a shift of the echo in k-space, resulting in three distinct types of artifacts in partial-Fourier DTI. Here, we present an improved DTI acquisition and reconstruction scheme, capable of generating high-quality and high-SNR DTI data without eddy current-induced artifacts. This new scheme consists of three components, respectively, addressing the three distinct types of artifacts. First, a k-space energy-anchored DTI sequence is designed to recover eddy current-induced signal loss (i.e., Type 1 artifact). Second, a multischeme partial-Fourier reconstruction is used to eliminate artificial signal elevation (i.e., Type 2 artifact) associated with the conventional partial-Fourier reconstruction. Third, a signal intensity correction is applied to remove artificial signal modulations due to eddy current-induced erroneous T2(∗) -weighting (i.e., Type 3 artifact). These systematic improvements will greatly increase the consistency and accuracy of DTI measurements, expanding the utility of DTI in translational applications where quantitative robustness is much needed.

Correction for Eddy Current-Induced Echo-Shifting Effect in Partial-Fourier Diffusion Tensor Imaging

PubMed Central

Truong, Trong-Kha; Song, Allen W.; Chen, Nan-kuei

2015-01-01

In most diffusion tensor imaging (DTI) studies, images are acquired with either a partial-Fourier or a parallel partial-Fourier echo-planar imaging (EPI) sequence, in order to shorten the echo time and increase the signal-to-noise ratio (SNR). However, eddy currents induced by the diffusion-sensitizing gradients can often lead to a shift of the echo in k-space, resulting in three distinct types of artifacts in partial-Fourier DTI. Here, we present an improved DTI acquisition and reconstruction scheme, capable of generating high-quality and high-SNR DTI data without eddy current-induced artifacts. This new scheme consists of three components, respectively, addressing the three distinct types of artifacts. First, a k-space energy-anchored DTI sequence is designed to recover eddy current-induced signal loss (i.e., Type 1 artifact). Second, a multischeme partial-Fourier reconstruction is used to eliminate artificial signal elevation (i.e., Type 2 artifact) associated with the conventional partial-Fourier reconstruction. Third, a signal intensity correction is applied to remove artificial signal modulations due to eddy current-induced erroneous T 2 ∗-weighting (i.e., Type 3 artifact). These systematic improvements will greatly increase the consistency and accuracy of DTI measurements, expanding the utility of DTI in translational applications where quantitative robustness is much needed. PMID:26413505

Molecular Mechanisms of Anticancer Effects of Phytoestrogens in Breast Cancer.

PubMed

Hsieh, Chia-Jung; Hsu, Ya-Ling; Huang, Ya-Fang; Tsai, Eing-Mei

2018-01-01

Phytoestrogens derived from plants exert estrogenic as well as antiestrogenic effects and multiple actions within breast cancer cells. Chemopreventive properties of phytoestrogens have emerged from epidemiological observations. In recent clinical research studies, phytoestrogens are safe and may even protect against breast cancer. In this brief review, the molecular mechanisms of phytoestrogens on regulation of cell cycle, apoptosis, estrogen receptors, cell signaling pathways, and epigenetic modulations in relation to breast cancer are discussed. Phytoestrogens have a preferential affinity for estrogen receptor (ER)-β, which appears to be associated with antiproliferative and anticarcinogenic effects. Moreover, while phytoestrogens not only inhibit ER-positive but also ER-negative breast cancer cells, the possibility of epigenetic modulation playing an important role is also discussed. In conclusion, as there are multiple targets and actions of phytoestrogens, extensive research is still necessary. However, due to low toxicity, low cost, and easy availability, their potent chemoprevention effects deserve further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Progesterone receptor modulates estrogen receptor-α action in breast cancer

PubMed Central

Mohammed, Hisham; Russell, I. Alasdair; Stark, Rory; Rueda, Oscar M.; Hickey, Theresa E.; Tarulli, Gerard A.; Serandour, Aurelien A. A.; Birrell, Stephen N.; Bruna, Alejandra; Saadi, Amel; Menon, Suraj; Hadfield, James; Pugh, Michelle; Raj, Ganesh V.; Brown, Gordon D.; D’Santos, Clive; Robinson, Jessica L. L.; Silva, Grace; Launchbury, Rosalind; Perou, Charles M.; Stingl, John; Caldas, Carlos; Tilley, Wayne D.; Carroll, Jason S.

2015-01-01

Summary Progesterone receptor (PR) expression is employed as a biomarker of estrogen receptor-α (ERα) function and breast cancer prognosis. We now show that PR is not merely an ERα-induced gene target, but is also an ERα-associated protein that modulates its behaviour. In the presence of agonist ligands, PR associates with ERα to direct ERα chromatin binding events within breast cancer cells, resulting in a unique gene expression programme that is associated with good clinical outcome. Progesterone inhibited estrogen-mediated growth of ERα+ cell line xenografts and primary ERα+ breast tumour explants and had increased anti-proliferative effects when coupled with an ERα antagonist. Copy number loss of PgR is a common feature in ERα+ breast cancers, explaining lower PR levels in a subset of cases. Our findings indicate that PR functions as a molecular rheostat to control ERα chromatin binding and transcriptional activity, which has important implications for prognosis and therapeutic interventions. PMID:26153859

Cardiac dose-sparing effects of deep-inspiration breath-hold in left breast irradiation : Is IMRT more beneficial than VMAT?

PubMed

Sakka, Mazen; Kunzelmann, Leonie; Metzger, Martin; Grabenbauer, Gerhard G

2017-10-01

Given the reduction in death from breast cancer, as well as improvements in overall survival, adjuvant radiotherapy is considered the standard treatment for breast cancer. However, left-sided breast irradiation was associated with an increased rate of fatal cardiovascular events due to incidental irradiation of the heart. Recently, considerable efforts have been made to minimize cardiac toxicity of left-sided breast irradiation by new treatment methods such as deep-inspiration breath-hold (DIBH) and new radiation techniques, particularly intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT). The primary aim of this study was to evaluate the effect of DIBH irradiation on cardiac dose compared with free-breathing (FB) irradiation, while the secondary objective was to compare the advantages of IMRT versus VMAT plans in both the FB and the DIBH position for left-sided breast cancer. In all, 25 consecutive left-sided breast cancer patients underwent CT simulation in the FB and DIBH position. Five patients were excluded with no cardiac displacement following DIBH-CT simulation. The other 20 patients were irradiated in the DIBH position using respiratory gating. Four different treatment plans were generated for each patient, an IMRT and a VMAT plan in the DIBH and in the FB position, respectively. The following parameters were used for plan comparison: dose to the heart, left anterior descending coronary artery (mean dose, maximum dose, D25% and D45%), ipsilateral, contralateral lung (mean dose, D20%, D30%) and contralateral breast (mean dose). The percentage in dose reduction for organs at risk achieved by DIBH for both IMRT and VMAT plans was calculated and compared for each patient by each treatment plan. DIBH irradiation significantly reduced mean dose to the heart and left anterior descending coronary artery (LADCA) using both IMRT (heart -20%; p = 0.0002, LADCA -9%; p = 0.001) and VMAT (heart -23%; p = 0.00003, LADCA -16%; p = 0.01) techniques as compared with FB radiation. There were no significant changes in left lung dose by IMRT; however, with VMAT planning, mean dose to the left lung was reduced by -4% (p = 0.0004). In addition, DIBH significantly increased the mean dose to the contralateral breast with IMRT (+14%, p = 0.002) and significantly reduced the dose to the contralateral breast with VMAT planning (-9%, p = 0.003) compared with the FB position. Additionally, in comparison with VMAT, the IMRT technique reduced mean heart dose both in the FB and the DIBH-position by -30% (p = 0.0004) and -26% (p = 0.002), respectively. Furthermore, IMRT increased the mean dose to the left lung in both the FB and the DIBH position (+5%, p = 0.003, p = 0.006), respectively. There were no significant changes in dose to the right lung and contralateral breast either in the FB or DIBH position between IMRT and VMAT techniques. Left-sided breast irradiation is best performed in the DIBH position, since a considerable dose sparing to the heart and LADCA can be achieved by using either IMRT or VMAT techniques. A significant additional decrease in heart and LADCA dose by IMRT in both FB and DIBH irradiation was seen compared with VMAT.

Isotropic differential phase contrast microscopy for quantitative phase bio-imaging.

PubMed

Chen, Hsi-Hsun; Lin, Yu-Zi; Luo, Yuan

2018-05-16

Quantitative phase imaging (QPI) has been investigated to retrieve optical phase information of an object and applied to biological microscopy and related medical studies. In recent examples, differential phase contrast (DPC) microscopy can recover phase image of thin sample under multi-axis intensity measurements in wide-field scheme. Unlike conventional DPC, based on theoretical approach under partially coherent condition, we propose a new method to achieve isotropic differential phase contrast (iDPC) with high accuracy and stability for phase recovery in simple and high-speed fashion. The iDPC is simply implemented with a partially coherent microscopy and a programmable thin-film transistor (TFT) shield to digitally modulate structured illumination patterns for QPI. In this article, simulation results show consistency of our theoretical approach for iDPC under partial coherence. In addition, we further demonstrate experiments of quantitative phase images of a standard micro-lens array, as well as label-free live human cell samples. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Leisure-time physical activity and breast cancer risk by hormone receptor status: effective life periods and exercise intensity.

PubMed

Suzuki, Reiko; Iwasaki, Motoki; Kasuga, Yoshio; Yokoyama, Shiro; Onuma, Hiroshi; Nishimura, Hideki; Kusama, Ritsu; Shimazu, Taichi; Tsugane, Shoichiro

2010-11-01

Physical activity may decrease breast cancer risk. However, it is unclear what intensity of exercise and during which life periods this effect on decreasing risk is efficiently expressed, and whether the associations differ by the estrogen-/progesterone- receptor (ER/PR) status of tumors. We investigated associations between age- and intensity-specific leisure-time physical activity and ER/PR-defined breast cancer risk. We conducted a hospital-based case-control study in Nagano, Japan. Subjects were 405 cases newly diagnosed (>99% known ER/PR) from 2001 to 2005, who were age-/area-matched with 405 controls. Activity was assessed with a self-reported questionnaire which considered intensity level (moderate and/or strenuous) at different ages (at 12 and 20 years, and in the previous 5 years). Odds ratios (ORs) and 95% confidence intervals were calculated using logistic regression. Strenuous but not moderate physical activity at age 12 was inversely associated with pre- and postmenopausal breast cancer risk across ER/PR subtypes [overall OR(≥ 5 days/week vs. none) = 0.24 (0.14-0.43)]. Moderate physical activity in the previous 5 years was significantly associated with a decrease in risk for postmenopausal ER + PR + tumors only [OR(≥ 1 day/week vs. none) = 0.35 (0.18-0.67)]. Strenuous activity in teens and moderate activity after menopause may contribute to a reduction in breast cancer risk.

Mechanisms of breast cancer risk in shift workers: association of telomere shortening with the duration and intensity of night work.

PubMed

Samulin Erdem, Johanna; Notø, Heidi Ødegaard; Skare, Øivind; Lie, Jenny-Anne S; Petersen-Øverleir, Marte; Reszka, Edyta; Pepłońska, Beata; Zienolddiny, Shanbeh

2017-08-01

Occupational factors such as shiftwork and especially night work that involves disruption of the circadian rhythm may contribute to increased breast cancer risk. Circadian disruption may also affect telomere length (TL). While short TL generally is associated with increased cancer risk, its association with breast cancer risk is inconclusive. We suggest that working schedules might be an important factor in assessment of effects of TL on breast cancer risk. Moreover, telomere shortening might be a potential mechanism for night work-related breast cancer. In this study, effects of shift work on TL and its association with breast cancer risk were investigated in a nested breast cancer case-control study of Norwegian nurses. TL was assessed by qPCR in DNA from 563 breast cancer patients and 619 controls. Here, we demonstrate that TL is affected by intensive night work schedules, as work with six consecutive night for a period of more than 5 years was associated with decreased telomere lengths (-3.18, 95% CI: -6.46 to -0.58, P = 0.016). Furthermore, telomere shortening is associated with increased breast cancer risk in workers with long periods of consecutive night shifts. Thus, nurses with longer telomere lengths had a lower risk for breast cancer if they had worked more than four (OR: 0.37, 95% CI: 0.16-0.79, P = 0.014) or five (OR: 0.31, 95% CI: 0.10-0.83, P = 0.029) consecutive night shifts for a period of 5 years or more. These data suggest that telomere shortening is associated with the duration and intensity of night work and may be a contributing factor for breast cancer risk among female shift workers. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Calculation and Prediction of the Effect of Respiratory Motion on Whole Breast Radiation Therapy Dose Distributions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Cao Junsheng; Roeske, John C.; Chmura, Steve J.

2009-07-01

The standard treatment technique used for whole-breast irradiation can result in undesirable dose distributions in the treatment site, leading to skin reaction/fibrosis and pulmonary and cardiac toxicities. Hence, the technique has evolved from conventional wedged technique (CWT) to segment intensity-modulated radiation therapy (SIMRT) and beamlet IMRT (IMRT). However, these newer techniques feature more highly modulated dose distributions that may be affected by respiration. The purpose of this work was to conduct a simple study of the clinical impact of respiratory motion on breast radiotherapy dose distributions for the three treatment planning techniques. The ultimate goal was to determine which patientsmore » would benefit most from the use of motion management. Eight patients with early-stage breast cancer underwent a free-breathing (FB) computed tomography (CT) simulation, with medial and lateral markers placed on the skin. Two additional CT scans were obtained at the end of inspiration (EI) and the end of expiration (EE). The FB-CT scan was used to develop treatment plans using each technique. Each plan was then applied to EI and EE-CT scans. Compared with the FB CT scan, the medial markers moved up to 1.8 cm in the anterior-superior direction at the end of inspiration (EI-scan), and on average 8 mm. The CWT and SIMRT techniques were not 'sensitive' to respiratory motion, because the % clinical target volume (CTV) receiving 95% of the prescription dose (V{sub 95%}) remained constant for both techniques. For patients that had large respiratory motion indicated by marker movement >0.6 cm, differences in coverage of the CTV at the V100% between FB and EI for beamlet IMRT plans were on the order of >10% and up to 18%. A linear model was developed to relate the dosimetric coverage difference introduced by respiration with the motion information. With this model, the dosimetric coverage difference introduced by respiratory motion could be evaluated during patient CT simulation. An appropriate treatment method can be chosen after the simulation.« less

Prognosis for Survival of Young Women with Breast Cancer by Quantitative p53 Immunohistochemistry

PubMed Central

Axelrod, David E.; Shah, Kinsuk; Yang, Qifeng; Haffty, Bruce G.

2015-01-01

p53 protein detected immunohistochemically has not been accepted as a biomarker for breast cancer patients because of disparate reports of the relationship between the amount of p53 protein detected and patient survival. The purpose of this study was to determine experimental conditions and methods of data analysis for which p53 stain intensity could be prognostic for survival of young breast cancer patients. A tissue microarray of specimens from 93 patients was stained with anti-p53 antibody, and stain intensity measured with a computer-aided image analysis system. A cut-point at one standard deviation below the mean of the distribution of p53 stain intensity separated patients into two groups with significantly different survival. These results were confirmed by Quantitative Nuclear Grade determined by DNA-specific Feulgen staining. P53 provided information beyond ER and PR status. Therefore, under the conditions reported here, p53 protein can be an effective prognostic factor for young breast cancer patients. PMID:26322145

Early feeding and neonatal hypoglycemia in infants of diabetic mothers

PubMed Central

Ramesh, Shilpa; Hillier, Kirsty; Giannone, Peter J; Nankervis, Craig A

2013-01-01

Objectives: To examine the effects of early formula feeding or breast-feeding on hypoglycemia in infants born to 303 A1-A2 and 88 Class B-RF diabetics. Methods: Infants with hypoglycemia (blood glucose < 40 mg/dL) were breast-fed or formula-fed, and those with recurrences were given intravenous dextrose. Results: Of 293 infants admitted to the well-baby nursery, 87 (30%) had hypoglycemia, corrected by early feeding in 75 (86%), while 12 (14%) required intravenous dextrose. In all, 98 infants were admitted to the newborn intensive care unit for respiratory distress (40%), prematurity (33%) or prevention of hypoglycemia (27%). Although all newborn intensive care unit patients received intravenous dextrose, 22 (22%) had hypoglycemia. Of 109 hypoglycemia episodes, 89 (82%) were single low occurrences. At discharge, 56% of well-baby nursery and 43% of newborn intensive care unit infants initiated breast-feeding. Conclusions: Hypoglycemia among infants of diabetic mothers can be corrected by early breast-feeding or formula feeding. PMID:26770697

Surgical treatment for women with breast cancer: do randomized clinical trials represent current medical practices?

PubMed

Frederick, Wayne A I; Ames, Sarah; Downing, Stephanie R; Oyetunji, Tolulope A; Chang, David C; Leffall, Lasalle D

2010-06-01

Randomized clinical trials have not shown survival differences between breast cancer patients who undergo breast-conserving surgery and those who undergo modified radical mastectomy (MRM). Recent studies however, have suggested that these randomized clinical trials findings may not be representative of the entire population or the nature of current patient care. A retrospective analysis of female invasive breast cancer patients who underwent surgery in the Surveillance, Epidemiology, and End Results database (1990-2003) was performed. Survival was compared amongst women who underwent partial mastectomy, partial mastectomy plus radiation (PMR), or MRM. Cox proportional hazards regressions were used to investigate the impact of method of treatment upon survival, after adjusting for patient and tumor characteristics. A total of 218,043 patients, mean age 62 years, were identified. MRM accounted for 51.5 per cent of the study population whereas PMR accounted for 34.9 per cent. On multivariate analyses, significant improvement was observed in patient survival associated with PMR when compared with MRM patients (hazard ratio = 0.71, 95% confidence interval = 0.67-0.74, P < 0.001). This population-based study suggests that there is a survival benefit for women undergoing PMR in the treatment of breast cancer.

Attachment, emotion regulation, and adaptation to breast cancer: assessment of a mediational hypothesis.

PubMed

Ávila, Marisa; Brandão, Tânia; Teixeira, Joana; Coimbra, Joaquim Luis; Matos, Paula Mena

2015-11-01

This study examines the links between attachment, adaptation to breast cancer, and the mediating role played by emotional regulation processes. Participants were 127 women with breast cancer recruited in two public hospitals of Porto and at the Portuguese Cancer League. Women completed measures of attachment, quality of life, and emotion regulation. Path models were used to examine the associations between the constructs and to test the mediational hypotheses. Significant associations were found between attachment and adaptation. Dimensions of emotion regulation totally or partially mediated the associations between attachment and adaptation outcomes. Attachment security effects on interpersonal relations were totally mediated by communicating emotions. Also, attachment anxiety effect on physical well-being was totally mediated by rumination. Attachment avoidance effects on psychological outcomes were totally mediated by emotional control and partially mediated by communicating emotions for the case of interpersonal relations. This study highlights the importance of addressing emotional regulation jointly with attachment to deepen the comprehension of the relational processes implicated in adaptation to breast cancer. Results supported a mediational hypothesis, presenting emotional regulation processes as relevant dimensions for the understanding of attachment associations with adaptation to breast cancer. Copyright © 2015 John Wiley & Sons, Ltd.

77 FR 50701 - Radiological Devices Panel of the Medical Devices Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-22

..., sponsored by Hologic, Inc. The Selenia Dimensions 3D System is currently approved for breast cancer... combination of DBT with synthetic 2D images to be used as another exam option for breast cancer screening. FDA... combination of FFDM with digital breast tomosynthesis (DBT). The new C-View Software Module can generate...

Damage in Monolithic Thin-Film Photovoltaic Modules Due to Partial Shade

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silverman, Timothy J.; Mansfield, Lorelle; Repins, Ingrid

2016-09-01

The typical configuration of monolithic thin-film photovoltaic modules makes it possible for partial shade to place one or more cells in such a module in reverse bias. Reverse bias operation leads to high voltage, current density, and power density conditions, which can act as driving forces for failure. We showed that a brief outdoor shadow event can cause a 7% permanent loss in power. We applied an indoor partial shade durability test that moves beyond the standard hot spot endurance test by using more realistic mask and bias conditions and by carefully quantifying the permanent change in performance due tomore » the stress. With the addition of a pass criterion based on change in maximum power, this procedure will soon be proposed as a part of the module-type qualification test. All six commercial copper indium gallium diselenide and cadmium telluride modules we tested experienced permanent damage due to the indoor partial shade test, ranging from 4% to 14% loss in maximum power. We conclude by summarizing ways to mitigate partial shade stress at the cell, module, and system levels.« less

Breast carcinoma cells modulate the chemoattractive activity of human bone marrow-derived mesenchymal stromal cells by interfering with CXCL12.

PubMed

Wobus, Manja; List, Catrin; Dittrich, Tobias; Dhawan, Abhishek; Duryagina, Regina; Arabanian, Laleh S; Kast, Karin; Wimberger, Pauline; Stiehler, Maik; Hofbauer, Lorenz C; Jakob, Franz; Ehninger, Gerhard; Anastassiadis, Konstantinos; Bornhäuser, Martin

2015-01-01

We investigated whether breast tumor cells can modulate the function of mesenchymal stromal cells (MSCs) with a special emphasis on their chemoattractive activity towards hematopoietic stem and progenitor cells (HSPCs). Primary MSCs as well as a MSC line (SCP-1) were cocultured with primary breast cancer cells, MCF-7, MDA-MB231 breast carcinoma or MCF-10A non-malignant breast epithelial cells or their conditioned medium. In addition, the frequency of circulating clonogenic hematopoietic progenitors was determined in 78 patients with breast cancer and compared with healthy controls. Gene expression analysis of SCP-1 cells cultured with MCF-7 medium revealed CXCL12 (SDF-1) as one of the most significantly downregulated genes. Supernatant from both MCF-7 and MDA-MB231 reduced the CXCL12 promoter activity in SCP-1 cells to 77% and 47%, respectively. Moreover, the CXCL12 mRNA and protein levels were significantly reduced. As functional consequence of lower CXCL12 levels, we detected a decreased trans-well migration of HSPCs towards MSC/tumor cell cocultures or conditioned medium. The specificity of this effect was confirmed by blocking studies with the CXCR4 antagonist AMD3100. Downregulation of SP1 and increased miR-23a levels in MSCs after contact with tumor cell medium as well as enhanced TGFβ1 expression were identified as potential molecular regulators of CXCL12 activity in MSCs. Moreover, we observed a significantly higher frequency of circulating colony-forming hematopoietic progenitors in patients with breast cancer compared with healthy controls. Our in vitro results propose a potential new mechanism by which disseminated tumor cells in the bone marrow may interfere with hematopoiesis by modulating CXCL12 in protected niches. © 2014 UICC.

Design of a small molecule against an oncogenic noncoding RNA.

PubMed

Velagapudi, Sai Pradeep; Cameron, Michael D; Haga, Christopher L; Rosenberg, Laura H; Lafitte, Marie; Duckett, Derek R; Phinney, Donald G; Disney, Matthew D

2016-05-24

The design of precision, preclinical therapeutics from sequence is difficult, but advances in this area, particularly those focused on rational design, could quickly transform the sequence of disease-causing gene products into lead modalities. Herein, we describe the use of Inforna, a computational approach that enables the rational design of small molecules targeting RNA to quickly provide a potent modulator of oncogenic microRNA-96 (miR-96). We mined the secondary structure of primary microRNA-96 (pri-miR-96) hairpin precursor against a database of RNA motif-small molecule interactions, which identified modules that bound RNA motifs nearby and in the Drosha processing site. Precise linking of these modules together provided Targaprimir-96 (3), which selectively modulates miR-96 production in cancer cells and triggers apoptosis. Importantly, the compound is ineffective on healthy breast cells, and exogenous overexpression of pri-miR-96 reduced compound potency in breast cancer cells. Chemical Cross-Linking and Isolation by Pull-Down (Chem-CLIP), a small-molecule RNA target validation approach, shows that 3 directly engages pri-miR-96 in breast cancer cells. In vivo, 3 has a favorable pharmacokinetic profile and decreases tumor burden in a mouse model of triple-negative breast cancer. Thus, rational design can quickly produce precision, in vivo bioactive lead small molecules against hard-to-treat cancers by targeting oncogenic noncoding RNAs, advancing a disease-to-gene-to-drug paradigm.

38 CFR 3.350 - Special monthly compensation ratings.

Code of Federal Regulations, 2010 CFR

2010-07-01

... constant inability to communicate by speech or, in the case of a woman veteran, loss of 25% or more of tissue from a single breast or both breasts in combination (including loss by mastectomy or partial... intermediate or next higher rate provisions outlined above, additional single permanent disability or...

The pharmacological and hormonal therapy of hot flushes in breast cancer survivors.

PubMed

Wiśniewska, Iwona; Jochymek, Bożena; Lenart-Lipińska, Monika; Chabowski, Mariusz

2016-03-01

The side effects of oncological treatment, which appear during or after therapy, are sometimes very annoying for patients and are not adequately treated by physicians. Among the symptoms experienced by breast cancer patients are hot flushes, which result from a natural or cancer therapy-induced menopause. The intensity of hot flushes in breast cancer patients may be more severe than those experienced by women undergoing a natural menopause. Taking into account the incidence of breast cancer and long-lasting hormone-suppression therapies, the problem of hot flushes will affect many women. Hormonal replacement therapy, the most effective therapeutic means for alleviating hot flushes, is usually contraindicated for breast cancer patients. For intense and severe hot flushes, pharmacological treatment using agents from a group of selective serotonin reuptake inhibitors and serotonin and norepinephrine reuptake inhibitors such as venlafaxine or citalopram may be introduced. Other agents from different pharmacological groups, such as clonidine, gabapentin, or pregabalin, have also proved to be effective in treating hot flushes. The efficacy of phytoestrogens has not been proven in randomized clinical trials. The importance of the placebo effect in decreasing vasomotor symptoms has also been reported in many research papers. Educating breast cancer patients in lifestyle changes which decrease the frequency and intensity of vasomotor symptoms can offer significant help too. This paper reviews the current state of research in order to assess the options for the treatment of hot flushes in breast cancer survivors.

Early Detection of Breast Cancer by Using Handycam Camera Manipulation as Thermal Camera Imaging with Images Processing Method

NASA Astrophysics Data System (ADS)

Riantana, R.; Arie, B.; Adam, M.; Aditya, R.; Nuryani; Yahya, I.

2017-02-01

One important thing to pay attention for detecting breast cancer is breast temperature changes. Indications symptoms of breast tissue abnormalities marked by a rise in temperature of the breast. Handycam in night vision mode interferences by external infrared can penetrate into the skin better and can make an infrared image becomes clearer. The program is capable to changing images from a camcorder into a night vision thermal image by breaking RGB into Grayscale matrix structure. The matrix rearranged in the new matrix with double data type so that it can be processed into contour color chart to differentiate the distribution of body temperature. In this program are also features of contrast scale setting of the image is processed so that the color can be set as desired. There was Also a contrast adjustment feature inverse scale that is useful to reverse the color scale so that colors can be changed opposite. There is improfile function used to retrieves the intensity values of pixels along a line what we want to show the distribution of intensity in a graph of relationship between the intensity and the pixel coordinates.

Computing mammographic density from a multiple regression model constructed with image-acquisition parameters from a full-field digital mammographic unit

PubMed Central

Lu, Lee-Jane W.; Nishino, Thomas K.; Khamapirad, Tuenchit; Grady, James J; Leonard, Morton H.; Brunder, Donald G.

2009-01-01

Breast density (the percentage of fibroglandular tissue in the breast) has been suggested to be a useful surrogate marker for breast cancer risk. It is conventionally measured using screen-film mammographic images by a labor intensive histogram segmentation method (HSM). We have adapted and modified the HSM for measuring breast density from raw digital mammograms acquired by full-field digital mammography. Multiple regression model analyses showed that many of the instrument parameters for acquiring the screening mammograms (e.g. breast compression thickness, radiological thickness, radiation dose, compression force, etc) and image pixel intensity statistics of the imaged breasts were strong predictors of the observed threshold values (model R2=0.93) and %density (R2=0.84). The intra-class correlation coefficient of the %-density for duplicate images was estimated to be 0.80, using the regression model-derived threshold values, and 0.94 if estimated directly from the parameter estimates of the %-density prediction regression model. Therefore, with additional research, these mathematical models could be used to compute breast density objectively, automatically bypassing the HSM step, and could greatly facilitate breast cancer research studies. PMID:17671343

Performance Comparison of 112-Gb/s DMT, Nyquist PAM4, and Partial-Response PAM4 for Future 5G Ethernet-Based Fronthaul Architecture

NASA Astrophysics Data System (ADS)

Eiselt, Nicklas; Muench, Daniel; Dochhan, Annika; Griesser, Helmut; Eiselt, Michael; Olmos, Juan Jose Vegas; Monroy, Idelfonso Tafur; Elbers, Joerg-Peter

2018-05-01

For a future 5G Ethernet-based fronthaul architecture, 100G trunk lines of a transmission distance up to 10 km standard single mode fiber (SSMF) in combination with cheap grey optics to daisy chain cell site network interfaces are a promising cost- and power-efficient solution. For such a scenario, different intensity modulation and direct detect (IMDD) Formats at a data rate of 112 Gb/s, namely Nyquist four-level pulse amplitude modulation (PAM4), discrete multi-tone Transmission (DMT) and partial-response (PR) PAM4 are experimentally investigated, using a low-cost electro-absorption modulated laser (EML), a 25G driver and current state-of-the-art high Speed 84 GS/s CMOS digital-to-analog converter (DAC) and analog-to-digital converter (ADC) test chips. Each modulation Format is optimized independently for the desired scenario and their digital signal processing (DSP) requirements are investigated. The performance of Nyquist PAM4 and PR PAM4 depend very much on the efficiency of pre- and post-equalization. We show the necessity for at least 11 FFE-taps for pre-emphasis and up to 41 FFE coefficients at the receiver side. In addition, PR PAM4 requires an MLSE with four states to decode the signal back to a PAM4 signal. On the contrary, bit- and power-loading (BL, PL) is crucial for DMT and an FFT length of at least 512 is necessary. With optimized parameters, all Modulation formats result in a very similar performances, demonstrating a transmission distance of up to 10 km over SSMF with bit error rates (BERs) below a FEC threshold of 4.4E-3, allowing error free transmission.

High-Intensity Focused Ultrasound: Current Status for Image-Guided Therapy

PubMed Central

Copelan, Alexander; Hartman, Jason; Chehab, Monzer; Venkatesan, Aradhana M.

2015-01-01

Image-guided high-intensity focused ultrasound (HIFU) is an innovative therapeutic technology, permitting extracorporeal or endocavitary delivery of targeted thermal ablation while minimizing injury to the surrounding structures. While ultrasound-guided HIFU was the original image-guided system, MR-guided HIFU has many inherent advantages, including superior depiction of anatomic detail and superb real-time thermometry during thermoablation sessions, and it has recently demonstrated promising results in the treatment of both benign and malignant tumors. HIFU has been employed in the management of prostate cancer, hepatocellular carcinoma, uterine leiomyomas, and breast tumors, and has been associated with success in limited studies for palliative pain management in pancreatic cancer and bone tumors. Nonthermal HIFU bioeffects, including immune system modulation and targeted drug/gene therapy, are currently being explored in the preclinical realm, with an emphasis on leveraging these therapeutic effects in the care of the oncology patient. Although still in its early stages, the wide spectrum of therapeutic capabilities of HIFU offers great potential in the field of image-guided oncologic therapy. PMID:26622104

SU-E-T-59: A Novel Multi-Beam Dynamic IMRT with Fixed-Jaw Technique for Left Breast Cancer Patients with Regional Lymph Nodes Radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, J; Yang, Z; Hu, W

2015-06-15

Purpose: This study was to investigate the dosimetric benefit of a novel intensity modulated radiation therapy (IMRT) technique for irradiating the left breast and regional lymph node (RLN). Methods: The breast and RLN (internal mammary node and periclavicular node) and normal tissue were contoured for 16 consecutive left-sided breast cancer patients previously treated with RT after lumpectomy. Nine equi-spaced fields IMRT (9 -field IMRT), tangential multi-beam IMRT (tangential-IMRT) and IMRT with fixed-jaw technique (FJT-IMRT) were developed and compared with three-dimensional conformal RT (3DCRT). Prescribed dose was 50 Gy in 25 fractions. Dose distributions and dose volume histograms were used tomore » evaluate plans. Results: All IMRTs achieved similar target coverage and substantially reduced heart V30 and V20 compared to the 3DCRT. The average heart mean dose had different changes, which were 9.0Gy for 9-field IMRT, 5.7Gy for tangential-IMRT and 4.2Gy for FJT-IMRT. For the contralateral lung and breast, the 9-field IMRT has the highest mean dose; and the FJT-IMRT and tangential-IMRT had similar lower value. For the thyroid, both 9-field IMRT and FJT-IMRT had similar V30 (20% and 22%) and were significantly lower than that of 3DCRT (34%) and tangential-IMRT (46%). Moreover, the thyroid mean dose of FJT-IMRT is the lowest. For cervical esophagus and humeral head, the FJT-IMRT also had the best sparing. Conclusion: All 9-field IMRT, tangential-IMRT and FJT-IMRT had superiority for targets coverage and substantially reduced the heart volume of high dose irradiation. The FJT-IMRT showed advantages of avoiding the contralateral breast and lung irradiation and decreasing the thyroid, humeral head and cervical esophagus radiation dose at the expense of a slight monitor units (MUs) increasing.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Small, Katherine; Kelly, Chris; Beldham-Collins, Rachael

A comparative study was conducted comparing the difference between (1) conformal radiotherapy (CRT) to the whole breast with sequential boost excision cavity plans and (2) intensity-modulated radiation therapy (IMRT) to the whole breast with simultaneously integrated boost to the excision cavity. The computed tomography (CT) data sets of 25 breast cancer patients were used and the results analysed to determine if either planning method produced superior plans. CT data sets from 25 past breast cancer patients were planned using (1) CRT prescribed to 50 Gy in 25 fractions (Fx) to the whole-breast planning target volume (PTV) and 10 Gy inmore » 5Fx to the excision cavity and (2) IMRT prescribed to 60 Gy in 25Fx, with 60 Gy delivered to the excision cavity PTV and 50 Gy delivered to the whole-breast PTV, treated simultaneously. In total, 50 plans were created, with each plan evaluated by PTV coverage using conformity indices, plan maximum dose, lung dose, and heart maximum dose for patients with left-side lesions. CRT plans delivered the lowest plan maximum doses in 56% of cases (average CRT = 6314.34 cGy, IMRT = 6371.52 cGy). They also delivered the lowest mean lung dose in 68% of cases (average CRT = 1206.64 cGy, IMRT = 1288.37 cGy) and V20 in 88% of cases (average CRT = 20.03%, IMRT = 21.73%) and V30 doses in 92% of cases (average CRT = 16.82%, IMRT = 17.97%). IMRT created more conformal plans, using both conformity index and conformation number, in every instance, and lower heart maximum doses in 78.6% of cases (average CRT = 5295.26 cGy, IMRT = 5209.87 cGy). IMRT plans produced superior dose conformity and shorter treatment duration, but a slightly higher planning maximum and increased lung doses. IMRT plans are also faster to treat on a daily basis, with shorter fractionation.« less

Computerized breast parenchymal analysis on DCE-MRI

NASA Astrophysics Data System (ADS)

Li, Hui; Giger, Maryellen L.; Yuan, Yading; Jansen, Sanaz A.; Lan, Li; Bhooshan, Neha; Newstead, Gillian M.

2009-02-01

Breast density has been shown to be associated with the risk of developing breast cancer, and MRI has been recommended for high-risk women screening, however, it is still unknown how the breast parenchymal enhancement on DCE-MRI is associated with breast density and breast cancer risk. Ninety-two DCE-MRI exams of asymptomatic women with normal MR findings were included in this study. The 3D breast volume was automatically segmented using a volume-growing based algorithm. The extracted breast volume was classified into fibroglandular and fatty regions based on the discriminant analysis method. The parenchymal kinetic curves within the breast fibroglandular region were extracted and categorized by use of fuzzy c-means clustering, and various parenchymal kinetic characteristics were extracted from the most enhancing voxels. Correlation analysis between the computer-extracted percent dense measures and radiologist-noted BIRADS density ratings yielded a correlation coefficient of 0.76 (p<0.0001). From kinetic analyses, 70% (64/92) of most enhancing curves showed persistent curve type and reached peak parenchymal intensity at the last postcontrast time point; with 89% (82/92) of most enhancing curves reaching peak intensity at either 4th or 5th post-contrast time points. Women with dense breast (BIRADS 3 and 4) were found to have more parenchymal enhancement at their peak time point (Ep) with an average Ep of 116.5% while those women with fatty breasts (BIRADS 1 and 2) demonstrated an average Ep of 62.0%. In conclusion, breast parenchymal enhancement may be associated with breast density and may be potential useful as an additional characteristic for assessing breast cancer risk.

[Tricostantin A inhibits self-renewal of breast cancer stem cells in vitro].

PubMed

Peng, Li; Li, Fu-Xi; Shao, Wen-Feng; Xiong, Jing-Bo

2013-10-01

To investigate the effect of tricostantin A (TSA) on self-renewal of breast cancer stem cells and explore the mechanisms. Breast cancer cell lines MDA-MB-468, MDA-MB-231, MCF-7 and SKBR3 were cultured in suspension and treated with different concentrations of TSA for 7 days, using 0.1% DMSO as the control. Secondary mammosphere formation efficiency and percentage of CD44(+)/CD24(-) sub-population in the primary mammospheres were used to evaluate the effects of TSA on self-renewal of breast cancer stem cells. The breast cancer stem cell surface marker CD44(+)/CD24(-) and the percentage of apoptosis in the primary mammospheres were assayed using flow cytometry. The mRNA expressions of Nanog, Sox2 and Oct4 in the primary mammospheres were assayed with quantitative PCR. TSA at both 100 and 500 nmol/L, but not at 10 nmol/L, partially inhibited the self-renewal of breast cancer stem cells from the 4 cell lines. TSA at 500 nmol/L induced cell apoptosis in the primary mammospheres. TSA down-regulated the mRNA expression of Nanog and Sox2 in the primary mammospheres. TSA can partially inhibit the self-renewal of breast cancer stem cells through a mechanism involving the down-regulation of Nanog and Sox2 expression, indicating the value of combined treatments with low-dose TSA and other anticancer drugs to achieve maximum inhibition of breast cancer stem cell self-renewal. The core transcriptional factor of embryonic stem cells Nanog and Sox2 can be potential targets of anticancer therapy.

Systematic review of peer support for breastfeeding continuation: metaregression analysis of the effect of setting, intensity, and timing.

PubMed

Jolly, Kate; Ingram, Lucy; Khan, Khalid S; Deeks, Jonathan J; Freemantle, Nick; MacArthur, Christine

2012-01-25

To examine the effect of setting, intensity, and timing of peer support on breast feeding. Systematic review and metaregression analysis of randomised controlled trials. Cochrane Library, Medline, CINAHL, the National Research Register, and British Nursing Index were searched from inception or from 1980 to 2011. Review methods Study selection, data abstraction, and quality assessment were carried out independently and in duplicate. Risk ratios and 95% confidence intervals were calculated for individual studies and pooled. Effects were estimated for studies grouped according to setting (high income countries, low or middle income countries, and the United Kingdom), intensity (<5 and ≥5 planned contacts), and timing of peer support (postnatal period with or without antenatal care), and analysed using metaregression for any and exclusive breast feeding at last study follow-up. Peer support interventions had a significantly greater effect on any breast feeding in low or middle income countries (P<0.001), reducing the risk of not breast feeding at all by 30% (relative risk 0.70, 95% confidence interval 0.60 to 0.82) compared with a reduction of 7% (0.93, 0.87 to 1.00) in high income countries. Similarly, the risk of non-exclusive breast feeding decreased significantly more in low or middle income countries than in high income countries: 37% (0.63, 0.52 to 0.78) compared with 10% (0.90, 0.85 to 0.97); P=0.01. No significant effect on breast feeding was observed in UK based studies. Peer support had a greater effect on any breastfeeding rates when given at higher intensity (P=0.02) and only delivered in the postnatal period (P<0.001), although no differences were observed of its effect on exclusive breastfeeding rates by intensity or timing. Although peer support interventions increase breastfeeding continuation in low or middle income countries, especially exclusive breast feeding, this does not seem to apply in high income countries, particularly the United Kingdom, where breastfeeding support is part of routine postnatal healthcare. Peer support of low intensity does not seem to be effective. Policy relating to provision of peer support should be based on more specific evidence on setting and any new peer services in high income countries need to undergo concurrent evaluation.

DOE Office of Scientific and Technical Information (OSTI.GOV)

NONE

Is Non-invasive Image-Guided Breast Brachytherapy Good? – Jess Hiatt, MS Non-invasive Image-Guided Breast Brachytherapy (NIBB) is an emerging therapy for breast boost treatments as well as Accelerated Partial Breast Irradiation (APBI) using HDR surface breast brachytherapy. NIBB allows for smaller treatment volumes while maintaining optimal target coverage. Considering the real-time image-guidance and immobilization provided by the NIBB modality, minimal margins around the target tissue are necessary. Accelerated Partial Breast Irradiation in brachytherapy: is shorter better? - Dorin Todor, PhD VCU A review of balloon and strut devices will be provided together with the origins of APBI: the interstitial multi-catheter implant.more » A dosimetric and radiobiological perspective will help point out the evolution in breast brachytherapy, both in terms of devices and the protocols/clinical trials under which these devices are used. Improvements in imaging, delivery modalities and convenience are among the factors driving the ultrashort fractionation schedules but our understanding of both local control and toxicities associated with various treatments is lagging. A comparison between various schedules, from a radiobiological perspective, will be given together with a critical analysis of the issues. to review and understand the evolution and development of APBI using brachytherapy methods to understand the basis and limitations of radio-biological ‘equivalence’ between fractionation schedules to review commonly used and proposed fractionation schedules Intra-operative breast brachytherapy: Is one stop shopping best?- Bruce Libby, PhD. University of Virginia A review of intraoperative breast brachytherapy will be presented, including the Targit-A and other trials that have used electronic brachytherapy. More modern approaches, in which the lumpectomy procedure is integrated into an APBI workflow, will also be discussed. Learning Objectives: To review past and current clinical trials for IORT To discuss lumpectomy-scan-plan-treat workflow for IORT.« less

Interim Cosmetic Results and Toxicity Using 3D Conformal External Beam Radiotherapy to Deliver Accelerated Partial Breast Irradiation in Patients With Early-Stage Breast Cancer Treated With Breast-Conserving Therapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Vicini, Frank A.; Chen, Peter; Wallace, Michelle

2007-11-15

Purpose: We present our ongoing clinical experience utilizing three-dimensional (3D)-conformal radiation therapy (3D-CRT) to deliver accelerated partial breast irradiation (APBI) in patients with early-stage breast cancer treated with breast-conserving therapy. Methods and Materials: Ninety-one consecutive patients were treated with APBI using our previously reported 3D-CRT technique. The clinical target volume consisted of the lumpectomy cavity plus a 10- to 15 -mm margin. The prescribed dose was 34 or 38.5 Gy in 10 fractions given over 5 consecutive days. The median follow-up was 24 months. Twelve patients have been followed for {>=}4 years, 20 for {>=}3.5 years, 29 for >3.0 years,more » 33 for {>=}2.5 years, and 46 for {>=}2.0 years. Results: No local recurrences developed. Cosmetic results were rated as good/excellent in 100% of evaluable patients at {>=} 6 months (n = 47), 93% at 1 year (n = 43), 91% at 2 years (n = 21), and in 90% at {>=}3 years (n = 10). Erythema, hyperpigmentation, breast edema, breast pain, telangiectasias, fibrosis, and fat necrosis were evaluated at 6, 24, and 36 months after treatment. All factors stabilized by 3 years posttreatment with grade I or II rates of 0%, 0%, 0%, 0%, 9%, 18%, and 9%, respectively. Only 2 patients (3%) developed grade III toxicity (breast pain), which resolved with time. Conclusions: Delivery of APBI with 3D-CRT resulted in minimal chronic ({>=}6 months) toxicity to date with good/excellent cosmetic results. Additional follow-up is needed to assess the long-term efficacy of this form of APBI.« less

Breast cancer therapy based on melatonin.

PubMed

Sanchez-Barcelo, Emilio J; Mediavilla, Maria D; Alonso-Gonzalez, Carolina; Rueda, Noemi

2012-05-01

The usefulness of melatonin and melatoninergic drugs in breast cancer therapy is based on its Selective Estrogen Receptor Modulator (SERM) and Selective Estrogen Enzyme Modulator (SEEM) properties. Because of the oncostatic properties of melatonin, its nocturnal suppression by light-at-night (LAN) has been considered a risk-factor for breast cancer. Melatonin's SERM actions include modulation of estrogen-regulated cell proliferation, invasiveness and expression of proteins, growth factors and proto-oncogenes (hTERT, p53, p21, TGFβ, E-cadherin, etc.). These actions are observable with physiologic doses of melatonin only in cells expressing ERα, and mediated by MT1 melatonin receptors. Melatonin acts like a SEEM, inhibiting expression and activity of P450 aromatase, estrogen sulfatase and type 1, 17β- hydroxysteroid dehydrogenase, but stimulating that of estrogen sulfotransferase. This double action mechanism (SERM and SEEM), and the specificity for ERα bestows melatonin with potential advantages for breast cancer treatments, associated with other antiestrogenic drugs, and idea already patented. LAN enhances the growth of rat mammary tumors by decreasing or suppressing melatonin production. Epidemiologic studies have also described increased breast cancer risk in women exposed to LAN. Since the strongest suppression of nocturnal melatonin occurs with wavelength light of the blue spectral region, optical and lightening devices filtering the blue light spectrum have been proposed to avoid the risks of light-induced suppression of nocturnal melatonin.

Artificial neural network-based exploration of gene-nutrient interactions in folate and xenobiotic metabolic pathways that modulate susceptibility to breast cancer.

PubMed

Naushad, Shaik Mohammad; Ramaiah, M Janaki; Pavithrakumari, Manickam; Jayapriya, Jaganathan; Hussain, Tajamul; Alrokayan, Salman A; Gottumukkala, Suryanarayana Raju; Digumarti, Raghunadharao; Kutala, Vijay Kumar

2016-04-15

In the current study, an artificial neural network (ANN)-based breast cancer prediction model was developed from the data of folate and xenobiotic pathway genetic polymorphisms along with the nutritional and demographic variables to investigate how micronutrients modulate susceptibility to breast cancer. The developed ANN model explained 94.2% variability in breast cancer prediction. Fixed effect models of folate (400 μg/day) and B12 (6 μg/day) showed 33.3% and 11.3% risk reduction, respectively. Multifactor dimensionality reduction analysis showed the following interactions in responders to folate: RFC1 G80A × MTHFR C677T (primary), COMT H108L × CYP1A1 m2 (secondary), MTR A2756G (tertiary). The interactions among responders to B12 were RFC1G80A × cSHMT C1420T and CYP1A1 m2 × CYP1A1 m4. ANN simulations revealed that increased folate might restore ER and PR expression and reduce the promoter CpG island methylation of extra cellular superoxide dismutase and BRCA1. Dietary intake of folate appears to confer protection against breast cancer through its modulating effects on ER and PR expression and methylation of EC-SOD and BRCA1. Copyright © 2016 Elsevier B.V. All rights reserved.

Direct breast-feeding in the neonatal intensive care unit: is it important?

PubMed

Pineda, R

2011-08-01

Rates of breast milk feeding at hospital discharge are low in premature infants due to the many associated challenges. Although there are many benefits associated with breast milk, the effects of direct breast-feeding in the neonatal intensive care unit (NICU) have not been identified. The purpose of this study was to investigate the relationship between direct breast-feeding (infant sucking directly from the breast) and duration and success with breast milk feedings until discharge in premature infants. This retrospective cohort was conducted on 66 very-low birth weight infants whose mothers initiated breast milk feedings in the NICU. Chart review revealed documented type (breast milk with or without fortifiers or type of infant formula), volume and mode (nasogastric tube, breast or bottle) of all gastric feeds for each day of NICU hospitalization. From this documentation, whether the mother initiated breast milk feedings, the number of times the mother put the infant to breast, the gestational age of the first direct breast-feeding, whether the first oral feeding was at the breast, the duration of breast milk feedings and whether breast milk feedings continued until NICU discharge were determined. Associations between breast-feeding participatory factors and breast milk feeding outcomes were investigated using linear and logistic regression. Positive associations were found between breast milk feedings at discharge and mothers putting their infants directly to breast in the NICU (P=0.0005). The duration of breast milk feedings was associated with: mothers putting their infants directly to breast (P=0.0110), whether the first oral sucking feeding was at the breast (P=0.0108) and the gestational age of the first breast-feeding attempt (P<0.0001). Breast milk feedings are encouraged in most NICU's, but direct breast-feeding is often overlooked as an important area of research in the tightly controlled environment of the NICU. This study demonstrates a link between direct breast-feeding behaviors in the NICU and success with provision of milk at discharge, as well as how early participation can be an important factor in the breast-feeding process for mothers of NICU infants. More research on the effects of direct breast-feeding is warranted.

GPER1-mediated IGFBP-1 induction modulates IGF-1-dependent signaling in tamoxifen-treated breast cancer cells.

PubMed

Vaziri-Gohar, Ali; Houston, Kevin D

2016-02-15

Tamoxifen, a selective estrogen receptor modulator, is a commonly prescribed adjuvant therapy for estrogen receptor-α (ERα)-positive breast cancer patients. To determine if extracellular factors contribute to the modulation of IGF-1 signaling after tamoxifen treatment, MCF-7 cells were treated with IGF-1 in conditioned medium (CM) obtained from 4-OHT-treated MCF-7 cells and the accumulation of phospho-Akt (S473) was measured. CM inhibited IGF-1-dependent cell signaling and suggesting the involvement of extracellular factors (ie. IGFBPs). A significant increase in IGFBP-1 mRNA and extracellular IGFBP-1 protein was observed in 4-OHT-treated MCF-7 cells. Knockdown experiments demonstrated that both GPER1 and CREB mediate IGFBP-1 induction. Furthermore, experiments showed that 4-OHT-dependent IGFBP-1 transcription is downstream of GPER1-activation in breast cancer cells. Additionally, neutralization and knockdown experiments demonstrated a role for IGFBP-1 in the observed inhibition of IGF-1 signaling. These results suggested that 4-OHT inhibits IGF-1 signaling via GPER1 and CREB mediated extracellular IGFBP-1 accumulation in breast cancer cells. Copyright © 2015 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

Comparison of morbidity-related seroma formation following conventional latissimus dorsi flap versus muscle-sparing latissimus dorsi flap breast reconstruction

PubMed Central

Numajiri, Toshiaki; Nakatsukasa, Katsuhiko; Sakaguchi, Koichi; Taguchi, Tetsuya

2017-01-01

Purpose The pedicled, descending-branch muscle-sparing latissimus dorsi (MSLD) flap has been widely used for breast reconstruction following total mastectomy. However, the superiority of the MSLD flap compared to the conventional latissimus dorsi (CLD) flap in preventing seroma formation has not been demonstrated. This study compares the morbidities related to seroma formation following pedicled MSLD flap and CLD flap breast reconstruction. Methods A total of 15 women who underwent partial mastectomy and immediate partial breast reconstruction with MSLD flaps were compared with 15 women under identical conditions with CLD flap breast reconstruction. The medical records were reviewed for both complications and demographic data. The authors compared morbidity, including donor-site seroma, total volume of drain discharge, indwelling period of drainage, and length of hospital stay following both MSLD flap and CLD flap breast reconstruction. Results The demographic data of the 2 groups were not significantly different. Donor-site seroma occurred in 2 MSLD patients (13.3%) and in 6 CLD patients (40.0%). The total volume of the drain discharge and the indwelling period of drainage at donor site were significantly lower in the MSLD group. The length of hospital stay was significantly shorter (by approximately a day and a half) for the MSLD group. Conclusion The MSLD flap, with its low complication rate and associated minimal functional and aesthetic deficits at the donor site, may be a useful option for small breast reconstruction if earlier discharge from hospital is demanded. PMID:28932726

Comparison of morbidity-related seroma formation following conventional latissimus dorsi flap versus muscle-sparing latissimus dorsi flap breast reconstruction.

PubMed

Sowa, Yoshihiro; Numajiri, Toshiaki; Nakatsukasa, Katsuhiko; Sakaguchi, Koichi; Taguchi, Tetsuya

2017-09-01

The pedicled, descending-branch muscle-sparing latissimus dorsi (MSLD) flap has been widely used for breast reconstruction following total mastectomy. However, the superiority of the MSLD flap compared to the conventional latissimus dorsi (CLD) flap in preventing seroma formation has not been demonstrated. This study compares the morbidities related to seroma formation following pedicled MSLD flap and CLD flap breast reconstruction. A total of 15 women who underwent partial mastectomy and immediate partial breast reconstruction with MSLD flaps were compared with 15 women under identical conditions with CLD flap breast reconstruction. The medical records were reviewed for both complications and demographic data. The authors compared morbidity, including donor-site seroma, total volume of drain discharge, indwelling period of drainage, and length of hospital stay following both MSLD flap and CLD flap breast reconstruction. The demographic data of the 2 groups were not significantly different. Donor-site seroma occurred in 2 MSLD patients (13.3%) and in 6 CLD patients (40.0%). The total volume of the drain discharge and the indwelling period of drainage at donor site were significantly lower in the MSLD group. The length of hospital stay was significantly shorter (by approximately a day and a half) for the MSLD group. The MSLD flap, with its low complication rate and associated minimal functional and aesthetic deficits at the donor site, may be a useful option for small breast reconstruction if earlier discharge from hospital is demanded.

Five-year results of a prospective clinical trial investigating accelerated partial breast irradiation using 3D conformal radiotherapy after lumpectomy for early stage breast cancer.

PubMed

Horst, Kathleen C; Fasola, Carolina; Ikeda, Debra; Daniel, Bruce; Ognibene, Grant; Goffinet, Don R; Dirbas, Frederick M

2016-08-01

Accelerated partial breast irradiation (APBI) is emerging as an alternative to whole-breast irradiation. This study presents the results of a prospective trial evaluating 3-dimensional conformal radiotherapy (3D-CRT) to deliver APBI for early-stage breast cancer. Patients with unifocal stage 0-II breast cancer measuring ≤2.5 cm without lymph node involvement were eligible. After lumpectomy, 3D-CRT APBI was delivered to the lumpectomy cavity + margin (34-38.5 Gy in 10 fractions over 5 days). 141 patients with 143 breast cancers (2 bilateral) were treated with 3D-CRT APBI. Median age was 60. Median tumor size was 1.1 cm. At a median follow up of 60 months (range, 5-113), the 5-year and 8-year cumulative incidence rate of a true recurrence is 0.9%. The 5-year and 8-year cumulative incidence rates of an elsewhere failure are 2.4% and 4.4%, respectively. The 5-year and 8-year overall survival is 100% and 94%, respectively. Among the 62 patients with follow up >5 years, 95% had excellent/good cosmetic results. Our experience with 3D-CRT APBI demonstrates excellent cosmesis and local control. Longer follow up will be necessary to evaluate long-term efficacy and toxicity of 3D-CRT APBI. CLINICALTRIALS. NCT00185744. Copyright © 2016 Elsevier Ltd. All rights reserved.

Direct-methods structure determination of a trypanosome RNA-editing substrate fragment with translational pseudosymmetry

DOE PAGES

Mooers, Blaine H. M.

2016-03-24

Using direct methods starting from random phases, the crystal structure of a 32-base-pair RNA (675 non-H RNA atoms in the asymmetric unit) was determined using only the native diffraction data (resolution limit 1.05 Å) and the computer program SIR2014. The almost three helical turns of the RNA in the asymmetric unit introduced partial or imperfect translational pseudosymmetry (TPS) that modulated the intensities when averaged by the lMiller indices but still escaped automated detection. Almost six times as many random phase sets had to be tested on average to reach a correct structure compared with a similar-sized RNA hairpin (27 nucleotides,more » 580 non-H RNA atoms) without TPS. Lastly, more sensitive methods are needed for the automated detection of partial TPS.« less

Direct-methods structure determination of a trypanosome RNA-editing substrate fragment with translational pseudosymmetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mooers, Blaine H. M.

Using direct methods starting from random phases, the crystal structure of a 32-base-pair RNA (675 non-H RNA atoms in the asymmetric unit) was determined using only the native diffraction data (resolution limit 1.05 Å) and the computer program SIR2014. The almost three helical turns of the RNA in the asymmetric unit introduced partial or imperfect translational pseudosymmetry (TPS) that modulated the intensities when averaged by the lMiller indices but still escaped automated detection. Almost six times as many random phase sets had to be tested on average to reach a correct structure compared with a similar-sized RNA hairpin (27 nucleotides,more » 580 non-H RNA atoms) without TPS. Lastly, more sensitive methods are needed for the automated detection of partial TPS.« less

Development of a trans-admittance mammography (TAM) using 60×60 electrode array

NASA Astrophysics Data System (ADS)

Zhao, Mingkang; Liu, Qin; In Oh, Tong; Woo, Eung Je; Seo, Jin Keun

2010-04-01

We have developed a trans-admittance mammography (TAM) system as a supplementary or alternative method of the X-ray mammography to diagnose the breast cancer. Mechanical structure of the system is similar to the X-ray mammography with the breast placed between two plates. The pair of plates is movable to accommodate breasts with different sizes and rotatable to provide multiple images with different projection angles. Without using ionizing radiation, it acquires a projection image of tissue admittivity values. One plate is a flat solid electrode where we apply a constant sinusoidal voltage with a variable frequency. The other is equipped with 60×60 array of current-sensing electrodes, of which potentials are kept at the signal reference level. The electrode array is connected to six switching modules and each module routes current signals from 600 electrodes to two ammeter modules. Each ammeter module includes six channels of ammeters and each one of them comprises an independent current-to-voltage converter, voltage amplifier, ADC and digital phase-sensitive demodulator. Each ammeter sequentially measures exit currents from 50 electrodes chosen by the corresponding switching module. An FPGA controls six ammeters to collect real- and imaginary-parts of trans-admittance data from 300 electrodes. A separate FPGA arbitrates data and command exchanges between a DSP-based main controller and ammeter modules. It also generates a sinusoidal voltage signal to be applied to the breast. All the 3600 complex current data from 12 ammeter modules are transferred to the main controller, which is interfaced to a PC through an isolated USB. The system is provided with a program to display real- and imaginary-parts of measured trans-admittance maps. The measured maps at multiple frequencies are incorporated into a frequency-difference anomaly detection algorithm. In this paper, we describe the design and construction of the system.

A Monte Carlo model for mean glandular dose evaluation in spot compression mammography.

PubMed

Sarno, Antonio; Dance, David R; van Engen, Ruben E; Young, Kenneth C; Russo, Paolo; Di Lillo, Francesca; Mettivier, Giovanni; Bliznakova, Kristina; Fei, Baowei; Sechopoulos, Ioannis

2017-07-01

To characterize the dependence of normalized glandular dose (DgN) on various breast model and image acquisition parameters during spot compression mammography and other partial breast irradiation conditions, and evaluate alternative previously proposed dose-related metrics for this breast imaging modality. Using Monte Carlo simulations with both simple homogeneous breast models and patient-specific breasts, three different dose-related metrics for spot compression mammography were compared: the standard DgN, the normalized glandular dose to only the directly irradiated portion of the breast (DgNv), and the DgN obtained by the product of the DgN for full field irradiation and the ratio of the mid-height area of the irradiated breast to the entire breast area (DgN M ). How these metrics vary with field-of-view size, spot area thickness, x-ray energy, spot area and position, breast shape and size, and system geometry was characterized for the simple breast model and a comparison of the simple model results to those with patient-specific breasts was also performed. The DgN in spot compression mammography can vary considerably with breast area. However, the difference in breast thickness between the spot compressed area and the uncompressed area does not introduce a variation in DgN. As long as the spot compressed area is completely within the breast area and only the compressed breast portion is directly irradiated, its position and size does not introduce a variation in DgN for the homogeneous breast model. As expected, DgN is lower than DgNv for all partial breast irradiation areas, especially when considering spot compression areas within the clinically used range. DgN M underestimates DgN by 6.7% for a W/Rh spectrum at 28 kVp and for a 9 × 9 cm 2 compression paddle. As part of the development of a new breast dosimetry model, a task undertaken by the American Association of Physicists in Medicine and the European Federation of Organizations of Medical Physics, these results provide insight on how DgN and two alternative dose metrics behave with various image acquisition and model parameters. © 2017 American Association of Physicists in Medicine.

Stromal-epithelial dynamics in response to fractionated radiotherapy

NASA Astrophysics Data System (ADS)

Qayyum, Muqeem Abdul

Radiotherapy is central to the management of a number of human cancers, either as an adjuvant or primary treatment modality. The principal objective in irradiating tumors is to permanently inhibit their proliferative ability. More than half of all malignancies are primarily treated with radiation, but the heterotypic nature of tumor cells greatly complicates their response to radiotherapy. The need for reliable parameters to predict tumor and normal tissue response to radiation is therefore a prime concern of clinical oncology. Post-operative radiotherapy has commonly been used for early stage breast cancer to treat residual disease. There is continued debate as to what might be the proper dose per fraction as well as the total dose of radiation that needs to be prescribed to prevent disease recurrence. Countries outside the US have adopted increased dose fractionation (i.e., hypofractionation) schemes for early stage breast cancer as a standard of practice; however there is a lack of confidence in these approaches in the United States. The tumor microenvironment plays a significant role in regulating the progression of carcinomas, although the mechanisms are not entirely clear. The primary objective of this work was to characterize, through mechanobiological and radiobiological modeling, a test bed for radiotherapy fractionation techniques assessment. Our goal is to understand how the tumor microenvironment responds to dose fractionation schemes for Breast Conserving Therapy (BCT). Although carcinomas are the major concern for oncology, in this project, the goal is to understand how the stromal microenvironment influences behavior of the cancer cell populations. By classifying 3-D cellular co-cultures as having a reactive or quiescent stroma using the mechanobiology profile (culture stiffness,cellular activation, differentiation, and proliferation) we aim to differentiate the effectiveness of various fractionation schemes. The benefits of understanding heterotypic signaling in post-surgical breast cancer recurrence would be to assist radiation oncologists in designing an improved therapeutic strategy. To relate the parameters of cellular function to therapeutic prescriptions which offer an enhanced clinical outcome would address the lack of knowledge regarding recurrence of disease, tumor control and whether the tumor microenvironment requires more aggressive treatments. In our work to date, we have developed a three-dimensional co-culture model to determine how alternative dose fractionations affect the post-surgical microenvironment. This work suggests that 3-D co-cultures provide the microenvironmental cues needed to reexamine the radiobiological basis underlying radiation therapy. The findings suggest dose escalation to the tumor region may deactivate the reactive stroma, thus minimizing the cancer promoting environment. Large-fraction irradiation may be used to sterilize residual tumor cells and inhibit activation of intracellular transduction pathways that are promoted during the post-surgical wound-healing period. Wound-healing mechanisms are characterized by angiogenesis, fibroplasia, collagen production and granulation tissue formation all of which impact patient prognosis. In fact, tumor dose escalation trials have been proven to reduce local recurrence rates and thus new approaches to partial breast irradiation and tumor bed boosting using external-beam electrons and intensity-modulated radiotherapy (IMRT) techniques are currently under use. These techniques minimize absorbed dose to healthy breast tissues. Treating the residual cancer cells and the reactive stroma that has been stimulated by wound healing requires that we look at the interplay between cell types as well as the mechanical and biochemical factors driving disease. We have discovered that the reason hypofractionation schemes (larger irradiation fractions per day with less total dose) offer therapeutic advantages to some patients could be that it is more effective at treating the reactive stroma. We can kill the cancer cells at the standard rate (180 cGy/fraction), but we have found the larger fractions specifically inhibit wound healing mechanisms by inactivating stromal fibroblasts. The long term goal would be to reduce recurrence rates for early stage breast cancer by treating postsurgical regions most likely to harbor residual tumor cells. Ionizing radiation stress and its effect on ECM mediated cellular functions continues to be an evolving area of research. This study is an initial step in my career plans to study stromal modulation of epithelial tumors. It is also my career goal to integrate basic science experiments and engineering tools into clinical practice.

Partial Shade Stress Test for Thin-Film Photovoltaic Modules: Preprint

DOE Office of Scientific and Technical Information (OSTI.GOV)

Silverman, Timothy J.; Deceglie, Michael G.; Deline, Chris

2015-09-02

Partial shade of monolithic thin-film PV modules can cause reverse-bias conditions leading to permanent damage. In this work, we propose a partial shade stress test for thin-film PV modules that quantifies permanent performance loss. We designed the test with the aid of a computer model that predicts the local voltage, current and temperature stress that result from partial shade. The model predicts the module-scale interactions among the illumination pattern, the electrical properties of the photovoltaic material and the thermal properties of the module package. The test reproduces shading and loading conditions that may occur in the field. It accounts formore » reversible light-induced performance changes and for additional stress that may be introduced by light-enhanced reverse breakdown. We present simulated and experimental results from the application of the proposed test.« less

DOE Office of Scientific and Technical Information (OSTI.GOV)

Öğretici, Akın, E-mail: akinogretici@gmail.com; Akbaş, Uğur; Köksal, Canan

The aim of this research was to investigate the fetal doses of pregnant patients undergoing conformal radiotherapy or intensity-modulated radiation therapy (IMRT) for breast cancers. An Alderson Rando phantom was chosen to simulate a pregnant patient with breast cancer who is receiving radiation therapy. This phantom was irradiated using the Varian Clinac DBX 600 system (Varian Medical System, Palo Alto, CA) linear accelerator, according to the standard treatment plans of both three-dimensional conformal radiation therapy (3-D CRT) and IMRT techniques. Thermoluminescent dosimeters were used to measure the irradiated phantom's virtually designated uterus area. Thermoluminescent dosimeter measurements (in the phantom) revealedmore » that the mean cumulative fetal dose for 3-D CRT is 1.39 cGy and for IMRT it is 8.48 cGy, for a pregnant breast cancer woman who received radiation treatment of 50 Gy. The fetal dose was confirmed to increase by 70% for 3-D CRT and 40% for IMRT, if it is closer to the irradiated field by 5 cm. The mean fetal dose from 3-D CRT is 1.39 cGy and IMRT is 8.48 cGy, consistent with theoretic calculations. The IMRT technique causes the fetal dose to be 5 times more than that of 3-D CRT. Theoretic knowledge concerning the increase in the peripheral doses as the measurements approached the beam was also practically proven.« less

Preoperative Intensity Modulated Radiation Therapy and Chemotherapy for Locally Advanced Vulvar Carcinoma: Analysis of Pattern of Relapse

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beriwal, Sushil, E-mail: beriwals@upmc.edu; Shukla, Gaurav; Shinde, Ashwin

2013-04-01

Purpose: To examine clinical outcomes and relapse patterns in locally advanced vulvar carcinoma treated using preoperative chemotherapy and intensity modulated radiation therapy (IMRT). Methods and Materials: Forty-two patients with stage I-IV{sub A} (stage I, n=3; stage II, n=13; stage III, n=23; stage IV{sub A}, n=3) vulvar cancer were treated with chemotherapy and IMRT via a modified Gynecological Oncology Group schema using 5-fluorouracil and cisplatin with twice-daily IMRT during the first and last weeks of treatment or weekly cisplatin with daily radiation therapy. Median dose of radiation was 46.4 Gy. Results: Thirty-three patients (78.6%) had surgery for resection of vulva; 13more » of these patients also had inguinal lymph node dissection. Complete pathologic response was seen in 48.5% (n=16) of these patients. Of these, 15 had no recurrence at a median time of 26.5 months. Of the 17 patients with partial pathological response, 8 (47.1%) developed recurrence in the vulvar surgical site within a median of 8 (range, 5-34) months. No patient had grade ≥3 chronic gastrointestinal/genitourinary toxicity. Of those having surgery, 8 (24.2%) developed wound infections requiring debridement. Conclusions: Preoperative chemotherapy/IMRT was well tolerated, with good pathologic response and clinical outcome. The most common pattern of recurrence was local in patients with partial response, and strategies to increase pathologic response rate with increasing dose or adding different chemotherapy need to be explored to help further improve outcomes.« less

Long non-coding RNA FEZF1-AS1 promotes breast cancer stemness and tumorigenesis via targeting miR-30a/Nanog axis.

PubMed

Zhang, Zhi; Sun, Liwei; Zhang, Yixuan; Lu, Guanming; Li, Yongqiang; Wei, Zhongheng

2018-05-24

Long non-coding RNAs (lncRNAs) have been verified to modulate the tumorigenesis of breast cancer at multiple levels. In present study, we aim to investigate the role of lncRNA FEZF1-AS1 on breast cancer-stem like cells (BCSC) and the potential regulatory mechanism. In breast cancer tissue, lncRNA FEZF1-AS1 was up-regulated compared with controls and indicated poor prognosis of breast cancer patients. In vitro experiments, FEZF1-AS1 was significantly over-expressed in breast cancer cells, especially in sphere subpopulation compared with parental subpopulation. Loss-of-functional indicated that, in BCSC cells (MDA-MB-231 CSC, MCF-7 CSC), FEZF1-AS1 knockdown reduced the CD44 + /CD24 - rate, the mammosphere-forming ability, stem factors (Nanog, Oct4, SOX2), and inhibited the proliferation, migration and invasion. In vivo, FEZF1-AS1 knockdown inhibited the breast cancer cells growth. Bioinformatics analysis tools and series of validation experiments confirmed that FEZF1-AS1 modulated BCSC and Nanog expression through sponging miR-30a, suggesting the regulation of FEZF1-AS1/miR-30a/Nanog. In summary, our study validate the important role of FEZF1-AS1/miR-30a/Nanog in breast cancer stemness and tumorigenesis, providing a novel insight and treatment strategy for breast cancer. © 2018 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals Inc.

Role of melatonin on electromagnetic radiation-induced oxidative stress and Ca2+ signaling molecular pathways in breast cancer.

PubMed

Naziroğlu, Mustafa; Tokat, Sümeyye; Demirci, Seda

2012-12-01

Exposure to electromagnetic radiation (EMR) may increase breast cancer risk by inducing oxidative stress and suppressing the production of melatonin. Aim of the present review is to discuss the mechanisms and risk factors of EMR and oxidative stress-induced breast cancer, to summarize the controlled studies evaluating measures for prevention, and to conclude with evidence-based strategies for prevention. Review of the relevant literature and results from our recent basic studies, as well as critical analyses of published systematic reviews were obtained from the Pubmed and the Science Citation Index. It has been proposed that chronic exposure to EMR may increase the risk of breast cancer by suppressing the production of melatonin; this suppression may affect the development of breast cancer either by increasing levels of circulation of estrogen or through over production of free oxygen radicals. Most epidemiological studies have also indicated overall effect of EMR exposure in premenopausal women, particularly for estrogen receptor positive breast tumors. Enhanced voltage-dependent Ca(2+) current and impaired inhibitory G-protein function, and derangement of intracellular organelles with a Ca(2+) buffering effect, such as endoplasmic reticulum and mitochondria have been also shown to contribute to disturbed Ca(2+) signaling in breast cancer. Melatonin may modulate breast cancer through modulation of enhanced oxidative stress and Ca(2+) influx in cell lines. However, there is not enough evidence on increased risk of breast cancer related to EMR exposure.

MO-E-BRD-03: Intra-Operative Breast Brachytherapy: Is One Stop Shopping Best? [Non-invasive Image-Guided Breast Brachytherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Libby, B.

2015-06-15

Is Non-invasive Image-Guided Breast Brachytherapy Good? – Jess Hiatt, MS Non-invasive Image-Guided Breast Brachytherapy (NIBB) is an emerging therapy for breast boost treatments as well as Accelerated Partial Breast Irradiation (APBI) using HDR surface breast brachytherapy. NIBB allows for smaller treatment volumes while maintaining optimal target coverage. Considering the real-time image-guidance and immobilization provided by the NIBB modality, minimal margins around the target tissue are necessary. Accelerated Partial Breast Irradiation in brachytherapy: is shorter better? - Dorin Todor, PhD VCU A review of balloon and strut devices will be provided together with the origins of APBI: the interstitial multi-catheter implant.more » A dosimetric and radiobiological perspective will help point out the evolution in breast brachytherapy, both in terms of devices and the protocols/clinical trials under which these devices are used. Improvements in imaging, delivery modalities and convenience are among the factors driving the ultrashort fractionation schedules but our understanding of both local control and toxicities associated with various treatments is lagging. A comparison between various schedules, from a radiobiological perspective, will be given together with a critical analysis of the issues. to review and understand the evolution and development of APBI using brachytherapy methods to understand the basis and limitations of radio-biological ‘equivalence’ between fractionation schedules to review commonly used and proposed fractionation schedules Intra-operative breast brachytherapy: Is one stop shopping best?- Bruce Libby, PhD. University of Virginia A review of intraoperative breast brachytherapy will be presented, including the Targit-A and other trials that have used electronic brachytherapy. More modern approaches, in which the lumpectomy procedure is integrated into an APBI workflow, will also be discussed. Learning Objectives: To review past and current clinical trials for IORT To discuss lumpectomy-scan-plan-treat workflow for IORT.« less

Breast Cancer Malignant Processes are Regulated by Pax-5 Through the Disruption of FAK Signaling Pathways

PubMed Central

Benzina, Sami; Harquail, Jason; Guerrette, Roxann; O'Brien, Pierre; Jean, Stéphanie; Crapoulet, Nicolas; Robichaud, Gilles A.

2016-01-01

The study of genetic factors regulating breast cancer malignancy is a top priority to mitigate the morbidity and mortality associated with this disease. One of these factors, Pax-5, modulates cancer aggressiveness through the regulation of various components of the epithelial to mesenchymal transitioning (EMT) process. We have previously reported that Pax-5 expression profiles in cancer tissues inversely correlate with those of the Focal Adhesion Kinase (FAK), a potent activator of breast cancer malignancy. In this study, we set out to elucidate the molecular and regulatory relationship between Pax-5 and FAK in breast cancer processes. Interestingly, we found that Pax-5 mediated suppression of breast cancer cell migration is dependent of FAK activity. Our mechanistic examination revealed that Pax-5 inhibits FAK expression and activation. We also demonstrate that Pax-5 is a potent modulator of FAK repressors (p53 and miR-135b) and activator (NFκB) which results in the overall suppression of FAK-mediated signaling cascades. Altogether, our findings bring more insight to the molecular triggers regulating phenotypic transitioning process and signaling cascades leading to breast cancer progression. PMID:28070224

MicroRNAs as biomarkers for early breast cancer diagnosis, prognosis and therapy prediction.

PubMed

Nassar, Farah J; Nasr, Rihab; Talhouk, Rabih

2017-04-01

Breast cancer is a major health problem that affects one in eight women worldwide. As such, detecting breast cancer at an early stage anticipates better disease outcome and prolonged patient survival. Extensive research has shown that microRNA (miRNA) are dysregulated at all stages of breast cancer. miRNA are a class of small noncoding RNA molecules that can modulate gene expression and are easily accessible and quantifiable. This review highlights miRNA as diagnostic, prognostic and therapy predictive biomarkers for early breast cancer with an emphasis on the latter. It also examines the challenges that lie ahead in their use as biomarkers. Noteworthy, this review addresses miRNAs reported in patients with early breast cancer prior to chemotherapy, radiotherapy, surgical procedures or distant metastasis (unless indicated otherwise). In this context, miRNA that are mentioned in this review were significantly modulated using more than one statistical test and/or validated by at least two studies. A standardized protocol for miRNA assessment is proposed starting from sample collection to data analysis that ensures comparative analysis of data and reproducibility of results. Copyright © 2016 Elsevier Inc. All rights reserved.

Assembly and evaluation of a training module and dataset with feedback for improved interpretation of digital breast tomosynthesis examinations

NASA Astrophysics Data System (ADS)

Gur, David; Zuley, Margarita L.; Sumkin, Jules H.; Hakim, Christiane M.; Chough, Denise M.; Lovy, Linda; Sobran, Cynthia; Logue, Durwin; Zheng, Bin; Klym, Amy H.

2012-02-01

The FDA recently approved Digital Breast Tomosynthesis (DBT) for use in screening for the early detection of breast cancer. However, MQSA qualification for interpreting DBT through training was noted as important. Performance issues related to training are largely unknown. Therefore, we assembled a unique computerized training module to assess radiologists' performances before and after using the training module. Seventy-one actual baseline mammograms (no priors) with FFDM and DBT images were assembled to be read before and after training with the developed module. Fifty examinations of FFDM and DBT images enriched with positive findings were assembled for the training module. Depicted findings were carefully reviewed, summarized, and entered into a specially designed training database where findings were identified by case number and synchronized to the display of the related FFDM plus DBT examinations on a clinical workstation. Readers reported any findings using screening BIRADS (0, 1, or 2) followed by instantaneous feedback of the verified truth. Six radiologists participated in the study and reader average sensitivity and specificity were compared before and after training. Average sensitivity improved and specificity remained relatively the same after training. Performance changes may be affected by disease prevalence in the training set.

bc-GenExMiner 3.0: new mining module computes breast cancer gene expression correlation analyses.

PubMed

Jézéquel, Pascal; Frénel, Jean-Sébastien; Campion, Loïc; Guérin-Charbonnel, Catherine; Gouraud, Wilfried; Ricolleau, Gabriel; Campone, Mario

2013-01-01

We recently developed a user-friendly web-based application called bc-GenExMiner (http://bcgenex.centregauducheau.fr), which offered the possibility to evaluate prognostic informativity of genes in breast cancer by means of a 'prognostic module'. In this study, we develop a new module called 'correlation module', which includes three kinds of gene expression correlation analyses. The first one computes correlation coefficient between 2 or more (up to 10) chosen genes. The second one produces two lists of genes that are most correlated (positively and negatively) to a 'tested' gene. A gene ontology (GO) mining function is also proposed to explore GO 'biological process', 'molecular function' and 'cellular component' terms enrichment for the output lists of most correlated genes. The third one explores gene expression correlation between the 15 telomeric and 15 centromeric genes surrounding a 'tested' gene. These correlation analyses can be performed in different groups of patients: all patients (without any subtyping), in molecular subtypes (basal-like, HER2+, luminal A and luminal B) and according to oestrogen receptor status. Validation tests based on published data showed that these automatized analyses lead to results consistent with studies' conclusions. In brief, this new module has been developed to help basic researchers explore molecular mechanisms of breast cancer. DATABASE URL: http://bcgenex.centregauducheau.fr

Identification of Novel Human Breast Carcinoma (MDA-MB-231) Cell Growth Modulators from a Carbohydrate-Based Diversity Oriented Synthesis Library.

PubMed

Lenci, Elena; Innocenti, Riccardo; Biagioni, Alessio; Menchi, Gloria; Bianchini, Francesca; Trabocchi, Andrea

2016-10-20

The application of a cell-based growth inhibition on a library of skeletally different glycomimetics allowed for the selection of a hexahydro-2 H -furo[3,2- b ][1,4]oxazine compound as candidate inhibitors of MDA-MB-231 cell growth. Subsequent synthesis of analogue compounds and preliminary biological studies validated the selection of a valuable hit compound with a novel polyhydroxylated structure for the modulation of the breast carcinoma cell cycle mechanism.

The early development phases of a European Organisation for Research and Treatment of Cancer (EORTC) module to assess patient reported outcomes (PROs) in women undergoing breast reconstruction.

PubMed

Thomson, H J; Winters, Z E; Brandberg, Y; Didier, F; Blazeby, J M; Mills, J

2013-03-01

A comprehensive evaluation of breast reconstruction (BRR) surgery includes measurement of patient reported outcomes (PROs). There is, however, a lack of validated BRR-specific PRO measures (PROMs) that adequately assess relevant issues. This study is developing a European Organisation for Research and Treatment of Cancer (EORTC) questionnaire/module specific for PROs in BRR to supplement the cancer-core and breast cancer EORTC questionnaires, respectively: the QLQ-C30 and QLQ-BR23. Phases I and II of questionnaire development followed EORTC guidelines including a systematic literature review to identify all potential 'issues' (concepts relevant to PROs) and semi-structured interviews with 89 patients and 9 European multi-disciplinary health care professionals (HCPs) (Sweden, Italy and the United Kingdom [UK]). Interviewers asked participants the 'relevance' of outcomes identified in the literature and captured additional 'issues' of importance. The literature search and interviews of patients and HCPs yielded 69 issues relating to BRR operationalised into 31 provisional items (single questions) for the module, which was conceptualised to contain five scales: treatment/surgery related symptoms (affecting the shoulder, arm and reconstructed breast), body image, sexuality, cosmetic outcomes (pertaining to three areas: breast, donor site and nipple) and overall satisfaction. The provisional development of the EORTC BRR module has 31 items addressing issues of importance to patients as well as HCPs. Further international testing is underway as a UK National Cancer Research Network trial to ensure that this PROM will be psychometrically and clinically robust and applicable for use in clinical trials, cohort studies, national audit and clinical practice. Copyright © 2012 Elsevier Ltd. All rights reserved.

Preoperative Accelerated Partial Breast Irradiation for Early-Stage Breast Cancer: Preliminary Results of a Prospective, Phase 2 Trial

DOE Office of Scientific and Technical Information (OSTI.GOV)

Nichols, Elizabeth, E-mail: Enichols1@umm.edu; Kesmodel, Susan B.; Bellavance, Emily

Purpose: To assess the feasibility of utilizing 3-dimensional conformal accelerated partial-breast irradiation (APBI) in the preoperative setting followed by standard breast-conserving therapy. Patients and Methods: This was a prospective trial testing the feasibility of preoperative APBI followed by lumpectomy for patients with early-stage invasive ductal breast cancer. Eligible patients had T1-T2 (<3 cm), N0 tumors. Patients received 38.5 Gy in 3.85-Gy fractions delivered twice daily. Surgery was performed >21 days after radiation therapy. Adjuvant therapy was given as per standard of care. Results: Twenty-seven patients completed treatment. With a median follow-up of 3.6 years (range, 0.5-5 years), there have been no local or regional failures.more » A complete pathologic response according to hematoxylin and eosin stains was seen in 4 patients (15%). There were 4 grade 3 seromas. Patient-reported cosmetic outcome was rated as good to excellent in 79% of patients after treatment. Conclusions: Preoperative 3-dimensional conformal radiation therapy−APBI is feasible and well tolerated in select patients with early-stage breast cancer, with no reported local recurrences and good to excellent cosmetic results. The pathologic response rates associated with this nonablative APBI dose regimen are particularly encouraging and support further exploration of this paradigm.« less

Breast cancer and protein biomarkers

PubMed Central

Gam, Lay-Harn

2012-01-01

Breast cancer is a healthcare concern of women worldwide. Despite procedures being available for diagnosis, prognosis and treatment of breast cancer, researchers are working intensively on the disease in order to improve the life quality of breast cancer patients. At present, there is no single treatment known to bring a definite cure for breast cancer. One of the possible solutions for combating breast cancer is through identification of reliable protein biomarkers that can be effectively used for early detection, prognosis and treatments of the cancer. Therefore, the task of identification of biomarkers for breast cancer has become the focus of many researchers worldwide. PMID:24520539

Caregiving Factors Affecting Breastfeeding Duration Within a Neonatal Intensive Care Unit.

PubMed

Casavant, Sharon G; McGrath, Jacqueline M; Burke, Georgine; Briere, Carrie-Ellen

2015-12-01

Increasingly, evidence supports oral feeding of very low birth-weight (VLBW) preterm infants exclusively at breast or with breast milk. Despite known breast milk benefits, outcomes related to exclusive breast milk provision are poor. Identifying factors that promote breast milk provision is critical. Breastfeeding practices of mothers of VLBW infants admitted to neonatal intensive care unit were explored to identify factors associated with mode of feeding at discharge. This retrospective study replicates previous work. Subjects were VLBW preterm infants consecutively admitted during a 24-month period. Primary outcomes included receiving any breast milk at discharge. Infant variables included gestational age, postmenstrual age of first direct breastfeeding, and comorbid conditions. Maternal variables included age and ethnicity. Nursing practice variables included first direct-to-breastfeeding, number of times to breast daily, and total direct-to-breastfeeding encounters 24 hours prior to discharge. A total of 96 VLBW infants (28.7 ± 2.8 weeks' gestational age) met inclusion criteria. Of these, 48% received breast milk at discharge. Controlling for significant effect of length of stay, infants receiving first oral feed at breast were more likely discharged home receiving breast milk (adjusted odds ratio = 8.7; 95% confidence interval, 2.9-32.3; P < .0001). There were both an independent effect of first oral feed at breast and an interaction where infants of nonmarried women also benefited from the first oral feed at breast. Significant associations were found between first oral feeding at breast and infant receiving any breast milk at discharge. Targeting VLBW infants to receive first oral feeding at breast may yield the best outcome even among sickest and smallest infants.

Poster - Thurs Eve-09: Evaluation of a commercial 2D ion-chamber array for intensity modulated radiation therapy dose measurements.

PubMed

Mei, X; Bracken, G; Kerr, A

2008-07-01

Experimental verification of calculated dose from a treatment planning system is often essential for quality assurance (QA) of intensity modulated radiation therapy (IMRT). Film dosimetry and single ion chamber measurements are commonly used for IMRT QA. Film dosimetry has very good spatial resolution, but is labor intensive and absolute dose is not reliable. Ion chamber measurements are still required for absolute dose after measurements using films. Dosimeters based on 2D detector arrays that can measure 2D dose in real-time are gaining wider use. These devices provide a much easier and reliable tool for IMRT QA. We report the evaluation of a commercial 2D ion chamber array, including its basic performance characteristics, such as linearity, reproducibility and uniformity of relative ion chamber sensitivities, and comparisons between measured 2D dose and calculated dose with a commercial treatment planning system. Our analysis shows this matrix has excellent linearity and reproducibility, but relative sensitivities are tilted such that the +Y region is over sensitive, while the -Y region is under sensitive. Despite this behavior, our results show good agreement between measured 2D dose profiles and Eclipse planned data for IMRT test plans and a few verification plans for clinical breast field-in-field plans. The gamma values (3% or 3 mm distance-to-agreement) are all less than 1 except for one or two pixels at the field edge This device provides a fast and reliable stand-alone dosimeter for IMRT QA. © 2008 American Association of Physicists in Medicine.

A diffusion-based truncated projection artifact reduction method for iterative digital breast tomosynthesis reconstruction

PubMed Central

Lu, Yao; Chan, Heang-Ping; Wei, Jun; Hadjiiski, Lubomir M

2014-01-01

Digital breast tomosynthesis (DBT) has strong promise to improve sensitivity for detecting breast cancer. DBT reconstruction estimates the breast tissue attenuation using projection views (PVs) acquired in a limited angular range. Because of the limited field of view (FOV) of the detector, the PVs may not completely cover the breast in the x-ray source motion direction at large projection angles. The voxels in the imaged volume cannot be updated when they are outside the FOV, thus causing a discontinuity in intensity across the FOV boundaries in the reconstructed slices, which we refer to as the truncated projection artifact (TPA). Most existing TPA reduction methods were developed for the filtered backprojection method in the context of computed tomography. In this study, we developed a new diffusion-based method to reduce TPAs during DBT reconstruction using the simultaneous algebraic reconstruction technique (SART). Our TPA reduction method compensates for the discontinuity in background intensity outside the FOV of the current PV after each PV updating in SART. The difference in voxel values across the FOV boundary is smoothly diffused to the region beyond the FOV of the current PV. Diffusion-based background intensity estimation is performed iteratively to avoid structured artifacts. The method is applicable to TPA in both the forward and backward directions of the PVs and for any number of iterations during reconstruction. The effectiveness of the new method was evaluated by comparing the visual quality of the reconstructed slices and the measured discontinuities across the TPA with and without artifact correction at various iterations. The results demonstrated that the diffusion-based intensity compensation method reduced the TPA while preserving the detailed tissue structures. The visibility of breast lesions obscured by the TPA was improved after artifact reduction. PMID:23318346

Quantitative Analysis of Diffusion-Weighted Imaging for Diagnosis of Puerperal Breast Abscess After Polyacrylamide Hydrogel Augmentation Mammoplasty: Compared with Other Conventional Modalities.

PubMed

Liu, Lihua; Long, Miaomiao; Wang, Junping; Liu, Ning; Ge, Xihong; Hu, Zhandong; Shen, Wen

2015-02-01

Puerperal breast abscess after polyacrylamide hydrogel (PAAG) augmentation mammoplasty can induce breast auto-inflation resulting in serious consequences. Mammography, ultrasound, and conventional MRI are poor at detecting related PAAG abnormality histologically. We evaluated the value of diffusion-weighted imaging (DWI) in the quantitative analysis of puerperal PAAG abscess after augmentation mammoplasty. This was a retrospective study, and a waiver for informed consent was granted. Sixteen puerperal women with breast discomfort underwent conventional breast non-enhanced MRI and axial DWI using a 3T MR scanner. Qualitative analysis of the signal intensity on DWI and conventional sequences was performed. The apparent diffusion coefficient (ADC) values of the affected and contralateral normal PAAG cysts were measured quantitatively. Paired t test was used to evaluate whether there was significant difference. Both affected and normal PAAG cysts showed equal signal intensity on conventional T1WI and fat saturation T2WI, which were not helpful in detecting puerperal PAAG abscess. However, the affected PAAG cysts had a significantly decreased ADC value of 1.477 ± 0.332 × 10(-3)mm(2)/s and showed obvious hypo-intensity on the ADC map and increased signal intensity on DWI compared with the ADC value of 2.775 ± 0.233 × 10(-3)mm(2)/s of the contralateral normal PAAG cysts. DWI and quantitative measurement of ADC values are of great value for the diagnosis of puerperal PAAG abscess. Standardized MRI should be suggested to these puerperal women with breast discomfort or just for the purpose of check up. DWI should be selected as the essential MRI sequence.

Bottle feeding and ideology in colonial Malaya: the production of change.

PubMed

Manderson, L

1982-01-01

Considerable attention has been paid to the correlation between high infant morbidity and mortality rates and the increased incidence of bottle feeding. The shift from prolonged breast feeding to a mixed regime or the exclusive use of sweetened condensed milk or infant formula has been related to the promotional activities of milk companies, and typically has been presented as a relatively recent development in Third World countries. However, the marketing of tinned and powdered milk only partially explains the increased use of these products. In colonial Malaya, condensed milk was marketed from the late 19th century. Infant formula was available from the turn of the century and was widely advertised, first in the English-language press and later also in the vernacular presses. At the same time, other social and cultural factors served to discourage breast feeding. There were changes in ideas regarding ideal body weight for both women and infants, and regarding infant care and diet; these ideas were presented in the mass media. In addition, maternal and child health clinics, established in the 1920s to reduce the high infant mortality rate, both propagated popular beliefs about infant weight and supplied milk and educated women to artificially feed their infants. Industry, the media, and health services all promoted, if not always intentionally, bottle feeding rather than breast feeding. Bottle feeding as an ideal, if not a reality, was thus well established before the intensive promotion of milk products by multinational corporations that followed the political independence of the colony.

Estimation of T2* Relaxation Time of Breast Cancer: Correlation with Clinical, Imaging and Pathological Features

PubMed Central

Seo, Mirinae; Jahng, Geon-Ho; Sohn, Yu-Mee; Rhee, Sun Jung; Oh, Jang-Hoon; Won, Kyu-Yeoun

2017-01-01

Objective The purpose of this study was to estimate the T2* relaxation time in breast cancer, and to evaluate the association between the T2* value with clinical-imaging-pathological features of breast cancer. Materials and Methods Between January 2011 and July 2013, 107 consecutive women with 107 breast cancers underwent multi-echo T2*-weighted imaging on a 3T clinical magnetic resonance imaging system. The Student's t test and one-way analysis of variance were used to compare the T2* values of cancer for different groups, based on the clinical-imaging-pathological features. In addition, multiple linear regression analysis was performed to find independent predictive factors associated with the T2* values. Results Of the 107 breast cancers, 92 were invasive and 15 were ductal carcinoma in situ (DCIS). The mean T2* value of invasive cancers was significantly longer than that of DCIS (p = 0.029). Signal intensity on T2-weighted imaging (T2WI) and histologic grade of invasive breast cancers showed significant correlation with T2* relaxation time in univariate and multivariate analysis. Breast cancer groups with higher signal intensity on T2WI showed longer T2* relaxation time (p = 0.005). Cancer groups with higher histologic grade showed longer T2* relaxation time (p = 0.017). Conclusion The T2* value is significantly longer in invasive cancer than in DCIS. In invasive cancers, T2* relaxation time is significantly longer in higher histologic grades and high signal intensity on T2WI. Based on these preliminary data, quantitative T2* mapping has the potential to be useful in the characterization of breast cancer. PMID:28096732

Is there a specific magnetic resonance phenotype characteristic of hereditary breast cancer?

PubMed

Trecate, Giovanna; Manoukian, Siranuosh; Suman, Laura; Vergnaghi, Daniele; Marchesini, Monica; Agresti, Roberto; Ferraris, Cristina; Peissel, Bernard; Scaramuzza, Davide; Bergonzi, Silvana

2010-01-01

The aim of the study was to investigate the growth rate of inherited breast cancer, to analyze its T2 signal intensity besides kinetic and morphologic aspects, and to verify whether there is any correlation between magnetic resonance imaging phenotype and BRCA status. Between June 2000 and September 2009, we enrolled 227 women at high genetic risk for breast cancer in a surveillance program, within a multicenter project of the Istituto Superiore di Sanità (Rome). Thirty-four cancers were detected among 31 subjects. One patient refused magnetic resonance imaging because of claustrophobia. Compared with sporadic disease, hereditary cancer showed some differences, in terms of biologic attitude and semeiotic patterns. These differences were mainly registered for magnetic resonance imaging, where the most frequent radiological variant was represented by the very high T2 signal intensity (73%). Moreover, the size of 8 of the neoplasms showed a significant increase in less than one year, 5 of them in less than 6 months. Six lesions were in BRCA1 patients and the remaining in BRCA2. Furthermore, cancers with a high growth rate also demonstrated a significant increment in T2 signal intensity. Our results confirmed the high growth rate within BRCA-related breast cancers, especially for BRCA1 mutation carriers. In our experience, we found a specific imaging phenotype, represented by the high T2 signal intensity of hereditary breast cancer. To our knowledge, this is the first report that points out this new semeiotic parameter, which is usually typical of benign lesions. Considering the correlation between high growth rate and high T2 signal intensity, the former seems to be related to the absence of induction of a desmoplastic reaction that could somehow restrict cancer growth.

Breast Cancer Prevention

MedlinePlus

... estrogen-only hormone therapy after hysterectomy, selective estrogen receptor modulators, or aromatase inhibitors and inactivators Estrogen-only ... who take estrogen after a hysterectomy. Selective estrogen receptor modulators Tamoxifen and raloxifene belong to the family ...

Direct-Conversion Molecular Breast Imaging of Invasive Breast Cancer: Imaging Features, Extent of Invasive Disease, and Comparison Between Invasive Ductal and Lobular Histology.

PubMed

Conners, Amy Lynn; Jones, Katie N; Hruska, Carrie B; Geske, Jennifer R; Boughey, Judy C; Rhodes, Deborah J

2015-09-01

The purposes of this study were to compare the tumor appearance of invasive breast cancer on direct-conversion molecular breast imaging using a standardized lexicon and to determine how often direct-conversion molecular breast imaging identifies all known invasive tumor foci in the breast, and whether this differs for invasive ductal versus lobular histologic profiles. Patients with prior invasive breast cancer and concurrent direct-conversion molecular breast imaging examinations were retrospectively reviewed. Blinded review of direct-conversion molecular breast imaging examinations was performed by one of two radiologists, according to a validated lexicon. Direct-conversion molecular breast imaging findings were matched with lesions described on the pathology report to exclude benign reasons for direct-conversion molecular breast imaging findings and to document direct-conversion molecular breast imaging-occult tumor foci. Associations between direct-conversion molecular breast imaging findings and tumor histologic profiles were examined using chi-square tests. In 286 patients, 390 invasive tumor foci were present in 294 breasts. A corresponding direct-conversion molecular breast imaging finding was present for 341 of 390 (87%) tumor foci described on the pathology report. Invasive ductal carcinoma (IDC) tumor foci were more likely to be a mass (40% IDC vs 15% invasive lobular carcinoma [ILC]; p < 0.001) and to have marked intensity than were ILC foci (63% IDC vs 32% ILC; p < 0.001). Direct-conversion molecular breast imaging correctly revealed all pathology-proven foci of invasive disease in 79.8% of cases and was more likely to do so for IDC than for ILC (86.1% vs 56.7%; p < 0.0001). Overall, direct-conversion molecular breast imaging showed all known invasive foci in 249 of 286 (87%) patients. Direct-conversion molecular breast imaging features of invasive cancer, including lesion type and intensity, differ by histologic subtype. Direct-conversion molecular breast imaging is less likely to show all foci of ILC compared with IDC.

The theory of modulated hormone therapy for the treatment of breast cancer in pre- and post-menopausal women

NASA Astrophysics Data System (ADS)

Wiley, Teresa S.; Haraldsen, Jason T.

2012-03-01

We present a theory that questions the standard of care for pre- and post-menopausal women with breast cancer. Through the use of modulated hormones to mimic the natural multiphasic fluctuations of estrogen and progesterone cycles of healthy young women, it can be expected that patients will not only exhibit increased quality of life such as better sleep, well-being, and libido, but also memory improvement and less joint pain. Additionally, this regimen may engage genetic pathways that protect women in youth from breast cancers. We present a mathematical basis for the coupling of the hormone cycles through the use of Gaussian curves that provides the foundation of a new format of hormone replacement in women.

The effects of virgin coconut oil (VCO) as supplementation on quality of life (QOL) among breast cancer patients.

PubMed

Law, Kim Sooi; Azman, Nizuwan; Omar, Eshaifol Azam; Musa, Muhammad Yusri; Yusoff, Narazah Mohd; Sulaiman, Siti Amrah; Hussain, Nik Hazlina Nik

2014-08-27

Breast cancer is the most common cancer amongst Malaysian women. Both the disease and its treatment can disrupt the lives of the woman and adversely affect all aspects of life and thus can alter a woman's quality of life. The aim of this study was to examine the effect of virgin coconut oil (VCO) on the quality of life (QOL) of patients diagnosed with breast cancer. This was a prospective study of breast cancer patients admitted into the Oncology Unit of Hospital Universiti Sains Malaysia, Kubang Kerian, Kelantan, Malaysia. The sample consisted of 60 patients with stage III and IV breast cancer allocated to either an intervention group (n = 30) or a control group (n = 30) using a simple random table. QOL was evaluated from the first cycle of chemotherapy to the sixth cycle, and data were collected using a validated Bahasa Malaysia version of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Breast Cancer Module (EORTC QLQ-C30) and its breast-specific module (QLQ-BR 23). The mean age of breast cancer patients was 50.2 (SD = 13.5) years. There were significant mean score differences for functioning and global QOL between groups (α < 0.01). The intervention group also had better scores for symptoms including fatigue, dyspnea, sleep difficulties, and loss of appetite compared to the control group. Although there are deteriorations for sexual enjoyment, the intervention group exhibited improvement in breast functioning and symptom scores for body image, sexual function, future perspective, breast symptoms, and systemic therapy side effects. VCO consumption during chemotherapy helped improve the functional status and global QOL of breast cancer patients. In addition, it reduced the symptoms related to side effects of chemotherapy.

Efficacy of low-frequency low-intensity electrotherapy in the treatment of breast cancer-related lymphoedema: a cross-over randomized trial.

PubMed

Belmonte, Roser; Tejero, Marta; Ferrer, Montse; Muniesa, Josep Maria; Duarte, Esther; Cunillera, Oriol; Escalada, Ferran

2012-07-01

To compare the efficacy of low-frequency low-intensity electrotherapy and manual lymphatic drainage in the treatment of chronic upper limb breast cancer-related lymphoedema. Cross-over single-blind random clinical trial. Rehabilitation service. Thirty-six women with chronic upper limb breast cancer-related lymphoedema. Patients were randomized to undergo 10 sessions of manual lymphatic drainage followed by 10 sessions of low-frequency low-intensity electrotherapy or to undergo first low-frequency low-intensity electrotherapy followed by manual lymphatic drainage. There was a month of washout time between treatments. Each patient was examined just before and after each treatment. Researchers and outcome assessors were blinded for assigned treatment. Outcomes were lymphoedema volume, pain, heaviness and tightness, and health-related quality of life measured with the Functional Assessment of Cancer Therapy Questionnaire for Breast Cancer version 4 (FACT-B+4). Carry-over, period and treatment effects were analysed. Treatment effect was assessed using paired t-test. Thirty patients finalized treatment. Comparing the changes in low-frequency low-intensity electrotherapy with manual lymphatic drainage changes, there were no significant differences. Low-frequency low-intensity electrotherapy did not reduce lymphoedema volume (mean of change = 19.77 mL, P = 0.36), but significant reductions were observed in pain, heaviness and tightness (mean of change = 13.1, 16.2 and 6.4 mm, respectively), and FACT-B+4 summaries improved significantly (Trial Outcome Index mean of change = 5.4, P = 0.015). Manual lymphatic drainage showed no significant changes in any of the outcomes Although there are no significant differences between treatment changes, the observed trend towards a better health-related quality of life is remarkable in low-frequency low-intensity electrotherapy.

Efficacy of low-frequency low-intensity electrotherapy in the treatment of breast cancer-related lymphoedema: a cross-over randomized trial

PubMed Central

Tejero, Marta; Ferrer, Montse; Muniesa, Josep M; Duarte, Esther; Cunillera, Oriol; Escalada, Ferran

2012-01-01

Objective: To compare the efficacy of low-frequency low-intensity electrotherapy and manual lymphatic drainage in the treatment of chronic upper limb breast cancer-related lymphoedema. Design: Cross-over single-blind random clinical trial. Setting: Rehabilitation service. Participants: Thirty-six women with chronic upper limb breast cancer-related lymphoedema. Methods: Patients were randomized to undergo 10 sessions of manual lymphatic drainage followed by 10 sessions of low-frequency low-intensity electrotherapy or to undergo first low-frequency low-intensity electrotherapy followed by manual lymphatic drainage. There was a month of washout time between treatments. Each patient was examined just before and after each treatment. Researchers and outcome assessors were blinded for assigned treatment. Measures: Outcomes were lymphoedema volume, pain, heaviness and tightness, and health-related quality of life measured with the Functional Assessment of Cancer Therapy Questionnaire for Breast Cancer version 4 (FACT-B+4). Carry-over, period and treatment effects were analysed. Treatment effect was assessed using paired t-test. Results: Thirty patients finalized treatment. Comparing the changes in low-frequency low-intensity electrotherapy with manual lymphatic drainage changes, there were no significant differences. Low-frequency low-intensity electrotherapy did not reduce lymphoedema volume (mean of change = 19.77 mL, P = 0.36), but significant reductions were observed in pain, heaviness and tightness (mean of change = 13.1, 16.2 and 6.4 mm, respectively), and FACT-B+4 summaries improved significantly (Trial Outcome Index mean of change = 5.4, P = 0.015). Manual lymphatic drainage showed no significant changes in any of the outcomes Conclusion: Although there are no significant differences between treatment changes, the observed trend towards a better health-related quality of life is remarkable in low-frequency low-intensity electrotherapy. PMID:22172923

Melatonin uses in oncology: breast cancer prevention and reduction of the side effects of chemotherapy and radiation.

PubMed

Sanchez-Barcelo, Emilio J; Mediavilla, Maria D; Alonso-Gonzalez, Carolina; Reiter, Russel J

2012-06-01

The possible oncostatic properties of melatonin on different types of neoplasias have been studied especially in hormone-dependent adenocarcinomas. Despite the promising results of these experimental investigations, the use of melatonin in breast cancer treatment in humans is still uncommon. This article reviews the usefulness of this indoleamine for specific aspects of breast cancer management, particularly in reference to melatonin's antiestrogenic and antioxidant properties: i) treatments oriented to breast cancer prevention, especially when the risk factors are obesity, steroid hormone treatment or chronodisruption by exposure to light at night (LAN); ii) treatment of the side effects associated with chemo- or radiotherapy. The clinical utility of melatonin depends on the appropriate identification of its actions. Because of its SERM (selective estrogen receptor modulators) and SEEM (selective estrogen enzyme modulators) properties, and its virtual absence of contraindications, melatonin could be an excellent adjuvant with the drugs currently used for breast cancer prevention (antiestrogens and antiaromatases). The antioxidant actions also make melatonin a suitable treatment to reduce oxidative stress associated with chemotherapy, especially with anthracyclines, and radiotherapy.

Implications of dietary ω-3 and ω-6 polyunsaturated fatty acids in breast cancer

PubMed Central

Zanoaga, Oana; Jurj, Ancuta; Raduly, Lajos; Cojocneanu-Petric, Roxana; Fuentes-Mattei, Enrique; Wu, Oscar; Braicu, Cornelia; Gherman, Claudia Diana; Berindan-Neagoe, Ioana

2018-01-01

Breast cancer represents one of the most common forms of cancer in women worldwide, with an increase in the number of newly diagnosed patients in the last decade. The role of fatty acids, particularly of a diet rich in ω-3 and ω-6 polyunsaturated fatty acids (PUFAs), in breast cancer development is not fully understood and remains controversial due to their complex mechanism of action. However, a large number of animal models and cell culture studies have demonstrated that high levels of ω-3 PUFAs have an inhibitory role in the development and progression of breast cancer, compared to ω-6 PUFAs. The present review focused on recent studies regarding the correlation between dietary PUFAs and breast cancer development, and aimed to emphasize the main molecular mechanisms involved in the modification of cell membrane structure and function, modulation of signal transduction pathways, gene expression regulation, and antiangiogenic and antimetastatic effects. Furthermore, the anticancer role of ω-3 PUFAs through the modulation of microRNA expression levels was also reviewed. PMID:29434704

Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers

PubMed Central

Raj, Ganesh V; Sareddy, Gangadhara Reddy; Ma, Shihong; Lee, Tae-Kyung; Viswanadhapalli, Suryavathi; Li, Rui; Liu, Xihui; Murakami, Shino; Chen, Chien-Cheng; Lee, Wan-Ru; Mann, Monica; Krishnan, Samaya Rajeshwari; Manandhar, Bikash; Gonugunta, Vijay K; Strand, Douglas; Tekmal, Rajeshwar Rao; Ahn, Jung-Mo; Vadlamudi, Ratna K

2017-01-01

The majority of human breast cancer is estrogen receptor alpha (ER) positive. While anti-estrogens/aromatase inhibitors are initially effective, resistance to these drugs commonly develops. Therapy-resistant tumors often retain ER signaling, via interaction with critical oncogenic coregulator proteins. To address these mechanisms of resistance, we have developed a novel ER coregulator binding modulator, ERX-11. ERX-11 interacts directly with ER and blocks the interaction between a subset of coregulators with both native and mutant forms of ER. ERX-11 effectively blocks ER-mediated oncogenic signaling and has potent anti-proliferative activity against therapy-sensitive and therapy-resistant human breast cancer cells. ERX-11 is orally bioavailable, with no overt signs of toxicity and potent activity in both murine xenograft and patient-derived breast tumor explant models. This first-in-class agent, with its novel mechanism of action of disrupting critical protein-protein interactions, overcomes the limitations of current therapies and may be clinically translatable for patients with therapy-sensitive and therapy-resistant breast cancers. DOI: http://dx.doi.org/10.7554/eLife.26857.001 PMID:28786813

Imidazenil prevention of alprazolam-induced acquisition deficit in patas monkeys is devoid of tolerance

PubMed Central

Auta, James; Guidotti, Alessandro; Costa, Erminio

2000-01-01

The partial allosteric modulators (PAMs) of γ-aminobutyric acid-gated Cl− current intensities at γ-aminobutyric acid type A receptors have high affinity but low intrinsic efficacy on benzodiazepine recognition sites. Unlike the full allosteric modulators (FAM), like alprazolam, triazolam, and diazepam, PAMs are virtually devoid of unwanted side effects, including tolerance. Imidazenil (IMD) is a PAM that elicits potent anxiolytic and anticonvulsant actions in rodents and nonhuman primates and retains its anticonvulsant and anxiolytic effects, even in rodents that are tolerant to FAMs. IMD antagonizes the side effects of FAMs in rodents and nonhuman primates. Using patas monkeys and a multiple schedule with repeated acquisition and performance of chain responses, we report that IMD administration for 17 days antagonized without showing tolerance ALP-induced disruption of acquisition. PMID:10696114

Single shot multi-wavelength phase retrieval with coherent modulation imaging.

PubMed

Dong, Xue; Pan, Xingchen; Liu, Cheng; Zhu, Jianqiang

2018-04-15

A single shot multi-wavelength phase retrieval method is proposed by combining common coherent modulation imaging (CMI) and a low rank mixed-state algorithm together. A radiation beam consisting of multi-wavelength is illuminated on the sample to be observed, and the exiting field is incident on a random phase plate to form speckle patterns, which is the incoherent superposition of diffraction patterns of each wavelength. The exiting complex amplitude of the sample including both the modulus and phase of each wavelength can be reconstructed simultaneously from the recorded diffraction intensity using a low rank mixed-state algorithm. The feasibility of this proposed method was verified with visible light experimentally. This proposed method not only makes CMI realizable with partially coherent illumination but also can extend its application to various traditionally unrelated fields, where several wavelengths should be considered simultaneously.

Investigation of flame structure and burning intensity of partially premixed methane enrichment of syngas using OH-PLIF and kinetic simulation

NASA Astrophysics Data System (ADS)

Pu, Ge; Huang, Beibei; Zhang, Xun; Du, Jiantai; Zhu, Tuanhui; Chen, Bei

2018-05-01

Various experiments were conducted to study the combustion characteristics of partially premixed methane enrichment of syngas by using the OH-PLIF technique. Experiments were conducted on a co-flow burner, and the methane concentration (XCH4 = CH4/(H2+CO+CH4)) was varied from 0 to 20%, the overall equivalence ratio was varied from 0.4 to 1.2 and the inner equivalence ratio was varied from 1.5 to 3.5. Kinetic simulation was conducted by using OPPDIF module of CHEMKIN-Pro software. Results show that an increase in XCH4 and ϕoverall weakens the OH signal intensity. Adding methane into the fuel greatly increases the height of the inner flame front, and the increase of methane concentration has a negative effect on flame propagation speed. Meanwhile, simulation results remain consistent with the experiments. The main OH radical production reaction changes from R46: H+HO2 = 2OH to R38: H+O2 = O+OH when methane concentration contained in the fuel mixture increases. Sensitivity analysis also indicates that reaction which plays a dominant effect on temperature changes with the increase of methane concentration.

Consistency in seroma contouring for partial breast radiotherapy: Impact of guidelines

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wong, Elaine K.; Truong, Pauline T.; Kader, Hosam A.

2006-10-01

Purpose: Inconsistencies in contouring target structures can undermine the precision of conformal radiation therapy (RT) planning and compromise the validity of clinical trial results. This study evaluated the impact of guidelines on consistency in target volume contouring for partial breast RT planning. Methods and Materials: Guidelines for target volume definition for partial breast radiation therapy (PBRT) planning were developed by members of the steering committee for a pilot trial of PBRT using conformal external beam planning. In phase 1, delineation of the breast seroma in 5 early-stage breast cancer patients was independently performed by a 'trained' cohort of four radiationmore » oncologists who were provided with these guidelines and an 'untrained' cohort of four radiation oncologists who contoured without guidelines. Using automated planning software, the seroma target volume (STV) was expanded into a clinical target volume (CTV) and planning target volume (PTV) for each oncologist. Means and standard deviations were calculated, and two-tailed t tests were used to assess differences between the 'trained' and 'untrained' cohorts. In phase 2, all eight radiation oncologists were provided with the same contouring guidelines, and were asked to delineate the seroma in five new cases. Data were again analyzed to evaluate consistency between the two cohorts. Results: The 'untrained' cohort contoured larger seroma volumes and had larger CTVs and PTVs compared with the 'trained' cohort in three of five cases. When seroma contouring was performed after review of contouring guidelines, the differences in the STVs, CTVs, and PTVs were no longer statistically significant. Conclusion: Guidelines can improve consistency among radiation oncologists performing target volume delineation for PBRT planning.« less

PRRX2 as a novel TGF-β-induced factor enhances invasion and migration in mammary epithelial cell and correlates with poor prognosis in breast cancer.

PubMed

Juang, Yu-Lin; Jeng, Yung-Ming; Chen, Chi-Long; Lien, Huang-Chun

2016-12-01

TGF-β and cancer progression share a multifaceted relationship. Despite the knowledge of TGF-β biology in the development of cancer, several factors that mediate the cancer-promoting role of TGF-β continue to be identified. This study aimed to identify and characterise novel factors potentially related to TGF-β-mediated tumour aggression in breast cells. We treated the human mammary epithelial cell line MCF10A with TGF-β and identified TGF-β-dependent upregulation of PRRX2, the gene encoding paired-related homeobox 2 transcription factor. Overexpression of PRRX2 enhanced migration, invasion and anchorage-independent growth of MCF10A cells and induced partial epithelial mesenchymal transition (EMT), as determined by partial fibroblastoid morphology of cells, upregulation of EMT markers and partially disrupted acinar structure in a three-dimensional culture. We further identified PLAT, the gene encoding tissue-type plasminogen activator (tPA), as the highest differentially expressed gene in PRRX2-overexpressing MCF10A cells, and demonstrated direct binding and transactivation of the PLAT promoter by PRRX2. Furthermore, PLAT knockdown inhibited PRRX2-mediated enhanced migration and invasion, suggesting that tPA may mediate PRRX2-induced migration and invasion. Finally, the significant correlation of PRRX2 expression with poor survival in 118 primary breast tumour samples (P = 0.027) and the increased PRRX2 expression in metaplastic breast carcinoma samples, which is pathogenetically related to EMT, validated the biological importance of PRRX2-enhanced migration and invasion and PRRX2-induced EMT. Thus, our data suggest that upregulation of PRRX2 may be a mechanism contributing to TGF-β-induced invasion and EMT in breast cancer. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Active smoking and risk of breast cancer in a Danish nurse cohort study.

PubMed

Andersen, Zorana Jovanovic; Jørgensen, Jeanette Therming; Grøn, Randi; Brauner, Elvira Vaclavik; Lynge, Elsebeth

2017-08-22

No scientific consensus has been reached on whether active tobacco smoking causes breast cancer. We examine the association between active smoking and breast cancer risk in Denmark, which has some of the highest smoking and breast cancer rates in women worldwide. We used the data from a nationwide Danish Nurse Cohort on 21,867 female nurses (age > 44 years) who at recruitment in 1993 or 1999 reported information on smoking status, onset, duration, and intensity, as well as breast cancer risk factors. We obtained data on incidence of breast cancer from Danish Cancer Registry until 2013, and used Cox regression models to analyze the association between smoking and breast cancer. Of 21,831 women (mean age 53.2 years) 1162 developed breast cancer during 15.7 years of follow-up. 33.7% of nurses were current and 30.0% former smokers at cohort baseline. Compared to never smokers, we found increased risk of breast cancer of 18% in ever (hazard ratio and 95% confidence interval: 1.18; 1.04-1.34) and 27% in current (1.27; 1.11-1.46) smokers. We detected a dose-response relationship with smoking intensity with the highest breast cancer risk in women smoking >15 g/day (1.31; 1.11-1.56) or >20 pack-years (1.32; 1.12-1.55). Parous women who smoked heavily (>10 pack-years) before first childbirth had the highest risk of breast cancer (1.58; 1.20-2.10). Association between smoking and breast cancer was not modified by menopausal status, obesity, alcohol or hormone therapy use, and seemed to be limited to the estrogen receptor positive breast cancer subtype. Active smoking increases risk of breast cancer, with smoking before first birth being the most relevant exposure window.

FIVE-YEAR RESULTS OF ADJUVANT RADIOTHER

PubMed Central

Osa, Etin-Osa O.; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Kerimian, Maria Fenton; Goldberg, Judith D.; Formenti, Silvia C.

2015-01-01

Purpose/Objective A technique of prone breast radiotherapy delivered by a regimen of accelerated intensity modulated radiation therapy (IMRT) with a concurrent boost to the tumor bed, was developed at our institution. We report the five year results of this approach. Methods and Materials Between 2003–2006, 404 patients with Stage I–II breast cancer were prospectively enrolled into two consecutive protocols, institutional trials 03–30 and 05–181, that used the same regimen of 40.5Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5Gy (total dose=48Gy). All patients were treated after segmental mastectomy, had negative margins, and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine set-up attempted, and chosen if found to better spare these organs. Results 92% of patients were treated prone, 8% supine. 72% had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 –228.27cc, mean: 19.65cc. In-field heart volume for left breast cancer patients ranged from 0–21.24cc, mean: 1.59cc. There was no heart in the field for right breast cancer patients. At a median follow-up of five years, the five-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% CI: 0.65–1.04). The five-year cumulative incidence of regional recurrence was 0.53% (95% CI:0.41–0.69) and the five-year overall cumulative death rate was 1.28% (95% CI: 0.48–3.38). 82% (95% CI: 77–85) of patients judged their final cosmetic result as excellent/good. Conclusions Prone accelerated IMRT with a concomitant boost results in excellent local control, optimal sparing of heart and lung, with good cosmesis. RTOG 10–05, a phase III, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and fractionation approach to standard six weeks radiotherapy with a sequential boost. PMID:24867535

Choosing wisely after publication of level I evidence in breast cancer radiotherapy.

PubMed

Niska, Joshua R; Keole, Sameer R; Pockaj, Barbara A; Halyard, Michele Y; Patel, Samir H; Northfelt, Donald W; Gray, Richard J; Wasif, Nabil; Vargas, Carlos E; Wong, William W

2018-01-01

Recent trials in early-stage breast cancer support hypofractionated whole-breast radiotherapy (WBRT) as part of breast-conserving therapy (BCT). Evidence also suggests that radiotherapy (RT) omission may be reasonable for some patients over 70 years. Among radiation-delivery techniques, intensity-modulated RT (IMRT) is more expensive than 3-dimensional conformal RT (3DCRT). Based on this evidence, in 2013, the American Society for Radiation Oncology (ASTRO) recommended hypofractionated schedules for women aged ≥50 years with early-stage breast cancer and avoiding routine use of IMRT for WBRT. To assess response to level I evidence and adherence to ASTRO recommendations, we evaluated the pattern of RT use for early-stage breast cancer at our National Comprehensive Cancer Network institution from 2006 to 2008 and 2011 to 2013 and compared the results with national trends. Data from a prospective database were extracted to include patients treated with BCT, aged ≥50 years, with histologic findings of invasive ductal carcinoma, stage T1-T2N0M0, estrogen receptor-positive, and HER2 normal. We retrospectively reviewed the medical records and estimated costs based on 2016 Hospital Outpatient Prospective Payment System (technical fees) and Medicare Physician Fee Schedule (professional fees). Among 55 cases from 2006 to 2008, treatment regimens were 11% hypofractionated, 69% traditional schedule, and 20% RT omission (29% of patients were aged >70 years). Among 83 cases from 2011 to 2013, treatment regimens were 54% hypofractionated, 19% traditional schedule, and 27% RT omission (48% of patients were aged >70 years). 3DCRT was used for all WBRT treatments. Direct medical cost estimates were as follows: 15 fractions 3DCRT, $7,197.87; 15 fractions IMRT, $11,232.33; 25 fractions 3DCRT, $9,731.39; and 25 fractions IMRT, $16,877.45. Despite apparent resistance to shorter radiation schedules in the United States, we demonstrate that rapid practice change in response to level I evidence is feasible. Wider adoption of evidence-based guidelines in early-stage breast cancer may substantially lower health care costs and improve convenience for patients without sacrificing oncologic outcomes.

Global Analysis of miRNA-mRNA Interaction Network in Breast Cancer with Brain Metastasis.

PubMed

Li, Zhixin; Peng, Zhiqiang; Gu, Siyu; Zheng, Junfang; Feng, Duiping; Qin, Qiong; He, Junqi

2017-08-01

MicroRNAs (miRNAs) have been linked to a number of cancer types including breast cancer. The rate of brain metastases is 10-30% in patients with advanced breast cancer which is associated with poor prognosis. The potential application of miRNAs in the diagnostics and therapeutics of breast cancer with brain metastasis is an area of intense interest. In an initial effort to systematically address the differential expression of miRNAs and mRNAs in primary breast cancer which may provide clues for early detection of brain metastasis, we analyzed the consequent changes in global patterns of gene expression in Gene Expression Omnibus (GEO) data set obtained by microarray from patients with in situ carcinoma and patients with brain metastasis. The miRNA-pathway regulatory network and miRNA-mRNA regulatory network were investigated in breast cancer specimens from patients with brain metastasis to screen for significantly dysregulated miRNAs followed by prediction of their target genes and pathways by Gene Ontology (GO) analysis. Functional coordination of the changes of gene expression can be modulated by individual miRNAs. Two miRNAs, hsa-miR-17-5p and hsa-miR-16-5p, were identified as having the highest associations with targeted mRNAs [such as B-cell lymphoma 2 (BCL2), small body size/mothers against decapentaplegic 3 (SMAD3) and suppressor of cytokine signaling 1 (SOCS1)] and pathways associated with epithelial-mesenchymal transitions and other processes linked with cancer metastasis (including cell cycle, adherence junctions and extracellular matrix-receptor interaction). mRNAs for two genes [HECT, UBA and WWE domain containing 1 (HUWE1) and BCL2] were found to have the highest associations with miRNAs, which were down-regulated in brain metastasis specimens of breast cancer. The change of 11 selected miRNAs was verified in The Cancer Genome Atlas (TCGA) breast cancer dataset. Up-regulation of hsa-miR-17-5p was detected in triple-negative breast cancer tissues in TCGA. Furthermore, a negative correlation of hsa-miR-17-5p with overall survival and phosphatase and tensin homolog (PTEN) and BCL2 target genes was found in TCGA breast cancer specimens. Our findings provide a functionally coordinated expression pattern of different families of miRNAs that may have potential to provide clinicians with a strategy to treat breast cancer with brain metastasis from a systems-rather than a single-gene perspective. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Does expecting more pain make it more intense? Factors associated with the first week pain trajectories after breast cancer surgery

PubMed Central

Sipilä, Reetta M.; Haasio, Lassi; Meretoja, Tuomo J.; Ripatti, Samuli; Estlander, Ann-Mari; Kalso, Eija A.

2017-01-01

Abstract The aim of this study was to identify clinical risk factors for unfavorable pain trajectories after breast cancer surgery, to better understand the association between pain expectation, psychological distress, and acute postoperative pain. This prospective study included 563 women treated for breast cancer. Psychological data included questionnaires for depressive symptoms and anxiety. Experimental pain tests for heat and cold were performed before surgery. The amount of oxycodone needed for satisfactory pain relief after surgery was recorded. Pain intensity in the area of operation before surgery and during the first postoperative week and expected intensity of postoperative pain were recorded using the Numerical Rating Scale (NRS 0-10). Pain trajectories were formed to describe both initial intensity (the intercept) and the direction of the pain path (the slope). Factors associated with higher initial pain intensity (the intercept) were the amount of oxycodone needed for adequate analgesia, psychological distress, type of axillary surgery, preoperative pain in the area of the operation, and expectation of postoperative pain. The higher the pain initially was, the faster it resolved over the week. Expectation of severe postoperative pain was associated with higher scores of both experimental and clinical pain intensity and psychological factors. The results confirm that acute pain after breast cancer surgery is a multidimensional phenomenon. Psychological distress, pain expectation, and the patients' report of preoperative pain in the area to be operated should be recognized before surgery. Patients having axillary clearance need more efficient analgesic approaches. PMID:28134654

A comparison between cobalt and linear accelerator-based treatment plans for conformal and intensity-modulated radiotherapy.

PubMed

Adams, E J; Warrington, A P

2008-04-01

The simplicity of cobalt units gives them the advantage of reduced maintenance, running costs and downtime when compared with linear accelerators. However, treatments carried out on such units are typically limited to simple techniques. This study has explored the use of cobalt beams for conformal and intensity-modulated radiotherapy (IMRT). Six patients, covering a range of treatment sites, were planned using both X-ray photons (6/10 MV) and cobalt-60 gamma rays (1.17 and 1.33 MeV). A range of conformal and IMRT techniques were considered, as appropriate. Conformal plans created using cobalt beams for small breast, meningioma and parotid cases were found to compare well with those created using X-ray photons. By using additional fields, acceptable conformal plans were also created for oesophagus and prostate cases. IMRT plans were found to be of comparable quality for meningioma, parotid and thyroid cases on the basis of dose-volume histogram analysis. We conclude that it is possible to plan high-quality radical radiotherapy treatments for cobalt units. A well-designed beam blocking/compensation system would be required to enable a practical and efficient alternative to multileaf collimator (MLC)-based linac treatments to be offered. If cobalt units were to have such features incorporated into them, they could offer considerable benefits to the radiotherapy community.

Structural insights into selective agonist actions of tamoxifen on human estrogen receptor alpha.

PubMed

Chakraborty, Sandipan; Biswas, Pradip Kumar

2014-08-01

Tamoxifen-an anti-estrogenic ligand in breast tissues used as a first-line treatment in estrogen receptor (ER)-positive breast cancers-is associated with the development of resistance followed by resumption of tumor growth in about 30 % of cases. Whether tamoxifen assists in proliferation in such cases or whether any ligand-independent pathway to transcription exists is not fully understood; also, no ERα mutants have been detected so far that could lead to tamoxifen resistance. Using in silico conformational analysis of the ERα ligand binding domain (LBD), in the absence and presence of selective agonist (diethylstilbestrol; DES), antagonist (Faslodex; ICI), and selective estrogen receptor modulator (SERM; 4-hydroxy tamoxifen; 4-OHT) ligands, we have elucidated ligand-responsive structural modulations of the ERα-LBD dimer in its agonist and antagonist complexes to address the issue of "tamoxifen resistance". DES and ICI were found to stabilize the dimer in their agonist and antagonist conformations, respectively. The ERα-LBD dimer without the presence of any bound ligand also led to a stable structure in agonist conformation. However, binding of 4-OHT to the antagonist structure led to a flexible conformation allowing the protein to visit conformations populated by agonists as was evident from principal component analysis and radius of gyration plots. Further, the relaxed conformations of the 4-OHT bound protein exhibited a diminished size of the co-repressor binding pocket in the LBD, thus signaling a partial blockage of the co-repressor binding motif. Thus, the ability of 4-OHT-bound ERα-LBD to assume flexible conformations visited by agonists and reduced co-repressor binding surface at the LBD provide crucial structural insights into tamoxifen-resistance that complement our existing understanding.

Design of a small molecule against an oncogenic noncoding RNA

PubMed Central

Velagapudi, Sai Pradeep; Cameron, Michael D.; Haga, Christopher L.; Rosenberg, Laura H.; Lafitte, Marie; Duckett, Derek R.; Phinney, Donald G.; Disney, Matthew D.

2016-01-01

The design of precision, preclinical therapeutics from sequence is difficult, but advances in this area, particularly those focused on rational design, could quickly transform the sequence of disease-causing gene products into lead modalities. Herein, we describe the use of Inforna, a computational approach that enables the rational design of small molecules targeting RNA to quickly provide a potent modulator of oncogenic microRNA-96 (miR-96). We mined the secondary structure of primary microRNA-96 (pri-miR-96) hairpin precursor against a database of RNA motif–small molecule interactions, which identified modules that bound RNA motifs nearby and in the Drosha processing site. Precise linking of these modules together provided Targaprimir-96 (3), which selectively modulates miR-96 production in cancer cells and triggers apoptosis. Importantly, the compound is ineffective on healthy breast cells, and exogenous overexpression of pri-miR-96 reduced compound potency in breast cancer cells. Chemical Cross-Linking and Isolation by Pull-Down (Chem-CLIP), a small-molecule RNA target validation approach, shows that 3 directly engages pri-miR-96 in breast cancer cells. In vivo, 3 has a favorable pharmacokinetic profile and decreases tumor burden in a mouse model of triple-negative breast cancer. Thus, rational design can quickly produce precision, in vivo bioactive lead small molecules against hard-to-treat cancers by targeting oncogenic noncoding RNAs, advancing a disease-to-gene-to-drug paradigm. PMID:27170187

Effects of a Mail and Telephone Intervention on Breast Health Behaviors

ERIC Educational Resources Information Center

Bowen, Deborah J.; Powers, Diane

2010-01-01

This study evaluated a mail and telephone intervention to improve breast health behaviors while maintaining quality of life. Women recruited from the general public were randomized to a stepped-intensity intervention consisting of mailings, telephone calls, and counseling (if requested or appropriate given a woman's genetic risk for breast cancer)…

Loss of PEDF: A Novel Mechanism of Antihormone Resistance in Breast Cancer

DTIC Science & Technology

2014-08-01

major chal- lenge in the management of ERa-positive breast cancer and is an area under intense investigation. While many studies point towards the cross...I, Morandi A, Robertson D, Pancholi S, Drury S, Dowsett M, Martin LA, Isacke CM: Targeting the receptor tyrosine kinase RET sensitizes breast cancer

Relationships among optimism, well-being, self-transcendence, coping, and social support in women during treatment for breast cancer.

PubMed

Matthews, Ellyn E; Cook, Paul F

2009-07-01

The impact of diagnosis and treatment for breast cancer, stressors that affect emotional well-being, is influenced by several psychosocial factors and the relationships among them. The purpose of this study was to investigate the relationship between optimism and emotional well-being (EWB) and the individual and combined mediation of this relationship by perceived social support (SS), problem focused coping (PFC), and self-transcendence in women with breast cancer during radiation therapy. Ninety-three women receiving radiation treatment for breast cancer completed questionnaires that measured EWB, optimism, SS, PFC, and self-transcendence. Correlational and multiple regression analysis revealed that optimism was positively related to EWB. Of the three mediators, self-transcendence alone was found to partially mediate the relationship between optimism and EWB. The relationship between optimism and PFC was not significant. Optimism was related to SS, but its indirect effect on EWB through SS did not reach significance. During breast cancer treatment, the positive effects of optimism on EWB are partially mediated by a woman's level of self-transcendence. Brief screening of women's optimism may help identify women at risk for psychological distress. Early detection and interventions to promote psychological adjustment throughout the cancer trajectory (e.g. enhancing self-transcendence) should receive attention in future research. (c) 2008 John Wiley & Sons, Ltd.

[Accelerated partial breast irradiation with multicatheters during breast conserving surgery for cancer].

PubMed

Rodríguez-Spiteri Sagredo, Natalia; Martínez Regueira, Fernando; Olartecoechea Linaje, Begoña; Arredondo Chaves, Jorge; Cambeiro Vázquez, Mauricio; Pina Insausti, Luis Javier; Elizalde Pérez, Arlette; y García-Lallana, Amaya; Sola Gallego, Jose Javier

2013-10-01

Accelerated partial breast irradiation (APBI) with multicatheters after lumpectomy for breast cancer (BC) may be an alternative to whole breast irradiation in selected patients. The aim is to show our 5 year experience. Between June 2007 and June 2012, 87 BC patients have been evaluated for APBI. Inclusion criteria were: age over 40 years, unifocal tumour, infiltrating ductal or intraductal carcinoma, tumour size smaller than 3 cm and no lymph node involvement. Complications, cosmetic results and local and distant recurrences were evaluated. Treatment was completed in 48 patients and contraindicated in 39. The average age of treated patients was 59 years. Operating time was 123 min with 9 implanted catheters in each patient. No complications were observed during surgery or radiotherapy. Patients were discharged from hospital after 4 days. Tumour size was 11 mm. Of these, 35 were infiltrating ductal and 13 intraductal carcinomas. A total of 44 patients received adjuvant treatment. Mean follow-up was 22 months with no evidence of local or distant recurrence. The cosmetic outcome was good or excellent in 66% of cases. APBI with multicatheter placed after lumpectomy for BC is feasible and safe but requires a strict selection of patients. Copyright © 2012 AEC. Published by Elsevier Espana. All rights reserved.

Use of a multiseparation fiber optic probe for the optical diagnosis of breast cancer.

PubMed

Zhu, Changfang; Palmer, Gregory M; Breslin, Tara M; Xu, Fushen; Ramanujam, Nirmala

2005-01-01

We explore the effects of the illumination and collection geometry on optical spectroscopic diagnosis of breast cancer. Fluorescence and diffuse reflectance spectroscopy in the UV-visible spectral range are made with a multiseparation probe at three illumination-collection separations of 735, 980, and 1225 microm, respectively, from 13 malignant and 34 nonmalignant breast tissues. Statistical analysis is carried out on two types of data inputs: (1) the fluorescence and diffuse reflectance spectra recorded at each of the three illumination-collection separations and (2) the integrated fluorescence (at each excitation wavelength) or diffuse reflectance over the entire spectrum at all three illumination-collection separations. The results show that using the integrated fluorescence intensities recorded at a single excitation wavelength at all three illumination-collection separations can discriminate malignant from nonmalignant breast tissues with similar classification accuracy to that using spectral data measured at several excitation wavelengths with a single illumination-collection separation. These findings have significant implications with respect to the design of an optical system for breast cancer diagnosis. Examining the intensity attenuation at a single wavelength rather than spectral intensities at multiple wavelengths can significantly reduce the measurement and data processing time in a clinical setting as well as the cost and complexity of the optical system. Copyright 2005 Society of Photo-Optical Instrumentation Engineers.

Partial Breast Radiation Therapy With Proton Beam: 5-Year Results With Cosmetic Outcomes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bush, David A., E-mail: dbush@llu.edu; Do, Sharon; Lum, Sharon

2014-11-01

Purpose: We updated our previous report of a phase 2 trial using proton beam radiation therapy to deliver partial breast irradiation (PBI) in patients with early stage breast cancer. Methods and Materials: Eligible subjects had invasive nonlobular carcinoma with a maximal dimension of 3 cm. Patients underwent partial mastectomy with negative margins; axillary lymph nodes were negative on sampling. Subjects received postoperative proton beam radiation therapy to the surgical bed. The dose delivered was 40 Gy in 10 fractions, once daily over 2 weeks. Multiple fields were treated daily, and skin-sparing techniques were used. Following treatment, patients were evaluated with clinical assessments andmore » annual mammograms to monitor toxicity, tumor recurrence, and cosmesis. Results: One hundred subjects were enrolled and treated. All patients completed the assigned treatment and were available for post-treatment analysis. The median follow-up was 60 months. Patients had a mean age of 63 years; 90% had ductal histology; the average tumor size was 1.3 cm. Actuarial data at 5 years included ipsilateral breast tumor recurrence-free survival of 97% (95% confidence interval: 100%-93%); disease-free survival of 94%; and overall survival of 95%. There were no cases of grade 3 or higher acute skin reactions, and late skin reactions included 7 cases of grade 1 telangiectasia. Patient- and physician-reported cosmesis was good to excellent in 90% of responses, was not changed from baseline measurements, and was well maintained throughout the entire 5-year follow-up period. Conclusions: Proton beam radiation therapy for PBI produced excellent ipsilateral breast recurrence-free survival with minimal toxicity. The treatment proved to be adaptable to all breast sizes and lumpectomy cavity configurations. Cosmetic results appear to be excellent and unchanged from baseline out to 5 years following treatment. Cosmetic results may be improved over those reported with photon-based techniques due to reduced breast tissue exposure with proton beam, skin-sparing techniques, and the dose fractionation schedule used in this trial.« less

Validation of the relative insensitivity of volumetric-modulated arc therapy (VMAT) plan quality to gantry space resolution

PubMed Central

Cora, Stefania; Khan, Ehsan Ullah

2017-01-01

Abstract Volumetric-modulated arc therapy (VMAT) is an efficient form of radiotherapy used to deliver intensity-modulated radiotherapy beams. The aim of this study was to investigate the relative insensitivity of VMAT plan quality to gantry angle spacing (GS). Most previous VMAT planning and dosimetric work for GS resolution has been conducted for single arc VMAT. In this work, a quantitative comparison of dose–volume indices (DIs) was made for partial-, single- and double-arc VMAT plans optimized at 2°, 3° and 4° GS, representing a large variation in deliverable multileaf collimator segments. VMAT plans of six prostate cancer and six head-and-neck cancer patients were simulated for an Elekta SynergyS® Linac (Elekta Ltd, Crawley, UK), using the SmartArc™ module of Pinnacle³ TPS, (version 9.2, Philips Healthcare). All optimization techniques generated clinically acceptable VMAT plans, except for the single-arc for the head-and-neck cancer patients. Plan quality was assessed by comparing the DIs for the planning target volume, organs at risk and normal tissue. A GS of 2°, with finest resolution and consequently highest intensity modulation, was considered to be the reference, and this was compared with GS 3° and 4°. The differences between the majority of reference DIs and compared DIs were <2%. The metrics, such as treatment plan optimization time and pretreatment (phantom) dosimetric calculation time, supported the use of a GS of 4°. The ArcCHECK™ phantom–measured dosimetric agreement verifications resulted in a >95.0% passing rate, using the criteria for γ (3%, 3 mm). In conclusion, a GS of 4° is an optimal choice for minimal usage of planning resources without compromise of plan quality. PMID:27974507

Oral microbial profile discriminates breast-fed from formula-fed infants.

PubMed

Holgerson, Pernilla L; Vestman, Nelly R; Claesson, Rolf; Ohman, Carina; Domellöf, Magnus; Tanner, Anne C R; Hernell, Olle; Johansson, Ingegerd

2013-02-01

Little is known about the effect of diet on the oral microbiota of infants, although diet is known to affect the gut microbiota. The aims of the present study were to compare the oral microbiota in breast-fed and formula-fed infants, and investigate growth inhibition of streptococci by infant-isolated lactobacilli. A total of 207 mothers consented to participation of their 3-month-old infants. A total of 146 (70.5%) infants were exclusively and 38 (18.4%) partially breast-fed, and 23 (11.1%) were exclusively formula-fed. Saliva from all of their infants was cultured for Lactobacillus species, with isolate identifications from 21 infants. Lactobacillus isolates were tested for their ability to suppress Streptococcus mutans and S sanguinis. Oral swabs from 73 infants were analysed by the Human Oral Microbe Identification Microarray (HOMIM) and by quantitative polymerase chain reaction for Lactobacillus gasseri. Lactobacilli were cultured from 27.8% of exclusively and partially breast-fed infants, but not from formula-fed infants. The prevalence of 14 HOMIM-detected taxa, and total salivary lactobacilli counts differed by feeding method. Multivariate modelling of HOMIM-detected bacteria and possible confounders clustered samples from breast-fed infants separately from formula-fed infants. The microbiota of breast-fed infants differed based on vaginal or C-section delivery. Isolates of L plantarum, L gasseri, and L vaginalis inhibited growth of the cariogenic S mutans and the commensal S sanguinis: L plantarum >L gasseri >L vaginalis. The microbiota of the mouth differs between 3-month-old breast-fed and formula-fed infants. Possible mechanisms for microbial differences observed include species suppression by lactobacilli indigenous to breast milk.

MO-E-BRD-01: Is Non-Invasive Image-Guided Breast Brachytherapy Good?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hiatt, J.

2015-06-15

Is Non-invasive Image-Guided Breast Brachytherapy Good? – Jess Hiatt, MS Non-invasive Image-Guided Breast Brachytherapy (NIBB) is an emerging therapy for breast boost treatments as well as Accelerated Partial Breast Irradiation (APBI) using HDR surface breast brachytherapy. NIBB allows for smaller treatment volumes while maintaining optimal target coverage. Considering the real-time image-guidance and immobilization provided by the NIBB modality, minimal margins around the target tissue are necessary. Accelerated Partial Breast Irradiation in brachytherapy: is shorter better? - Dorin Todor, PhD VCU A review of balloon and strut devices will be provided together with the origins of APBI: the interstitial multi-catheter implant.more » A dosimetric and radiobiological perspective will help point out the evolution in breast brachytherapy, both in terms of devices and the protocols/clinical trials under which these devices are used. Improvements in imaging, delivery modalities and convenience are among the factors driving the ultrashort fractionation schedules but our understanding of both local control and toxicities associated with various treatments is lagging. A comparison between various schedules, from a radiobiological perspective, will be given together with a critical analysis of the issues. to review and understand the evolution and development of APBI using brachytherapy methods to understand the basis and limitations of radio-biological ‘equivalence’ between fractionation schedules to review commonly used and proposed fractionation schedules Intra-operative breast brachytherapy: Is one stop shopping best?- Bruce Libby, PhD. University of Virginia A review of intraoperative breast brachytherapy will be presented, including the Targit-A and other trials that have used electronic brachytherapy. More modern approaches, in which the lumpectomy procedure is integrated into an APBI workflow, will also be discussed. Learning Objectives: To review past and current clinical trials for IORT To discuss lumpectomy-scan-plan-treat workflow for IORT.« less

Report on the Clinical Outcomes of Permanent Breast Seed Implant for Early-Stage Breast Cancers

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pignol, Jean-Philippe, E-mail: j.p.pignol@erasmusmc.nl; Radiation Oncology Department, Erasmus Medical Center Cancer Institute, Rotterdam; Caudrelier, Jean-Michel

Purpose: Permanent breast seed implant is an accelerated partial breast irradiation technique realizing the insertion of {sup 103}Pd seeds in the seroma after lumpectomy. We report the 5-year efficacy and tolerance for a cohort, pooling patients from 3 clinical trials. Methods and Materials: The trials accrued postmenopausal patients with infiltrating ductal carcinoma or ductal carcinoma in situ ≤3 cm and clear surgical margins, who were node negative, and had a planning target volume <120 cm{sup 3}. The outcomes included overall and disease-free survival and local and contralateral recurrence at 5 years. The true local recurrence rate was compared using 2-tailed paired t testsmore » for estimates calculated using the Tufts University ipsilateral breast tumor recurrence and Memorial Sloan Kettering ductal carcinoma in situ nomograms. Results: The cohort included 134 patients, and the observed local recurrence rate at a median follow-up period of 63 months was 1.2% ± 1.2%, similar to the estimate for whole breast irradiation (P=.23), significantly better than for surgery alone (relative risk 0.27; P<.001), and significantly lower than contralateral recurrence (relative risk 0.33; P<.001). The 5-year overall survival rate was 97.4% ± 1.9%, and the disease-free survival rate was 96.4% ± 2.1%. At 2 months, 42% of the patients had erythema, 20% induration, and 16% moist desquamation. The rate of mainly grade 1 telangiectasia was 22.4% at 2 years and 24% at 5 years. The rate of asymptomatic induration was 23% at 2 years and 40% at 5 years. Conclusions: The 5-year data suggest that permanent breast seed implantation is a safe accelerated partial breast irradiation option after lumpectomy for early-stage breast cancer with a tolerance profile similar to that of whole breast irradiation.« less

Analysis of Treatment Efficacy, Cosmesis, and Toxicity Using the MAMMOSITE Breast Brachytherapy Catheter to Deliver Accelerated Partial-Breast Irradiation: The William Beaumont Hospital Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chao, K. Kenneth; Vicini, Frank A.; Wallace, Michelle

2007-09-01

Purpose: To review our institution's experience of treating patients with the MammoSite (Cytyc Corp., Marlborough, MA) breast brachytherapy catheter to deliver accelerated partial-breast irradiation (APBI), for determining short-term treatment efficacy, cosmesis, and toxicity. Methods and Materials: From January 2000 to April 2006, 80 patients treated with breast-conserving therapy (BCT) received adjuvant radiation using the MammoSite (34 Gy in 3.4-Gy fractions prescribed to 1.0 cm from the balloon surface). Twenty-three patients (29%) had Stage 0 breast cancer, 46 (57%) had Stage I breast cancer, and 11 (14%) had Stage II breast cancer. The median follow-up was 22.1 months. Results: Two ipsilateralmore » breast-tumor recurrences (IBTRs) (2.5%) developed for a 3-year actuarial rate of 2.9% (no regional failures were observed). On molecular-based clonality assay evaluation, both recurrences were clonally related. Younger age at diagnosis was the only variable associated with IBTR (continuous variable, p = 0.044; categorical variable [<55 years vs. {>=}55 years], p = 0.012). The percentages of patients with good/excellent cosmetic results at 12 and 36 months were 96.9% and 88.2%, respectively (p = NS). Patients with applicator-to-skin spacing <7 mm and those who received adjuvant systemic chemotherapy exhibited lower rates of good/excellent cosmetic results, though the association was not statistically significant. The overall incidence of symptomatic seromas and any seromas was 10% and 45%, respectively. The overall incidence of fat necrosis and infections was 8.8% and 11.3%, respectively. Conclusions: Early-stage breast-cancer patients treated with adjuvant APBI using the MammoSite catheter exhibited a 3-year treatment efficacy, cosmesis, and toxicity similar to those observed with other forms of interstitial APBI at this length of follow-up.« less

Quantification of FDG-PET/CT with delayed imaging in patients with newly diagnosed recurrent breast cancer.

PubMed

Baun, Christina; Falch, Kirsten; Gerke, Oke; Hansen, Jeanette; Nguyen, Tram; Alavi, Abass; Høilund-Carlsen, Poul-Flemming; Hildebrandt, Malene G

2018-05-09

Several studies have shown the advantage of delayed-time-point imaging with 18F-FDG-PET/CT to distinguish malignant from benign uptake. This may be relevant in cancer diseases with low metabolism, such as breast cancer. We aimed at examining the change in SUV from 1 h (1h) to 3 h (3h) time-point imaging in local and distant lesions in patients with recurrent breast cancer. Furthermore, we investigated the effect of partial volume correction in the different types of metastases, using semi-automatic quantitative software (ROVER™). One-hundred and two patients with suspected breast cancer recurrence underwent whole-body PET/CT scans 1h and 3h after FDG injection. Semi-quantitative standardised uptake values (SUVmax, SUVmean) and partial volume corrected SUVmean (cSUVmean), were estimated in malignant lesions, and as reference in healthy liver tissue. The change in quantitative measures from 1h to 3h was calculated, and SUVmean was compared to cSUVmean. Metastases were verified by biopsy. Of the 102 included patients, 41 had verified recurrent disease with in median 15 lesions (range 1-70) amounting to a total of 337 malignant lesions included in the analysis. SUVmax of malignant lesions increased from 6.4 ± 3.4 [0.9-19.7] (mean ± SD, min and max) at 1h to 8.1 ± 4.4 [0.7-29.7] at 3h. SUVmax in breast, lung, lymph node and bone lesions increased significantly (p < 0.0001) between 1h and 3h by on average 25, 40, 33, and 27%, respectively. A similar pattern was observed with (uncorrected) SUVmean. Partial volume correction increased SUVmean significantly, by 63 and 71% at 1h and 3h imaging, respectively. The highest impact was in breast lesions at 3h, where cSUVmean increased by 87% compared to SUVmean. SUVs increased from 1h to 3h in malignant lesions, SUVs of distant recurrence were in general about twice as high as those of local recurrence. Partial volume correction caused significant increases in these values. However, it is questionable, if these relatively modest quantitative advances of 3h imaging are sufficient to warrant delayed imaging in this patient group. ClinicalTrails.gov NCT01552655 . Registered 28 February 2012, partly retrospectively registered.

History of breast feeding and risk of incident endometriosis: prospective cohort study

PubMed Central

Eliassen, A Heather; Tamimi, Rulla M; Spiegelman, Donna; Michels, Karin B; Missmer, Stacey A

2017-01-01

Objective To investigate the association between lifetime breast feeding, exclusive breast feeding, postpartum amenorrhea, and incidence of endometriosis among parous women. Design Prospective cohort study. Setting Nurses’ Health Study II, 1989-2011. Participants 72 394women who reported having one or more pregnancies that lasted at least six months, 3296 of whom had laparoscopically confirmed endometriosis. For each pregnancy, women reported duration of total breast feeding, exclusive breast feeding, and postpartum amenorrhea. Main outcome measures Incident self reported laparoscopically confirmed endometriosis (96% concordance with medical record) in parous women. Multivariable Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for diagnosis of endometriosis. Results Duration of total and exclusive breast feeding was significantly associated with decreased risk of endometriosis. Among women who reported a lifetime total length of breast feeding of less than one month, there were 453 endometriosis cases/100 000 person years compared with 184 cases/100 000 person years in women who reported a lifetime total of ≥36 months of breast feeding. For every additional three months of total breast feeding per pregnancy, women experienced an 8% lower risk of endometriosis (hazard ratio 0.92, 95% confidence interval 0.90 to 0.94; P<0.001 for trend) and a 14% lower risk for every additional three months of exclusive breast feeding per pregnancy (0.86, 0.81 to 0.90; P<0.001 for trend). Women who breastfed for ≥36 months in total across their reproductive lifetime had a 40% reduced risk of endometriosis compared with women who never breast fed (0.60, 0.50 to 0.72). The protective association with breast feeding was strongest among women who gave birth within the past five years (P=0.04 for interaction). The association with total breast feeding and exclusive breast feeding on endometriosis was partially influenced by postpartum amenorrhea (% mediated was 34% (95% confidence interval 15% to 59%) for total breast feeding and 57% (27% to 82%) for exclusive breast feeding). Conclusion Among women who experienced at least one pregnancy that lasted at least six months, breast feeding was inversely associated with risk of incident endometriosis. This association was partially, but not fully, influenced by postpartum amenorrhea, suggesting that breast feeding could influence the risk of endometriosis both through amenorrhea and other mechanisms. Given the chronic and incurable nature of endometriosis, breast feeding should be further investigated as an important modifiable behavior to mitigate risk for pregnant women. PMID:28851765

Latissimus dorsi breast reconstruction: how much nerve resection is necessary to prevent postoperative muscle twitching?

PubMed

Schroegendorfer, Klaus F; Hacker, Stefan; Nickl, Stefanie; Vierhapper, Martin; Nedomansky, Jakob; Haslik, Werner

2014-12-01

The latissimus dorsi muscle flap represents a valuable option in breast reconstruction but can result in postoperative twitching and retraction, discomfort, arm movement limitations, and breast deformation. These complications can be avoided by denervation of the thoracodorsal nerve; however, the optimal method of nerve management is unknown. This study presents the authors' experience with the outcomes of latissimus dorsi flaps for breast reconstruction in the light of thoracodorsal nerve management strategies. The authors retrospectively collected data from 74 patients who underwent partial or total breast reconstruction with a latissimus dorsi flap alone or with an implant between January of 1999 and October of 2011. Follow-up data were collected at 12 and 24 months postoperatively. In 56 patients (75.7 percent), the latissimus dorsi muscle was denervated at the time of surgery, whereas the thoracodorsal nerve remained intact in 18 patients (24.3 percent). No partial or total flap loss was observed. At 12 and 24 months' follow-up, all patients with an intact thoracodorsal nerve showed twitching of the muscle, and 50 percent and 67.9 percent, respectively, of the denervated patients showed twitching (p < 0.001). No patient had twitching if more than 4 cm of nerve was excised at 12 or 24 months postoperatively, and the length of nerve resection was predictive of the presence of twitching. Denervation of the latissimus dorsi is a safe and reliable procedure that should be performed at the time of breast reconstruction and should include more than 4 cm to achieve a nontwitching breast with a stable volume and shape.

Qualitative Exploration of Sexual Health Among Diverse Breast Cancer Survivors.

PubMed

Tat, Susana; Doan, Therese; Yoo, Grace J; Levine, Ellen G

2018-04-01

Although the physical and emotional impact of surgical removal of partial or complete removal of the breast as well as effects of breast cancer treatment on the individual have been well documented, little research is available on sexuality and sexual health of breast cancer survivors in a relationship context. Sexual health concerns of breast cancer survivors remain an unmet need for many. The present study consisted of qualitative interviews with 135 racially diverse, female breast cancer survivors who completed treatment to better understand their perspectives on sexual health and management of sexual problems in their potential and existing relationships after breast cancer. Key thematic findings include that breast cancer survivors have to (1) adapt to the physical and emotional traumas of breast cancer surgery and treatment, (2) navigate complicated sexual communications with potential and existing partners, and (3) negotiate intimacy and closeness without sexual intercourse with existing partners. This study demonstrates the need for healthcare providers to discuss sexual health after breast cancer with all of their patients as it is a concern that faces single and partnered breast cancer survivors months and years after treatment.

[Guideline development for rehabilitation of breast cancer patients - phase 2: findings from the classification of therapeutic procedures, KTL-data-analysis].

PubMed

Domann, U; Brüggemann, S; Klosterhuis, H; Weis, J

2007-08-01

Aim of this project is the development of an evidence based guideline for the rehabilitation of breast cancer patients, funded by the German Pension Insurance scheme. The project consists of four phases. This paper is focused on the 2nd phase, i.e., analysis of procedures in rehabilitation based on evidence based therapeutic modules. As a result of a systematic literature review 14 therapeutic modules were defined. From a total of 840 possible KTL Codes (Klassifikation Therapeutischer Leistungen, Classification of therapeutic procedures), 229 could be assigned to these modules. These analyses are based on 24685 patients in 57 rehabilitation clinics, who had been treated in 2003. For these modules the number of patients having received those interventions as well as the duration of the modules were calculated. The data were analysed with respect to the influence of age and comorbidity. Moreover, differences between rehabilitation clinics were investigated according to the category of interventions. Our findings show great variability in the use of the therapeutic modules. Therapeutic modules like Physiotherapy (91.6%), Training Therapy (85.2%) and Information (97.8%) are provided to most of the patients. Younger patients receive more treatments than older patients, and patients with higher comorbidity receive more Physiotherapie, Lymphoedema Therapy and Psychological Interventions than patients without comorbidities. Data analysis shows wide interindividual variability with regard to the therapeutic modules. This variability is related to age and comorbidity of the patients. Furthermore, great differences were found between the rehabilitation clinics concerning the use of the various interventions. This variability supports the necessity of developing and implementing an evidence based guideline for the rehabilitation of breast cancer patients. The next step will be discussing these findings with experts from science and clinical practice.

In-silico QTL mapping of postpubertal mammary ductal development in the mouse uncovers potential human breast cancer risk loci

USDA-ARS?s Scientific Manuscript database

Genetic background plays a dominant role in mammary gland development and breast cancer (BrCa). Despite this, the role of genetics is only partially understood. This study used strain-dependent variation in an inbred mouse mapping panel, to identify quantitative trait loci (QTL) underlying structura...

Targeting Androgen Receptor in Breast Cancer: Enzalutamide as a Novel Breast Cancer Therapeutic

DTIC Science & Technology

2014-09-01

of Medivation. JG, FG, IEA, and EMcC are employed by Fundacion Ciencia & Vida in Santiago, Chile and receive partial funding from Medivation. The...CA 94105, USA. 3Fundación Ciencia & Vida, Avda. Zañartu 1482 - Ñuñoa, Santiago 7780272, Chile. 4Department of Medicine, Division of Oncology

HYPNOSIS FOR SYMPTOM MANAGEMENT IN WOMEN WITH BREAST CANCER: A Pilot Study

PubMed Central

Jensen, Mark P.; Gralow, Julie R.; Braden, Alan; Gertz, Kevin J.; Fann, Jesse R.; Syrjala, Karen L.

2018-01-01

Eight women who were in treatment for breast cancer (n = 4) or breast cancer survivors (n = 4), presenting with 1 or more of 4 symptoms (chronic pain, fatigue, hot flashes, and sleep difficulties), were given 4 to 5 sessions of self-hypnosis training for symptom management. Analyses revealed (a) significant pre- to posttreatment decreases in pain intensity, fatigue, and sleep problems and (b) that pain intensity continued to decrease from posttreatment to 6-month follow-up. Although there was a slight increase in fatigue severity and sleep problems from posttreatment to 6-month follow-up, the follow-up scores did not return to pretreatment levels. The findings provide initial support for using hypnosis to manage symptoms in women who are breast cancer survivors. Clinical trials evaluating hypnosis efficacy over and above other treatments are warranted. PMID:22443523

Comparative study of contrast-enhanced ultrasound qualitative and quantitative analysis for identifying benign and malignant breast tumor lumps.

PubMed

Liu, Jian; Gao, Yun-Hua; Li, Ding-Dong; Gao, Yan-Chun; Hou, Ling-Mi; Xie, Ting

2014-01-01

To compare the value of contrast-enhanced ultrasound (CEUS) qualitative and quantitative analysis in the identification of breast tumor lumps. Qualitative and quantitative indicators of CEUS for 73 cases of breast tumor lumps were retrospectively analyzed by univariate and multivariate approaches. Logistic regression was applied and ROC curves were drawn for evaluation and comparison. The CEUS qualitative indicator-generated regression equation contained three indicators, namely enhanced homogeneity, diameter line expansion and peak intensity grading, which demonstrated prediction accuracy for benign and malignant breast tumor lumps of 91.8%; the quantitative indicator-generated regression equation only contained one indicator, namely the relative peak intensity, and its prediction accuracy was 61.5%. The corresponding areas under the ROC curve for qualitative and quantitative analyses were 91.3% and 75.7%, respectively, which exhibited a statistically significant difference by the Z test (P<0.05). The ability of CEUS qualitative analysis to identify breast tumor lumps is better than with quantitative analysis.

miR-7 suppresses brain metastasis of breast cancer stem-like cells by modulating KLF4

PubMed Central

Okuda, Hiroshi; Xing, Fei; Pandey, Puspa R; Sharma, Sambad; Watabe, Misako; Pai, Sudha K.; Mo, Yin-Yuan; Iiizumi-Gairani, Megumi; Hirota, Shigeru; Liu, Yin; Wu, Kerui; Pochampally, Radhika; Watabe, Kounosuke

2012-01-01

Despite significant improvement in survival rates of breast cancer patients, prognosis of metastatic disease is still dismal. Cancer stem-like cells (CSCs) are considered to play a role in metastatic progression of breast cancer; however, the exact pathological role of CSCs is yet to be elucidated. In this report, we found that CSCs (CD24−/CD44+/ESA+) isolated from metastatic breast cell lines are significantly more metastatic than non-CSC populations in an organ specific manner. The results of our microRNA profile analysis for these cells revealed that CSCs that are highly metastatic to bone and brain expressed significantly lower level of miR-7 and that this microRNA was capable of modulating one of the essential genes for induced pluripotent stem cell, KLF4. Interestingly, high expression of KLF4 was significantly and inversely correlated to brain- but not bone-metastasis free survival of breast cancer patients, and we indeed found that the expression of miR-7 significantly suppressed the ability of CSCs to metastasize to brain but not to bone in our animal model. We also examined the expression of miR-7 and KLF4 in brain-metastatic lesions and found that these genes were significantly down- or up-regulated, respectively, in the tumor cells in brain. Furthermore, the results of our in vitro experiments indicate that miR-7 attenuates the abilities of invasion and self-renewal of CSCs by modulating KLF4 expression. These results suggest that miR-7 and KLF4 may serve as biomarkers or therapeutic targets for brain metastasis of breast cancer. PMID:23384942

Breast Implant-Associated Anaplastic Large Cell Lymphoma: Case Report and Review of the Literature.

PubMed

Berlin, Eva; Singh, Kunwar; Mills, Christopher; Shapira, Ilan; Bakst, Richard L; Chadha, Manjeet

2018-01-01

We are reporting the case of a 58-year-old woman with history of bilateral silicone breast implants for cosmetic augmentation. At 2-year interval from receiving the breast implants, she presented with swelling of the right breast with associated chest wall mass, effusion around the implant, and axillary lymphadenopathy. Pathology confirmed breast implant-associated anaplastic large cell lymphoma (stage III, T4N2M0, using BIA-ALCL TNM staging and stage IIAE, using Ann-Arbor staging). The patient underwent bilateral capsulectomy and right partial mastectomy with excision of the right breast mass and received adjuvant CHOP chemotherapy and radiation to the right breast and regional nodes. Since completion of multimodality therapy, the patient has sustained remission on both clinical exam and PET/CT scan. We report this case and review of the literature on this rare form of lymphoma.

Breast Implant-Associated Anaplastic Large Cell Lymphoma: Case Report and Review of the Literature

PubMed Central

Singh, Kunwar; Mills, Christopher; Shapira, Ilan

2018-01-01

We are reporting the case of a 58-year-old woman with history of bilateral silicone breast implants for cosmetic augmentation. At 2-year interval from receiving the breast implants, she presented with swelling of the right breast with associated chest wall mass, effusion around the implant, and axillary lymphadenopathy. Pathology confirmed breast implant-associated anaplastic large cell lymphoma (stage III, T4N2M0, using BIA-ALCL TNM staging and stage IIAE, using Ann-Arbor staging). The patient underwent bilateral capsulectomy and right partial mastectomy with excision of the right breast mass and received adjuvant CHOP chemotherapy and radiation to the right breast and regional nodes. Since completion of multimodality therapy, the patient has sustained remission on both clinical exam and PET/CT scan. We report this case and review of the literature on this rare form of lymphoma. PMID:29607225

UWB based low-cost and non-invasive practical breast cancer early detection

NASA Astrophysics Data System (ADS)

Vijayasarveswari, V.; Khatun, S.; Fakir, M. M.; Jusoh, M.; Ali, S.

2017-03-01

Breast cancer is one of the main causes of women death worldwide. Breast tumor is an early stage of cancer that locates in cells of a human breast. As there is no remedy, early detection is crucial. Towards this, Ultra-Wideband (UWB) is a prominent candidate. It is a wireless communication technology which can achieve high bandwidth with low power utilization. UWB is suitable to be used for short range communication systems including breast cancer detection since it is secure, non-invasive and human health friendly. This paper presents the low-cost and non-invasive early breast cancer detection strategy using UWB sensor (or antenna). Emphasis is given here to detect breast tumor in 2D and 3D environments. The developed system consisted of hardware and software. Hardware included UWB transceiver and a pair of home-made directional sensor/antenna. The software included feed-forward back propagation Neural Network (NN) module to detect the tumor existence, size and location along with soft interface between software and hardware. Forward scattering technique was used by placing two sensors diagonally opposite sides of a breast phantom. UWB pulses were transmitted from one side of phantom and received from other side, controlled by the software interface in PC environment. Collected received signals were then fed into the NN module for training, testing and validation. The system exhibited detection efficiency on tumor existence, location (x, y, z), and size were approximately 100%, (78.17%, 70.66%, 92.46%), 85.86% respectively. The proposed UWB based early breast cancer detection system could be more practical with low-cost, user friendly and non-harmful features. This project may help users to monitor their breast health regularly at their home.

Breast-Feeding Modulates the Influence of the Peroxisome Proliferator–Activated Receptor-γ (PPARG2) Pro12Ala Polymorphism on Adiposity in Adolescents

PubMed Central

Verier, Caroline; Meirhaeghe, Aline; Bokor, Szilvia; Breidenassel, Christina; Manios, Yannis; Molnár, Dénes; Artero, Enrique G.; Nova, Esther; De Henauw, Stefaan; Moreno, Luis A.; Amouyel, Philippe; Labayen, Idoia; Bevilacqua, Noemi; Turck, Dominique; Béghin, Laurent; Dallongeville, Jean; Gottrand, Frédéric

2010-01-01

OBJECTIVE The peroxisome proliferator–activated receptor-γ2 (PPARG2) Pro12Ala polymorphism has been associated with a higher BMI and a lower risk of type 2 diabetes in adulthood. The association between adiposity and PPARG variants can be influenced by environmental factors such as early growth, dietary fat, and (as recently shown) breast-feeding. The objectives of this study were to assess 1) the influence of the PPARG2 Pro12Ala polymorphism on adiposity markers in adolescents and 2) a possible modulating effect of breast-feeding on these associations. RESEARCH DESIGN AND METHODS Data on breast-feeding duration, BMI, and genotypes for the Pro12Ala polymorphism were available for 945 adolescents (mean age 14.7 years). The breast-feeding duration was obtained from parental records. We measured weight, height, waist circumference, and six skinfold thicknesses. RESULTS No significant associations between the Pro12Ala polymorphism and any of the above-mentioned anthropometric parameters were found. There were significant interactions between the PPARG2 Pro12Ala polymorphism and breast-feeding with regard to adiposity measurements (all adjusted P < 0.05). Indeed, in children who had not been breast-fed, Ala12 allele carriers had higher adiposity parameters (e.g., Δ BMI +1.88 kg/m2, adjusted for age, sex, and center, P = 0.007) than Pro12Pro adolescents. In contrast, in breast-fed subjects, there was no significant difference between Ala12 allele carriers and Pro12Pro children in terms of adiposity measurements, whatever the duration of breast-feeding. CONCLUSIONS Breast-feeding appears to counter the deleterious effect of the PPARG2 Pro12Ala polymorphism on anthropometric parameters in adolescents. PMID:19846795

Selective androgen receptor modulators (SARMs) negatively regulate triple-negative breast cancer growth and epithelial:mesenchymal stem cell signaling.

PubMed

Narayanan, Ramesh; Ahn, Sunjoo; Cheney, Misty D; Yepuru, Muralimohan; Miller, Duane D; Steiner, Mitchell S; Dalton, James T

2014-01-01

The androgen receptor (AR) is the most highly expressed steroid receptor in breast cancer with 75-95% of estrogen receptor (ER)-positive and 40-70% of ER-negative breast cancers expressing AR. Though historically breast cancers were treated with steroidal androgens, their use fell from favor because of their virilizing side effects and the emergence of tamoxifen. Nonsteroidal, tissue selective androgen receptor modulators (SARMs) may provide a novel targeted approach to exploit the therapeutic benefits of androgen therapy in breast cancer. Since MDA-MB-453 triple-negative breast cancer cells express mutated AR, PTEN, and p53, MDA-MB-231 triple-negative breast cancer cells stably expressing wildtype AR (MDA-MB-231-AR) were used to evaluate the in vitro and in vivo anti-proliferative effects of SARMs. Microarray analysis and epithelial:mesenchymal stem cell (MSC) co-culture signaling studies were performed to understand the mechanisms of action. Dihydrotestosterone and SARMs, but not bicalutamide, inhibited the proliferation of MDA-MB-231-AR. The SARMs reduced the MDA-MB-231-AR tumor growth and tumor weight by greater than 90%, compared to vehicle-treated tumors. SARM treatment inhibited the intratumoral expression of genes and pathways that promote breast cancer development through its actions on the AR. SARM treatment also inhibited the metastasis-promoting paracrine factors, IL6 and MMP13, and subsequent migration and invasion of epithelial:MSC co-cultures. 1. AR stimulation inhibits paracrine factors that are important for MSC interactions and breast cancer invasion and metastasis. 2. SARMs may provide promise as novel targeted therapies to treat AR-positive triple-negative breast cancer.

Selective Androgen Receptor Modulators (SARMs) Negatively Regulate Triple-Negative Breast Cancer Growth and Epithelial:Mesenchymal Stem Cell Signaling

PubMed Central

Narayanan, Ramesh; Ahn, Sunjoo; Cheney, Misty D.; Yepuru, Muralimohan; Miller, Duane D.; Steiner, Mitchell S.; Dalton, James T.

2014-01-01

Abstract Introduction The androgen receptor (AR) is the most highly expressed steroid receptor in breast cancer with 75–95% of estrogen receptor (ER)-positive and 40–70% of ER-negative breast cancers expressing AR. Though historically breast cancers were treated with steroidal androgens, their use fell from favor because of their virilizing side effects and the emergence of tamoxifen. Nonsteroidal, tissue selective androgen receptor modulators (SARMs) may provide a novel targeted approach to exploit the therapeutic benefits of androgen therapy in breast cancer. Materials and Methods Since MDA-MB-453 triple-negative breast cancer cells express mutated AR, PTEN, and p53, MDA-MB-231 triple-negative breast cancer cells stably expressing wildtype AR (MDA-MB-231-AR) were used to evaluate the in vitro and in vivo anti-proliferative effects of SARMs. Microarray analysis and epithelial:mesenchymal stem cell (MSC) co-culture signaling studies were performed to understand the mechanisms of action. Results Dihydrotestosterone and SARMs, but not bicalutamide, inhibited the proliferation of MDA-MB-231-AR. The SARMs reduced the MDA-MB-231-AR tumor growth and tumor weight by greater than 90%, compared to vehicle-treated tumors. SARM treatment inhibited the intratumoral expression of genes and pathways that promote breast cancer development through its actions on the AR. SARM treatment also inhibited the metastasis-promoting paracrine factors, IL6 and MMP13, and subsequent migration and invasion of epithelial:MSC co-cultures. Conclusion 1. AR stimulation inhibits paracrine factors that are important for MSC interactions and breast cancer invasion and metastasis. 2. SARMs may provide promise as novel targeted therapies to treat AR-positive triple-negative breast cancer. PMID:25072326

Phase retrieval with tunable phase transfer function based on the transport of intensity equation

NASA Astrophysics Data System (ADS)

Martinez-Carranza, J.; Stepien, P.; Kozacki, T.

2017-06-01

Recovering phase information with Deterministic approaches as the Transport of Intensity Equation (TIE) has recently emerged as an alternative tool to the interferometric techniques because it is experimentally easy to implement and provides fast and accurate results. Moreover, the potential of employing partially coherent illumination (PCI) in such techniques allow obtaining high quality phase reconstructions providing that the estimation of the corresponding Phase Transfer Function (PTF) is carried out correctly. Hence, accurate estimation of the PTF requires that the physical properties of the optical system are well known. Typically, these parameters are assumed constant in all the set of measurements, which might not be optimal. In this work, we proposed the use of an amplitude Spatial Light Modulator (aSLM) for tuning the degree of coherence of the optical system. The aSLM will be placed at the Fourier plane of the optical system, and then, band pass filters will be displayed. This methodology will perform amplitude modulation of the propagated field and as a result, the state of coherence of the optical system can be modified. Theoretical and experimental results that validate our proposed technique will be shown.

Molecular biology of breast cancer stem cells: potential clinical applications.

PubMed

Nguyen, Nam P; Almeida, Fabio S; Chi, Alex; Nguyen, Ly M; Cohen, Deirdre; Karlsson, Ulf; Vinh-Hung, Vincent

2010-10-01

Breast cancer stem cells (CSC) have been postulated recently as responsible for failure of breast cancer treatment. The purpose of this study is to review breast CSCs molecular biology with respect to their mechanism of resistance to conventional therapy, and to develop treatment strategies that may improve survival of breast cancer patients. A literature search has identified in vitro and in vivo studies of breast CSCs. Breast CSCs overexpress breast cancer resistance protein (BCRP) which allows cancer cells to transport actively chemotherapy agents out of the cells. Radioresistance is modulated through activation of Wnt signaling pathway and overexpression of genes coding for glutathione. Lapatinib can selectively target HER-2 positive breast CSCs and improves disease-free survival in these patients. Metformin may target basal type breast CSCs. Parthenolide and oncolytic viruses are promising targeting agents for breast CSCs. Future clinical trials for breast cancer should include anti-cancer stem cells targeting agents in addition to conventional chemotherapy. Hypofractionation radiotherapy may be indicated for residual disease post chemotherapy. 2010 Elsevier Ltd. All rights reserved.

Improved in-plane visibility of tumors using breast tomosynthesis

NASA Astrophysics Data System (ADS)

Ruschin, Mark; Timberg, Pontus; Svahn, Tony; Andersson, Ingvar; Hemdal, Bengt; Mattsson, Sören; Båth, Magnus; Tingberg, Anders

2007-03-01

The purpose of this work was to evaluate and compare the visibility of tumors in digital mammography (DM) and breast tomosynthesis (BT) images. Images of the same women were acquired on both a DM system (Mammomat Novation, Siemens) and a BT prototype system adapted from the same type of DM system. Simulated 3D tumors (average dimension: 8.4 mm x 6.6 mm x 5 mm) were projected and added to each DM image as well as each BT projection image prior to 3D reconstruction. The same beam quality and approximately the same total absorbed dose were used for each breast image acquisition on both systems. Two simulated tumors were added to each of thirty breast scans, yielding sixty cases. A series of 4-alternative forced choice (4-AFC) human observer performance experiments were conducted in order to determine what projected tumor signal intensity in the DM images would be needed to achieve the same detectability as in the reconstructed BT images. Nine observers participated. For the BT experiment, when the tumor signal intensity on the central projection was 0.010 the mean percent of correct responses (PC) was measured to be 81.5%, which converted to a detectability index value (d') of 1.96. For the DM experiments, the same detectability was achieved at a signal intensity determined to be 0.038. Equivalent tumor detection in BT images were thus achieved at around four times less projected signal intensity than in DM images, indicating that the use of BT may lead to earlier detection of breast cancer.

Comparison of the Effects of the Selective Estrogen Receptor Modulators Ospemifene, Raloxifene, and Tamoxifen on Breast Tissue in Ex Vivo Culture.

PubMed

Eigeliene, Natalija; Erkkola, Risto; Härkönen, Pirkko

2016-01-01

Explant tissue culture provides a model for studying the direct effects of steroid hormones, their analogs, and novel hormonally active compounds on normal freshly isolated human breast tissues (HBTs). For this purpose, pre- and postmenopausal HBTs can be maintained in this culture system. The results demonstrate that the morphological integrity of HBT explants can be maintained in tissue culture up to 2 weeks and expression of differentiation markers, steroid hormone receptors, proliferation and apoptosis ratios can be evaluated as a response to hormonal stimulation. This chapter describes an ex vivo culture model that we have applied to study the effects of various hormonally active substances, including 17β-estradiol and selective estrogen receptor modulators (SERMs), on normal human breast tissues.

The anticancer potential of steroidal saponin, dioscin, isolated from wild yam (Dioscorea villosa) root extract in invasive human breast cancer cell line MDA-MB-231 in vitro

USDA-ARS?s Scientific Manuscript database

Previously, we observed that wild yam (Dioscorea villosa) root extract (WYRE) was able to activate GATA3 in human breast cancer cells targeting epigenome. This study aimed to 'nd out if dioscin (DS), a bioactive compound of WYRE, can modulate GATA3 functions and cellular invasion in human breast can...

The Breast Cancer DNA Interactome

DTIC Science & Technology

2014-12-01

Research and Education 8. PERFORMING ORGANIZATION REPORT NUMBER Palo Alto, CA 94304 9 . SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10...act as a growth modulator (7- 9 ). While correlations between serum levels of IGFBP3 and breast cancer have yielded contradictory results (3-5, 10...receptor (EGFR), another breast cancer related gene. EGFR is located approximately 9 Mb from IGFBP3 on chromosome 7. To examine this long-range

Endoxifen, 4-Hydroxytamoxifen and an Estrogenic Derivative Modulate Estrogen Receptor Complex Mediated Apoptosis in Breast Cancer.

PubMed

Maximov, Philipp Y; Abderrahman, Balkees; Fanning, Sean W; Sengupta, Surojeet; Fan, Ping; Curpan, Ramona F; Quintana Rincon, Daniela Maria; Greenland, Jeffery A; Rajan, Shyamala S; Greene, Geoffrey L; Jordan, V Craig

2018-05-08

Estrogen therapy was used to treat advanced breast cancer in postmenopausal women for decades until the introduction of tamoxifen. Resistance to long-term estrogen deprivation (LTED) with tamoxifen and aromatase inhibitors used as a treatment for breast cancer inevitably occurs, but unexpectedly low dose estrogen can cause regression of breast cancer and increase disease free survival in some patients. This therapeutic effect is attributed to estrogen-induced apoptosis in LTED breast cancer. Here we describe modulation of the estrogen receptor liganded with antiestrogens (endoxifen, 4-hydroxytamoxifen) and an estrogenic triphenylethylene (TPE) EthoxyTPE (EtOXTPE) on estrogen-induced apoptosis in LTED breast cancer cells. Our results show that the angular TPE estrogen (EtOXTPE) is able to induce the ER-mediated apoptosis only at a later time compared to planar estradiol in these cells. Using RT-PCR, ChIP, Western blotting, molecular modelling and X-ray crystallography techniques we report novel conformations of the ER complex with an angular estrogen EtOXTPE and endoxifen. We propose that alteration of the conformation of the ER complexes, with changes in coactivator binding, governs estrogen-induced apoptosis through the PERK sensor system to trigger an Unfolded Protein Response (UPR). The American Society for Pharmacology and Experimental Therapeutics.

Development of a Unique Small Molecule Modulator of CXCR4

PubMed Central

Yoon, Younghyoun; Lin, Songbai; Sasaki, Maiko; Klapproth, Jan-Michael A.; Yang, Hua; Grossniklaus, Hans E.; Xu, Jianguo; Rojas, Mauricio; Voll, Ronald J.; Goodman, Mark M.; Arrendale, Richard F.; Liu, Jin; Yun, C. Chris; Snyder, James P.; Liotta, Dennis C.; Shim, Hyunsuk

2012-01-01

Background Metastasis, the spread and growth of tumor cells to distant organ sites, represents the most devastating attribute and plays a major role in the morbidity and mortality of cancer. Inflammation is crucial for malignant tumor transformation and survival. Thus, blocking inflammation is expected to serve as an effective cancer treatment. Among anti-inflammation therapies, chemokine modulation is now beginning to emerge from the pipeline. CXC chemokine receptor-4 (CXCR4) and its ligand stromal cell-derived factor-1 (CXCL12) interaction and the resulting cell signaling cascade have emerged as highly relevant targets since they play pleiotropic roles in metastatic progression. The unique function of CXCR4 is to promote the homing of tumor cells to their microenvironment at the distant organ sites. Methodology/Principal Findings We describe the actions of N,N′-(1,4-phenylenebis(methylene))dipyrimidin-2-amine (designated MSX-122), a novel small molecule and partial CXCR4 antagonist with properties quite unlike that of any other reported CXCR4 antagonists, which was prepared in a single chemical step using a reductive amination reaction. Its specificity toward CXCR4 was tested in a binding affinity assay and a ligand competition assay using 18F-labeled MSX-122. The potency of the compound was determined in two functional assays, Matrigel invasion assay and cAMP modulation. The therapeutic potential of MSX-122 was evaluated in three different murine models for inflammation including an experimental colitis, carrageenan induced paw edema, and bleomycin induced lung fibrosis and three different animal models for metastasis including breast cancer micrometastasis in lung, head and neck cancer metastasis in lung, and uveal melanoma micrometastasis in liver in which CXCR4 was reported to play crucial roles. Conclusions/Significance We developed a novel small molecule, MSX-122, that is a partial CXCR4 antagonist without mobilizing stem cells, which can be safer for long-term blockade of metastasis than other reported CXCR4 antagonists. PMID:22485156

Breast Cancer Risk and Ovariectomy, Hysterectomy, and Tubal Sterilization in the Women's Contraceptive and Reproductive Experiences Study

PubMed Central

Press, David J.; Sullivan-Halley, Jane; Ursin, Giske; Deapen, Dennis; McDonald, Jill A.; Strom, Brian L.; Norman, Sandra A.; Simon, Michael S.; Marchbanks, Polly A.; Folger, Suzanne G.; Liff, Jonathan M.; Burkman, Ronald T.; Malone, Kathleen E.; Weiss, Linda K.; Spirtas, Robert; Bernstein, Leslie

2011-01-01

Removal or impairment of ovaries before menopause may affect a woman's breast cancer risk by altering her cumulative exposure to ovarian hormones. The Women's Contraceptive and Reproductive Experiences Study, a population-based, multicenter case-control study of incident invasive breast cancer, recruited women aged 35–64 years (4,490 cases and 4,611 controls) who provided data on ovariectomy, hysterectomy, and tubal sterilization during in-person interviews. Controls were frequency-matched to cases by age, race, and study site. Unconditional logistic regression analysis was used. Women who had not undergone premenopausal reproductive surgery were the referent group. Bilateral ovariectomy was associated with reduced breast cancer risk overall (odds ratio (OR) = 0.59, 95% confidence interval (CI): 0.50, 0.69) and among women <45 years of age (ORs ranged from 0.31 to 0.52), but not among those who were older at surgery. It was also associated with a reduced risk for estrogen and progesterone receptor–positive tumors (OR = 0.63, 95% CI: 0.52, 0.75) but not receptor-negative tumors. Hysterectomy with ovarian conservation (OR = 0.83, 95% CI: 0.72, 0.96) and hysterectomy with partial ovary removal (OR = 0.73, 95% CI: 0.59, 0.91) were also associated with lower risk. No association with breast cancer risk was observed with tubal sterilization only or partial ovariectomy without hysterectomy. Reproductive organ surgeries may alter ovarian hormone levels, thereby affecting breast cancer risk. PMID:21109566

HER2 mutated breast cancer responds to treatment with single agent neratinib, a second generation HER2/EGFR tyrosine kinase inhibitor

PubMed Central

Ben–Baruch, Noa Efrat; Bose, Ron; Kavuri, Shyam M.; Ma, Cynthia X.; Ellis, Matthew J.

2015-01-01

Activating mutations in the HER2 tyrosine kinase have been identified in human breast cancers that lack HER2 gene amplification. These patients are not candidates for HER2 targeted drugs under current standards of care, but preclinical data strongly suggest that these patients will benefit from anti-HER2 drugs. In this case report, we describe a young woman with metastatic breast cancer whose tumor was found to carry a HER2 L755S mutation, which is in the kinase domain of HER2. Treatment with the second generation HER2/EGFR tyrosine kinase inhibitor, neratinib, resulted in partial response and dramatic improvement in the patient’s function status. This partial response lasted 11 months and when the patient’s cancer progressed, she was treated with neratinib plus capecitabine and her cancer again responded. This second response parallels the benefit seen with continuing trastuzumab in HER2 amplified breast cancer after disease progression. This case is the first report, to our knowledge, of successful single agent treatment of HER2 mutated breast cancer. Two clinical trials of neratinib for HER2 mutated, metastatic breast cancer are currently enrolling patients. Further, data from The Cancer Genome Atlas project have identified HER2 mutations in a wide range of solid tumors, including bladder, colorectal, and non-small cell lung cancer, suggesting that clinical trials of neratinib or neratinib-based combinations for HER2 mutated solid tumors is warranted. PMID:26358790

Breast cancer risk and ovariectomy, hysterectomy, and tubal sterilization in the women's contraceptive and reproductive experiences study.

PubMed

Press, David J; Sullivan-Halley, Jane; Ursin, Giske; Deapen, Dennis; McDonald, Jill A; Strom, Brian L; Norman, Sandra A; Simon, Michael S; Marchbanks, Polly A; Folger, Suzanne G; Liff, Jonathan M; Burkman, Ronald T; Malone, Kathleen E; Weiss, Linda K; Spirtas, Robert; Bernstein, Leslie

2011-01-01

Removal or impairment of ovaries before menopause may affect a woman's breast cancer risk by altering her cumulative exposure to ovarian hormones. The Women's Contraceptive and Reproductive Experiences Study, a population-based, multicenter case-control study of incident invasive breast cancer, recruited women aged 35-64 years (4,490 cases and 4,611 controls) who provided data on ovariectomy, hysterectomy, and tubal sterilization during in-person interviews. Controls were frequency-matched to cases by age, race, and study site. Unconditional logistic regression analysis was used. Women who had not undergone premenopausal reproductive surgery were the referent group. Bilateral ovariectomy was associated with reduced breast cancer risk overall (odds ratio (OR) = 0.59, 95% confidence interval (CI): 0.50, 0.69) and among women <45 years of age (ORs ranged from 0.31 to 0.52), but not among those who were older at surgery. It was also associated with a reduced risk for estrogen and progesterone receptor-positive tumors (OR = 0.63, 95% CI: 0.52, 0.75) but not receptor-negative tumors. Hysterectomy with ovarian conservation (OR = 0.83, 95% CI: 0.72, 0.96) and hysterectomy with partial ovary removal (OR = 0.73, 95% CI: 0.59, 0.91) were also associated with lower risk. No association with breast cancer risk was observed with tubal sterilization only or partial ovariectomy without hysterectomy. Reproductive organ surgeries may alter ovarian hormone levels, thereby affecting breast cancer risk.

Seven fractions to deliver partial breast irradiation: the toxicity is Low.

PubMed

Trovo, Marco; Avanzo, Michele; Vinante, Lorenzo; Furlan, Carlo; Fiorica, Francesco; Perin, Tiziana; Militello, Loredana; Spazzapan, Simon; Berretta, Massimiliano; Jena, Rajesh; Stancanello, Joseph; Piccoli, Erica; Mileto, Mario; Micheli, Elvia; Roncadin, Mario; Massarut, Samuele

2017-05-23

To assess toxicity and clinical outcome, in breast cancer patients treated with external beam partial breast irradiation (PBI) consisting of 35 Gy in 7 daily fractions (5 Gy/fraction). Patients affected by early-stage breast cancer were enrolled in this phase II trial. Patients had to be 60 years old or over and treated with breast conservative surgery for early stage invasive carcinoma. Seventy-three patients were analyzed. Median follow-up was 40 months. The proposed schedule was well tolerated. No Grade 3 toxicity was documented. Late toxicity was assessable for all the treated patients. Two patients (2.7%) developed Grade 2 pain 6 months after PBI. Four patients (5%) developed asymptomatic fat necrosis. Grade 2 fibrosis was observed in 5 patients (6.7%). No correlation was found between early and late toxicity and the type of adjuvant systemic therapy (no therapy vs. hormonal therapy vs. chemotherapy). No statistical correlation between dosimetric parameters and toxicity was found. Patients who developed Grade 2 radiation fibrosis had not higher radiation volumes to the untreated normal breast than those without fibrosis. Cosmesis was judged good/excellent in the majority of the cases (93%). One patient relapsed locally, and one developed distant metastases, corresponding to a 5-year local control and distant metastases-free survival of 98% and 96.7%, respectively. 35 Gy in 7 daily fractions is an effective and well-tolerated regimen to deliver PBI.

Metabolic imaging for breast cancer detection and treatment: a role for mitochondrial Complex I function

NASA Astrophysics Data System (ADS)

Ramanujan, V. Krishnan

2018-02-01

Cancer cells are known to display a variety of metabolic reprogramming strategies to fulfill their own growth and proliferative agenda. With the advent of high resolution imaging strategies, metabolomics techniques etc., there is an increasing appreciation of critical role that tumor cell metabolism plays in the overall breast cancer (BC) growth. A recent study from our laboratory demonstrated that the development of invasive cancers could be causally connected to deficits in mitochondrial function. Using this study as a rationale, we hypothesize that the widely accepted multistep tumor growth model might have a strong metabolic component as well. In this study, we explore the possibility of targeting mitochondrial Complex I enzyme system for not only metabolic detection of cancer-associated redox changes but also for modulating breast cancer cell growth characteristics. As a proof-of-principle, we demonstrate two approaches (pharmacological and genetic) for modulating mitochondrial Complex I function so as to achieve breast cancer control.

SK4 channels modulate Ca2+ signalling and cell cycle progression in murine breast cancer.

PubMed

Steudel, Friederike A; Mohr, Corinna J; Stegen, Benjamin; Nguyen, Hoang Y; Barnert, Andrea; Steinle, Marc; Beer-Hammer, Sandra; Koch, Pierre; Lo, Wing-Yee; Schroth, Werner; Hoppe, Reiner; Brauch, Hiltrud; Ruth, Peter; Huber, Stephan M; Lukowski, Robert

2017-09-01

Oncogenic signalling via Ca 2+ -activated K + channels of intermediate conductance (SK4, also known as K Ca 3.1 or IK) has been implicated in different cancer entities including breast cancer. Yet, the role of endogenous SK4 channels for tumorigenesis is unclear. Herein, we generated SK4-negative tumours by crossing SK4-deficient (SK4 KO) mice to the polyoma middle T-antigen (PyMT) and epidermal growth factor receptor 2 (cNeu) breast cancer models in which oncogene expression is driven by the retroviral promoter MMTV. Survival parameters and tumour progression were studied in cancer-prone SK4 KO in comparison with wild-type (WT) mice and in a syngeneic orthotopic mouse model following transplantation of SK4-negative or WT tumour cells. SK4 activity was modulated by genetic or pharmacological means using the SK4 inhibitor TRAM-34 in order to establish the role of breast tumour SK4 for cell growth, electrophysiological signalling, and [Ca 2+ ] i oscillations. Ablation of SK4 and TRAM-34 treatment reduced the SK4-generated current fraction, growth factor-dependent Ca 2+ entry, cell cycle progression and the proliferation rate of MMTV-PyMT tumour cells. In vivo, PyMT oncogene-driven tumorigenesis was only marginally affected by the global lack of SK4, whereas tumour progression was significantly delayed after orthotopic implantation of MMTV-PyMT SK4 KO breast tumour cells. However, overall survival and progression-free survival time in the MMTV-cNeu mouse model were significantly extended in the absence of SK4. Collectively, our data from murine breast cancer models indicate that SK4 activity is crucial for cell cycle control. Thus, the modulation of this channel should be further investigated towards a potential improvement of existing antitumour strategies in human breast cancer. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

Subtype-Specific Radiation Response and Therapeutic Effect of FAS Death Receptor Modulation in Human Breast Cancer.

PubMed

Lee, Chen-Ting; Zhou, Yingchun; Roy-Choudhury, Kingshuk; Siamakpour-Reihani, Sharareh; Young, Kenneth; Hoang, Peter; Kirkpatrick, John P; Chi, Jen-Tsan A; Dewhirst, Mark W; Horton, Janet K

2017-08-01

Breast cancer is the most common malignancy diagnosed among women and represents a heterogeneous group of subtypes. Radiation therapy is a critical component of treatment for breast cancer patients. However, little is known about radiation response among these intrinsic subtypes. In previous studies, we identified a significant induction of FAS after irradiation in biologically favorable breast cancer patients and breast cancer cell lines. Here, we expanded our study and investigated radiation response in a mouse model of breast cancer. MCF7 (luminal), HCC1954 (HER2 + ) or SUM159 (basal) cells were implanted orthotopically into the dorsal mammary fat pad of nude mice. These mice were then treated with different doses of radiation to assess tumor growth control. We further investigated the therapeutic effect of FAS modulation by silencing FAS in radiation-responsive tumors and injecting FAS agonist antibody into radiation-resistant tumors. Exposure to radiation inhibited MCF7, and to a lesser extent HCC1954 tumor growth in a dose-dependent manner. In contrast, SUM159 tumors were resistant to radiation. The estimated TCD 50 values were 19.3 Gy for MCF7 and 44.9 Gy for SUM159. Radiation induced FAS expression in MCF7 tumors, but not SUM159 tumors. We found that silencing of FAS did not negatively impact radiation response in MCF7 tumors, possibly due to compensation by other apoptotic pathways. On the other hand, FAS activating antibody in combination with radiation treatment delayed SUM159 and HCC1954 tumor growth. However, it did not reach statistical significance compared to radiation treatment alone. Our results suggest that there is intrinsic variation in radiation response among breast cancer subtypes. FAS activation concurrent with radiation slows tumor growth in the radiation-resistant subtypes, but the effect was not significant. Alternative subtype-specific modulators of radiation response are under investigation.

A dosimetric comparison of 3D-CRT, IMRT, and static tomotherapy with an SIB for large and small breast volumes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Michalski, Andrea; Central Coast Cancer Centre, Gosford Hospital, Gosford, New South Wales; Atyeo, John, E-mail: john.atyeo@sydney.edu.au

2014-07-01

Radiation therapy to the breast is a complex task, with many different techniques that can be employed to ensure adequate dose target coverage while minimizing doses to the organs at risk. This study compares the dose planning outcomes of 3 radiation treatment modalities, 3 dimensional conformal radiation therapy (3D-CRT), intensity-modulated radiation therapy (IMRT), and static tomotherapy, for left-sided whole-breast radiation treatment with a simultaneous integrated boost (SIB). Overall, 20 patients with left-sided breast cancer were separated into 2 cohorts, small and large, based on breast volume. Dose plans were produced for each patient using 3D-CRT, IMRT, and static tomotherapy. Allmore » patients were prescribed a dose of 45 Gy in 20 fractions to the breast with an SIB of 56 Gy in 20 fractions to the tumor bed and normalized so that D{sub 98%} > 95% of the prescription dose. Dosimetric comparisons were made between the 3 modalities and the interaction of patient size. All 3 modalities offered adequate planning target volume (PTV) coverage with D{sub 98%} > 95% and D{sub 2%} < 107%. Static tomotherapy offered significantly improved (p = 0.006) dose homogeneity to the PTV{sub boost} {sub eval} (0.079 ± 0.011) and breast minus the SIB volume (Breast{sub SIB}) (p < 0.001, 0.15 ± 0.03) compared with the PTV{sub boost} {sub eval} (0.085 ± 0.008, 0.088 ± 0.12) and Breast{sub SIB} (0.22 ± 0.05, 0.23 ± 0.03) for IMRT and 3D-CRT, respectively. Static tomotherapy also offered statistically significant reductions (p < 0.001) in doses to the ipsilateral lung mean dose of 6.79 ± 2.11 Gy compared with 7.75 ± 2.54 Gy and 8.29 ± 2.76 Gy for IMRT and 3D-CRT, respectively, and significantly (p < 0.001) reduced heart doses (mean = 2.83 ± 1.26 Gy) compared to both IMRT and 3D-CRT (mean = 3.70 ± 1.44 Gy and 3.91 ± 1.58 Gy). Static tomotherapy is the dosimetrically superior modality for the whole breast with an SIB compared with IMRT and 3D-CRT. IMRT is superior to 3D-CRT in both PTV dose conformity and reduction of mean doses to the ipsilateral lung.« less

Radiation techniques used in patients with breast cancer: Results of a survey in Spain

PubMed Central

Algara, Manuel; Arenas, Meritxell; De las Peñas Eloisa Bayo, Dolores; Muñoz, Julia; Carceller, José Antonio; Salinas, Juan; Moreno, Ferran; Martínez, Francisco; González, Ezequiel; Montero, Ángel

2012-01-01

Aim To evaluate the resources and techniques used in the irradiation of patients with breast cancer after lumpectomy or mastectomy and the status of implementation of new techniques and therapeutic schedules in our country. Background The demand for cancer care has increased among the Spanish population, as long as cancer treatment innovations have proliferated. Radiation therapy in breast cancer has evolved exponentially in recent years with the implementation of three-dimensional conformal radiotherapy, intensity modulated radiotherapy, image guided radiotherapy and hypofractionation. Material and Methods An original survey questionnaire was sent to institutions participating in the SEOR-Mama group (GEORM). In total, the standards of practice in 969 patients with breast cancer after surgery were evaluated. Results The response rate was 70% (28/40 centers). In 98.5% of cases 3D conformal treatment was used. All the institutions employed CT-based planning treatment. Boost was performed in 56.4% of patients: electrons in 59.8%, photons in 23.7% and HDR brachytherapy in 8.8%. Fractionation was standard in 93.1% of patients. Supine position was the most frequent. Only 3 centers used prone position. The common organs of risk delimited were: homolateral lung (80.8%) and heart (80.8%). In 84% histograms were used. An 80.8% of the centers used isocentric technique. In 62.5% asymmetric fields were employed. CTV was delimited in 46.2%, PTV in 65% and both in 38.5%. A 65% of the centers checked with portal films. IMRT and hypofractionation were used in 1% and in 5.5% respectively. Conclusion In most of centers, 3D conformal treatment and CT-based planning treatment were used. IMRT and hypofractionation are currently poorly implemented in Spain. PMID:24377012

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pacaci, P; Cebe, M; Mabhouti, H

Purpose: In this study, dosimetric comparison of field in field (FIF) and intensity modulated radiation therapy (IMRT) techniques used for treatment of whole breast radiotherapy (WBRT) were made. The dosimetric accuracy of treatment planning system (TPS) for Anisotropic Analytical Algorithm (AAA) and Acuros XB (AXB) algorithms in predicting PTV and OAR doses was also investigated. Methods: Two different treatment planning techniques of left-sided breast cancer were generated for rando phantom. FIF and IMRT plans were compared for doses in PTV and OAR volumes including ipsilateral lung, heart, left ascending coronary artery, contralateral lung and the contralateral breast. PTV and OARsmore » doses and homogeneity and conformality indexes were compared between two techniques. The accuracy of TPS dose calculation algorithms was tested by comparing PTV and OAR doses measured by thermoluminescent dosimetry with the dose calculated by the TPS using AAA and AXB for both techniques. Results: IMRT plans had better conformality and homogeneity indexes than FIF technique and it spared OARs better than FIF. While both algorithms overestimated PTV doses they underestimated all OAR doses. For IMRT plan, PTV doses, overestimation up to 2.5 % was seen with AAA algorithm but it decreased to 1.8 % when AXB algorithm was used. Based on the results of the anthropomorphic measurements for OAR doses, underestimation greater than 7 % is possible by the AAA. The results from the AXB are much better than the AAA algorithm. However, underestimations of 4.8 % were found in some of the points even for AXB. For FIF plan, similar trend was seen for PTV and OARs doses in both algorithm. Conclusion: When using the Eclipse TPS for breast cancer, AXB the should be used instead of the AAA algorithm, bearing in mind that the AXB may still underestimate all OAR doses.« less

[Doses to organs at risk in conformational radiotherapy and stereotaxic irradiation: The heart].

PubMed

Vandendorpe, B; Servagi Vernat, S; Ramiandrisoa, F; Bazire, L; Kirova, Y M

2017-10-01

Radiation therapy of breast cancer, Hodgkin lymphoma, lung cancer and others thoracic irradiations induce an ionizing radiation dose to the heart. Irradiation of the heart, associated with patient cardiovascular risk and cancer treatment-induced cardiotoxicity, increase cardiovascular mortality. The long survival after breast or Hodgkin lymphoma irradiation requires watching carefully late treatment toxicity. The over-risk of cardiac events is related to the dose received by the heart and the irradiated cardiac volume. The limitation of cardiac irradiation should be a priority in the planning of thoracic irradiations. Practices have to be modified, using modern techniques to approach of the primary objective of radiotherapy which is to optimize the dose to the target volume, sparing healthy tissues, in this case the heart. We have reviewed the literature on cardiac toxicity induced by conformational tridimensional radiation therapy, intensity-modulated radiation therapy or stereotactic body radiation therapy, in order to evaluate the possibilities to limit cardiotoxicity. Finally, we summarise the recommendations on dose constraints to the heart and coronary arteries. Copyright © 2017 Société française de radiothérapie oncologique (SFRO). Published by Elsevier SAS. All rights reserved.

Low Intensity and Frequency Pulsed Electromagnetic Fields Selectively Impair Breast Cancer Cell Viability

PubMed Central

Crocetti, Sara; Beyer, Christian; Schade, Grit; Egli, Marcel; Fröhlich, Jürg; Franco-Obregón, Alfredo

2013-01-01

Introduction A common drawback of many anticancer therapies is non-specificity in action of killing. We investigated the potential of ultra-low intensity and frequency pulsed electromagnetic fields (PEMFs) to kill breast cancer cells. Our criteria to accept this technology as a potentially valid therapeutic approach were: 1) cytotoxicity to breast cancer cells and; 2) that the designed fields proved innocuous to healthy cell classes that would be exposed to the PEMFs during clinical treatment. Methods MCF7 breast cancer cells and their normal counterparts, MCF10 cells, were exposed to PEMFs and cytotoxic indices measured in order to design PEMF paradigms that best kill breast cancer cells. The PEMF parameters tested were: 1) frequencies ranging from 20 to 50 Hz; 2) intensities ranging from 2 mT to 5 mT and; 3) exposure durations ranging from 30 to 90 minutes per day for up to three days to determine the optimum parameters for selective cancer cell killing. Results We observed a discrete window of vulnerability of MCF7 cells to PEMFs of 20 Hz frequency, 3 mT magnitude and exposure duration of 60 minutes per day. The cell damage accrued in response to PEMFs increased with time and gained significance after three days of consecutive daily exposure. By contrast, the PEMFs parameters determined to be most cytotoxic to breast cancer MCF-7 cells were not damaging to normal MCF-10 cells. Conclusion Based on our data it appears that PEMF-based anticancer strategies may represent a new therapeutic approach to treat breast cancer without affecting normal tissues in a manner that is non-invasive and can be potentially combined with existing anti-cancer treatments. PMID:24039828

Increased breast density correlates with the proliferation-seeking radiotracer (99m)Tc(V)-DMSA uptake in florid epithelial hyperplasia and in mixed ductal carcinoma in situ with invasive ductal carcinoma but not in pure invasive ductal carcinoma or in mild epithelial hyperplasia.

PubMed

Papantoniou, Vassilios; Valsamaki, Pipitsa; Sotiropoulou, Evangelia; Tsaroucha, Angeliki; Tsiouris, Spyridon; Sotiropoulou, Maria; Marinopoulos, Spyridon; Kounadi, Evangelia; Karianos, Theodore; Fothiadaki, Athina; Archontaki, Aikaterini; Syrgiannis, Konstantinos; Ptohis, Nikolaos; Makris, Nikolaos; Limouris, Georgios; Antsaklis, Aris

2011-10-01

The purpose of this study was to assess the relationship of mammographic breast density (BD) and cell proliferation/focal adhesion kinase activation-seeking radiotracer technetium 99m pentavalent dimercaptosuccinic acid (99mTc(V)-DMSA) uptake in women with different breast histologies, that is, mild epithelial hyperplasia (MEH), florid epithelial hyperplasia (FEH), mixed ductal carcinoma in situ with invasive ductal carcinoma (DCIS + IDC), and pure IDC. Fifty-five women with histologically confirmed mammary pathologies were submitted preoperatively to mammography and 99mTc(V)-DMSA scintimammography. The percentage and intensity of 99mTc(V)-DMSA uptake and the percentage of BD were calculated by computer-assisted methods and compared (t-test) between the breast pathologies. In breasts with increased BD, FEH and DCIS + IDC were found. On the contrary, pure IDC and MEH were identified in breasts with significantly lower BD values. In breasts with increased 99mTc(V)-DMSA area and intensity of uptake, FEH was the main lesion found compared to all other histologies. Linear regression analysis between BD and 99mTc(V)-DMSA uptake area and intensity revealed significant coefficients of correlation (r  =  .689, p < .001 and r  =  .582, p < .001, respectively). Increased BD correlates with the presence of FEH and mixed DCIS + IDC but not with pure IDC or MEH. Its close relationship to 99mTc(V)-DMSA, which also showed an affinity to FEH, indicates that stromal microenvironment may constitute a specific substrate leading to progression to different subtypes of cancerous lesions originating from different pathways.

Effect of Antenatal Expression of Breast Milk at Term in Reducing Breast Feeding Failures.

PubMed

Singh, G; Chouhan, R; Sidhu, K

2009-04-01

Though breast feeding is natural, during the first 2-3 days, when enough breast milk is not available with mother, she may introduce bottle feeding erroneously for improving nutrition to her baby. We studied the effect of antenatal expression of breast milk at term in reducing breast feeding failure as compared to conventional method of initiation of breast feeding. A prospective study was carried out in 180 booked cases at term. Daily expression of breast milk at least once a day after 37 weeks of pregnancy was introduced in randomly selected 90 pregnant ladies. Prior examination was done to exclude any inverted or cracked nipples and appropriate treatment instituted. The study group who expressed breast milk daily after 37 weeks did not find it difficult to initiate breast feeding after vaginal or cesarean delivery. Sufficient milk started flowing within half an hour of initiation of breast feeding in most 85 (94.4%) subjects of study group as compared to 63 (70%) patients of control group, which was statistically significant. There was no increase in any delivery complication. There were two partial breast feeding failures in control group but none in study group. Daily antenatal breast milk expression after 37 completed weeks of pregnancy significantly reduced the time for establishing full breast feeding and reduced breast feeding failures.

Review of advanced catheter technologies in radiation oncology brachytherapy procedures

PubMed Central

Zhou, Jun; Zamdborg, Leonid; Sebastian, Evelyn

2015-01-01

The development of new catheter and applicator technologies in recent years has significantly improved treatment accuracy, efficiency, and outcomes in brachytherapy. In this paper, we review these advances, focusing on the performance of catheter imaging and reconstruction techniques in brachytherapy procedures using magnetic resonance images and electromagnetic tracking. The accuracy of catheter reconstruction, imaging artifacts, and other notable properties of plastic and titanium applicators in gynecologic treatments are reviewed. The accuracy, noise performance, and limitations of electromagnetic tracking for catheter reconstruction are discussed. Several newly developed applicators for accelerated partial breast irradiation and gynecologic treatments are also reviewed. New hypofractionated high dose rate treatment schemes in prostate cancer and accelerated partial breast irradiation are presented. PMID:26203277

Estimating the costs of intensity-modulated and 3-dimensional conformal radiotherapy in Ontario.

PubMed

Yong, J H E; McGowan, T; Redmond-Misner, R; Beca, J; Warde, P; Gutierrez, E; Hoch, J S

2016-06-01

Radiotherapy is a common treatment for many cancers, but up-to-date estimates of the costs of radiotherapy are lacking. In the present study, we estimated the unit costs of intensity-modulated radiotherapy (imrt) and 3-dimensional conformal radiotherapy (3D-crt) in Ontario. An activity-based costing model was developed to estimate the costs of imrt and 3D-crt in prostate cancer. It included the costs of equipment, staff, and supporting infrastructure. The framework was subsequently adapted to estimate the costs of radiotherapy in breast cancer and head-and-neck cancer. We also tested various scenarios by varying the program maturity and the use of volumetric modulated arc therapy (vmat) alongside imrt. From the perspective of the health care system, treating prostate cancer with imrt and 3D-crt respectively cost $12,834 and $12,453 per patient. The cost of radiotherapy ranged from $5,270 to $14,155 and was sensitive to analytic perspective, radiation technique, and disease site. Cases of head-and-neck cancer were the most costly, being driven by treatment complexity and fractions per treatment. Although imrt was more costly than 3D-crt, its cost will likely decline over time as programs mature and vmat is incorporated. Our costing model can be modified to estimate the costs of 3D-crt and imrt for various disease sites and settings. The results demonstrate the important role of capital costs in studies of radiotherapy cost from a health system perspective, which our model can accommodate. In addition, our study established the need for future analyses of imrt cost to consider how vmat affects time consumption.

SU-F-T-58: Dosimetric Evaluation of Breast Tissue Composition for Electronic Brachytherapy (BET) Source In High Dose Rate Accelerated Partial Breast (APBI) Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Taylor, W; Johnson, D; Ahmad, S

Purpose: To quantitatively evaluate the dosimetric impact of differing breast tissue compositions for electronic brachytherapy source for high dose rate accelerated partial breast irradiation. Methods: A series of Monte Carlo Simulation were created using the GEANT4 toolkit (version 10.0). The breast phantom was modeled as a semi-circle with a radius of 5.0 cm. A water balloon with a radius of 1.5 cm was located in the phantom with the Xoft AxxentTM EBT source placed at center as a point source. A mixed of two tissue types (adipose and glandular tissue) was assigned as the materials for the breast phantom withmore » different weight ratios. The proportionality of glandular and adipose tissue was simulated in four different fashions, 80/20, 70/30, 50/50 and 30/70 respectively. The custom energy spectrum for the 50 kVp XOFT source was provided via the manufacturer and used to generate incident photons. The dose distributions were recorded using a parallel three dimensional mesh with a size of 30 × 30 × 30 cm3 with 1 × 1 × 1 mm3 voxels. The simulated doses absorbed along the transverse axis were normalized at the distance of 1 cm and then compared with the calculations using standard TG-43 formalism. Results: All simulations showed underestimation of dose beyond balloon surface compared to standard TG-43 calculations. The maximum percentage differences within 2 cm distance from balloon surface were found to be 18%, 11%, 10% and 8% for the fat breast (30/70), standard breast (50/50), dense breast (70/30 and 80/20), respectively. Conclusion: The accuracy of dose calculations for low energy EBT source was limited when considering tissue heterogeneous composition. The impact of atomic number on photo-electric effect for lower energy Brachytherapy source is not accounted for and resulting in significant errors in dose calculation.« less

Increased Detection of Lymphatic Vessel Invasion by D2-40 (Podoplanin) in Early Breast Cancer: Possible Influence on Patient Selection for Accelerated Partial Breast Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Debald, Manuel, E-mail: debald@uni-bonn.d; Poelcher, Martin; Flucke, Uta

2010-07-15

Purpose: Several international trials are currently investigating accelerated partial breast irradiation (APBI) for patients with early-stage breast cancer. According to existing guidelines, patients with lymphatic vessel invasion (LVI) do not qualify for APBI. D2-40 (podoplanin) significantly increases the frequency of LVI detection compared with conventional hematoxylin and eosin (HE) staining in early-stage breast cancer. Our purpose was to retrospectively assess the hypothetical change in management from APBI to whole breast radiotherapy with the application of D2-40. Patients and Methods: Immunostaining with D2-40 was performed on 254 invasive breast tumors of 247 patients. The following criteria were used to determine themore » eligibility for APBI: invasive ductal adenocarcinoma of {<=}3 cm, negative axillary node status (N0), and unifocal disease. Of the 247 patients, 74 with available information concerning LVI, as detected by D2-40 immunostaining and routine HE staining, formed our study population. Results: Using D2-40, our results demonstrated a significantly greater detection rate (p = .031) of LVI compared with routine HE staining. LVI was correctly identified by D2-40 (D2-40-positive LVI) in 10 (13.5%) of 74 tumors. On routine HE staining, 4 tumors (5.4%) were classified as HE-positive LVI. Doublestaining of these specimens with D2-40 unmasked false-positive LVI status in 2 (50%) of the 4 tumors. According to the current recommendations for APBI, immunostaining with D2-40 would have changed the clinical management from APBI to whole breast radiotherapy in 8 (10.8%) of 74 patients and from whole breast radiotherapy to APBI in 2 patients (2.7%). Conclusion: These data support the implementation of D2-40 immunostaining in the routine workup to determine a patient's eligibility for APBI.« less

Predictors of Adverse Cosmetic Outcome in the RAPID Trial: An Exploratory Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peterson, David; Truong, Pauline T.; Parpia, Sameer

Purpose: To evaluate factors associated with adverse cosmesis outcome in breast cancer patients randomized to accelerated partial breast irradiation (APBI) using 3-dimensional conformal radiation therapy or whole-breast irradiation in the RAPID (Randomized Trial of Accelerated Partial Breast Irradiation) trial. Methods and Materials: Subjects were trial participants with nurse-assessed global cosmetic scores at baseline and at 3 years. Adverse cosmesis was defined as a score of fair or poor. Cosmetic deterioration was defined as any adverse change in score from baseline to 3 years. The analysis is based on data from the previously reported interim analysis. Logistic regression models were used to assessmore » the association of risk factors for these outcomes among all patients and those treated with APBI only. Results: Clinicopathologic characteristics were similar between subjects randomized to APBI (n=569) or whole-breast irradiation (n=539). For all subjects, factors associated with adverse cosmesis at 3 years were older age, central/inner tumor location, breast infection, smoking, seroma volume, breast volume, and use of APBI; factors associated with cosmetic deterioration were smoking, seroma volume, and use of APBI (P<.05). For APBI subjects, tumor location, smoking, age, and seroma volume were associated with adverse cosmesis (P<.05), and smoking was associated with cosmetic deterioration (P=.02). An independent association between the V95/whole-breast volume ratio and adverse cosmesis (P=.28) or cosmetic deterioration (P=.07) was not detected. On further exploration a V95/whole-breast volume ratio <0.15 was associated with a lower risk of cosmetic deterioration (p=.04), but this accounted for only 11% of patients. Conclusion: In the RAPID trial, a number of patient tumor and treatment-related factors, including the use of APBI, were associated with adverse cosmesis and cosmetic deterioration. For patients treated with APBI alone, the high-dose treatment volume was not independently associated with an adverse cosmetic outcome, and a useful clinical threshold could not be identified.« less

Extending the data rate of non-line-of-sight UV communication with polarization modulation

NASA Astrophysics Data System (ADS)

Yin, Hongwei; Jia, Honghui; Zhang, Hailiang; Wang, Xiaofeng; Chang, Shengli; Yang, Juncai

2012-10-01

With low radiation background of solar-blind UV and strong scattering of UV photons by atmospheric particles, UV communication can be made use of to set up a non-line-of-sight (NLOS) free-space optical communication link. Polarization modulation, besides the traditional intensity modulation, is presented to enhance the data rate of the UV communication system. The configuration and the working process of the dually modulated UV communication system with intensity modulation and polarization, the theoretical evaluation of polarization modulation, and a numerical of the scattering matrix are presented, with the conclusion that polarization modulation is achievable. By adding the polarizing devices and changing the coding procedures, the existing singly-modulated UV communication systems with intensity modulation are easily modified to be dually-modulated ones with polarization modulation and intensity modulation. Ideally speaking, the data rate of the dually-modulated UV communication system is the product of the data rate of the singly modulated system and the number of polarization modulation.

Hybrid phosphorescence and fluorescence native spectroscopy for breast cancer detection.

PubMed

Alimova, Alexandra; Katz, A; Sriramoju, Vidyasagar; Budansky, Yuri; Bykov, Alexei A; Zeylikovich, Roman; Alfano, R R

2007-01-01

Fluorescence and phosphorescence measurements are performed on normal and malignant ex vivo human breast tissues using UV LED and xenon lamp excitation. Tryptophan (trp) phosphorescence intensity is higher in both normal glandular and adipose tissue when compared to malignant tissue. An algorithm based on the ratio of trp fluorescence intensity at 345 nm to phosphorescence intensity at 500 nm is successfully used to separate normal from malignant tissue types. Normal specimens consistently exhibited a low I(345)I(500) ratio (<10), while for malignant specimens, the I(345)I(500) ratio is consistently high (>15). The ratio analysis correlates well with histopathology. Intensity ratio maps with a spatial resolution of 0.5 mm are generated in which local regions of malignancy could be identified.

MO-DE-210-06: Development of a Supercompounded 3D Volumetric Ultrasound Image Guidance System for Prone Accelerated Partial Breast Irradiation (APBI)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Chiu, T; Hrycushko, B; Zhao, B

2015-06-15

Purpose: For early-stage breast cancer, accelerated partial breast irradiation (APBI) is a cost-effective breast-conserving treatment. Irradiation in a prone position can mitigate respiratory induced breast movement and achieve maximal sparing of heart and lung tissues. However, accurate dose delivery is challenging due to breast deformation and lumpectomy cavity shrinkage. We propose a 3D volumetric ultrasound (US) image guidance system for accurate prone APBI Methods: The designed system, set beneath the prone breast board, consists of a water container, an US scanner, and a two-layer breast immobilization cup. The outer layer of the breast cup forms the inner wall of watermore » container while the inner layer is attached to patient breast directly to immobilization. The US transducer scans is attached to the outer-layer of breast cup at the dent of water container. Rotational US scans in a transverse plane are achieved by simultaneously rotating water container and transducer, and multiple transverse scanning forms a 3D scan. A supercompounding-technique-based volumetric US reconstruction algorithm is developed for 3D image reconstruction. The performance of the designed system is evaluated with two custom-made gelatin phantoms containing several cylindrical inserts filled in with water (11% reflection coefficient between materials). One phantom is designed for positioning evaluation while the other is for scaling assessment. Results: In the positioning evaluation phantom, the central distances between the inserts are 15, 20, 30 and 40 mm. The distances on reconstructed images differ by −0.19, −0.65, −0.11 and −1.67 mm, respectively. In the scaling evaluation phantom, inserts are 12.7, 19.05, 25.40 and 31.75 mm in diameter. Measured inserts’ sizes on images differed by 0.23, 0.19, −0.1 and 0.22 mm, respectively. Conclusion: The phantom evaluation results show that the developed 3D volumetric US system can accurately localize target position and determine target volume, and is a promising image-guidance tool for prone APBI.« less

The Kite Latissimus Dorsi Flap for Breast Reconstruction: An Attempt to Reduce Lateral Chest Wall Deformity and Axillary Bulking.

PubMed

Correia Anacleto, J; Mavioso, C; Gouveia, P F; Magalhães, A; Bastos Martins, J; Moura, A; Pinto, D; Cardoso, M J

2016-08-01

The latissimus dorsi flap is a commonly used tissue transfer for volume replacement in partial or total breast reconstruction. In this era of cosmetic awareness and oncoplastic breast surgery, two main defects are related to the conventional technique: the back scar and the bulkiness on the lateral chest wall, under the axilla. Axillary bulking, a disturbing defect for the majority of patients, is a persistent consequence, independent of the technique used, even when the proximal tendon is cut. We describe a new approach, the kite latissimus dorsi flap, consisting of harvesting the flap, partially or totally, with pedicle dissection from the muscle, extending dissection, perforator style if needed, until the external border of the breast (anterior axillary line) is reached. The muscle is then cut at that level, leaving no unnecessary volume under the axilla, which would cause bulkiness and chest wall deformity. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

Preoperative weight loss program targeting women with overweight and hypertrophy of the breast - a pilot study.

PubMed

Geiker, N R W; Horn, J; Astrup, A

2017-04-01

Among women with hypertrophic breasts, the clear majority are overweight or obese. Owing to increased risk of complications, women with a body mass index (BMI) above 25 kg m -2 are precluded from reduction mammaplasty. The primary aim was to investigate if intensive weight loss could ready women with overweight for breast reduction surgery. Six women, all overweight [BMI 30.9 {28.5; 35.8} kg m -2 ] with symptomatic hypertrophy of the breast, were included a 12-week weight loss program. All women desired reduction mammaplasty and were motivated for preoperational weight loss. The first 8 weeks consisted of a formula-based diet supplying 800 kcal daily, in the subsequent 4 weeks regular foods were reintroduced increasing the intake to 1200 kcal daily. Five women completed the trial, and achieved a median (range) weight loss of 10.2 (6.5; 19) kg. Initial breast volume was 1100-2500 mL per breast, this was reduced by 300 (200; 500) mL after the intervention; equivalent to approximately 19%. Waist, hip, upper arm and thorax circumference were significantly reduced following weight loss. At end of study, all the women still suffered from symptomatic breast hypertrophy to substantiate reduction mammaplasty. Surgeries were performed 2 months thereafter. A 12-week intensive preoperative weight loss program enabled women with obesity for breast reduction surgery. Breast size was reduced proportionally more than total weight loss among women with hypertrophy. © 2017 World Obesity Federation.

Discovery of estrogen receptor α modulators from natural compounds in Si-Wu-Tang series decoctions using estrogen-responsive MCF-7 breast cancer cells.

PubMed

Liu, Li; Ma, Hongyue; Tang, Yuping; Chen, Wenxing; Lu, Yin; Guo, Jianming; Duan, Jin-Ao

2012-01-01

The binding between the estrogen receptor α (ER-α) and a variety of compounds in traditional Chinese formulae, Si-Wu-Tang (SWT) series decoctions, was studied using a stably-transfected human breast cancer cell line (MVLN). In 38 compounds tested from SWT series decoctions, the estrogen-like activity of 22 compounds was above 60% in 20 μg mL(-1). Furthermore, theoretical affinity of these compounds was certificated using the functional virtual screen of ER-α modulators by FlexX-Pharm. The accuracy of functional virtual screening of ER-α modulators could reach to 77.27%. The results showed that some compounds, such as organic acids and flavones in SWT series decoctions could be used as selective estrogen receptor modulators (SERMs) and could be selected for further development as potential agents for estrogen related diseases. Copyright © 2011 Elsevier Ltd. All rights reserved.

Dynamic modulated brachytherapy (DMBT) and intensity modulated brachytherapy (IMBT) for the treatment of rectal and breast carcinomas

NASA Astrophysics Data System (ADS)

Webster, Matthew Julian

The ultimate goal of any treatment of cancer is to maximize the likelihood of killing the tumor while minimizing the chance of damaging healthy tissues. One of the most effective ways to accomplish this is through radiation therapy, which must be able to target the tumor volume with a high accuracy while minimizing the dose delivered to healthy tissues. A successful method of accomplishing this is brachytherapy which works by placing the radiation source in very close proximity to the tumor. However, most current applications of brachytherapy rely mostly on the geometric manipulation of isotropic sources, which limits the ability to specifically target the tumor. The purpose of this work is to introduce several types of shielded brachytherapy applicators which are capable of targeting tumors with much greater accuracy than existing technologies. These applicators rely on the modulation of the dose profile through a high-density tungsten alloy shields to create anisotropic dose distributions. Two classes of applicators have been developed in this work. The first relies on the active motion of the shield, to aim a highly directional radiation profile. This allows for very precise control of the dose distribution for treatment, achieving unparalleled dose coverage to the tumor while sparing healthy tissues. This technique has been given the moniker of Dynamic Modulated Brachytherapy (DMBT). The second class of applicators, designed to reduce treatment complexity uses static applicators. These applicators retain the use of the tungsten shield, but the shield is motionless during treatment. By intelligently designing the shield, significant improvements over current methods have been demonstrated. Although these static applicators fail to match the dosimetric quality of DMBT applicators the simplified setup and treatment procedure gives them significant appeal. The focus of this work has been to optimize these shield designs, specifically for the treatment of rectal and breast carcinomas. The use of Monte Carlo methods and development of optimization algorithms have played a prominent role in accomplishing this. The use of shielded applicators, such as the ones described here, is the next logical step in the rapidly evolving field of brachytherapy.

Fluorescent polymer-based post-translational differentiation and subtyping of breast cancer cells.

PubMed

Scott, Michael D; Dutta, Rinku; Haldar, Manas K; Wagh, Anil; Gustad, Thomas R; Law, Benedict; Friesner, Daniel L; Mallik, Sanku

2012-12-07

Herein, we report the application of synthesized fluorescent, water soluble polymers for post-translational subtyping and differentiation of breast cancer cells in vitro. The fluorescence emission spectra from these polymers were modulated differently in the presence of conditioned cell culture media from various breast cancer cells. These polymers differentiate at a post-translation level possibly due to their ability to interact with extracellular enzymes that are over-expressed in cancerous conditions.

Cardiac Exposure in the Dynamic Conformal Arc Therapy, Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy of Lung Cancer

PubMed Central

Ming, Xin; Feng, Yuanming; Liu, Huan; Zhang, Ying; Zhou, Li; Deng, Jun

2015-01-01

Purpose To retrospectively evaluate the cardiac exposure in three cohorts of lung cancer patients treated with dynamic conformal arc therapy (DCAT), intensity-modulated radiotherapy (IMRT), or volumetric modulated arc therapy (VMAT) at our institution in the past seven years. Methods and Materials A total of 140 lung cancer patients were included in this institutional review board approved study: 25 treated with DCAT, 70 with IMRT and 45 with VMAT. All plans were generated in a same commercial treatment planning system and have been clinically accepted and delivered. The dose distribution to the heart and the effects of tumor laterality, the irradiated heart volume and the beam-to-heart distance on the cardiac exposure were investigated. Results The mean dose to the heart among all 140 plans was 4.5 Gy. Specifically, the heart received on average 2.3, 5.2 and 4.6 Gy in the DCAT, IMRT and VMAT plans, respectively. The mean heart doses for the left and right lung tumors were 4.1 and 4.8 Gy, respectively. No patients died with evidence of cardiac disease. Three patients (2%) with preexisting cardiac condition developed cardiac disease after treatment. Furthermore, the cardiac exposure was found to increase linearly with the irradiated heart volume while decreasing exponentially with the beam-to-heart distance. Conclusions Compared to old technologies for lung cancer treatment, modern radiotherapy treatment modalities demonstrated better heart sparing. But the heart dose in lung cancer radiotherapy is still higher than that in the radiotherapy of breast cancer and Hodgkin’s disease where cardiac complications have been extensively studied. With strong correlations of mean heart dose with beam-to-heart distance and irradiated heart volume, cautions should be exercised to avoid long-term cardiac toxicity in the lung cancer patients undergoing radiotherapy. PMID:26630566

Pink Breast Milk: Serratia marcescens Colonization

PubMed Central

Valle, Cipatli Ayuzo del; Salinas, Emilio Treviño

2014-01-01

Background Breast milk can turn pink with Serratia marcescens colonization, this bacterium has been associated with several diseases and even death. It is seen most commonly in the intensive care settings. Discoloration of the breast milk can lead to premature termination of nursing. We describe two cases of pink-colored breast milk in which S. marsescens was isolated from both the expressed breast milk. Antimicrobial treatment was administered to the mothers. Return to breastfeeding was successful in both the cases. Conclusions Pink breast milk is caused by S. marsescens colonization. In such cases,early recognition and treatment before the development of infection is recommended to return to breastfeeding. PMID:25452881

An 11-Channel Radio Frequency Phased Array Coil for Magnetic Resonance Guided High Intensity Focused Ultrasound of the Breast

PubMed Central

Minalga, E.; Payne, A.; Merrill, R.; Todd, N.; Vijayakumar, S.; Kholmovski, E.; Parker, D. L.; Hadley, J. R.

2012-01-01

In this study, a radio-frequency (RF) phased array coil was built to image the breast in conjunction with a Magnetic Resonance guided High Intensity Focused Ultrasound (MRgHIFU) device designed specifically to treat the breast in a treatment cylinder with reduced water volume. The MRgHIFU breast coil was comprised of a 10-channel phased array coil placed around an MRgHIFU treatment cylinder where nearest-neighbor decoupling was achieved with capacitive decoupling in a shared leg. In addition a single loop coil was placed at the chest wall making a total of 11-channels. The RF coil array design presented in this work was chosen based on ease of implementation, increased visualization into the treatment cylinder, image reconstruction speed, temporal resolution, and resulting signal-to-noise-ratio (SNR) profiles. This work presents a dedicated 11-channel coil for imaging of the breast tissue in the MRgHIFU setup without obstruction of the ultrasound beam and, specifically, compares its performance in SNR, overall imaging time, and temperature measurement accuracy to that of the standard single chest-loop coil typically used in breast MRgHIFU. PMID:22431301

LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.

PubMed

Yue, Zhiying; Yuan, Zengjin; Zeng, Li; Wang, Ying; Lai, Li; Li, Jing; Sun, Peng; Xue, Xiwen; Qi, Junyi; Yang, Zhengfeng; Zheng, Yansen; Fang, Yuanzhang; Li, Dali; Siwko, Stefan; Li, Yi; Luo, Jian; Liu, Mingyao

2018-05-01

The fourth member of the leucine-rich repeat-containing GPCR family (LGR4, frequently referred to as GPR48) and its cognate ligands, R-spondins (RSPOs) play crucial roles in the development of multiple organs as well as the survival of adult stem cells by activation of canonical Wnt signaling. Wnt/β-catenin signaling acts to regulate breast cancer; however, the molecular mechanisms determining its spatiotemporal regulation are largely unknown. In this study, we identified LGR4 as a master controller of Wnt/β-catenin signaling-mediated breast cancer tumorigenesis, metastasis, and cancer stem cell (CSC) maintenance. LGR4 expression in breast tumors correlated with poor prognosis. Either Lgr4 haploinsufficiency or mammary-specific deletion inhibited mouse mammary tumor virus (MMTV)- PyMT- and MMTV- Wnt1-driven mammary tumorigenesis and metastasis. Moreover, LGR4 down-regulation decreased in vitro migration and in vivo xenograft tumor growth and lung metastasis. Furthermore, Lgr4 deletion in MMTV- Wnt1 tumor cells or knockdown in human breast cancer cells decreased the number of functional CSCs by ∼90%. Canonical Wnt signaling was impaired in LGR4-deficient breast cancer cells, and LGR4 knockdown resulted in increased E-cadherin and decreased expression of N-cadherin and snail transcription factor -2 ( SNAI2) (also called SLUG), implicating LGR4 in regulation of epithelial-mesenchymal transition. Our findings support a crucial role of the Wnt signaling component LGR4 in breast cancer initiation, metastasis, and breast CSCs.-Yue, Z., Yuan, Z., Zeng, L., Wang, Y., Lai, L., Li, J., Sun, P., Xue, X., Qi, J., Yang, Z., Zheng, Y., Fang, Y., Li, D., Siwko, S., Li, Y., Luo, J., Liu, M. LGR4 modulates breast cancer initiation, metastasis, and cancer stem cells.

Relationships among optimism, well-being, self-transcendence, coping, and social support in women during treatment for breast cancer

PubMed Central

Matthews, Ellyn E.; Cook, Paul F.

2011-01-01

Objective The impact of diagnosis and treatment for breast cancer, stressors that affect emotional well-being, is influenced by several psychosocial factors and the relationships among them. The purpose of this study was to investigate the relationship between optimism and emotional well-being (EWB) and the individual and combined mediation of this relationship by perceived social support (SS), problem focused coping (PFC), and self-transcendence in women with breast cancer during radiation therapy. Methods Ninety-three women receiving radiation treatment for breast cancer completed questionnaires that measured EWB, optimism, SS, PFC, and self-transcendence. Results Correlational and multiple regression analysis revealed that optimism was positively related to EWB. Of the three mediators, self-transcendence alone was found to partially mediate the relationship between optimism and EWB. The relationship between optimism and PFC was not significant. Optimism was related to SS, but its indirect effect on EWB through SS did not reach significance. Conclusions and implications During breast cancer treatment, the positive effects of optimism on EWB are partially mediated by a woman’s level of self-transcendence. Brief screening of women’s optimism may help identify women at risk for psychological distress. Early detection and interventions to promote psychological adjustment throughout the cancer trajectory (e.g. enhancing self-transcendence) should receive attention in future research. PMID:19034884

Effects of Partial Substitution of Lean Meat with Pork Backfat or Canola Oil on Sensory Properties of Korean Traditional Meat Patties (Tteokgalbi)

PubMed Central

Imm, Bue-Young; Kim, Chung Hwan; Imm, Jee-Young

2014-01-01

Korean traditional meat patties (Tteokgalbi) were prepared by replacing part of the lean meat content with either pork backfat or canola oil and the effect of substitution on sensory quality of the meat patties was investigated. Compared to the control patties, pork-loin Tteokgalbi with 10% pork backfat or 10% canola oil had significantly higher overall acceptability and higher perceived intensity of meat flavor, sweetness, umami, and oiliness. The pork-loin patties containing 10% fat also had lower perceived firmness, toughness, and chalkiness of than the control Tteokgalbi. The chicken breast Tteokgalbi with 10% canola oil had the lowest perceived firmness and chalkiness (control > pork backfat > canola oil). No significant difference was noted in the overall acceptability of chicken breast patties with 10% pork backfat and those with 10% canola oil. These results indicate that substituting 10% of lean meat of Tteokgalbi with fat improved the sensory acceptability of the product for Korean customers regardless of the lean meat and/or fat source used in the patties. Lean meat patties formulated with a limited amount of vegetable oil such as canola oil can be a healthy option for Korean consumers by providing desirable fatty acid profiles without sacrificing sensory quality of the product. PMID:26761287

Effects of Partial Substitution of Lean Meat with Pork Backfat or Canola Oil on Sensory Properties of Korean Traditional Meat Patties (Tteokgalbi).

PubMed

Imm, Bue-Young; Kim, Chung Hwan; Imm, Jee-Young

2014-01-01

Korean traditional meat patties (Tteokgalbi) were prepared by replacing part of the lean meat content with either pork backfat or canola oil and the effect of substitution on sensory quality of the meat patties was investigated. Compared to the control patties, pork-loin Tteokgalbi with 10% pork backfat or 10% canola oil had significantly higher overall acceptability and higher perceived intensity of meat flavor, sweetness, umami, and oiliness. The pork-loin patties containing 10% fat also had lower perceived firmness, toughness, and chalkiness of than the control Tteokgalbi. The chicken breast Tteokgalbi with 10% canola oil had the lowest perceived firmness and chalkiness (control > pork backfat > canola oil). No significant difference was noted in the overall acceptability of chicken breast patties with 10% pork backfat and those with 10% canola oil. These results indicate that substituting 10% of lean meat of Tteokgalbi with fat improved the sensory acceptability of the product for Korean customers regardless of the lean meat and/or fat source used in the patties. Lean meat patties formulated with a limited amount of vegetable oil such as canola oil can be a healthy option for Korean consumers by providing desirable fatty acid profiles without sacrificing sensory quality of the product.

External Beam Accelerated Partial-Breast Irradiation Using 32 Gy in 8 Twice-Daily Fractions: 5-Year Results of a Prospective Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Pashtan, Itai M.; Recht, Abram; Ancukiewicz, Marek

Purpose: External beam accelerated partial breast irradiation (APBI) is an increasingly popular technique for treatment of patients with early stage breast cancer following breast-conserving surgery. Here we present 5-year results of a prospective trial. Methods and Materials: From October 2003 through November 2005, 98 evaluable patients with stage I breast cancer were enrolled in the first dose step (32 Gy delivered in 8 twice-daily fractions) of a prospective, multi-institutional, dose escalation clinical trial of 3-dimensional conformal external beam APBI (3D-APBI). Median age was 61 years; median tumor size was 0.8 cm; 89% of tumors were estrogen receptor positive; 10% hadmore » a triple-negative phenotype; and 1% had a HER-2-positive subtype. Median follow-up was 71 months (range, 2-88 months; interquartile range, 64-75 months). Results: Five patients developed ipsilateral breast tumor recurrence (IBTR), for a 5-year actuarial IBTR rate of 5% (95% confidence interval [CI], 1%-10%). Three of these cases occurred in patients with triple-negative disease and 2 in non-triple-negative patients, for 5-year actuarial IBTR rates of 33% (95% CI, 0%-57%) and 2% (95% CI, 0%-6%; P<.0001), respectively. On multivariable analysis, triple-negative phenotype was the only predictor of IBTR, with borderline statistical significance after adjusting for tumor grade (P=.0537). Conclusions: Overall outcomes were excellent, particularly for patients with estrogen receptor-positive disease. Patients in this study with triple-negative breast cancer had a significantly higher IBTR rate than patients with other receptor phenotypes when treated with 3D-APBI. Larger, prospective 3D-APBI clinical trials should continue to evaluate the effect of hormone receptor phenotype on IBTR rates.« less

External beam accelerated partial-breast irradiation using 32 gy in 8 twice-daily fractions: 5-year results of a prospective study.

PubMed

Pashtan, Itai M; Recht, Abram; Ancukiewicz, Marek; Brachtel, Elena; Abi-Raad, Rita F; D'Alessandro, Helen A; Levy, Antonin; Wo, Jennifer Y; Hirsch, Ariel E; Kachnic, Lisa A; Goldberg, Saveli; Specht, Michelle; Gadd, Michelle; Smith, Barbara L; Powell, Simon N; Taghian, Alphonse G

2012-11-01

External beam accelerated partial breast irradiation (APBI) is an increasingly popular technique for treatment of patients with early stage breast cancer following breast-conserving surgery. Here we present 5-year results of a prospective trial. From October 2003 through November 2005, 98 evaluable patients with stage I breast cancer were enrolled in the first dose step (32 Gy delivered in 8 twice-daily fractions) of a prospective, multi-institutional, dose escalation clinical trial of 3-dimensional conformal external beam APBI (3D-APBI). Median age was 61 years; median tumor size was 0.8 cm; 89% of tumors were estrogen receptor positive; 10% had a triple-negative phenotype; and 1% had a HER-2-positive subtype. Median follow-up was 71 months (range, 2-88 months; interquartile range, 64-75 months). Five patients developed ipsilateral breast tumor recurrence (IBTR), for a 5-year actuarial IBTR rate of 5% (95% confidence interval [CI], 1%-10%). Three of these cases occurred in patients with triple-negative disease and 2 in non-triple-negative patients, for 5-year actuarial IBTR rates of 33% (95% CI, 0%-57%) and 2% (95% CI, 0%-6%; P<.0001), respectively. On multivariable analysis, triple-negative phenotype was the only predictor of IBTR, with borderline statistical significance after adjusting for tumor grade (P=.0537). Overall outcomes were excellent, particularly for patients with estrogen receptor-positive disease. Patients in this study with triple-negative breast cancer had a significantly higher IBTR rate than patients with other receptor phenotypes when treated with 3D-APBI. Larger, prospective 3D-APBI clinical trials should continue to evaluate the effect of hormone receptor phenotype on IBTR rates. Copyright © 2012 Elsevier Inc. All rights reserved.

Cosmetic changes following surgery and accelerated partial breast irradiation using HDR interstitial brachytherapy : Evaluation by a multidisciplinary/multigender committee.

PubMed

Soror, Tamer; Kovács, György; Seibold, Nina; Melchert, Corinna; Baumann, Kristin; Wenzel, Eike; Stojanovic-Rundic, Suzana

2017-05-01

Patients with early-stage breast cancer can benefit from adjuvant accelerated partial breast irradiation (APBI) following breast-conserving surgery (BCS). This work reports on cosmetic results following APBI using multicatheter high-dose-rate interstitial brachytherapy (HDR-IBT). Between 2006 and 2014, 114 patients received adjuvant APBI using multicatheter HDR-IBT. For each patient, two photographs were analyzed: the first was taken after surgery (baseline image) and the second at the last follow-up visit. Cosmesis was assessed by a multigender multidisciplinary team using the Harvard Breast Cosmesis Scale. Dose-volume histogram (DVH) parameters and the observed cosmetic results were investigated for potential correlations. The median follow-up period was 3.5 years (range 0.6-8.5 years). The final cosmetic scores were 30% excellent, 52% good, 14.5% fair, and 3.5% poor. Comparing the baseline and follow-up photographs, 59.6% of patients had the same score, 36% had a better final score, and 4.4% had a worse final score. Only lower target dose nonuniformity ratio (DNR) values (0.3 vs. 0.26; p = 0.009) were significantly associated with improved cosmetic outcome vs. same/worse cosmesis. APBI using multicatheter HDR-IBT adjuvant to BCS results in favorable final cosmesis. Deterioration in breast cosmesis occurs in less than 5% of patients. The final breast cosmetic outcome in patients treated with BCS and APBI using multicatheter HDR-IBT is influenced primarily by the cosmetic result of the surgery. A lower DNR value is significantly associated with a better cosmetic outcome.

Outcomes of breast cancer patients with triple negative receptor status treated with accelerated partial breast irradiation.

PubMed

Wilkinson, J Ben; Reid, Robert E; Shaitelman, Simona F; Chen, Peter Y; Mitchell, Christine K; Wallace, Michelle F; Marvin, Kimberly S; Grills, Inga S; Margolis, Jeffrey M; Vicini, Frank A

2011-11-01

Triple negative receptor status (TNRS) of patients undergoing breast-conserving therapy treated with whole-breast irradiation has been associated with increased distant metastasis and decreased disease-free and overall survival. This paper reports the outcomes of TNRS patients treated with accelerated partial breast irradiation (APBI). We studied 455 patients who received APBI at our institution, using interstitial, intracavitary, and three-dimensional conformal radiation therapy. TNRS was assigned if a patient tested negative for all three (ER [estrogen receptor], PR [progesterone receptor], and HER2/neu) receptors. Of 202 patients with all receptor results available, 20 patients were designated TNRS, and 182 patients had at least one receptor positive (RP). We analyzed ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), distant metastasis (DM), and overall survival (OS). Mean follow-up was 4.1 years for the TNRS group and 5.1 years for the RP cohort (p = 0.11). TNRS patients had a higher histologic grade (59% TNRS vs. 13% RP; p < 0.001). Mean tumor size, stage N1 disease, and margin status were similar. Based on a 5-year actuarial analysis, the TNRS cohort experienced no IBTR, RNF, or DM, with an OS of 100% versus rates of 1.4% IBTR, 1.5% RNF, and 2.8% DM in the RP cohort (p > 0.52). OS for the RP cohort was 93% at 5 years (p > 0.28). In our patient population, TNRS conferred a clinical outcome similar to that of patients with RP disease treated with APBI. Further investigation with larger patient populations and longer follow-up periods is warranted to confirm that APBI is a safe and effective treatment for patients with localized TNRS breast cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

[Abdominal perforator flap (DIEP) and autologous latissimus dorsi in breast reconstruction. A retrospective comparative study about the first 60 cases of a same surgeon].

PubMed

Pluvy, I; Bellidenty, L; Ferry, N; Benassarou, M; Tropet, Y; Pauchot, J

2014-04-01

Autologous techniques for breast reconstruction get the best cosmetic results. Aesthetic satisfaction with breast reconstruction is an important evaluation criterion. The indication is based on technical criteria (morphological, medical history) and the wishes of the patient. A rigorous evaluation of the results is necessary to assist the patients in their choice of reconstruction. Thirty-three DIEP and 27 latissimus dorsi were involved. A satisfaction questionnaire was sent to patients to collect the aesthetic evaluation of their reconstructed breast, sequelae at the donor site of the flap as well as their overall satisfaction. Post-operative photographs of the patients were subject to aesthetical evaluation by two groups of observers. Complications were analyzed. The DIEP tends to get higher aesthetic satisfaction regarding the symmetry of the breasts and the volume of the reconstructed breast (P=0.05), and a better overall satisfaction (P=0.02). The uniformity of the colour of the reconstructed breast was considered superior by observers in the latissimus dorsi group (P=0.005). Donor site scar of DIEP was considered more unsightly while the latissimus dorsi was considered more painful (P=0.04) and uncomfortable, with more frequently contour abnormalities (P=0.03). We noted two total flap necrosis and three partial necrosis in the group DIEP, and two partial flap necrosis in the group latissimus dorsi. This study provides evidence that can guide the patient and the surgeon in the complex process of therapeutic decision, without exempting the latter from a careful selection of indications. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Outcomes of Breast Cancer Patients With Triple Negative Receptor Status Treated With Accelerated Partial Breast Irradiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilkinson, J. Ben; Reid, Robert E.; Shaitelman, Simona F.

2011-11-01

Purpose: Triple negative receptor status (TNRS) of patients undergoing breast-conserving therapy treated with whole-breast irradiation has been associated with increased distant metastasis and decreased disease-free and overall survival. This paper reports the outcomes of TNRS patients treated with accelerated partial breast irradiation (APBI). Methods and Materials: We studied 455 patients who received APBI at our institution, using interstitial, intracavitary, and three-dimensional conformal radiation therapy. TNRS was assigned if a patient tested negative for all three (ER [estrogen receptor], PR [progesterone receptor], and HER2/neu) receptors. Of 202 patients with all receptor results available, 20 patients were designated TNRS, and 182 patientsmore » had at least one receptor positive (RP). We analyzed ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), distant metastasis (DM), and overall survival (OS). Results: Mean follow-up was 4.1 years for the TNRS group and 5.1 years for the RP cohort (p = 0.11). TNRS patients had a higher histologic grade (59% TNRS vs. 13% RP; p < 0.001). Mean tumor size, stage N1 disease, and margin status were similar. Based on a 5-year actuarial analysis, the TNRS cohort experienced no IBTR, RNF, or DM, with an OS of 100% versus rates of 1.4% IBTR, 1.5% RNF, and 2.8% DM in the RP cohort (p > 0.52). OS for the RP cohort was 93% at 5 years (p > 0.28). Conclusions: In our patient population, TNRS conferred a clinical outcome similar to that of patients with RP disease treated with APBI. Further investigation with larger patient populations and longer follow-up periods is warranted to confirm that APBI is a safe and effective treatment for patients with localized TNRS breast cancer.« less

Results With Accelerated Partial Breast Irradiation in Terms of Estrogen Receptor, Progesterone Receptor, and Human Growth Factor Receptor 2 Status

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wilder, Richard B.; Curcio, Lisa D.; Khanijou, Rajesh K.

2010-11-01

Purpose: To report our results with accelerated partial breast irradiation (APBI) in terms of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2/neu) status. Methods and Materials: Between February 2003 and June 2009, 209 women with early-stage breast carcinomas were treated with APBI using multicatheter, MammoSite, or Contura brachytherapy to 34 Gy in 10 fractions twice daily over 5-7 days. Three patient groups were defined by receptor status: Group 1: ER or PR (+) and HER-2/neu (-) (n = 180), Group 2: ER and PR (-) and HER-2/neu (+) (n = 10), and Group 3:more » ER, PR, and HER-2/neu (-) (triple negative breast cancer, n = 19). Median follow-up was 22 months. Results: Group 3 patients had significantly higher Scarff-Bloom-Richardson scores (p < 0.001). The 3-year ipsilateral breast tumor control rates for Groups 1, 2, and 3 were 99%, 100%, and 100%, respectively (p = 0.15). Group 3 patients tended to experience relapse in distant sites earlier than did non-Group 3 patients. The 3-year relapse-free survival rates for Groups 1, 2, and 3 were 100%, 100%, and 81%, respectively (p = 0.046). The 3-year cause-specific and overall survival rates for Groups 1, 2, and 3 were 100%, 100%, and 89%, respectively (p = 0.002). Conclusions: Triple negative breast cancer patients typically have high-grade tumors with significantly worse relapse-free, cause-specific, and overall survival. Longer follow-up will help to determine whether these patients also have a higher risk of ipsilateral breast tumor relapse.« less

Patterns of intrafractional motion and uncertainties of treatment setup reference systems in accelerated partial breast irradiation for right- and left-sided breast cancer.

PubMed

Yue, Ning J; Goyal, Sharad; Kim, Leonard H; Khan, Atif; Haffty, Bruce G

2014-01-01

This study investigated the patterns of intrafractional motion and accuracy of treatment setup strategies in 3-dimensional conformal radiation therapy of accelerated partial breast irradiation (APBI) for right- and left-sided breast cancers. Sixteen right-sided and 17 left-sided breast cancer patients were enrolled in an institutional APBI trial in which gold fiducial markers were strategically sutured to the surgical cavity walls. Daily pre- and postradiation therapy kV imaging were performed and were matched to digitally reconstructed radiographs based on bony anatomy and fiducial markers, respectively, to determine the intrafractional motion. The positioning differences of the laser-tattoo and the bony anatomy-based setups with respect to the marker-based setup (benchmark) were determined to evaluate their accuracy. Statistical differences were found between the right- and left-sided APBI treatments in vector directions of intrafractional motion and treatment setup errors in the reference systems, but less in their overall magnitudes. The directional difference was more pronounced in the lateral direction. It was found that the intrafractional motion and setup reference systems tended to deviate in the right direction for the right-sided breast treatments and in the left direction for the left-sided breast treatments. It appears that the fiducial markers placed in the seroma cavity exhibit side dependent directional intrafractional motion, although additional data may be needed to further validate the conclusion. The bony anatomy-based treatment setup improves the accuracy over laser-tattoo. But it is inadequate to rely on bony anatomy to assess intrafractional target motion in both magnitude and direction. Copyright © 2014 American Society for Radiation Oncology. Published by Elsevier Inc. All rights reserved.

Screening of biomarkers for prediction of response to and prognosis after chemotherapy for breast cancers.

PubMed

Bing, Feng; Zhao, Yu

2016-01-01

To screen the biomarkers having the ability to predict prognosis after chemotherapy for breast cancers. Three microarray data of breast cancer patients undergoing chemotherapy were collected from Gene Expression Omnibus database. After preprocessing, data in GSE41112 were analyzed using significance analysis of microarrays to screen the differentially expressed genes (DEGs). The DEGs were further analyzed by Differentially Coexpressed Genes and Links to construct a function module, the prognosis efficacy of which was verified by the other two datasets (GSE22226 and GSE58644) using Kaplan-Meier plots. The involved genes in function module were subjected to a univariate Cox regression analysis to confirm whether the expression of each prognostic gene was associated with survival. A total of 511 DEGs between breast cancer patients who received chemotherapy or not were obtained, consisting of 421 upregulated and 90 downregulated genes. Using the Differentially Coexpressed Genes and Links package, 1,244 differentially coexpressed genes (DCGs) were identified, among which 36 DCGs were regulated by the transcription factor complex NFY (NFYA, NFYB, NFYC). These 39 genes constructed a gene module to classify the samples in GSE22226 and GSE58644 into three subtypes and these subtypes exhibited significantly different survival rates. Furthermore, several genes of the 39 DCGs were shown to be significantly associated with good (such as CDC20) and poor (such as ARID4A) prognoses following chemotherapy. Our present study provided a serial of biomarkers for predicting the prognosis of chemotherapy or targets for development of alternative treatment (ie, CDC20 and ARID4A) in breast cancer patients.

Partial least squares based gene expression analysis in estrogen receptor positive and negative breast tumors.

PubMed

Ma, W; Zhang, T-F; Lu, P; Lu, S H

2014-01-01

Breast cancer is categorized into two broad groups: estrogen receptor positive (ER+) and ER negative (ER-) groups. Previous study proposed that under trastuzumab-based neoadjuvant chemotherapy, tumor initiating cell (TIC) featured ER- tumors response better than ER+ tumors. Exploration of the molecular difference of these two groups may help developing new therapeutic strategies, especially for ER- patients. With gene expression profile from the Gene Expression Omnibus (GEO) database, we performed partial least squares (PLS) based analysis, which is more sensitive than common variance/regression analysis. We acquired 512 differentially expressed genes. Four pathways were found to be enriched with differentially expressed genes, involving immune system, metabolism and genetic information processing process. Network analysis identified five hub genes with degrees higher than 10, including APP, ESR1, SMAD3, HDAC2, and PRKAA1. Our findings provide new understanding for the molecular difference between TIC featured ER- and ER+ breast tumors with the hope offer supports for therapeutic studies.

An unusual subcutaneous breast cancer metastasis in a 86-year-old woman.

PubMed

Metere, A; Di Cosimo, C; Chiesa, C; Esposito, A; Giacomelli, L; Redler, A

2012-04-01

The most common metastasis site of breast cancer are the local and distant lymph nodes, bone, lungs, liver and brain. We report a 86-year-old woman with an unusual abdominal subcutaneous metastasis of breast cancer. The patient was diagnosed with invasive lobular breast cancer and had been treated six months earlier with modified radical mastectomy. Later she presented a painless mass on the middle upper abdominal wall. She was subsequently admitted to the hospital to perform a whole body CT scan, confirming the presence of the abdominal mass in epigastric region, causing a partial compression of the stomach. Histopathological studies confirmed that the abdominal mass was a rare subcutaneous metastatic lesion of breast origin. The patient underwent a surgical intervention to remove the metastasis and she recovered fully.

[Patient-reported outcome of their breast reconstruction after mastectomy].

PubMed

Robiolle, C; Quillet, A; Dagregorio, G; Huguier, V

2015-06-01

The overall care of patients with breast cancer is a major public health issue. Breast reconstruction is a part of it, and could be modulated by factors related to their personal life or surgical management. The aim of our study was to investigate a statistical link between these factors of variability, and overall satisfaction after breast reconstruction. We evaluated in a retrospective study patients' satisfaction in Plastic, Reconstructive and Aesthetic Surgery Department of the University Hospital, Poitiers, after breast reconstruction using different sources of variability: elements of life at the moment of reconstruction decision, reconstruction management and the feeling of involvement in decisions related to reconstruction. Satisfaction was quantified by modified BREAST-Q pre- and postoperative questionnaires ("reconstruction" module) complemented by an open question to address patients experience. From January 2005 to May 2011, 148 patients underwent surgery, 60.1% accepted to complete the survey (89 patients). Postoperative overall satisfaction was 89.1 out of 100. Satisfaction gradually decreased (P=0.022), postoperative overall satisfaction was non-significantly higher with autologous reconstruction, regardless of the variability factor studied. Secondary reconstruction with autologous reconstruction enhanced physical well-being (P<0.001). Patients expressed a high request for information about the different kinds of reconstruction, postoperative, as well as support groups. This study shows that patients are generally very satisfied, but do not explain the causes of dissatisfaction. It paves the way for development of satisfaction with breast reconstruction databases. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

A review of the source and function of microbiota in breast milk.

PubMed

Latuga, M Susan; Stuebe, Alison; Seed, Patrick C

2014-01-01

Breast milk contains a rich microbiota composed of viable skin and non-skin bacteria. The extent of the breast milk microbiota diversity has been revealed through new culture-independent studies using microbial DNA signatures. However, the extent to which the breast milk microbiota are transferred from mother to infant and the function of these breast milk microbiota for the infant are only partially understood. Here, we appraise hypotheses regarding the formation of breast milk microbiota, including retrograde infant-to-mother transfer and enteromammary trafficking, and we review current knowledge of mechanisms determining the extent of breast milk microbiota transfer from mother to infant. We highlight known functions of constituents in the breast milk microbiota-to enhance immunity, liberate nutrients, synergize with breast milk oligosaccharides to enhance intestinal barrier function, and strengthen a functional gut-brain axis. We also consider the pathophysiology of maternal mastitis with respect to a dysbiosis or abnormal shift in the breast milk microbiota. In conclusion, through a complex, highly evolved process in the early stages of discovery, mothers transfer the breast milk microbiota to their infants to impact infant growth and development. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

History of breast feeding and risk of incident endometriosis: prospective cohort study.

PubMed

Farland, Leslie V; Eliassen, A Heather; Tamimi, Rulla M; Spiegelman, Donna; Michels, Karin B; Missmer, Stacey A

2017-08-29

Objective  To investigate the association between lifetime breast feeding, exclusive breast feeding, postpartum amenorrhea, and incidence of endometriosis among parous women. Design  Prospective cohort study. Setting  Nurses' Health Study II, 1989-2011. Participants  72 394women who reported having one or more pregnancies that lasted at least six months, 3296 of whom had laparoscopically confirmed endometriosis. For each pregnancy, women reported duration of total breast feeding, exclusive breast feeding, and postpartum amenorrhea. Main outcome measures  Incident self reported laparoscopically confirmed endometriosis (96% concordance with medical record) in parous women. Multivariable Cox proportional hazard models were used to calculate hazard ratios and 95% confidence intervals for diagnosis of endometriosis. Results  Duration of total and exclusive breast feeding was significantly associated with decreased risk of endometriosis. Among women who reported a lifetime total length of breast feeding of less than one month, there were 453 endometriosis cases/100 000 person years compared with 184 cases/100 000 person years in women who reported a lifetime total of ≥36 months of breast feeding. For every additional three months of total breast feeding per pregnancy, women experienced an 8% lower risk of endometriosis (hazard ratio 0.92, 95% confidence interval 0.90 to 0.94; P<0.001 for trend) and a 14% lower risk for every additional three months of exclusive breast feeding per pregnancy (0.86, 0.81 to 0.90; P<0.001 for trend). Women who breastfed for ≥36 months in total across their reproductive lifetime had a 40% reduced risk of endometriosis compared with women who never breast fed (0.60, 0.50 to 0.72). The protective association with breast feeding was strongest among women who gave birth within the past five years (P=0.04 for interaction). The association with total breast feeding and exclusive breast feeding on endometriosis was partially influenced by postpartum amenorrhea (% mediated was 34% (95% confidence interval 15% to 59%) for total breast feeding and 57% (27% to 82%) for exclusive breast feeding). Conclusion  Among women who experienced at least one pregnancy that lasted at least six months, breast feeding was inversely associated with risk of incident endometriosis. This association was partially, but not fully, influenced by postpartum amenorrhea, suggesting that breast feeding could influence the risk of endometriosis both through amenorrhea and other mechanisms. Given the chronic and incurable nature of endometriosis, breast feeding should be further investigated as an important modifiable behavior to mitigate risk for pregnant women. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Applicability of active infrared thermography for screening of human breast: a numerical study

NASA Astrophysics Data System (ADS)

Dua, Geetika; Mulaveesala, Ravibabu

2018-03-01

Active infrared thermography is a fast, painless, noncontact, and noninvasive imaging method, complementary to mammography, ultrasound, and magnetic resonance imaging methods for early diagnosis of breast cancer. This technique plays an important role in early detection of breast cancer to women of all ages, including pregnant or nursing women, with different sizes of breast, irrespective of either fatty or dense breast. This proposed complementary technique makes use of infrared emission emanating from the breast. Emanating radiations from the surface of the breast under test are detected with an infrared camera to map the thermal gradients over it, in order to reveal hidden tumors inside it. One of the reliable active infrared thermographic technique, linear frequency modulated thermal wave imaging is adopted to detect tumors present inside the breast. Further, phase and amplitude images are constructed using frequency and time-domain data analysis schemes. Obtained results show the potential of the proposed technique for early diagnosis of breast cancer in fatty as well as dense breasts.

Color-coded automated signal intensity curves for detection and characterization of breast lesions: preliminary evaluation of a new software package for integrated magnetic resonance-based breast imaging.

PubMed

Pediconi, Federica; Catalano, Carlo; Venditti, Fiammetta; Ercolani, Mauro; Carotenuto, Luigi; Padula, Simona; Moriconi, Enrica; Roselli, Antonella; Giacomelli, Laura; Kirchin, Miles A; Passariello, Roberto

2005-07-01

The objective of this study was to evaluate the value of a color-coded automated signal intensity curve software package for contrast-enhanced magnetic resonance mammography (CE-MRM) in patients with suspected breast cancer. Thirty-six women with suspected breast cancer based on mammographic and sonographic examinations were preoperatively evaluated on CE-MRM. CE-MRM was performed on a 1.5-T magnet using a 2D Flash dynamic T1-weighted sequence. A dosage of 0.1 mmol/kg of Gd-BOPTA was administered at a flow rate of 2 mL/s followed by 10 mL of saline. Images were analyzed with the new software package and separately with a standard display method. Statistical comparison was performed of the confidence for lesion detection and characterization with the 2 methods and of the diagnostic accuracy for characterization compared with histopathologic findings. At pathology, 54 malignant lesions and 14 benign lesions were evaluated. All 68 (100%) lesions were detected with both methods and good correlation with histopathologic specimens was obtained. Confidence for both detection and characterization was significantly (P < or = 0.025) better with the color-coded method, although no difference (P > 0.05) between the methods was noted in terms of the sensitivity, specificity, and overall accuracy for lesion characterization. Excellent agreement between the 2 methods was noted for both the determination of lesion size (kappa = 0.77) and determination of SI/T curves (kappa = 0.85). The novel color-coded signal intensity curve software allows lesions to be visualized as false color maps that correspond to conventional signal intensity time curves. Detection and characterization of breast lesions with this method is quick and easily interpretable.

Selection of tumor antigens as targets for immune attack using immunohistochemistry: protein antigens.

PubMed

Zhang, S; Zhang, H S; Cordon-Cardo, C; Ragupathi, G; Livingston, P O

1998-11-01

The relative expression of mucin antigens MUC1, MUC2, MUC3, MUC4, MUC5AC, MUC5B, and MUC7 and glycoprotein antigens KSA, carcinoembryonic antigen, prostate-specific membrane antigen (PSMA), HER-2/neu, and human chorionic gonadotropin-beta on different cancers and normal tissues is difficult to determine from available reports. We have compared the distribution of these antigens by immunohistology on a broad range of malignant and normal tissues. MUC1 expression was most intense in cancers of breast, lung, ovarian, and endometrial origin; MUC2 was most intense in cancers of colon and prostate origin; and MUC5AC was most intense in cancers of breast and gastric origin. MUC4 was intensely expressed in 50% of cancers of colon and pancreas origin, and MUC3, MUC5B, and MUC7 were expressed in a variety of epithelial cancers, but not so intensely. KSA was intensely and uniformly expressed on all epithelial cancers; carcinoembryonic antigen was expressed in most cancers of breast, lung, colon, pancreas, and gastric origin; and PSMA was expressed only in cancers of prostate origin. Human chorionic gonadotropin-beta was expressed on the majority of sarcomas and cancers of breast, lung, and pancreas origin, although intense staining was not seen. Staining on normal tissues was restricted to one or many normal epithelial tissues ranging from MUC3, MUC4, and PSMA, which were expressed only on epithelia of pancreas, stomach, and prostate origin, respectively, to MUC1 and KSA, which were expressed on most normal epithelia. Expression was restricted to the secretory borders of these epithelia while stroma and other normal tissues were completely negative. These results plus the results of the two previous papers (S. Zhang et al, Int. J. Cancer, 73: 42-49, 1997; S. Zhang et al., Int. J. Cancer, 73: 50-56, 1997) in this series provide the basis for selection of multiple cell surface antigens as targets for antibody-mediated attack against these cancers.

Neurosurgical treatment of breast cancer metastases to the neurocranium.

PubMed

Stark, Andreas M

2010-12-16

Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4-11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present as solid, cystic, or partially cystic lesions with marked contrast enhancement and perilesional edema. The therapeutic option of choice is microsurgical resection whenever possible. Adjuvant treatment includes radiotherapy, radiosurgery, and/or chemotherapy.

Neurosurgical Treatment of Breast Cancer Metastases to the Neurocranium

PubMed Central

Stark, Andreas M.

2011-01-01

Breast cancer metastases to the neurocranium might involve the bone, the dura, or the brain parenchyma. The latter location is the far most common. The annual incidence of brain metastases in patients with breast cancer is in the range of 4–11 per 100.000 persons per year. Symptoms and findings mainly result from the location of the lesion. The diagnostic method of choice is magnetic resonance imaging before and after administration of contrast material. Breast cancer brain metastases present as solid, cystic, or partially cystic lesions with marked contrast enhancement and perilesional edema. The therapeutic option of choice is microsurgical resection whenever possible. Adjuvant treatment includes radiotherapy, radiosurgery, and/or chemotherapy. PMID:21209717

Exposure of the Heart in Breast Cancer Radiation Therapy: A Systematic Review of Heart Doses Published During 2003 to 2013.

PubMed

Taylor, Carolyn W; Wang, Zhe; Macaulay, Elizabeth; Jagsi, Reshma; Duane, Frances; Darby, Sarah C

2015-11-15

Breast cancer radiation therapy cures many women, but where the heart is exposed, it can cause heart disease. We report a systematic review of heart doses from breast cancer radiation therapy that were published during 2003 to 2013. Eligible studies were those reporting whole-heart dose (ie, dose averaged over the whole heart). Analyses considered the arithmetic mean of the whole-heart doses for the CT plans for each regimen in each study. We termed this "mean heart dose." In left-sided breast cancer, mean heart dose averaged over all 398 regimens reported in 149 studies from 28 countries was 5.4 Gy (range, <0.1-28.6 Gy). In regimens that did not include the internal mammary chain (IMC), average mean heart dose was 4.2 Gy and varied with the target tissues irradiated. The lowest average mean heart doses were from tangential radiation therapy with either breathing control (1.3 Gy; range, 0.4-2.5 Gy) or treatment in the lateral decubitus position (1.2 Gy; range, 0.8-1.7 Gy), or from proton radiation therapy (0.5 Gy; range, 0.1-0.8 Gy). For intensity modulated radiation therapy mean heart dose was 5.6 Gy (range, <0.1-23.0 Gy). Where the IMC was irradiated, average mean heart dose was around 8 Gy and varied little according to which other targets were irradiated. Proton radiation therapy delivered the lowest average mean heart dose (2.6 Gy, range, 1.0-6.0 Gy), and tangential radiation therapy with a separate IMC field the highest (9.2 Gy, range, 1.9-21.0 Gy). In right-sided breast cancer, the average mean heart dose was 3.3 Gy based on 45 regimens in 23 studies. Recent estimates of typical heart doses from left breast cancer radiation therapy vary widely between studies, even for apparently similar regimens. Maneuvers to reduce heart dose in left tangential radiation therapy were successful. Proton radiation therapy delivered the lowest doses. Inclusion of the IMC doubled typical heart dose. Copyright © 2015 Elsevier Inc. All rights reserved.

The allegheny general modification of the Harvard Breast Cosmesis Scale for the retreated breast.

PubMed

Trombetta, Mark; Julian, Thomas B; Kim, Yongbok; Werts, E Day; Parda, David

2009-10-01

The use of brachytherapy--and to a lesser extent, external-beam radiotherapy--in the management of locally recurrent breast cancer following ipsilateral breast tumor recurrence (IBTR) followed by repeat breast-conservation surgery and irradiation is currently an area of intense study. The current cosmetic scoring system is inadequate to score the outcome resulting from retreatment because it does not account for the cosmetic effect of the initial treatment. We propose a modification of the scale for patients who undergo retreatment--the Allegheny General Modification of the Harvard/NSABP/RTOG scoring scale.

Cyclic AMP Modulation of Estrogen-Induced Effects: A Novel Mechanism for Hormonal Resistance in Breast Cancer

DTIC Science & Technology

1997-10-01

arising from the use of pure antioestrogens on oestrogen-responsive (MCF-7) and oestrogen growth- independent ( K3 ) human breast cancer cells. Endocrine...Observations arising from the use of pure antioestrogens on oestrogen-responsive (MCF-7) and oestrogen growth-independent ( K3 ) human breast cancer...oestroge/i growth-independent variant K3 (Katzenellenbogen i-t al. 1987, Clarke et al. 1989, Cho et al. 1991, Ree:.. & Katzenellenbogen 1992) of this

Fast and accurate de novo genome assembly from long uncorrected reads

PubMed Central

Vaser, Robert; Sović, Ivan; Nagarajan, Niranjan

2017-01-01

The assembly of long reads from Pacific Biosciences and Oxford Nanopore Technologies typically requires resource-intensive error-correction and consensus-generation steps to obtain high-quality assemblies. We show that the error-correction step can be omitted and that high-quality consensus sequences can be generated efficiently with a SIMD-accelerated, partial-order alignment–based, stand-alone consensus module called Racon. Based on tests with PacBio and Oxford Nanopore data sets, we show that Racon coupled with miniasm enables consensus genomes with similar or better quality than state-of-the-art methods while being an order of magnitude faster. PMID:28100585