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Sample records for breast 5-year survival

  1. Trends in 5-year survival rates among breast cancer patients by hormone receptor status and stage

    PubMed Central

    Chen, Lu; Linden, Hannah M.; Anderson, Benjamin O.; Li, Christopher I.

    2014-01-01

    Purpose Improvement in breast cancer survival has been observed in recent decades in the U.S., but it is unclear if similar survival gains are consistent across breast cancer subtypes, especially with regards to more advanced stages of the disease. Methods Data were from 13 population-based cancer registries participating in the Surveillance, Epidemiology and End Results (SEER) program, consisting of women between 20–79 years of age diagnosed with invasive breast cancer between 1992 and 2008. 2-year (1992–2008) and 5-year (1992–2006) breast cancer cause-specific survival rates were calculated and stratified by estrogen receptor (ER)/progesterone receptor (PR) status, stage and race. Annual percent changes in survival rates were assessed. Results From 1992 through 1998–1999, 5-year and 2-year cause specific survival rates significantly improved across ER+/PR+, ER−/PR− and ER+/PR− subtypes, with an annual increase ranging from 0.5%–1.0%. From 1998–1999 to 2006, different patterns were observed by ER/PR subtypes with survival rates slightly improving for ER+/PR+, continuing to improve at a rate of 0.5% per year for ER−/PR−, and dropping 0.3% annually for ER+/PR− No significant survival gains were experienced by patients with ER−/PR+ cancer during the study period. In terms of advanced diseases, greatest annual increases in survival rates were seen for patients with stage III–IV ER+/PR+ and ER−/PR− tumors but less progress was observed for advanced ER+/PR− breast cancers. Conclusion Steady improvements in survival rates for breast cancer have been achieved over the past several decades. However, 5-year survival rates for stage IV disease remained dismally below 20% for most ER/PR subtypes. PMID:25164974

  2. Disease Management Project Breast Cancer in Hesse – 5-Year Survival Data

    PubMed Central

    Jackisch, C.; Funk, A.; König, K.; Lubbe, D.; Misselwitz, B.; Wagner, U.

    2014-01-01

    Introduction: The Disease Management Project Breast Cancer (DMP Breast Cancer) was first launched in Hesse in 2004. The project is supported by the health insurance companies in Hesse and the Professional Association of Gynaecologists in Hesse. The aim is to offer structured treatment programmes to all women diagnosed with breast cancer in Hesse by creating intersectoral cooperations between coordinating clinics, associated hospitals and gynaecologists in private practice who registered in the DMP programme. Method: Between 1 January 2005 and 30 June 2011, 13 973 women were enrolled in the DMP programme. Results: After data cleansing, survival rates were calculated for a total of 11 214 women. The 5-year overall survival (OS) rate was 86.3 %; survival rates according to tumour stage on presentation were 92.2 % (pT1) and 82.3 % (pT2), respectively. The impact of steroid hormone receptor status on survival (87.8 % for receptor-positive cancers vs. 78.9 % for receptor-negative cancers) and of age at first diagnosis on survival (≤ 35 years = 91 %) were calculated. Conclusion: The project showed that intersectoral cooperation led to significant improvements in the quality of treatment over time, as measured by quality indicators and outcomes after treatment. PMID:24882878

  3. Disease Management Project Breast Cancer in Hesse - 5-Year Survival Data: Successful Model of Intersectoral Communication for Quality Assurance.

    PubMed

    Jackisch, C; Funk, A; König, K; Lubbe, D; Misselwitz, B; Wagner, U

    2014-03-01

    Introduction: The Disease Management Project Breast Cancer (DMP Breast Cancer) was first launched in Hesse in 2004. The project is supported by the health insurance companies in Hesse and the Professional Association of Gynaecologists in Hesse. The aim is to offer structured treatment programmes to all women diagnosed with breast cancer in Hesse by creating intersectoral cooperations between coordinating clinics, associated hospitals and gynaecologists in private practice who registered in the DMP programme. Method: Between 1 January 2005 and 30 June 2011, 13 973 women were enrolled in the DMP programme. Results: After data cleansing, survival rates were calculated for a total of 11 214 women. The 5-year overall survival (OS) rate was 86.3 %; survival rates according to tumour stage on presentation were 92.2 % (pT1) and 82.3 % (pT2), respectively. The impact of steroid hormone receptor status on survival (87.8 % for receptor-positive cancers vs. 78.9 % for receptor-negative cancers) and of age at first diagnosis on survival (≤ 35 years = 91 %) were calculated. Conclusion: The project showed that intersectoral cooperation led to significant improvements in the quality of treatment over time, as measured by quality indicators and outcomes after treatment. PMID:24882878

  4. Disease Management Project Breast Cancer in Hesse - 5-Year Survival Data: Successful Model of Intersectoral Communication for Quality Assurance.

    PubMed

    Jackisch, C; Funk, A; König, K; Lubbe, D; Misselwitz, B; Wagner, U

    2014-03-01

    Introduction: The Disease Management Project Breast Cancer (DMP Breast Cancer) was first launched in Hesse in 2004. The project is supported by the health insurance companies in Hesse and the Professional Association of Gynaecologists in Hesse. The aim is to offer structured treatment programmes to all women diagnosed with breast cancer in Hesse by creating intersectoral cooperations between coordinating clinics, associated hospitals and gynaecologists in private practice who registered in the DMP programme. Method: Between 1 January 2005 and 30 June 2011, 13 973 women were enrolled in the DMP programme. Results: After data cleansing, survival rates were calculated for a total of 11 214 women. The 5-year overall survival (OS) rate was 86.3 %; survival rates according to tumour stage on presentation were 92.2 % (pT1) and 82.3 % (pT2), respectively. The impact of steroid hormone receptor status on survival (87.8 % for receptor-positive cancers vs. 78.9 % for receptor-negative cancers) and of age at first diagnosis on survival (≤ 35 years = 91 %) were calculated. Conclusion: The project showed that intersectoral cooperation led to significant improvements in the quality of treatment over time, as measured by quality indicators and outcomes after treatment.

  5. Prone Breast Intensity Modulated Radiation Therapy: 5-Year Results

    SciTech Connect

    Osa, Etin-Osa O.; DeWyngaert, Keith; Roses, Daniel; Speyer, James; Guth, Amber; Axelrod, Deborah; Fenton Kerimian, Maria; Goldberg, Judith D.; Formenti, Silvia C.

    2014-07-15

    Purpose: To report the 5-year results of a technique of prone breast radiation therapy delivered by a regimen of accelerated intensity modulated radiation therapy with a concurrent boost to the tumor bed. Methods and Materials: Between 2003 and 2006, 404 patients with stage I-II breast cancer were prospectively enrolled into 2 consecutive protocols, institutional trials 03-30 and 05-181, that used the same regimen of 40.5 Gy/15 fractions delivered to the index breast over 3 weeks, with a concomitant daily boost to the tumor bed of 0.5 Gy (total dose 48 Gy). All patients were treated after segmental mastectomy and had negative margins and nodal assessment. Patients were set up prone: only if lung or heart volumes were in the field was a supine setup attempted and chosen if found to better spare these organs. Results: Ninety-two percent of patients were treated prone, 8% supine. Seventy-two percent had stage I, 28% stage II invasive breast cancer. In-field lung volume ranged from 0 to 228.27 cm{sup 3}, mean 19.65 cm{sup 3}. In-field heart volume for left breast cancer patients ranged from 0 to 21.24 cm{sup 3}, mean 1.59 cm{sup 3}. There was no heart in the field for right breast cancer patients. At a median follow-up of 5 years, the 5-year cumulative incidence of isolated ipsilateral breast tumor recurrence was 0.82% (95% confidence interval [CI] 0.65%-1.04%). The 5-year cumulative incidence of regional recurrence was 0.53% (95% CI 0.41%-0.69%), and the 5-year overall cumulative death rate was 1.28% (95% CI 0.48%-3.38%). Eighty-two percent (95% CI 77%-85%) of patients judged their final cosmetic result as excellent/good. Conclusions: Prone accelerated intensity modulated radiation therapy with a concomitant boost results in excellent local control and optimal sparing of heart and lung, with good cosmesis. Radiation Therapy Oncology Group protocol 1005, a phase 3, multi-institutional, randomized trial is ongoing and is evaluating the equivalence of a similar dose and

  6. Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival

    MedlinePlus

    ... Cancer Screening Research Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival For some women with breast ... took it for 5 years. (See the table.) Breast Cancer Recurrence and Death 5 to 14 Years after ...

  7. Breast-Conserving Treatment With Partial or Whole Breast Irradiation for Low-Risk Invasive Breast Carcinoma-5-Year Results of a Randomized Trial

    SciTech Connect

    Polgar, Csaba Fodor, Janos; Major, Tibor; Nemeth, Gyoergy; Loevey, Katalin; Orosz, Zsolt; Sulyok, Zoltan; Takacsi-Nagy, Zoltan; Kasler, Miklos

    2007-11-01

    Purpose: To report the 5-year results of a randomized study comparing the survival and cosmetic results of breast-conserving treatment with partial breast irradiation (PBI) or conventional whole breast irradiation (WBI). Methods and Materials: Between 1998 and 2004, 258 selected patients with T1 N0-1mi, Grade 1-2, nonlobular breast cancer without presence of extensive intraductal component and resected with negative margins were randomized after breast-conserving surgery to receive 50 Gy/25 fractions WBI (n = 130) or PBI (n = 128). The latter consisted of either 7 x 5.2 Gy high-dose-rate (HDR) multicatheter brachytherapy (BT; n = 88) or 50 Gy/25 fractions electron beam (EB) irradiation (n = 40). Results: At a median follow-up of 66 months, the 5-year actuarial rate of local recurrence was 4.7% and 3.4% in the PBI and WBI arms, respectively (p = 0.50). There was no significant difference in the 5-year probability of overall survival (94.6% vs. 91.8%), cancer-specific survival (98.3% vs. 96.0%), and disease-free survival (88.3% vs. 90.3%). The rate of excellent to good cosmetic result was 77.6% in the PBI group (81.2% after HDR BT; 70.0% after EB) and 62.9% in the control group (52.2% after telecobalt; 65.6% after 6-9-MV photons; p{sub WBI/PBI} = 0.009). Conclusions: Partial breast irradiation using interstitial HDR implants or EB to deliver radiation to the tumor bed alone for a selected group of early-stage breast cancer patients produces 5-year results similar to those achieved with conventional WBI. Significantly better cosmetic outcome can be achieved with carefully designed HDR multicatheter implants compared with the outcome after WBI.

  8. Partial Breast Radiation Therapy With Proton Beam: 5-Year Results With Cosmetic Outcomes

    SciTech Connect

    Bush, David A.; Do, Sharon; Lum, Sharon; Garberoglio, Carlos; Mirshahidi, Hamid; Patyal, Baldev; Grove, Roger; Slater, Jerry D.

    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 and 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

  9. Survival of breast cancer patients. Our experience.

    PubMed

    Marrazzoa, Antonio; Taormina, Pietra; David, Massimo; Riili, Ignazio; Casà, Luigi; Catalano, Filippo; Lo Gerfo, Domenico; Noto, Antonio

    2007-01-01

    Life expectancy for patients with breast carcinoma has changed in Europe over the last two decades. In Italy, the overall survival rate is about 77% at 5 years. When considering the situation in Sicily, the EUROCARE 2 study examined survival data from the Ragusa Cancer Registry, showing that the curves are worse than in other regions of Italy. Starting from these considerations we decide to evaluate whether these data from the Ragusa Cancer Registry corresponded to Palermo data. So we analysed data from 575 consecutive patients with breast cancer, treated in our Breast Unit from 1990 to 2003 according to the St. Gallen Recommendations and followed for a median period of 5 years. The prognostic role of age, tumour size, nodal status, TNM, stage, grading and hormonal receptors (OR, PR) were analysed and survival curves at 5 and 10 years were produced using the actuarial survival methods. All causes of death were considered. The median follow-up was 33 months. The Log rank test and univariate cox proportional model were used to demonstrate the association between prognostic factors and outcome. When considering T and N status, the curves showed an inverse correlation between survival and increases in these parameters. Overall survival was 92.9% at 5 years and 81.4% at 10 years for T1, 78.4% at 5 years and 61.4% at 10 years for T2 and 40.8% for T3-T4 at 5 and 10 years. Overall survival for NO was 92.1% and 78.2%, respectively, at 5 and 10 years, but decreased to 72.0% and 59.9% at 5 and 10 years for N1. In N2 patients we found that only about 50% of patients were still alive at 5 and 10 years, while for N3 patients the figures were 57.2% and 40%, respectively. PMID:17663369

  10. Accelerated Partial Breast Irradiation: 5-Year Results of the German-Austrian Multicenter Phase II Trial Using Interstitial Multicatheter Brachytherapy Alone After Breast-Conserving Surgery

    SciTech Connect

    Strnad, Vratislav; Hildebrandt, Guido; Poetter, Richard; Hammer, Josef; Hindemith, Marion; Resch, Alexandra; Spiegl, Kurt; Lotter, Michael; Uter, Wolfgang; Bani, Mayada; Kortmann, Rolf-Dieter; Beckmann, Matthias W.; Fietkau, Rainer; Ott, Oliver J.

    2011-05-01

    Purpose: To evaluate the impact of accelerated partial breast irradiation on local control, side effects, and cosmesis using multicatheter interstitial brachytherapy as the sole method for the adjuvant local treatment of patients with low-risk breast cancer. Methods and Materials: 274 patients with low-risk breast cancer were treated on protocol. Patients were eligible for the study if the tumor size was < 3 cm, resection margins were clear by at least 2 mm, no lymph node metastases existed, age was >35 years, hormone receptors were positive, and histologic grades were 1 or 2. Of the 274 patients, 175 (64%) received pulse-dose-rate brachytherapy (D{sub ref} = 50 Gy). and 99 (36%) received high-dose-rate brachytherapy (D{sub ref} = 32.0 Gy). Results: Median follow-up was 63 months (range, 9-103). Only 8 of 274 (2.9%) patients developed an ipsilateral in-breast tumor recurrence at the time of analysis. The 5-year actuarial local recurrence-free survival probability was 98%. The 5- year overall and disease-free survival probabilities of all patients were 97% and 96%, respectively. Contralateral in-breast malignancies were detected in 2 of 274 (0.7%) patients, and distant metastases occurred in 6 of 274 (2.2%). Late side effects {>=}Grade 3 (i.e., breast tissue fibrosis and telangiectasia) occurred in 1 patient (0.4%, 95%CI:0.0-2.0%) and 6 patients (2.2%, 95%CI:0.8-4.7%), respectively. Cosmetic results were good to excellent in 245 of 274 patients (90%). Conclusions: The long-term results of this prospective Phase II trial confirm that the efficacy of accelerated partial breast irradiation using multicatheter brachytherapy is comparable with that of whole breast irradiation and that late side effects are negligible.

  11. Exemestane Following Tamoxifen Reduces Breast Cancer Recurrences and Prolongs Survival

    Cancer.gov

    Postmenopausal women with early-stage hormone receptor-positive breast cancer had delayed disease recurrence and longer survival after taking 2-3 years of tamoxifen followed by exemestane for a total of 5 years compared to taking tamoxifen for 5 years.

  12. Survival Rate of Short, Locking Taper Implants with a Plateau Design: A 5-Year Retrospective Study

    PubMed Central

    Demiralp, Kemal Özgür; Akbulut, Nihat; Kursun, Sebnem; Argun, Didem; Bagis, Nilsun; Orhan, Kaan

    2015-01-01

    Background. Short implants have become popular in the reconstruction of jaws, especially in cases with limited bone height. Shorter implants, those with locking tapers and plateau root shapes, tend to have longer survival times. We retrospectively investigated the cumulative survival rates of Bicon short implants (<8 mm) according to patient variables over a 5-year period. Materials and Methods. This study included 111 consecutively treated patients with 371 implants supporting fixed or removable prosthetics. Data were evaluated to acquire cumulative survival rates according to gender, age, tobacco use, surgical procedure, bone quality, and restoration type. Statistics were performed using chi-square, Mann-Whitney, and Kruskal Wallis H tests. Results. The survival rate was 97.3% with, on average, 22.8 months of follow-up. Patients older than 60 years had higher failure rate than the other age groups (P < 0.05). Placed region, age, and bone quality had adverse effects on survival rate in the <8 mm implant group with statistically significant difference (P < 0.05). Conclusions. Approximately 23-month follow-up data indicate that short implants with locking tapers and plateau-type roots have comparable survival rates as other types of dental implants. However, due to limitations of study, these issues remain to be further investigated in future randomized controlled clinical trials. PMID:25961004

  13. Intraoperative Radiotherapy as a Boost During Breast-Conserving Surgery Using Low-Kilovoltage X-Rays: The First 5 Years of Experience With a Novel Approach

    SciTech Connect

    Wenz, Frederik; Welzel, Grit; Blank, Elena; Hermann, Brigitte; Steil, Volker; Suetterlin, Marc; Kraus-Tiefenbacher, Uta

    2010-08-01

    Purpose: Intraoperative radiotherapy (IORT) during breast-conserving surgery (BCS) has been recently introduced using different devices. We report the first 5 years of a single-center experience after introduction of a novel approach to deliver IORT as a tumor bed boost during BCS for breast cancer. Methods and Materials: A total of 155 breast cancers in 154 women (median age, 63 years; range, 30-83 years; T1/T2 = 100/55; N0/N+ = 108/47) were treated between February 2002 and December 2007 at the University Medical Center Mannheim, in whom IORT as tumor bed boost was applied using 50-kV X-rays (20 Gy) followed by 46-50 Gy whole-breast external-beam radiotherapy (EBRT). Chemotherapy, if indicated, was given before EBRT. The median interval between BCS plus IORT and EBRT was 40 days. Median follow-up was 34 months (maximum 80 months, 1 patient lost to follow-up). Overall survival and local relapse-free survival were calculated at 5 years using the Kaplan-Meier method. Seventy-nine patients were evaluated at 3-year follow-up for late toxicity according to the Late Effects in Normal Tissues-Subjective, Objective, Management, and Analytic system. Results: Ten patients died, 2 had in-breast relapse, and 8 developed distant metastases (5-year overall survival = 87.0%; 5-year local relapse-free survival = 98.5%). Grade 3 fibroses of the tumor bed were detected in 5% of the patients after 3 years. Skin toxicity was mild (telangiectases and hyperpigmentations in approximately 6% each). Conclusions: Intraoperative radiotherapy as a tumor bed boost during BCS for breast cancer using low-kilovoltage X-rays followed by EBRT yields low recurrence and toxicity rates.

  14. Predictors of long term survival after hepatic resection for hilar cholangiocarcinoma: A retrospective study of 5-year survivors

    PubMed Central

    Abd ElWahab, Mohamed; El Nakeeb, Ayman; El Hanafy, Ehab; Sultan, Ahmad M; Elghawalby, Ahmed; Askr, Waleed; Ali, Mahmoud; Abd El Gawad, Mohamed; Salah, Tarek

    2016-01-01

    AIM: To determine predictors of long term survival after resection of hilar cholangiocarcinoma (HC) by comparing patients surviving > 5 years with those who survived < 5 years. METHODS: This is a retrospective study of patients with pathologically proven HC who underwent surgical resection at the Gastroenterology Surgical Center, Mansoura University, Egypt between January 2002 and April 2013. All data of the patients were collected from the medical records. Patients were divided into two groups according to their survival: Patients surviving less than 5 years and those who survived > 5 years. RESULTS: There were 34 (14%) long term survivors (5 year survivors) among the 243 patients. Five-year survivors were younger at diagnosis than those surviving less than 5 years (mean age, 50.47 ± 4.45 vs 54.59 ± 4.98, P = 0.001). Gender, clinical presentation, preoperative drainage, preoperative serum bilirubin, albumin and serum glutamic-pyruvic transaminase were similar between the two groups. The level of CA 19-9 was significantly higher in patients surviving < 5 years (395.71 ± 31.43 vs 254.06 ± 42.19, P = 0.0001). Univariate analysis demonstrated nine variables to be significantly associated with survival > 5 year, including young age (P = 0.001), serum CA19-9 (P = 0.0001), non-cirrhotic liver (P = 0.02), major hepatic resection (P = 0.001), caudate lobe resection (P = 0.006), well differentiated tumour (P = 0.03), lymph node status (0.008), R0 resection margin (P = 0.0001) and early postoperative liver cell failure (P = 0.02). CONCLUSION: Liver status, resection of caudate lobe, lymph node status, R0 resection and CA19-9 were demonstrated to be independent risk factors for long term survival. PMID:27358676

  15. Microscopy image analysis of p63 immunohistochemically stained laryngeal cancer lesions for predicting patient 5-year survival.

    PubMed

    Ninos, Konstantinos; Kostopoulos, Spiros; Kalatzis, Ioannis; Sidiropoulos, Konstantinos; Ravazoula, Panagiota; Sakellaropoulos, George; Panayiotakis, George; Economou, George; Cavouras, Dionisis

    2016-01-01

    The aim of the present study was to design a microscopy image analysis (MIA) system for predicting the 5-year survival of patients with laryngeal squamous cell carcinoma, employing histopathology images of lesions, which had been immunohistochemically (IHC) stained for p63 expression. Biopsy materials from 42 patients, with verified laryngeal cancer and follow-up, were selected from the archives of the University Hospital of Patras, Greece. Twenty six patients had survived more than 5 years and 16 less than 5 years after the first diagnosis. Histopathology images were IHC stained for p63 expression. Images were first processed by a segmentation method for isolating the p63-expressed nuclei. Seventy-seven features were evaluated regarding texture, shape, and physical topology of nuclei, p63 staining, and patient-specific data. Those features, the probabilistic neural network classifier, the leave-one-out (LOO), and the bootstrap cross-validation methods, were used to design the MIA-system for assessing the 5-year survival of patients with laryngeal cancer. MIA-system accuracy was about 90 % and 85 %, employing the LOO and the Bootstrap methods, respectively. The image texture of p63-expressed nuclei appeared coarser and contained more edges in the 5-year non-survivor group. These differences were at a statistically significant level (p < 0.05). In conclusion, this study has proposed an MIA-system that may be of assistance to physicians, as a second opinion tool in assessing the 5-year survival of patients with laryngeal cancer, and it has revealed useful information regarding differences in nuclei texture between 5-year survivors and non-survivors. PMID:26285779

  16. Sentinel Lymph Node Occult Metastases Have Minimal Survival Effect in Some Breast Cancer Patients

    Cancer.gov

    Detailed examination of sentinel lymph node tissue from breast cancer patients revealed previously unidentified metastases in about 16% of the samples, but the difference in 5-year survival between patients with and without these metastases was very small

  17. Extended (5-year) Outcomes of Accelerated Partial Breast Irradiation Using MammoSite Balloon Brachytherapy: Patterns of Failure, Patient Selection, and Dosimetric Correlates for Late Toxicity

    SciTech Connect

    Vargo, John A.; Verma, Vivek; Kim, Hayeon; Kalash, Ronny; Heron, Dwight E.; Johnson, Ronald; Beriwal, Sushil

    2014-02-01

    Purpose: Accelerated partial breast irradiation (APBI) with balloon and catheter-based brachytherapy has gained increasing popularity in recent years and is the subject of ongoing phase III trials. Initial data suggest promising local control and cosmetic results in appropriately selected patients. Long-term data continue to evolve but are limited outside of the context of the American Society of Breast Surgeons Registry Trial. Methods and Materials: A retrospective review of 157 patients completing APBI after breast-conserving surgery and axillary staging via high-dose-rate {sup 192}Ir brachytherapy from June 2002 to December 2007 was made. APBI was delivered with a single-lumen MammoSite balloon-based applicator to a median dose of 34 Gy in 10 fractions over a 5-day period. Tumor coverage and critical organ dosimetry were retrospectively collected on the basis of computed tomography completed for conformance and symmetry. Results: At a median follow-up time of 5.5 years (range, 0-10.0 years), the 5-year and 7-year actuarial incidences of ipsilateral breast control were 98%/98%, of nodal control 99%/98%, and of distant control 99%/99%, respectively. The crude rate of ipsilateral breast recurrence was 2.5% (n=4); of nodal failure, 1.9% (n=3); and of distant failure, 0.6% (n=1). The 5-year and 7-year actuarial overall survival rates were 89%/86%, with breast cancer–specific survival of 100%/99%, respectively. Good to excellent cosmetic outcomes were achieved in 93.4% of patients. Telangiectasia developed in 27% of patients, with 1-year, 3-year, and 5-year actuarial incidence of 7%/24%/33%; skin dose >100% significantly predicted for the development of telangiectasia (50% vs 14%, P<.0001). Conclusions: Long-term single-institution outcomes suggest excellent tumor control, breast cosmesis, and minimal late toxicity. Skin toxicity is a function of skin dose, which may be ameliorated with dosimetric optimization afforded by newer multicatheter brachytherapy

  18. 5-year follow-up after sentinel node mapping for breast cancer demonstrates better than expected treatment outcomes.

    PubMed

    Fuhrman, George M; Gambino, Jamie; Bolton, John S; Farr, Gist; Jiang, Xiaozhang

    2005-07-01

    We conducted this study to provide one of the initial assessments of treatment outcomes for breast cancer patients evaluated with sentinel node mapping. All patients diagnosed with breast carcinoma, evaluated with sentinel node mapping, and followed for 5 years were divided into three groups depending on sentinel node(s) status. Group I (node negative) included 91 patients, 77 with invasive cancer, and 7 lost to follow-up. Of the remaining 70 patients, 3 (4.3%) suffered a distant recurrence and died, 1 developed an in-breast recurrence, and 9 (12.9%) developed a contralateral cancer during the study. Group II (IHC positive) included 28 patients. One (3.6%) developed a distant recurrence and died of breast cancer, and one developed a contralateral cancer during follow. Group III (H&E positive) included 36 patients with 1 lost to follow-up. Five patients (14.3%) died of breast cancer and two (5.7%) developed contralateral carcinomas during follow-up. The most striking observation was a lower than expected rate of distant recurrences in these patients followed for 5 years after a diagnosis of breast cancer and staging with sentinel node mapping. The ability to identify subtle nodal metastasis and design appropriate systemic therapeutic strategies may explain this finding. PMID:16089119

  19. Breast cancer survival and health iniquities.

    PubMed

    Guerra, Maximiliano Ribeiro; Silva, Gulnar Azevedo e; Nogueira, Mário Círio; Leite, Isabel Cristina Gonçalves; Oliveira, Raquel de Vasconcellos Carvalhaes de; Cintra, Jane Rocha Duarte; Bustamante-Teixeira, Maria Teresa

    2015-08-01

    Breast cancer is the most frequent neoplasm in women, and some studies have shown social inequalities in incidence and survival, which are poorly investigated in Brazil. To assess iniquity in prognosis, a hospital-based cohort study was carried out. Follow-up was made by active search in medical records and in the Mortality Information System, phone calls, and consultation on Individual Tax-Collection Record status. Survival functions were estimated by the Kaplan-Meier method, and the Cox proportional hazards model was employed for prognostic assessment. Disease-specific survival was estimated at 76.3% (95%CI: 71.9-81.0) in 5 years. Women seen at public facilities had worse prognosis (HR = 1.79; 95%CI: 1.09-2.94), which was particularly due to the disease being diagnosed at a more advanced stage. These findings point to inequalities of access to screening actions, as women of lower social conditions with later diagnostic and therefore with worse prognostic. PMID:26375646

  20. Clinical performance and survival of space maintainers: evaluation over a period of 5 years.

    PubMed

    Rajab, Lamis D

    2002-01-01

    The study investigated the clinical performance of 387 space maintainers fitted in 358 patients aged from 3 to 9 years in the Department of Pediatric Dentistry at the Faculty of Dentistry-University of Jordan from 1996 to 2000. Failure occurred in 119 appliances (30.7%), of which 49.6% were due to solder breakage, 32.8% from cement loss, 11% from soft tissue lesions, 4.2% from eruption interference, and 2.5% were completely lost. By using the Kaplan-Meier method, the estimated median survival time for space maintainers was 18 months. Lingual arches had the lowest median survival time of 14 months. Bands and loops, Nance appliances, and removable partial dentures had similar probability of survival. Fixed bilateral mandibular appliances recorded lower survival time than fixed bilateral maxillary appliances. Gender, age, type of dentition, fixed vs. removable, year of placement of the appliance and number of space maintainers fitted simultaneously in the same patient had no significant effect on survival of the appliances.

  1. Survival of rock-colonizing organisms after 1.5 years in outer space.

    PubMed

    Onofri, Silvano; de la Torre, Rosa; de Vera, Jean-Pierre; Ott, Sieglinde; Zucconi, Laura; Selbmann, Laura; Scalzi, Giuliano; Venkateswaran, Kasthuri J; Rabbow, Elke; Sánchez Iñigo, Francisco J; Horneck, Gerda

    2012-05-01

    Cryptoendolithic microbial communities and epilithic lichens have been considered as appropriate candidates for the scenario of lithopanspermia, which proposes a natural interplanetary exchange of organisms by means of rocks that have been impact ejected from their planet of origin. So far, the hardiness of these terrestrial organisms in the severe and hostile conditions of space has not been tested over extended periods of time. A first long-term (1.5 years) exposure experiment in space was performed with a variety of rock-colonizing eukaryotic organisms at the International Space Station on board the European EXPOSE-E facility. Organisms were selected that are especially adapted to cope with the environmental extremes of their natural habitats. It was found that some-but not all-of those most robust microbial communities from extremely hostile regions on Earth are also partially resistant to the even more hostile environment of outer space, including high vacuum, temperature fluctuation, the full spectrum of extraterrestrial solar electromagnetic radiation, and cosmic ionizing radiation. Although the reported experimental period of 1.5 years in space is not comparable with the time spans of thousands or millions of years believed to be required for lithopanspermia, our data provide first evidence of the differential hardiness of cryptoendolithic communities in space.

  2. Cosmetic outcome 1-5 years after breast conservative surgery, irradiation and systemic therapy.

    PubMed

    Kelemen, Gyöngyi; Varga, Zoltán; Lázár, György; Thurzó, László; Kahán, Zsuzsanna

    2012-04-01

    The late side-effects of the local therapy of early breast cancer depend on many patient- and therapy-related parameters. We aimed at investigating the factors that influence the cosmetic and functional outcomes among our breast cancer patients after breast-conserving surgery and conformal radiotherapy, with or without adjuvant systemic therapy. A study was made of the association of the cosmetic outcome after a median follow-up time of 2.4 years and the clinical data on 198 patients extracted from a prospectively compiled database. Breast tenderness occurred more frequently among patients ≤50 years old (p < 0.05). Long-term side effects were related to radiotherapy-related factors the most, while no effect of the systemic therapy could be detected. The risk of hyperpigmentation, breast edema and breast fibrosis increased by 18%, 23% and 7%, respectively for every 100 cm(3) increase in the irradiated breast volume, while that of breast edema and breast fibrosis increased by 21% and 12%, respectively for every 10 cm(3) increase in the boost volume. Patients who received a photon boost were significantly more likely to develop breast edema and fibrosis than those who received electrons (p < 0.005). Dose inhomogeneity was related to the volume of the irradiated breast (p = 0.037). Dyspigmentation developed more often among patients older than 50 years, while smoking favoured both dyspigmentation and teleangiectasia. Breast edema was related to dyspigmentation (p = 0.003), fibrosis (p < 0.001) and breast asymmetry (p = 0.032), whereas none of these abnormalities were associated with teleangiectasia. Body image changes were more frequent at a younger age (p < 0.005), while the need to change clothing habits occurred more often at an older age (p < 0.05). Radiotherapy-related parameters appear to exert the greatest effect on the overall cosmetic outcome after breast-conserving surgery and postoperative radiotherapy.

  3. [A report of 40 cases of esophageal carcinoma surviving for more than 5 years after treatment with drugs].

    PubMed

    Wang, R L

    1993-07-01

    From August 1974 to January 1987, 650 cases of moderately and advanced esophageal carcinoma were treated with a combination of chemotherapy and Rabdosia rubescens or Rabdosia rubescens and/or tradition chinese medicinal prescription. After treatment, 40 patients survived for over 5 years (5-year survival rate 6.15%): 32 for over 6 years, 23 for more than 10 years, 5 for more than 15 years and 20 die of tumors (16 cases) or other diseases (4 cases). There were 20 patients who are still living and some of them have been living for more than 18 years. Analyzing the data, it is believed that the age, the state of activity, the length of illness, the effectiveness of primary treatment, the multi-course extensive therapy, long-term maintenance treatment, etc, are all important factors affecting the results of drug treatment. PMID:8174469

  4. Survival after local treatment for early breast cancer.

    PubMed

    Hacking, E A; Dent, D M; Gudgeon, C A; Prescott, R

    1985-05-25

    A 10-year survival rate of 82% was found in 517 women with early localized breast cancer (pathological stage T1-2N0M0) who had been treated with local therapy alone (total mastectomy and axillary clearance). Factors influencing survival were tumour size (T1 versus T2) and age; patients older than 50 years fared better than younger patients at 5 years but this advantage had disappeared at 10 years. Receptor status influenced disease-free survival, but not survival. Recurrence developed in 93 patients--systemic in 46 and local in 47. Support for the contention that all breast cancer is systemic was thus not found at 10 years, and the value of local therapy alone in node-negative women was endorsed.

  5. A prospective study of the survival of chemically activated anterior resin composite restorations in general dental practice: 5-year results.

    PubMed

    van Noort, R; Davis, L G

    1993-08-01

    The principals of 26 general dental practices agreed to use six chemically activated resin composite restorative materials to restore Class III and Class V lesions and record information concerning their performance over a period of 5 years. The information collected was analysed by actuarial methods to assess the clinical longevity and reasons for replacement as perceived by the dentists operating in the General Dental Service in England. At the end of 5 years, 14 dentists provided sufficient returns for their data to be considered suitable for analysis. The database consisted of 2399 Class III and 1093 Class V restorations. The overall probability of survival at 5 years of Class III and Class V restorations was 62.9% and 71.8% respectively. The difference in performance between the six restorative materials was small, with the probability of survival varying from 70.4 +/- 2.9% to 56.3 +/- 2.9% for the Class III restorations and 78.6 +/- 3.7% to 67.7 +/- 4.2% for the Class V restorations. The main reasons for replacement were general surface discoloration, secondary caries and fracture. The chemically activated composite restorative materials available at the time of initiating this study produced comparable performances in general dental practice when used without enamel and dentine bonding techniques. This suggests that more general practice-based clinical studies are needed to determine whether or not improvements in materials and techniques are effectively transferred to the general practice situation.

  6. Long term survival of radiotherapy for esophageal cancer: analysis of 1136 patients surviving for more than 5 years

    SciTech Connect

    Yang, Z.Y.; Gu, X.; Zhao, S.

    1983-12-01

    One thousand one hundred and thirty-six patients surviving for more than five years after radiotherapy were studied. The important prognostic factors are: lesion less than 5 cm in length, lesion located in the upper-third segment and lesion that is radiosensitive. The radiation dose given to long term survivors varies greatly, i.e., 2700 to 9300 rad. Yet, for the sensitive type of lesion, doses lower than 5000 rad could also effect a cure. The delivery of an optimum dose determined by serial examinations during radiotherapy could improve the result of treatment. For local recurrent lesions, the value of a second course of radiation is extremely limited and surgery is the only means to offer a cure. For metastasis in the lymph nodes, radiation offers some hope of cure, although the long term outcome may not be satisfactory. For second primary cancer of the esophagus, aggressive radiation still gives encouraging results.

  7. Practices That Reduce the Latina Survival Disparity After Breast Cancer

    PubMed Central

    Carrillo, J. Emilio; Ang, Alfonzo; Pérez-Stable, Eliseo J.

    2013-01-01

    Abstract Objectives Latina breast cancer patients are 20 percent more likely to die within 5 years after diagnosis compared with white women, even though they have a lower incidence of breast cancer, lower general mortality rates, and some better health behaviors. Existing data only examine disparities in the utilization of breast cancer care; this research expands the study question to which utilization factors drive the shorter survival in Latina women compared with white women. Methods This longitudinal linked Surveillance Epidemiology and End Results (SEER)-Medicare cohort study examined early stage breast cancer patients diagnosed between 1992 and 2000 and followed for 5–11 years after diagnosis (N=44,999). Modifiable utilization factors included consistent visits to primary care providers and to specialists after diagnosis, consistent post-diagnosis mammograms, and receipt of initial care consistent with current standards of care. Results Of the four utilization factors potentially driving this disparity, a lack of consistent post-diagnosis mammograms was the strongest driver of the Latina breast cancer survival disparity. Consistent mammograms attenuated the hazard of death from 23% [hazard ratio, HR, (95% confidence interval, 95%CI)=1.23 (1.1,1.4)] to a nonsignificant 12% [HR (95%CI)=1.12 (0.7,1.3)] and reduced the excess hazard of death in Latina women by 55%. Effect modification identified that visits to primary care providers have a greater protective impact on the survival of Latina compared to white women [HR (95%CI)=0.9 (0.9,0.9)]. Conclusions We provide evidence that undetected new or recurrent breast cancers due to less consistent post-diagnosis mammograms contribute substantially to the long-observed Latina survival disadvantage. Interventions involving primary care providers may be especially beneficial to this population. PMID:24106867

  8. Survival and other clinical outcomes of maintenance hemodialysis patients in Taiwan: a 5-year multicenter follow-up study.

    PubMed

    Chen, Huan-Sheng; Cheng, Chun-Ting; Hou, Chun-Cheng; Liou, Hung-Hsiang; Lim, Paik-Seong

    2014-10-01

    The increasing aging and diabetes mellitus (DM) patients in dialysis population make the quality maintenance of dialysis an imperative issue. Recently, an increasing number of dialysis centers were run by private dialysis providers, many of which apply quality assurance programs and performance management systems to dialysis care. We studied patients in dialysis facilities in Taiwan run by a private chain to see clinical outcomes of centers operating under these systemic strategies. Hemodialysis patients from January 1, 2008 to December 31, 2012 in 25 dialysis facilities in Taiwan, which received the management and consultation from a dialysis service provider, NephroCare (NC), were included. Data pivotal to quality of dialysis were analyzed. During a 5-year interval, 5161 hemodialysis patients were included. For volume control, the proportion of patients with weight gain ≥4.5% decreases from 41.7% to 30.2%. Mean Kt/V is 1.74 ± 0.28. Mean albumin level is 3.92 ± 0.38 g/dL. Patients with phosphate <5.5 mg/dL is up to 71.8%. The mean hemoglobin level is 10.70 ± 1.40 g/dL. More than 80% of patients have adequate iron status. Further, 73% of patients use native arteriovenous fistula. Hospitalization-free survival rate was 56% at the fifth year. Patient survival rate at the fifth year was 66.4%. Overall clinical performances were maintained very stable in NC facilities from this temporal data analysis. The hospitalization and survival rate also compare favorably with those reported internationally. These results warrant further studies to justify the application of this kind of quality assurance programs and performance management systems in dialysis care. PMID:24766262

  9. [Survived breast cancer, but unemployed].

    PubMed

    Bruinvels, David J

    2014-01-01

    A recent Danish retrospective cohort study of 14,750 women concluded that the duration of the period of unemployment before breast cancer may be the most important determinant of unemployment following breast cancer treatment. This finding allows for the identification of a particularly vulnerable group of patients in need of rehabilitation. The generalizability of the findings of the Danish study is discussed in this article. Can these findings be applied to Dutch daily practice too? Further research is required to answer this question because of differences between the Danish and Dutch systems of social insurance. A similar Dutch retrospective cohort study is under way, and preliminary results are expected to be published in 2014. Findings from both studies may be used to develop rehabilitation and vocational therapy interventions aiming to prevent unemployment and to increase work participation. PMID:25004788

  10. [Quality of life of over 60-year-old patients with breast and uterine carcinoma, 5 years after primary operation].

    PubMed

    Neises, M; Soedradjat, F; Strittmatter, H J; Wischnik, A; Melchert, F

    1996-01-01

    In the 5-year follow-up period, we studied the quality of life of 145 patients who were at least 60 years old at the time of primary operation. Of the patients, 70 women had breast cancer and 75 endometrium cancer. We used the questionnaire "short form health survey: medical outcomes study". The areas which were analyzed were stress due to therapy, body image/femininity and social contacts. The Karnofsky-Index was determined by the physician. In both groups, most stress was felt due to the operation and at the first knowledge of the diagnosis. In the area of emotional stress 1/3 of the patients of both groups declared continuous stress due to feelings of fear, helplessness and passivity. In the area of body image/femininity half the patients with breast cancer and 2/3 with endometrial cancer felt stress. In the area of social contact 2/3 of the patients felt uncertainty in contact with others and this led to social retreat in 1/3 of the women. The Karnofsky-Index of all patients was between 50-100%. Our study supports the view that older patients with cancer should also be offered psychosocial counseling.

  11. Two Genes Might Help Predict Breast Cancer Survival

    MedlinePlus

    ... fullstory_160503.html Two Genes Might Help Predict Breast Cancer Survival Research suggests that tracking DNA activity patterns ... activity of two genes may help predict certain breast cancer patients' chances of survival and guide their treatment, ...

  12. The prognostic significance of race and survival from breast cancer: a model for assessing the reliability of reported survival differences.

    PubMed Central

    Roach, M.; Alexander, M.

    1995-01-01

    For more than 20 years, black women with breast cancer have been reported to have a lower survival rate than white women with breast cancer. Despite correcting for stage and socioeconomic status, some studies continue to report race-related excess mortality. A reliability scoring system was developed, based primarily on the precision of the staging system used, and the likelihood that the quality of treatment was comparable. Studies that compared the survival of blacks and whites treated for breast cancer from 1968 to 1988 were included in this study. Studies that demonstrated relatively large differences in the 5-year survival between blacks and whites were associated with low reliability scores. Studies that reported little or no difference in 5-year survival rates were associated with relatively high reliability scores. This model and the literature on which it is based suggest that the reported survival differences associated with race can be explained by differences in stage at presentation and by differences in the quality of care received. Efforts directed at early detection and improvements in the quality of care delivered are likely to reduce the excess breast cancer mortality experienced by black women. PMID:7731072

  13. Improvement of survival and prospect of cure in patients with metastatic breast cancer.

    PubMed

    Cheng, Yee Chung; Ueno, Naoto T

    2012-07-01

    Patients with metastatic breast cancer have traditionally been considered incurable with conventional treatment. However, 5-10% of those patients survive more than 5 years, and 2-5% survive more than 10 years. Recent studies suggest that the survival of patients with metastatic breast cancer has been slowly improving. In this review, we examine the possible curative approach for a certain group of patients with metastatic breast cancer. We identify that patients most likely to benefit from such an aggressive approach are young and have good performance status, adequate body functional reserve, long disease-free interval before recurrence, oligometastatic disease, and low systemic tumor load. An aggressive multidisciplinary approach including both local treatment of macroscopic disease and systemic treatment of microscopic disease can result in prolonged disease control in certain patients with metastatic breast cancer. Whether patients with prolonged disease control are "cured" remains controversial.

  14. Survival rate of breast cancer patients in Malaysia: a population-based study.

    PubMed

    Abdullah, Nor Aini; Wan Mahiyuddin, Wan Rozita; Muhammad, Nor Asiah; Ali, Zainudin Mohamad; Ibrahim, Lailanor; Ibrahim Tamim, Nor Saleha; Mustafa, Amal Nasir; Kamaluddin, Muhammad Amir

    2013-01-01

    Breast cancer is the most common cancer among Malaysian women. Other than hospital-based results, there are no documented population-based survival rates of Malaysian women for breast cancers. This population- based retrospective cohort study was therefore conducted. Data were obtained from Health Informatics Centre, Ministry of Health Malaysia, National Cancer Registry and National Registration Department for the period from 1st Jan 2000 to 31st December 2005. Cases were captured by ICD-10 and linked to death certificates to identify the status. Only complete data were analysed. Survival time was calculated from the estimated date of diagnosis to the date of death or date of loss to follow-up. Observed survival rates were estimated by Kaplan- Meier method using SPSS Statistical Software version 17. A total of 10,230 complete data sets were analysed. The mean age at diagnosis was 50.6 years old. The overall 5-year survival rate was 49% with median survival time of 68.1 months. Indian women had a higher survival rate of 54% compared to Chinese women (49%) and Malays (45%). The overall 5-year survival rate of breast cancer patient among Malaysian women was still low for the cohort of 2000 to 2005 as compared to survival rates in developed nations. Therefore, it is necessary to enhance the strategies for early detection and intervention.

  15. Ten Years of Tamoxifen Reduces Breast Cancer Recurrences, Improves Survival

    Cancer.gov

    Taking adjuvant tamoxifen for 10 years after primary treatment leads to a greater reduction in breast cancer recurrences and deaths than taking the drug for only 5 years, according to the results of a large international clinical trial.

  16. Postoperative Complications, In-Hospital Mortality and 5-Year Survival After Surgical Resection for Patients with a Pancreatic Neuroendocrine Tumor: A Systematic Review.

    PubMed

    Jilesen, Anneke P J; van Eijck, Casper H J; in't Hof, K H; van Dieren, S; Gouma, Dirk J; van Dijkum, Els J M Nieveen

    2016-03-01

    Studies on postoperative complications and survival in patients with pancreatic neuroendocrine tumors (pNET) are sparse and randomized controlled trials are not available. We reviewed all studies on postoperative complications and survival after resection of pNET. A systematic search was performed in the Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE from 2000-2013. Inclusion criteria were studies of resected pNET, which described postoperative complications separately for each surgical procedure and/or 5-year survival after resection. Prospective and retrospective studies were pooled separately and overall pooled if heterogeneity was below 75%. The random-effect model was used. Overall, 2643 studies were identified and after full-text analysis 62 studies were included. Pancreatic fistula (PF) rate of the prospective studies after tumor enucleation was 45%; PF-rates after distal pancreatectomy, pancreatoduodenectomy, or central pancreatectomy were, respectively, 14-14-58%. Delayed gastric emptying rates were, respectively, 5-5-18-16%. Postoperative hemorrhage rates were, respectively, 6-1-7-4%. In-hospital mortality rates were, respectively, 3-4-6-4%. The 5-year overall survival (OS) and disease-specific survival (DSS) of resected pNET without synchronous resected liver metastases were, respectively, 85-93%. Heterogeneity between included studies on 5-year OS in patients with synchronous resected liver metastases was too high to pool all studies. The 5-year DSS in patients with liver metastases was 80%. Morbidity after pancreatic resection for pNET was mainly caused by PF. Liver resection in patients with liver metastases seems to have a positive effect on DSS. To reduce heterogeneity, ISGPS criteria and uniform patient groups should be used in the analysis of postoperative outcome and survival.

  17. Social Support and Survival in Young Women with Breast Carcinoma

    PubMed Central

    Chou, Ann F.; Stewart, Susan L.; Wild, Robert C.; Bloom, Joan R.

    2010-01-01

    Purpose While previous evidence has shown increased likelihood for survival in cancer patients who have social support, little is known about changes in social support during illness and their impact on survival. This study examines the relationship between social support and survival among women diagnosed with breast carcinoma, specifically assessing the effect of network size and changes in social contact post-diagnosis. Methods A population-based sample of 584 women was followed for up to 12.5 years (median follow-up =10.3 years). The mean age at diagnosis was 44 years, 81% were married, and 29% were racial/ethnic minorities. Cox regression analysis was used to estimate survival as a function of social support (changes in social contact and the size of social support), disease severity, treatment, health status, and socio-demographic factors. Results Fifty-four-percent of the women had local and 44% had regional stage disease. About 53% underwent mastectomy, 68% received chemotherapy, and 55% had radiation. Regression results showed that disease stage, estrogen receptor status, and mastectomy were associated with greater risk of dying. Although network size was not related to survival, increased contact with friends/family post-diagnosis was associated with lower risk of death, with a hazard ratio of 0.31 (95% CI, 0.17-0.57). Conclusion Findings from this study have identified an important aspect of a woman’s social network that impacts survival. An increase in the amount of social contact, representing greater social support, may increase the likelihood of the women’s survival by enhancing their coping skills, providing emotional support, and expanding opportunities for information-sharing. PMID:20967848

  18. Descriptive epidemiology of breast cancer in China: incidence, mortality, survival and prevalence.

    PubMed

    Li, Tong; Mello-Thoms, Claudia; Brennan, Patrick C

    2016-10-01

    Breast cancer is the most common neoplasm diagnosed amongst women worldwide and is the leading cause of female cancer death. However, breast cancer in China is not comprehensively understood compared with Westernised countries, although the 5-year prevalence statistics indicate that approximately 11 % of worldwide breast cancer occurs in China and that the incidence has increased rapidly in recent decades. This paper reviews the descriptive epidemiology of Chinese breast cancer in terms of incidence, mortality, survival and prevalence, and explores relevant factors such as age of manifestation and geographic locations. The statistics are compared with data from the Westernised world with particular emphasis on the United States and Australia. Potential causal agents responsible for differences in breast cancer epidemiology between Chinese and other populations are also explored. The need to minimise variability and discrepancies in methods of data acquisition, analysis and presentation is highlighted.

  19. Incidence, mortality and survival of female breast cancer during 2003-2011 in Jiangsu province, China

    PubMed Central

    Yan, Xinran; Han, Renqiang; Zhou, Jinyi; Yu, Hao; Yang, Jie

    2016-01-01

    Objective To assess the incidence, mortality and survival status of female breast cancer in Jiangsu province of China. Methods Population-based cancer registry data in Jiangsu province were collected during 2003-2011. Crude rates, age-specific rates, age-standardized rates and annual percent changes of incidence and mortality were calculated to describe the epidemiologic characteristics and time trends. Patients diagnosed from 2003 to 2005 were chosen for analyzing the survival status of breast cancer. Results From 2003 to 2011, 17,605 females were diagnosed with breast cancer and 4,883 died in selected registry areas in Jiangsu province. The crude incidence rate was 25.18/100,000, and the age-standardized rates by Chinese population (ASRC) and by world population (ASRW) were 19.03/100,000 and 17.92/100,000, respectively. During the same period, the crude mortality rate was 6.98/100,000 and the ASRC and ASRW were 4.93/100,000 and 4.80/100,000, respectively. From 2003 to 2011, the incidence and mortality increased with annual percent change of 11.37% and 5.78%, respectively. For survival analysis, 1,392 patients in 7 areas were identified in 2003-2005 and finished 5 years of follow-up. Survival rates were found to decrease with survival years, the 5-year observed survival rate was 45.9% and the relative survival rate was 52.0%. We also found that the survival rate varied across the province, which was lower in the north and higher in the south of Jiangsu province. Conclusions Breast cancer has become a significant public health problem in Jiangsu province and China. More resources should be invested in primary prevention, earlier diagnosis and better health services in order to increase survival rates among Chinese females. PMID:27478317

  20. Trends of population-based breast cancer survival in Germany and the US: Decreasing discrepancies, but persistent survival gap of elderly patients in Germany

    PubMed Central

    2012-01-01

    Background Studies have revealed both higher cancer survival in the US than in Germany and substantial improvement of cancer survival in the past in these countries. This population-based study aims at comparing most recent 5-year relative survival of breast cancer patients and preceding trends in both countries. Methods Women with a first invasive breast cancer diagnosed and followed up between 1988 and 2008 from Germany and the US (utilizing data from the Saarland Cancer Registry and the Surveillance, Epidemiology, and End Results Program, respectively) were included. Period analysis was used to derive most up-to-date 5-year relative survival and preceding survival trends according to age and stage. Results Since 1993, age standardized relative survival has steadily improved in Germany and the US to 83% and 88%, respectively. In the period 2005–08, relative survival of localized cancer was above 97% in both countries, and 79% and 83% for locally/regionally spread breast cancer, respectively. Prognosis of metastasized disease has remained very poor overall, with improvement essentially being restricted to younger patients. The proportion of patients diagnosed with localized breast cancer was consistently higher in the US. If adjusted for stage, the differences in relative survival between both countries diminished over time and eventually disappeared. Conclusions Similar survival is now observed in both countries for patients below the age of 70 years, but in Germany survival is still much lower for elderly patients. The observed trends point to treatment advances as a major cause for improved survival. However, substantial differences in mammography usage existed between both countries and might probably also account for the observed differences (to a lesser extent, also differences in health care systems, and delivery of cancer care). Encouraging, survival of breast cancer patients has improved in Germany to a much greater extent than in the US, albeit the

  1. A practice-based clinical evaluation of the survival and success of metal-ceramic and zirconia molar crowns: 5-year results.

    PubMed

    Rinke, S; Kramer, K; Bürgers, R; Roediger, M

    2016-02-01

    This practice-based study evaluates the survival and success of conventionally luted metal-ceramic and zirconia molar crowns fabricated by using a prolonged cooling period for the veneering porcelain. Fifty-three patients were treated from 07/2008 to 07/2009 with either metal-ceramic crowns (MCC) or zirconia crowns (ZC). Forty-five patients (26 female) with 91 restorations (obser-vational period: 64.0 ± 4.8 months) participated in a clinical follow-up examination and were included in the study. Estimated cumulative survival (ECSv), success (ECSc) and veneering ceramic success (ECVCSc) were calculated (Kaplan-Meier) and analysed by the crown fabrication technique and the position of the restoration (Cox regression model) (P < 0.05). Five complete failures (MCC: 2, ZC: 3) were recorded (5-year ECSv: MCC: 97.6%, (95% confidence interval (95%-CI): [93%; 100%]/ZC: 94.0%, (95%-CI): [87%; 100%]). Of the MCCs (n = 41), 85.0%, [95%-CI: (77%; 96%)] remained event-free, whereas the ECSc for the ZCs (n = 50) was 74.3% (95%-CI): [61%; 87%]. No significant differences in ECSv (P = 0.51), ECSc (P = 0.43) and ECVCSc (P = 0.36) were detected between the two fabrication techniques. Restorations placed on terminal abutments (n = 44) demonstrated a significantly lower ECVCSc (P = 0.035), (5-year VCF-rate: 14.8%) than crowns placed on tooth-neighboured abutments (n = 47), (5-year VCF-rate: 4.3%). In the present study, zirconia molar crowns demonstrated a 5-year ECSv, ECSc and ECVCSc comparable to MCCs. Irrespective of the fabrication technique, crowns on terminal abutments bear a significantly increased risk for VCFs. Clinical investigations with an increased number of restorations are needed.

  2. Survival of women with metastatic breast cancer at Yale from 1920 to 1980.

    PubMed

    Todd, M; Shoag, M; Cadman, E

    1983-06-01

    The tumor registry at Yale--New Haven Hospital, which began recording data in 1920, was utilized to examine the ultimate outcome of all breast cancer patients who were initially diagnosed at Yale with metastatic breast cancer. Of the 5,898 patients with breast cancer seen from 1920 to 1980, 574 initially had metastatic cancer. The median survival of these patients increased steadily from 21 months in 1920 to 41 months in the decade from 1970 to 1980. The percentage of women actually surviving 5 years increased from 5% in the 1920s to approximately 25% in the 1960s. Despite the use of combination drug programs in the 1970s, the percentage of these patients remaining alive at 5 years remained near 25%. Firm conclusions cannot be made from a retrospective study spanning 60 years, although the trends depicted and lack of continued improvement indicate that our current therapeutic approach to metastatic breast cancer may not result in dramatic improvement in overall survival.

  3. Prediction of Breast Cancer Survival Through Knowledge Discovery in Databases

    PubMed Central

    Afshar, Hadi Lotfnezhad; Ahmadi, Maryam; Roudbari, Masoud; Sadoughi, Farahnaz

    2015-01-01

    The collection of large volumes of medical data has offered an opportunity to develop prediction models for survival by the medical research community. Medical researchers who seek to discover and extract hidden patterns and relationships among large number of variables use knowledge discovery in databases (KDD) to predict the outcome of a disease. The study was conducted to develop predictive models and discover relationships between certain predictor variables and survival in the context of breast cancer. This study is Cross sectional. After data preparation, data of 22,763 female patients, mean age 59.4 years, stored in the Surveillance Epidemiology and End Results (SEER) breast cancer dataset were analyzed anonymously. IBM SPSS Statistics 16, Access 2003 and Excel 2003 were used in the data preparation and IBM SPSS Modeler 14.2 was used in the model design. Support Vector Machine (SVM) model outperformed other models in the prediction of breast cancer survival. Analysis showed SVM model detected ten important predictor variables contributing mostly to prediction of breast cancer survival. Among important variables, behavior of tumor as the most important variable and stage of malignancy as the least important variable were identified. In current study, applying of the knowledge discovery method in the breast cancer dataset predicted the survival condition of breast cancer patients with high confidence and identified the most important variables participating in breast cancer survival. PMID:25946945

  4. Prediction of breast cancer survival through knowledge discovery in databases.

    PubMed

    Lotfnezhad Afshar, Hadi; Ahmadi, Maryam; Roudbari, Masoud; Sadoughi, Farahnaz

    2015-01-26

    The collection of large volumes of medical data has offered an opportunity to develop prediction models for survival by the medical research community. Medical researchers who seek to discover and extract hidden patterns and relationships among large number of variables use knowledge discovery in databases (KDD) to predict the outcome of a disease. The study was conducted to develop predictive models and discover relationships between certain predictor variables and survival in the context of breast cancer. This study is Cross sectional. After data preparation, data of 22,763 female patients, mean age 59.4 years, stored in the Surveillance Epidemiology and End Results (SEER) breast cancer dataset were analyzed anonymously. IBM SPSS Statistics 16, Access 2003 and Excel 2003 were used in the data preparation and IBM SPSS Modeler 14.2 was used in the model design. Support Vector Machine (SVM) model outperformed other models in the prediction of breast cancer survival. Analysis showed SVM model detected ten important predictor variables contributing mostly to prediction of breast cancer survival. Among important variables, behavior of tumor as the most important variable and stage of malignancy as the least important variable were identified. In current study, applying of the knowledge discovery method in the breast cancer dataset predicted the survival condition of breast cancer patients with high confidence and identified the most important variables participating in breast cancer survival.

  5. Early ipsilateral breast tumor recurrences after breast conservation affect survival: An analysis of the National Cancer Institute randomized trial

    SciTech Connect

    Brooks, Joseph P.; Danforth, David N.; Albert, Paul; Sciuto, Linda C. B.S.N.; Smith, Sharon L.; Camphausen, Kevin A.; Poggi, Matthew M. . E-mail: MMPoggi@Bethesda.med.navy.mil

    2005-07-01

    Purpose: To evaluate the effect of an ipsilateral breast tumor recurrence (IBTR) after breast-conservation therapy (BCT) on survival. Methods and Materials: One hundred twenty-one women were randomized to BCT. Patients with an IBTR were analyzed to determine survival. Analysis was performed with Kaplan-Meier estimates, log-rank tests, and time-dependent covariate Cox models. Results: At a median follow-up of 18.4 years, 27 patients had an IBTR. The median survival time after IBTR was 13.1 years. The 5-year survival rate was 91.8% (95% confidence interval [CI], 81.5-100%). The 10-year survival rate was 54.3% (95% CI, 35.8-82.6%). According to a Cox model with time-dependent covariates, the hazard ratio or relative risk of dying for those with an IBTR at <5.3 years after BCT relative to patients without an IBTR after BCT is 1.47 (95% CI, 1.02-2.12%; p = 0.04). The hazard ratio for those who relapse after 5.3 years is 0.59 (95% CI, 0.22-1.61%; p = 0.31). Age at randomization, original tumor size, and the presence of positive regional nodes at initial presentation were not found to be associated with decreased survival. Conclusions: There seems to be a significant association of early IBTR after BCT with decreased survival. Local control should be maximized.

  6. Breast feeding, nutritional state, and child survival in rural Bangladesh

    PubMed Central

    Briend, André; Wojtyniak, Bogdan; Rowland, Michael G M

    1988-01-01

    The effect of breast feeding on nutritional state, morbidity, and child survival was examined prospectively in a community in rural Bangladesh. Every month for six months health workers inquired about breast feeding and illness and measured arm circumference in an average of 4612 children aged 12-36 months. Data from children who died within one month of a visit were compared with those from children who survived. Roughly one third of the deaths in the age range 18-36 months were attributable to absence of breast feeding. Within this age range protection conferred by breast feeding was independent of age but was evident only in severely malnourished children. In communities with a high prevalence of malnutrition breast feeding may substantially enhance child survival up to 3 years of age. PMID:3129058

  7. Organochlorine insecticides DDT and chlordane in relation to survival following breast cancer.

    PubMed

    Parada, Humberto; Wolff, Mary S; Engel, Lawrence S; White, Alexandra J; Eng, Sybil M; Cleveland, Rebecca J; Khankari, Nikhil K; Teitelbaum, Susan L; Neugut, Alfred I; Gammon, Marilie D

    2016-02-01

    Organochlorine insecticides have been studied extensively in relation to breast cancer incidence, and results from two meta-analyses have been null for late-life residues, possibly due to measurement error. Whether these compounds influence survival remains to be fully explored. We examined associations between organochlorine insecticides [p,p'-DDT (dichlorodiphenyltrichloroethane), its primary metabolite, p,p'-DDE, and chlordane] assessed shortly after diagnosis and survival among women with breast cancer. A population-based sample of women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997 and with available organochlorine blood measures (n = 633) were followed for vital status through 2011. After follow-up of 5 and 15 years, we identified 55 and 189 deaths, of which 36 and 74, respectively, were breast cancer-related. Using Cox regression models, we estimated the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lipid-adjusted organochlorine concentrations with all-cause and breast cancer-specific mortality. At 5 years after diagnosis, the highest tertile of DDT concentration was associated with all-cause (HR = 2.19; 95% CI: 1.02, 4.67) and breast cancer-specific (HR = 2.72; 95% CI: 1.04, 7.13) mortality. At 15 years, middle tertile concentrations of DDT (HR = 1.42; 95% CI 0.99, 2.06) and chlordane (HR = 1.42; 95% CI: 0.94, 2.12) were modestly associated with all-cause and breast cancer-specific mortality. Third tertile DDE concentrations were inversely associated with 15-year all-cause mortality (HR = 0.66; 95% CI: 0.44, 0.99). This is the first population-based study in the United States to show that DDT may adversely impact survival following breast cancer diagnosis. Further studies are warranted given the high breast cancer burden and the ubiquity of these chemicals. PMID:26285160

  8. Organochlorine insecticides DDT and chlordane in relation to survival following breast cancer.

    PubMed

    Parada, Humberto; Wolff, Mary S; Engel, Lawrence S; White, Alexandra J; Eng, Sybil M; Cleveland, Rebecca J; Khankari, Nikhil K; Teitelbaum, Susan L; Neugut, Alfred I; Gammon, Marilie D

    2016-02-01

    Organochlorine insecticides have been studied extensively in relation to breast cancer incidence, and results from two meta-analyses have been null for late-life residues, possibly due to measurement error. Whether these compounds influence survival remains to be fully explored. We examined associations between organochlorine insecticides [p,p'-DDT (dichlorodiphenyltrichloroethane), its primary metabolite, p,p'-DDE, and chlordane] assessed shortly after diagnosis and survival among women with breast cancer. A population-based sample of women diagnosed with a first primary invasive or in situ breast cancer in 1996-1997 and with available organochlorine blood measures (n = 633) were followed for vital status through 2011. After follow-up of 5 and 15 years, we identified 55 and 189 deaths, of which 36 and 74, respectively, were breast cancer-related. Using Cox regression models, we estimated the multivariable-adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for lipid-adjusted organochlorine concentrations with all-cause and breast cancer-specific mortality. At 5 years after diagnosis, the highest tertile of DDT concentration was associated with all-cause (HR = 2.19; 95% CI: 1.02, 4.67) and breast cancer-specific (HR = 2.72; 95% CI: 1.04, 7.13) mortality. At 15 years, middle tertile concentrations of DDT (HR = 1.42; 95% CI 0.99, 2.06) and chlordane (HR = 1.42; 95% CI: 0.94, 2.12) were modestly associated with all-cause and breast cancer-specific mortality. Third tertile DDE concentrations were inversely associated with 15-year all-cause mortality (HR = 0.66; 95% CI: 0.44, 0.99). This is the first population-based study in the United States to show that DDT may adversely impact survival following breast cancer diagnosis. Further studies are warranted given the high breast cancer burden and the ubiquity of these chemicals.

  9. Eribulin Improves Survival of Women with Metastatic Breast Cancer

    Cancer.gov

    Treatment with eribulin (Halaven™) improved overall survival in women with metastatic breast cancer whose disease progressed despite multiple rounds of prior chemotherapy, according to the results of a phase III clinical trial called EMBRACE.

  10. Bone fractures among postmenopausal patients with endocrine-responsive early breast cancer treated with 5 years of letrozole or tamoxifen in the BIG 1-98 trial

    PubMed Central

    Rabaglio, M.; Sun, Z.; Castiglione-Gertsch, M.; Hawle, H.; Thürlimann, B.; Mouridsen, H.; Campone, M.; Forbes, J. F.; Paridaens, R. J.; Colleoni, M.; Pienkowski, T.; Nogaret, J.-M.; Láng, I.; Smith, I.; Gelber, R. D.; Goldhirsch, A.; Coates, A. S.

    2009-01-01

    Background: To compare the incidence and timing of bone fractures in postmenopausal women treated with 5 years of adjuvant tamoxifen or letrozole for endocrine-responsive early breast cancer in the Breast International Group (BIG) 1-98 trial. Methods: We evaluated 4895 patients allocated to 5 years of letrozole or tamoxifen in the BIG 1-98 trial who received at least some study medication (median follow-up 60.3 months). Bone fracture information (grade, cause, site) was collected every 6 months during trial treatment. Results: The incidence of bone fractures was higher among patients treated with letrozole [228 of 2448 women (9.3%)] versus tamoxifen [160 of 2447 women (6.5%)]. The wrist was the most common site of fracture in both treatment groups. Statistically significant risk factors for bone fractures during treatment included age, smoking history, osteoporosis at baseline, previous bone fracture, and previous hormone replacement therapy. Conclusions: Consistent with other trials comparing aromatase inhibitors to tamoxifen, letrozole was associated with an increase in bone fractures. Benefits of superior disease control associated with letrozole and lower incidence of fracture with tamoxifen should be considered with the risk profile for individual patients. PMID:19474112

  11. Clinical and Histological Prognostic Factors in Axillary Node-Negative BreastCancer: Univariate and Multivariate Analysis with Relation to 5-Year Recurrence.

    PubMed

    Khanna; Tokuda; Shibuya; Tanaka; Sekine; Tajima; Osamura; Mitomi

    1995-04-30

    In the recent years several studies have shown that about 30% of cases with axillary node-nagative breast cancer suffer relapse of the disease. Our attempt was made to evaluate the most significant prognostic factors to predict this high risk group which may be benefited from adjuvant treatment. For this purpose, we selected 9 patients out of 80 cases of node-negative breast cancer who had been followed up at least for 5 years and had the recurrence of the disease. For comparison, 16 patients from the same group who did not have relapse were selected on a random basis. Histology, receptor status, AgNOR, DNA flow cytometry and various immunohistochemical parameters were compared between the groups with recurrence and that without recurrence. On univariate analysis, tumor size, immunohistochemical expressions of PCNA, MIB-1, c-erbB-2 and S-phase fraction were significantly different between the above two groups. By multivariate analysis, immunohistochemical c-erbB-2 expression (more than 50% of cancer cells) was an independent parameter. As a summary from our studies, c-erbB-2 immunohistochemical staining on paraffin sections might be the best independent prognostic factor in axillary node-negative breast cancers.

  12. Dietary Fat in Breast Cancer Survival

    PubMed Central

    Makarem, Nour; Chandran, Urmila; Bandera, Elisa V.; Parekh, Niyati

    2013-01-01

    Laboratory evidence suggests a plausible role for dietary fat in breast cancer pathophysiology. We conducted a systematic literature review to assess the epidemiological evidence on the impact of total dietary fat and fat subtypes, measured pre- and/or postcancer diagnosis, in relation to breast cancer–specific and all-cause mortality among breast cancer survivors. Studies were included if they were in English, had a sample size ≥200, and presented the hazard ratio/rate ratio for recurrence, diseasespecific mortality, or all-cause mortality (n = 18). Although the results are mixed, most studies suggested that higher saturated fat intake prediagnosis was associated with increased risk of breast cancer–specific and all-cause mortality. Postdiagnostic trans fat intake was associated with a 45% and 78% increased risk of all-cause mortality. Higher monounsaturated fat intake before and after diagnosis was generally associated with increased risk of all-cause and breast cancer–specific mortality, albeit the majority of the studies were statistically nonsignificant. Two studies evaluating omega-3 fat intake suggested an inverse association with all-cause mortality. Although there were too few studies on fat subtypes to draw definitive conclusions, high consumption of saturated fatmay exert a detrimental effect on breast cancer–specific and all-cause mortality, whereas omega-3 fat may be beneficial. The inconsistent and limited evidence warrants research to assess the impact of consumption of fat subtypes on breast cancer recurrence and mortality. PMID:23701588

  13. The Effect of Pre-Diagnostic Alcohol Consumption on Survival after Breast Cancer in Young Women

    PubMed Central

    Reding, Kerryn W.; Daling, Janet R.; Doody, David R.; O’Brien, Cecilia A.; Peggy, L. Porter; Malone., Kathleen E.

    2008-01-01

    Background Alcohol consumption has been comprehensively investigated as an etiologic risk factor for breast cancer but has received little attention in terms of its impact on prognosis after breast cancer, particularly for young women. Methods 1286 women diagnosed with invasive breast cancer at or before 45 years of age from two population-based case-control studies in the Seattle-Puget Sound region were followed from their diagnosis of breast cancer (between January 1983 and December 1992) for survival through June 2002, during which time 364 women had died. Cox proportional hazards modeling was used to assess the effect of pre-diagnostic alcohol consumption on the risk of dying. Results After adjusting for age and diagnosis year, compared to non-drinkers, women who consumed alcohol in the 5 years prior to diagnosis had a decreased risk of death [>0 to <3 drinks per week: HR(hazard ratio) = 0.7 (95% CI: 0.6–0.95); 3 to <7 drinks per week: RR = 0.6 (95% CI: 0.4–0.8); ≥ 7 drinks per week: RR = 0.7 (95% CI: 0.5–0.9)]. This association was unchanged upon additional adjustment for potential confounders including most notably treatment, stage at diagnosis, and mammogram history. Conclusion These results suggest that women who consume alcohol prior to a diagnosis of breast cancer have improved survival which does not appear to be attributable to differences in stage, screening or treatment. PMID:18664549

  14. Brain metastases free survival differs between breast cancer subtypes

    PubMed Central

    Berghoff, A; Bago-Horvath, Z; De Vries, C; Dubsky, P; Pluschnig, U; Rudas, M; Rottenfusser, A; Knauer, M; Eiter, H; Fitzal, F; Dieckmann, K; Mader, R M; Gnant, M; Zielinski, C C; Steger, G G; Preusser, M; Bartsch, R

    2012-01-01

    Background: Brain metastases (BM) are frequently diagnosed in patients with HER-2-positive metastatic breast cancer; in addition, an increasing incidence was reported for triple-negative tumours. We aimed to compare brain metastases free survival (BMFS) of breast cancer subtypes in patients treated between 1996 until 2010. Methods: Brain metastases free survival was measured as the interval from diagnosis of extracranial breast cancer metastases until diagnosis of BM. HER-2 status was analysed by immunohistochemistry and reanalysed by fluorescent in situ hybridisation if a score of 2+ was gained. Oestrogen-receptor (ER) and progesterone-receptor (PgR) status was analysed by immunohistochemistry. Brain metastases free survival curves were estimated with the Kaplan–Meier method and compared with the log-rank test. Results: Data of 213 patients (46 luminal/124 HER-2/43 triple-negative subtype) with BM from breast cancer were available for the analysis. Brain metastases free survival differed significantly between breast cancer subtypes. Median BMFS in triple-negative tumours was 14 months (95% CI: 11.34–16.66) compared with 18 months (95% CI: 14.46–21.54) in HER-2-positive tumours (P=0.001) and 34 months (95% CI: 23.71–44.29) in luminal tumours (P=0.001), respectively. In HER-2-positive patients, co-positivity for ER and HER-2 prolonged BMFS (26 vs 15 m; P=0.033); in luminal tumours, co-expression of ER and PgR was not significantly associated with BMFS. Brain metastases free survival in patients with lung metastases was significantly shorter (17 vs 21 months; P=0.014). Conclusion: Brain metastases free survival in triple-negative breast cancer, as well as in HER-2-positive/ER-negative, is significantly shorter compared with HER-2/ER co-positive or luminal tumours, mirroring the aggressiveness of these breast cancer subtypes. PMID:22233926

  15. Long-term effect of the North Carolina graduated driver licensing system on licensed driver crash incidence: a 5-year survival analysis.

    PubMed

    Masten, Scott V; Foss, Robert D

    2010-11-01

    Several studies document the success of graduated driver licensing (GDL) systems in reducing young teen crash rates, but it is not yet clear whether any portion of the crash reduction is achieved by producing more capable drivers. The purpose of this study was to determine whether young teen drivers licensed under the North Carolina GDL system remain crash-free longer than those licensed prior to GDL, independent of the crude reductions in exposure (i.e., decreasing and delaying licensure) that may be responsible for most documented effects of GDL. Survival analysis was used to compare retrospective cohorts of 16-17 year olds before (n=105,569) and after (n=327,054) the North Carolina GDL system was implemented. The crash incidence of GDL-licensed 16-17 year olds (combined) was 10% lower than that for pre-GDL teens for at least 5 years after being licensed to drive independently (hazard ratio [HR]=0.90; 95% confidence interval [CI]=0.89, 0.91). However, more refined analysis revealed the reductions to only be among females (7%; HR=0.93; CI=0.91, 0.94) and males (15%; HR=0.85, CI=0.84, 0.87) licensed at age 16 and not among females (0%; HR=1.00; CI=0.95, 1.06) and males (0%; HR=1.00; CI=0.92, 1.09) licensed at age 17. Sixteen-year-old drivers licensed under the North Carolina GDL system experienced lower first-crash incidence during the first 5 years of unsupervised driving than did those licensed under the previous system. The benefits are greater for males, who tend to have higher crash rates. The findings contradict conventional wisdom that the entire benefit of GDL results merely from decreasing or delaying licensure among young drivers.

  16. Total ‘rib’-preservation technique of internal mammary vessel exposure for free flap breast reconstruction: A 5-year prospective cohort study and instructional video

    PubMed Central

    Rosich-Medina, Anais; Bouloumpasis, Serafeim; Di Candia, Michele; Malata, Charles M.

    2015-01-01

    Introduction The total ‘rib’-preservation method of dissecting out the internal mammary vessels (IMV) during microvascular breast reconstruction aims to reduce free flap morbidity at the recipient site. We review our five-year experience with this technique. Patients & methods An analysis of a prospectively collected free flap data cohort was undertaken to determine the indications, operative details and reconstructive outcomes in all breast reconstruction patients undergoing IMV exposure using the total ‘rib’-preservation method by a single surgeon. Results 178 consecutive breast free flaps (156 unilateral, 11 bilateral) were performed from 1st June 2008 to 31st May 2013 in 167 patients with a median age of 50 years (range 28–71). There were 154 DIEP flaps, 14 SIEA flaps, 7 muscle-sparing free TRAMs, 2 IGAP flaps and one free latissimus dorsi flap. 75% of the reconstructions (133/178) were immediate, 25% (45/178) were delayed. The mean inter-costal space distance was 20.9 mm (range 9–29). The mean time taken to expose and prepare the recipient IMV's was 54 min (range 17–131). The mean flap ischaemia time was 95 min (range 38–190). Free flap survival was 100%, although 2.2% (4 flaps) required a return to theatre for exploration and flap salvage. No patients complained of localised chest pain or tenderness at the recipient site and no chest wall contour deformity has been observed. Discussion & conclusion The total ‘rib’-preservation technique of IMV exposure is a safe, reliable and versatile method for microvascular breast reconstruction and should be considered as a valid alternative to the ‘rib’-sacrificing techniques. PMID:26468373

  17. Improvements in US Breast Cancer Survival and Proportion Explained by Tumor Size and Estrogen-Receptor Status

    PubMed Central

    Park, Ju-Hyun; Anderson, William F.; Gail, Mitchell H.

    2015-01-01

    Purpose Breast cancer mortality began declining in many Western countries during the late 1980s. We estimated the proportion of improvements in stage- and age-specific breast cancer survival in the United States explained by tumor size or estrogen receptor (ER) status. Methods We estimated hazard ratios for breast cancer–specific death from time of invasive breast cancer diagnosis in the National Cancer Institute's Surveillance, Epidemiology, and End Results 9 Registries Database from 1973 to 2010, with and without stratification by tumor size and ER status. Results Hazards from breast cancer–specific death declined from 1973 to 2010, not only in the first 5 years after diagnosis, but also thereafter. Stratification by tumor size explained less than 17% of the improvements comparing 2005 to 2010 versus 1973 to 1979, except for women age ≥ 70 years with local (49%) or regional (38%) disease. Tumor size usually accounted for more of the improvement in the first 5 years after diagnosis than later. Additional adjustment for ER status (positive, negative, or unknown) from 1990 to 2010 did not explain much more of the improvement, except for women age ≥ 70 years within 5 years after diagnosis. Conclusion Most stage-specific survival improvement in women younger than age 70 years old is unexplained by tumor size and ER status, suggesting a key role for treatment. In the first 5 years after diagnosis, tumor size contributed importantly for women ≥ 70 years old with local and regional stage, and stratification by tumor size and ER status explained even more of the survival improvement among women age ≥ 70 years. PMID:26195709

  18. Time-varying effects of prognostic factors associated with disease-free survival in breast cancer.

    PubMed

    Natarajan, Loki; Pu, Minya; Parker, Barbara A; Thomson, Cynthia A; Caan, Bette J; Flatt, Shirley W; Madlensky, Lisa; Hajek, Richard A; Al-Delaimy, Wael K; Saquib, Nazmus; Gold, Ellen B; Pierce, John P

    2009-06-15

    Early detection and effective treatments have dramatically improved breast cancer survivorship, yet the risk of relapse persists even 15 years after the initial diagnosis. It is important to identify prognostic factors for late breast cancer events. The authors investigated time-varying effects of tumor characteristics on breast-cancer-free survival using data on 3,088 breast cancer survivors from 4 US states who participated in a randomized dietary intervention trial in 1995-2006, with maximum follow-up through 15 years (median, 9 years). A piecewise constant penalized spline approach incorporating time-varying coefficients was adopted, allowing for deviations from the proportional hazards assumption. This method is more flexible than standard approaches, provides direct estimates of hazard ratios across time intervals, and is computationally tractable. Having a stage II or III tumor was associated with a 3-fold higher hazard of breast cancer than having a stage I tumor during the first 2.5 years after diagnosis; this hazard ratio decreased to 2.1 after 7.7 years, but higher tumor stage remained a significant risk factor. Similar diminishing effects were found for poorly differentiated tumors. Interestingly, having a positive estrogen receptor status was protective up to 4 years after diagnosis but detrimental after 7.7 years (hazard ratio = 1.5). These results emphasize the importance of careful statistical modeling allowing for possibly time-dependent effects in long-term survivorship studies. PMID:19403844

  19. Time-Varying Effects of Prognostic Factors Associated With Disease-Free Survival in Breast Cancer

    PubMed Central

    Natarajan, Loki; Pu, Minya; Parker, Barbara A.; Thomson, Cynthia A.; Caan, Bette J.; Flatt, Shirley W.; Madlensky, Lisa; Hajek, Richard A.; Al-Delaimy, Wael K.; Saquib, Nazmus; Gold, Ellen B.

    2009-01-01

    Early detection and effective treatments have dramatically improved breast cancer survivorship, yet the risk of relapse persists even 15 years after the initial diagnosis. It is important to identify prognostic factors for late breast cancer events. The authors investigated time-varying effects of tumor characteristics on breast-cancer-free survival using data on 3,088 breast cancer survivors from 4 US states who participated in a randomized dietary intervention trial in 1995–2006, with maximum follow-up through 15 years (median, 9 years). A piecewise constant penalized spline approach incorporating time-varying coefficients was adopted, allowing for deviations from the proportional hazards assumption. This method is more flexible than standard approaches, provides direct estimates of hazard ratios across time intervals, and is computationally tractable. Having a stage II or III tumor was associated with a 3-fold higher hazard of breast cancer than having a stage I tumor during the first 2.5 years after diagnosis; this hazard ratio decreased to 2.1 after 7.7 years, but higher tumor stage remained a significant risk factor. Similar diminishing effects were found for poorly differentiated tumors. Interestingly, having a positive estrogen receptor status was protective up to 4 years after diagnosis but detrimental after 7.7 years (hazard ratio = 1.5). These results emphasize the importance of careful statistical modeling allowing for possibly time-dependent effects in long-term survivorship studies. PMID:19403844

  20. Breast density and mode of detection in relation to breast cancer specific survival: a cohort study

    PubMed Central

    2014-01-01

    Background The aim of this study was to examine breast density in relation to breast cancer specific survival and to assess if this potential association was modified by mode of detection. An additional aim was to study whether the established association between mode of detection and survival is modified by breast density. Methods The study included 619 cases from a prospective cohort, The Malmö Diet and Cancer Study. Breast density estimated qualitatively, was analyzed in relation to breast cancer death, in non-symptomatic and symptomatic women, using Cox regression calculating hazard ratios (HR) with 95% confidence intervals. Adjustments were made in several steps for; diagnostic age, tumour size, axillary lymph node involvement, grade, hormone receptor status, body mass index (baseline), diagnostic period, use of hormone replacement therapy at diagnosis and mode of detection. Detection mode in relation to survival was analyzed stratified for breast density. Differences in HR following different adjustments were analyzed by Freedmans%. Results After adjustment for age and other prognostic factors, women with dense, as compared to fatty breasts, had an increased risk of breast cancer death, HR 2.56:1.07-6.11, with a statistically significant trend over density categories, p = 0.04. In the stratified analysis, the effect was less pronounced in non-symptomatic women, HR 2.04:0.49-8.49 as compared to symptomatic, HR 3.40:1.06-10.90. In the unadjusted model, symptomatic women had a higher risk of breast cancer death, regardless of breast density. Analyzed by Freedmans%, age, tumour size, lymph nodes, grade, diagnostic period, ER and PgR explained 55.5% of the observed differences in mortality between non-symptomatic and symptomatic cases. Additional adjustment for breast density caused only a minor change. Conclusions High breast density at diagnosis may be associated with decreased breast cancer survival. This association appears to be stronger in women with

  1. Does obesity compromise survival in women with breast cancer?

    PubMed

    Carmichael, A R; Bendall, S; Lockerbie, L; Prescott, R J; Bates, T

    2004-04-01

    Obesity, measured by high body mass index (BMI >30 kg/m2) is associated with an increased risk of postmenopausal breast cancer but the effect of obesity on prognosis is not clear. A prospectively accrued and regularly validated database of 1579 patients with breast cancer treated in a district general hospital between 1963 and 1999 was analysed for clinical and pathological tumour characteristics including the family history, grade, tumour type, treatment and outcome. The risk factors and outcome of obese and non-obese patients were compared. Breast cancer in obese women was associated with significantly larger tumour size and worse Nottingham prognostic index. There was no statistically significant difference in overall and disease-free survival between obese and non-obese group. Hazard ratios (95% Cl) were 0.81 (0.62-1.06) and 0.80 (0.63-1.01), respectively. In the present study, obesity is not an indicator of worst prognosis of breast cancer.

  2. The global breast cancer burden: variations in epidemiology and survival.

    PubMed

    Hortobagyi, Gabriel N; de la Garza Salazar, Jaime; Pritchard, Kathleen; Amadori, Dino; Haidinger, Renate; Hudis, Clifford A; Khaled, Hussein; Liu, Mei-Ching; Martin, Miguel; Namer, Moise; O'Shaughnessy, Joyce A; Shen, Zhen Zhou; Albain, Kathy S

    2005-12-01

    Breast cancer is the most common type of cancer and the most common cause of cancer-related mortality among women worldwide. However, the burden is not evenly distributed, and, according to the best available data, there are large variations in the incidence, mortality, and survival between different countries and regions and within specific regions. Many complex factors underlie these variations, including population structure (eg, age, race, and ethnicity), lifestyle, environment, socioeconomic status, risk factor prevalence, mammography use, disease stage at diagnosis, and access to high-quality care. We review recent breast cancer incidence and mortality statistics and explore why these vary so greatly across the world. Further research is needed to fully understand the reasons for variations in breast cancer outcomes. This will aid the development of tailored strategies to improve outcomes in general as well as the standard of care for underserved populations and reduce the burden of breast cancer worldwide.

  3. History of Recreational Physical Activity and Survival After Breast Cancer

    PubMed Central

    Lu, Yani; John, Esther M.; Sullivan-Halley, Jane; Vigen, Cheryl; Gomez, Scarlett Lin; Kwan, Marilyn L.; Caan, Bette J.; Lee, Valerie S.; Roh, Janise M.; Shariff-Marco, Salma; Keegan, Theresa H. M.; Kurian, Allison W.; Monroe, Kristine R.; Cheng, Iona; Sposto, Richard; Wu, Anna H.; Bernstein, Leslie

    2015-01-01

    Recent epidemiologic evidence suggests that prediagnosis physical activity is associated with survival in women diagnosed with breast cancer. However, few data exist for racial/ethnic groups other than non-Latina whites. To examine the association between prediagnosis recreational physical activity and mortality by race/ethnicity, we pooled data from the California Breast Cancer Survivorship Consortium for 3 population-based case-control studies of breast cancer patients (n = 4,608) diagnosed from 1994 to 2002 and followed up through 2010. Cox proportional hazards models provided estimates of the relative hazard ratio for mortality from all causes, breast cancer, and causes other than breast cancer associated with recent recreational physical activity (i.e., in the 10 years before diagnosis). Among 1,347 ascertained deaths, 826 (61%) were from breast cancer. Compared with women with the lowest level of recent recreational physical activity, those with the highest level had a marginally decreased risk of all-cause mortality (hazard ratio = 0.88, 95% confidence interval: 0.76, 1.01) and a statistically significant decreased risk of mortality from causes other than breast cancer (hazard ratio = 0.63, 95% confidence interval: 0.49, 0.80), and particularly from cardiovascular disease. No association was observed for breast cancer–specific mortality. These risk patterns did not differ by race/ethnicity (non-Latina white, African American, Latina, and Asian American). Our findings suggest that physical activity is beneficial for overall survival regardless of race/ethnicity. PMID:25925388

  4. Breast Cancer in Developing Countries: Opportunities for Improved Survival

    PubMed Central

    Shulman, Lawrence N.; Willett, Walter; Sievers, Amy; Knaul, Felicia M.

    2010-01-01

    Breast cancer survival in the USA has continually improved over the last six decades and has largely been accredited to the use of mammography, advanced surgical procedures, and adjuvant therapies. Data indicate, however, that there were substantial improvements in survival in the USA even prior to these technological and diagnostic advances, suggesting important opportunities for early detection and treatment in low- and middle-income countries where these options are often unavailable and/or unaffordable. Thus, while continuing to strive for increased access to more advanced technology, improving survival in these settings should be more immediately achievable through increased awareness of breast cancer and of the potential for successful treatment, a high-quality primary care system without economic or cultural barriers to access, and a well-functioning referral system for basic surgical and hormonal treatment. PMID:21253541

  5. Smoking and survival in male breast cancer patients.

    PubMed

    Padron-Monedero, Alicia; Koru-Sengul, Tulay; Tannenbaum, Stacey L; Miao, Feng; Hansra, Damien; Lee, David J; Byrne, Margaret M

    2015-10-01

    The purpose of the article was to assess whether smoking affects survival in male breast cancer patients for the overall population and when stratified by race, ethnicity, and socioeconomic status. Data were obtained by linking the 1996-2007 Florida Cancer Data System, the Florida Agency for Health Care Administration, and the US Census. Inclusion criteria were males ≥18 years, diagnosed with breast cancer and residing in Florida (n = 1573). To analyze the association between smoking and survival, we performed sequential multivariate Cox proportional hazards regression models with progressive adjustment for main confounders. Compared to never smokers, worse survival was found in current (hazard ratio = 1.63; 95 % CI = 1.23-2.16) but not in former smokers (1.26; 0.99-1.59). Those who smoked ≥1 packs/day had worse survival (2.48; 1.59-3.87) than never smokers with a significant dose-response (P for linear trend <0.001). Race-ethnic stratified models comparing current and former smokers with never smokers found significant differences among Whites [(1.88; 1.44-2.44) and (1.31; 1.04-1.65, respectively)] and non-Hispanics, [(1.73; 1.31-2.28) and (1.31; 1.04-1.66, respectively)]. Overall, current smokers were found to have significantly reduced survival, which was worse by intensity of smoking. Also, any smoking history is associated with worse survival in White and non-Hispanic male breast cancer patients compared to never smokers. Thus, male breast cancer patients should be advised to quit smoking.

  6. The impact of oophorectomy on survival after breast cancer in BRCA1-positive breast cancer patients.

    PubMed

    Huzarski, T; Byrski, T; Gronwald, J; Cybulski, C; Oszurek, O; Szwiec, M; Gugała, K; Stawicka, M; Morawiec, Z; Mierzwa, T; Falco, M; Janiszewska, H; Kilar, E; Marczyk, E; Kozak-Klonowska, B; Siołek, M; Surdyka, D; Wiśniowski, R; Posmyk, M; Domagała, P; Sun, P; Lubiński, J; Narod, S A

    2016-04-01

    The aim of the study is to identify treatments which predict survival for women with a BRCA1 mutation, including oophorectomy and chemotherapy. 476 women with stage I to stage III breast cancer who carried a BRCA1 mutation were followed from diagnosis until April 2015. Information on treatment was obtained from chart review and patient questionnaires. Dates of death were obtained from the Poland vital statistics registry. Survival curves were compared for different subgroups according to treatment received. Predictors of overall survival were determined using the Cox proportional hazards model. The ten-year overall survival was 78.3 % (95 % CI 74.2-82.6 %) and the ten-year breast cancer-specific survival was 84.2 % (95 % CI 80.5-88.0 %). Sixty-two patients died of breast cancer, 14 patients died of ovarian cancer, and 2 patients died of peritoneal cancer. Oophorectomy was associated with a significant reduction in all-cause mortality in the entire cohort (adjusted HR = 0.41; 95 % CI 0.24-0.69; p = 0.0008) and in breast cancer-specific mortality among ER-negative breast cancer patients (HR = 0.44; 95 % CI 0.22-0.89; p = 0.02). Among women with breast cancer and a BRCA1 mutation, survival is greatly improved by oophorectomy due to the prevention of deaths from both breast and ovarian cancer. PMID:26983446

  7. Identification of Novel Genetic Markers of Breast Cancer Survival

    PubMed Central

    Guo, Qi; Schmidt, Marjanka K.; Kraft, Peter; Canisius, Sander; Chen, Constance; Khan, Sofia; Tyrer, Jonathan; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Lush, Michael; Kar, Siddhartha; Beesley, Jonathan; Dunning, Alison M.; Shah, Mitul; Czene, Kamila; Darabi, Hatef; Eriksson, Mikael; Lambrechts, Diether; Weltens, Caroline; Leunen, Karin; Bojesen, Stig E.; Nordestgaard, Børge G.; Nielsen, Sune F.; Flyger, Henrik; Chang-Claude, Jenny; Rudolph, Anja; Seibold, Petra; Flesch-Janys, Dieter; Blomqvist, Carl; Aittomäki, Kristiina; Fagerholm, Rainer; Muranen, Taru A.; Couch, Fergus J.; Olson, Janet E.; Vachon, Celine; Andrulis, Irene L.; Knight, Julia A.; Glendon, Gord; Mulligan, Anna Marie; Broeks, Annegien; Hogervorst, Frans B.; Haiman, Christopher A.; Henderson, Brian E.; Schumacher, Fredrick; Le Marchand, Loic; Hopper, John L.; Tsimiklis, Helen; Apicella, Carmel; Southey, Melissa C.; Cox, Angela; Cross, Simon S.; Reed, Malcolm W. R.; Giles, Graham G.; Milne, Roger L.; McLean, Catriona; Winqvist, Robert; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Grip, Mervi; Hooning, Maartje J.; Hollestelle, Antoinette; Martens, John W. M.; van den Ouweland, Ans M. W.; Marme, Federik; Schneeweiss, Andreas; Yang, Rongxi; Burwinkel, Barbara; Figueroa, Jonine; Chanock, Stephen J.; Lissowska, Jolanta; Sawyer, Elinor J.; Tomlinson, Ian; Kerin, Michael J.; Miller, Nicola; Brenner, Hermann; Dieffenbach, Aida Karina; Arndt, Volker; Holleczek, Bernd; Mannermaa, Arto; Kataja, Vesa; Kosma, Veli-Matti; Hartikainen, Jaana M.; Li, Jingmei; Brand, Judith S.; Humphreys, Keith; Devilee, Peter; Tollenaar, Rob A. E. M.; Seynaeve, Caroline; Radice, Paolo; Peterlongo, Paolo; Bonanni, Bernardo; Mariani, Paolo; Fasching, Peter A.; Beckmann, Matthias W.; Hein, Alexander; Ekici, Arif B.; Chenevix-Trench, Georgia; Balleine, Rosemary; Phillips, Kelly-Anne; Benitez, Javier; Zamora, M. Pilar; Arias Perez, Jose Ignacio; Menéndez, Primitiva; Jakubowska, Anna; Lubinski, Jan; Jaworska-Bieniek, Katarzyna; Durda, Katarzyna; Hamann, Ute; Kabisch, Maria; Ulmer, Hans Ulrich; Rüdiger, Thomas; Margolin, Sara; Kristensen, Vessela; Nord, Silje; Evans, D. Gareth; Abraham, Jean E.; Earl, Helena M.; Hiller, Louise; Dunn, Janet A.; Bowden, Sarah; Berg, Christine; Campa, Daniele; Diver, W. Ryan; Gapstur, Susan M.; Gaudet, Mia M.; Hankinson, Susan E.; Hoover, Robert N.; Hüsing, Anika; Kaaks, Rudolf; Machiela, Mitchell J.; Willett, Walter; Barrdahl, Myrto; Canzian, Federico; Chin, Suet-Feung; Caldas, Carlos; Hunter, David J.; Lindstrom, Sara; García-Closas, Montserrat; Hall, Per; Easton, Douglas F.; Eccles, Diana M.; Rahman, Nazneen; Nevanlinna, Heli; Pharoah, Paul D. P.

    2015-01-01

    Background: Survival after a diagnosis of breast cancer varies considerably between patients, and some of this variation may be because of germline genetic variation. We aimed to identify genetic markers associated with breast cancer–specific survival. Methods: We conducted a large meta-analysis of studies in populations of European ancestry, including 37954 patients with 2900 deaths from breast cancer. Each study had been genotyped for between 200000 and 900000 single nucleotide polymorphisms (SNPs) across the genome; genotypes for nine million common variants were imputed using a common reference panel from the 1000 Genomes Project. We also carried out subtype-specific analyses based on 6881 estrogen receptor (ER)–negative patients (920 events) and 23059 ER-positive patients (1333 events). All statistical tests were two-sided. Results: We identified one new locus (rs2059614 at 11q24.2) associated with survival in ER-negative breast cancer cases (hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.55 to 2.47, P = 1.91 x 10–8). Genotyping a subset of 2113 case patients, of which 300 were ER negative, provided supporting evidence for the quality of the imputation. The association in this set of case patients was stronger for the observed genotypes than for the imputed genotypes. A second locus (rs148760487 at 2q24.2) was associated at genome-wide statistical significance in initial analyses; the association was similar in ER-positive and ER-negative case patients. Here the results of genotyping suggested that the finding was less robust. Conclusions: This is currently the largest study investigating genetic variation associated with breast cancer survival. Our results have potential clinical implications, as they confirm that germline genotype can provide prognostic information in addition to standard tumor prognostic factors. PMID:25890600

  8. Social networks and survival after breast cancer diagnosis

    PubMed Central

    Beasley, Jeannette M.; Newcomb, Polly A.; Trentham-Dietz, Amy; Hampton, John M.; Ceballos, Rachel M.; Titus-Ernstoff, Linda; Egan, Kathleen M.; Holmes, Michelle

    2010-01-01

    Introduction Evidence has been inconsistent regarding the impact of social networks on survival after breast cancer diagnosis. We prospectively examined the relation between components of social integration and survival in a large cohort of breast cancer survivors. Methods Women (N=4,589) diagnosed with invasive breast cancer were recruited from a population-based, multi-center, case-control study. A median of 5.6 years (Interquartile Range 2.7–8.7) after breast cancer diagnosis, women completed a questionnaire on recent post-diagnosis social networks and other lifestyle factors. Social networks were measured using components of the Berkman-Syme Social Networks Index to create a measure of social connectedness. Based on a search of the National Death Index, 552 deaths (146 related to breast cancer) were identified. Adjusted hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional hazards regression. Results Higher scores on a composite measure of social connectedness as determined by the frequency of contacts with family and friends, attendance of religious services, and participation in community activities was associated with a 15–28% reduced risk of death from any cause (p-trend=0.02). Inverse trends were observed between all-cause mortality and frequency of attendance at religious services (p-trend =0.0001) and hours per week engaged in community activities (p-trend =0.0005). No material associations were identified between social networks and breast cancer-specific mortality. Conclusions Engagement in activities outside the home was associated with lower overall mortality after breast cancer diagnosis. PMID:20652435

  9. Racial and Ethnic Differences in Breast Cancer Survival

    PubMed Central

    Curtis, Elana; Quale, Chris; Haggstrom, David; Smith-Bindman, Rebecca

    2009-01-01

    Background The reasons for race/ethnicity (R/E) differences in breast cancer survival have been difficult to disentangle. Methods Surveillance, Epidemiology, and End Results (SEER)-Medicare data were used to identify 41,020 women aged ≥68 years with incident breast cancer between 1994–1999 including African American (2479), Hispanic (1172), Asian/ Pacific Island (1086), and white women (35,878). A Cox proportional hazards model assessed overall and stage-specific (0/I, II/III, and IV) R/E differences in breast cancer survival after adjusting for mammography screening, tumor characteristics at diagnosis, biologic markers, treatment, comorbidity, and demographics. Results African American women had worse survival than white women, although controlling for predictor variables reduced this difference among all stage breast cancer (hazards ratio [HR], 1.08; 95% confidence interval [95% CI], 0.97–1.20). Adjustment for predictors reduced, but did not eliminate, disparities in the analysis limited to women diagnosed with stage II/III disease (HR, 1.30; 95% CI, 1.10–1.54). Screening mammography, tumor characteristics at diagnosis, biologic markers, and treatment each produced a similar reduction in HRs for women with stage II/III cancers. Asian and Pacific Island women had better survival than white women before and after accounting for all predictors (adjusted all stages HR, 0.61 [95% CI, 0.47–0.79]; adjusted stage II/III HR, 0.61 [95% CI, 0.47–0.79]). Hispanic women had better survival than white women in all and stage II/III analysis (all stage HR, 0.88; 95% CI, 0.75–1.04) and stage II/III analysis (HR, 0.88; 95% CI, 0.75–1.04), although these findings did not reach statistical significance. There was no significant difference in survival by R/E noted among women diagnosed with stage IV disease. Conclusions Predictor variables contribute to, but do not fully explain, R/E differences in breast cancer survival for elderly American women. Future analyses

  10. Clinicopathological Features and Prognostic Factors Affecting Survival Outcomes in Isolated Locoregional Recurrence of Breast Cancer: Single-Institutional Series

    PubMed Central

    Kim, Hae Su; Lee, Ji Yun; Lim, Sung Hee; Lee, Jeong Eon; Kim, Seok Won; Nam, Seok Jin; Ahn, Jin Seok; Im, Young-Hyuck; Park, Yeon Hee

    2016-01-01

    Purpose The purpose of this study was to investigate the clinicopathologic features and prognostic factors affecting outcome in patients with isolated locoregional recurrence of breast cancer (ILRR). Methods We retrospectively analyzed the medical records of 104 patients who were diagnosed with ILRR and underwent curative surgery from January 2000 to December 2010 at Samsung Medical Center. Results Among 104 patients, 43 (41%) underwent total mastectomy and 61 (59%) underwent breast-conserving surgery for primary breast cancer. The median time from initial operation to ILRR was 35.7 months (4.5–132.3 months). After diagnosis of ILRR, 45 (43%) patients were treated with mastectomy, 41 (39%) with excision of recurred lesion, and 18 (17%) with node dissection. During a median follow-up of 8.9 years, the 5-year overall survival was 77% and 5-year distant metastasis-free survival (DMFS) was 54%. On multivariate analysis, younger age (< 35 years), higher stage, early onset of elapse (≤ 24 months), lymph node recurrences, and subtype of triple negative breast cancer (TNBC) were found to be independently associated with DMFS. Patients in the no chemotherapy group showed a longer DMFS after surgery for ILRR than those treated with chemotherapy (median 101.5 vs. 48.0 months, p = 0.072) but without statistical significance. Conclusion Our analysis showed that younger age (< 35 years), higher stage, early onset of relapse (≤ 24 months), lymph node recurrence, and subtype of TNBC are the worst prognostic factors for ILRR. PMID:27648567

  11. Breast cancer in elderly women: presentation, survival, and treatment options.

    PubMed

    Law, T M; Hesketh, P J; Porter, K A; Lawn-Tsao, L; McAnaw, R; Lopez, M J

    1996-04-01

    Recent data suggest that breast cancer in elderly women does not present as more advanced disease, nor is survival significantly inferior to that in younger women. Unfortunately, until recently, older women have been excluded from clinical trials that have determined survival benefit in both screening and treatment modalities. Unless co-morbid conditions adversely affect one's life expectancy or tolerance to therapy, older women should be treated with standard surgical procedures (including breast conservation, if so desired) for early-stage disease, as outcome is comparable to that in younger patients. Adjuvant tamoxifen therapy has proven survival benefit in women over 70 years of age with estrogen receptor-positive tumors and should be considered in all women with tumors greater than 1 cm in size. Older women may experience more chemotherapy-related toxicities. However, for those with a significant risk of recurrence due to tumor size or lymph node status, chemotherapy can be safely administered when factors such as age-related decline in creatinine clearance and co-morbid conditions are considered. Hormonal therapy (tamoxifen) is usually the first-line treatment option over chemotherapy for metastatic disease in the elderly unless the patient has an estrogen receptor-negative tumor, visceral-dominant disease, or significant disease-related symptoms. In the latter settings, chemotherapy can provide improved or more rapid response proportions but does not affect long-term survival.

  12. Diet and subsequent survival in women with breast cancer.

    PubMed Central

    Ingram, D.

    1994-01-01

    Our findings from a previous study, that increased consumption of beta-carotene and vitamin C is associated with favourable prognostic indices in patients with breast cancer, have been borne out by our current study of patient survival over a 6-year period. The results of the current study point to beta-carotene consumption as the dietary variable most significantly associated with improved survival. Only one death occurred in the group with the highest consumption of beta-carotene, while there were eight and 12 deaths in the intermediate and lowest groups of consumption respectively. The possible antiproliferative effects of beta-carotene have been recognised for some time, with investigations being focused more recently on its derivative, retinoic acid, which has been found to improve differentiation in many tissues, including cell lines derived from mammary carcinomas. Retinoids have been associated with significant clinical responses in a variety of tumours, and chemoprevention trials using beta-carotene have been undertaken for many malignancies. However, beta-carotene has not yet been used in clinical trials to evaluate its potential for the treatment of breast cancer. A large-scale clinical trial is necessary to determine the effectiveness of beta-carotene in reducing the chances of recurrence of breast cancer, and in preventing the development of new cancers. PMID:8123493

  13. Breast cancer survival gap between urban and rural female population in Podlaskie Voivodship, Poland, in 2001–2002. Population study.

    PubMed

    Krzyżak, Michalina; Maślach, Dominik; Bielska-Lasota, Magdalena; Juczewska, Marzena; Rabczenko, Daniel; Marcinkowski, Jerzy T; Szpak, Andrzej

    2010-01-01

    The aim of the study was to evaluate differences in breast cancer 5-year relative survival rates between the urban and rural female population in Podlaskie Voivodship in 2001-2002, before the introduction of the Population Screening Programme in 2006. The analysis was based on 659 breast cancer cases diagnosed in 2001-2002 and registered in CR in Białystok (Voivodship Cancer Registry). Relative survival and relative excess of risk of death after 5 years of diagnosis as function of age and stage among urban and rural women population were calculated. The results showed that survival rates in Podlaskie Voivodship were low (69.4%) in comparison to the European average (79.4%), and they differed between urban and rural areas. Patients living in rural areas had a much lower survival rate than those living in urban areas at local and regional stage of disease, whereas survivals were higher at the metastatic stage. In all age groups considered in the study, the survivals in rural areas were lower than in urban areas. The multivariate analysis confirmed that both the cancer stage and place of residence are independent prognostic factors. Relationship with age was not confirmed. The research results indicate low curability of breast cancer in Podlaskie Voivodship, and significant differences between urban and rural areas. These results need to be considered in the planning and monitoring of further intervention in order to increase the effectiveness of prevention and treatment standards for more disadvantaged rural areas. It is particularly significant when implementing the National Cancer Control Programme.

  14. [A 5-year survival case of locally advanced cancer of the pancreatic body treated by distal pancreatectomy with en bloc celiac axis resection after neoadjuvant chemoradiation therapy].

    PubMed

    Iseki, Masahiro; Motoi, Fuyuhiko; Mizuma, Masamichi; Hayashi, Hiroki; Nakagawa, Kei; Okada, Takaho; Otsuka, Hideo; Ottomo, Shigeru; Sakata, Naoaki; Fukase, Koji; Yoshida, Hiroshi; Onogawa, Tohru; Naito, Takeshi; Katayose, Yu; Egawa, Shinichi; Unno, Michiaki

    2012-11-01

    A 59-year-old man was diagnosed with locally advanced cancer of the pancreatic body, involving the nerve plexus around the celiac axis, the common hepatic artery, and the splenic artery. He was treated with a combination of irradiation (2 Gy/day, total 24 Gy) and 600 mg/m2 of gemcitabine(GEM)biweekly. The tumor size and the involved plexus area were not diminished, but CA19-9 was reduced by half. Distal pancreatectomy with en bloc celiac axis resection(DP-CAR)was performed. The histological findings indicated extensive invasion into the nerve plexus, including that adjacent to the stump of the pancreas, and thus the R classification was R1. After surgery, 1,000 mg/m2 of GEM was administered biweekly. The chemotherapy has been performed for 5 years to prevent local and systemic recurrence. No recurrence has been found 5 years after surgery. Multidisciplinary treatment, combined with neoadjuvant chemoradiation therapy, curative-intent resection, and postoperative chemotherapy is important for effective treatment of locally advanced pancreatic cancer. PMID:23267939

  15. Adjuvant Radiation Therapy and Survival for Pure Tubular Breast Carcinoma-Experience From the SEER Database

    SciTech Connect

    Li Baoqing; Chen, Margaret; Nori, Dattatreyudu; Chao, K.S. Clifford; Chen, Allen M.; Chen, Steven L.

    2012-09-01

    Purpose: Pure tubular carcinoma of the breast (PTCB) represents a distinct subtype of invasive ductal carcinoma (IDC) that is generally thought to be associated with better prognosis than even low-grade IDC. There has been controversy as to the role of adjuvant radiation therapy (RT) in this population. We hypothesized that adjuvant RT would demonstrate a survival improvement. Methods and Materials: We queried the Surveillance, Epidemiology and End Results database for the years 1992-2007 to identify patients with pure tubular carcinomas of the breast. Patient demographics, tumor characteristics, and surgical and RT treatments were collected. Survival analysis was performed using the Kaplan-Meier method for univariate comparisons and Cox proportional hazards modeling for multivariate comparisons, stratifying on the basis of age with a cutoff age of 65. Results: A total of 6465 patients were identified: 3624 (56.1%) patients underwent lumpectomy with RT (LUMP+RT), 1525 (23.6%) patients underwent lumpectomy alone (LUMP), 1266 (19.6%) patients received mastectomy alone (MAST), and 50 (0.8%) patients underwent mastectomy with RT (MAST+RT). When we compared the LUMP+RT and LUMP groups directly, those receiving adjuvant RT tended to be younger and were less likely to be hormone receptor-positive. Overall survival was 95% for LUMP+RT and 90% for LUMP patients at 5 years. For those 65 or younger, the absolute overall survival benefit of LUMP+RT over LUMP was 1% at 5 years and 3% at 10 years. On stratified multivariate analysis, adjuvant RT remained a significant predictor in both age groups (P=.003 in age {<=}65 and P=.04 in age >65 patients). Other significant unfavorable factors were older age and higher T stage (age >65 only). Conclusions: Since sufficiently powered large scale clinical trials are unlikely, we would recommend that adjuvant radiation be considered in PTCB patients age 65 or younger, although consideration of the small absolute survival benefit is

  16. Do Asian breast cancer patients have poorer survival than their western counterparts? A comparison between Singapore and Stockholm

    PubMed Central

    Tan, Benita Kiat Tee; Lim, Gek Hsiang; Czene, Kamila; Hall, Per; Chia, Kee Seng

    2009-01-01

    Introduction The difference in breast cancer incidence and prognosis between ethnic groups seeks an explanation. We have recently shown that Swedish women are two to three times more likely to be diagnosed with breast cancer compared with Singaporean women. In the present paper, we compare breast cancer survival in the two countries. Methods We compared the survival of 10,287 Singaporean women and 17,090 Swedish women with breast cancer. Relative survival ratios were used to describe the prognosis in the two populations. A Poisson regression model was used to calculate relative risks for different follow-up periods, age groups, time of diagnosis and disease stages. Results The majority of the Swedish women had local cancer (80%) compared with Singaporean women (51%). The overall 5-year relative survival of the Swedish women appeared better (80%) than that of the Singaporean women (70%). A similar survival pattern was observed, however, between the two countries in a stage-by-stage comparison. Survival improved for all women in Singapore over the two decades, but only in the premenopausal women in Stockholm. In 1980 to 1989, premenopausal Singaporean women had 27% increased risk of death compared with Swedish women, adjusted for stage and year of follow-up, while the postmenopausal women had 48% increased risk. In 1990 to 1999, this risk decreased by 19% and 22% for the premenopausal and postmenopausal Singaporean women compared with the Swedish women. Conclusions The stage-dependent prognosis was similar for Singaporean women and for Swedish women. Singaporean women, both premenopausal and postmenopausal, had pronounced improvement in prognosis over the calendar periods, probably contributed by marked economic improvement, leading to better medical facilities and management with increased awareness of patients to diagnosis and treatment, as well as improved treatment options. Improvement seen only in the premenopausal women in Stockholm was probably due to improved

  17. Clinical Nomogram for Predicting Survival Outcomes in Early Mucinous Breast Cancer

    PubMed Central

    Jiang, Mengjie; Li, Dan; Jiang, Ting; Hong, Zhongwu; Wang, Fan; Li, Shuguang

    2016-01-01

    Background The features related to the prognosis of patients with mucinous breast cancer (MBC) remain controversial. We aimed to explore the prognostic factors of MBC and develop a nomogram for predicting survival outcomes. Methods The Surveillance, Epidemiology, and End Results (SEER) database was searched to identify 139611 women with resectable breast cancer from 1990 to 2007. Survival curves were generated using Kaplan-Meier methods. The 5-year and 10-year cancer-specific survival (CSS) rates were calculated using the Life-Table method. Based on Cox models, a nomogram was constructed to predict the probabilities of CSS for an individual patient. The competing risk regression model was used to analyse the specific survival of patients with MBC. Results There were 136569 (97.82%) infiltrative ductal cancer (IDC) patients and 3042 (2.18%) MBC patients. Patients with MBC had less lymph node involvement, a higher frequency of well-differentiated lesions, and more estrogen receptor (ER)-positive tumors. Patients with MBC had significantly higher 5 and10-year CSS rates (98.23 and 96.03%, respectively) than patients with IDC (91.44 and 85.48%, respectively). Univariate and multivariate analyses showed that MBC was an independent factor for better prognosis. As for patients with MBC, the event of death caused by another disease exceeded the event of death caused by breast cancer. A competing risk regression model further showed that lymph node involvement, poorly differentiated grade and advanced T-classification were independent factors of poor prognosis in patients with MBC. The Nomogram can accurately predict CSS with a high C-index (0.816). Risk scores developed from the nomogram can more accurately predict the prognosis of patients with MBC (C-index = 0.789) than the traditional TNM system (C-index = 0.704, P< 0.001). Conclusions Patients with MBC have a better prognosis than patients with IDC. Nomograms could help clinicians make more informed decisions in

  18. pN0(i+) Breast Cancer: Treatment Patterns, Locoregional Recurrence, and Survival Outcomes

    SciTech Connect

    Karam, Irene; Lesperance, Maria F.; Berrang, Tanya; Speers, Caroline; Tyldesley, Scott; Truong, Pauline T.

    2013-11-15

    Purpose: To examine treatment patterns, recurrence, and survival outcomes in patients with pN0(i+) breast cancer. Methods and Materials: Subjects were 5999 women with AJCC (6th edition) pT1-3, pN0-N1a, M0 breast cancer diagnosed between 2003 and 2006. Of these, 4342 (72%) had pN0, 96 (2%) had pN0(i+), 349 (6%) had pNmic (micrometastases >0.2 mm to ≤2 mm), and 1212 (20%) had pN1a (1-3 positive macroscopic nodes) disease. Treatment characteristics and 5-year Kaplan-Meier local recurrence, regional recurrence (RR), locoregional recurrence (LRR), and overall survival were compared between nodal subgroups. Multivariable analysis was performed using Cox regression modeling. A 1:3 case-match analysis examined outcomes in pN0(i+) cases compared with pN0 controls matched for similar tumor and treatment characteristics. Results: Median follow-up was 4.8 years. Adjuvant systemic therapy use increased with nodal stage: 81%, 92%, 95%, and 94% in pN0, pN0(i+), pNmic, and pN1a disease, respectively (P<.001). Nodal radiation therapy (RT) use also increased with nodal stage: 1.7% in pN0, 27% in pN0(i+), 33% in pNmic, and 63% in pN1a cohorts (P<.001). Five-year Kaplan-Meier outcomes in pN0 versus pN0(i+) cases were as follows: local recurrence 1.7% versus 3.7% (P=.20), RR 0.5% versus 2.2% (P=.02), and LRR 2.1% versus 5.8% (P=.02). There were no RR events in 26 patients with pN0(i+) disease who received nodal RT and 2 RR events in 70 patients who did not receive nodal RT. On multivariable analysis, pN0(i+) was not associated with worse locoregional control or survival. On case-match analysis, LRR and overall survival were similar between pN0(i+) and matched pN0 counterparts. Conclusions: Nodal involvement with isolated tumor cells is not a significant prognostic factor for LRR or survival in this study's multivariable and case-match analyses. These data do not support the routine use of nodal RT in the setting of pN0(i+) disease. Prospective studies are needed to define optimal

  19. Clinical value of morphometric and DNA flow cytometric variables as independent predictors of survival in epithelial ovarian carcinoma: a 5-year follow-up study.

    PubMed

    Veerman, Margot M; van der Wurff, Anneke A M; van de Water, Marije; Kruitwagen, Roy F P M; Feijen, Harrie W H; Vos, Maria Caroline

    2009-09-01

    The aim of this follow-up study is to validate the clinical significance of quantitative morphometric and DNA flow cytometric variables as independent prognostic factors of overall survival and progression-free survival in epithelial ovarian carcinoma. Tumor samples were collected from 135 patients with epithelial ovarian carcinoma at 3 hospitals in the Netherlands. Evaluated clinico-pathologic variables were age, histologic subtype, differentiation grade, clinical stage [International Federation of Gynecology and Obstetrics (FIGO)], presence of ascites, serum CA-125, and the completeness of debulking surgery. Morphometry and DNA flow cytometric techniques were assessed on each tumor sample to determine the mitotic activity index (MAI), volume percentage epithelium, mean nuclear area (MNA), standard deviation of MNA (SD MNA), nuclear perimeter (NP), and DNA ploidy. Univariate analysis showed that differentiation grade, FIGO stage, presence of ascites, preoperative CA-125 levels, DNA ploidy, and MAI, NP, and MNA were of significant prognostic value. After multivariate analysis (using forward Cox proportional hazard analysis), only differentiation grade and FIGO stage remained significant. From this study, we can conclude that morphometry and DNA flow cytometry are not independent prognosticators and therefore have no clinical value in predicting prognosis in ovarian carcinoma.

  20. Effect of Interval to Definitive Breast Surgery on Clinical Presentation and Survival in Early-Stage Invasive Breast Cancer

    SciTech Connect

    Vujovic, Olga; Yu, Edward; Cherian, Anil; Perera, Francisco; Dar, A. Rashid; Stitt, Larry; Hammond, A.

    2009-11-01

    Purpose: To examine the effect of clinical presentation and interval to breast surgery on local recurrence and survival in early-stage breast cancer. Methods and Materials: The data from 397 patients with Stage T1-T2N0 breast carcinoma treated with conservative surgery and breast radiotherapy between 1985 and 1992 were reviewed at the London Regional Cancer Program. The clinical presentation consisted of a mammogram finding or a palpable lump. The intervals from clinical presentation to definitive breast surgery used for analysis were 0-4, >4-12, and >12 weeks. The Kaplan-Meier estimates of the time to local recurrence, disease-free survival, and cause-specific survival were determined for the three groups. Cox regression analysis was used to evaluate the effect of clinical presentation and interval to definitive surgery on survival. Results: The median follow-up was 11.2 years. No statistically significant difference was found in local recurrence as a function of the interval to definitive surgery (p = .424). A significant difference was noted in disease-free survival (p = .040) and cause-specific survival (p = .006) with an interval of >12 weeks to definitive breast surgery. However, the interval to definitive surgery was dependent on the presentation for cause-specific survival, with a substantial effect for patients with a mammographic presentation and a negligible effect for patients with a lump presentation (interaction p = .041). Conclusion: The results of this study suggest that an interval of >12 weeks to breast surgery might be associated with decreased survival for patients with a mammographic presentation, but it appeared to have no effect on survival for patients presenting with a palpable breast lump.

  1. Population-based incidence and 5-year survival for hospital-admitted traumatic brain and spinal cord injury, Western Australia, 2003-2008.

    PubMed

    Moorin, Rachael; Miller, Ted R; Hendrie, Delia

    2014-09-01

    This study aimed at analysing first-time hospitalisations for traumatic brain injury (TBI) and spinal cord injury (SCI) in Western Australia (WA), in terms of socio-demographic profile, cause of injury, relative risks and survival, using tabular and regression analyses of linked hospital discharge and mortality census files and comparing results with published standardised mortality rates (SMRs) for TBI. Participants were all 9,114 first hospital admissions for TBI or SCI from 7/2003 to 6/2008, linked to mortality census data through 12/2008, and the main outcome measures were number of cases by cause, SMRs in hospital and post-discharge by year through year 5. Road crashes accounted for 34 % of hospitalised TBI and 52 % of hospitalised SCI. 8,460 live TBI discharges experienced 580 deaths during 24,494 person-years of follow-up. The life-table expectation of deaths in the cohort was 164. Post-discharge SMRs were 7.66 in year 1, 3.86 in year 2 and averaged 2.31 in years 3 through 5. 317 live SCI discharges experienced 18 deaths during 929 years of follow-up. Post-discharge SMRs were 7.36 in year 1 and a fluctuating average of 2.13 in years 2 through 5. Use of data from model systems does not appear to yield biased SMRs. Similarly no systematic variation was observed between all-age studies and the more numerous studies that focused on those aged 14 to 16 and older. Based on two studies, SMRs for TBI, however, may be higher in year 2 post-discharge in Australia than elsewhere. That possibility and its cause warrant exploration. Expanding public TBI/SCI compensation in WA from road crash to all causes might triple TBI compensation and double SCI compensation. PMID:24952617

  2. Prostate-Specific Antigen at 4 to 5 Years After Low-Dose-Rate Prostate Brachytherapy Is a Strong Predictor of Disease-Free Survival

    SciTech Connect

    Lo, Andrea C.; Morris, W. James; Lapointe, Vincent; Hamm, Jeremy; Keyes, Mira; Pickles, Tom; McKenzie, Michael; Spadinger, Ingrid

    2014-01-01

    Purpose: To determine (1) the prognostic utility of prostate-specific antigen (PSA) concentration at 45 to 60 months (48mPSA) after low-dose-rate prostate brachytherapy (LDR-PB); (2) the predictors of 48mPSA; and (3) the prognostic utility of directional trends between PSA levels at 24, 36, and 48 months after LDR-PB. Methods and Materials: Between 1998 and 2008, 2223 patients with low- and intermediate-risk prostate cancer received LDR-PB monotherapy. A cohort of 1434 of these patients was identified with a documented 48mPSA and no evidence of disease relapse prior to the 48mPSA. In addition, a subset of this cohort (n=585) was identified with ≥72 months of follow-up and documented PSA values at both 24 and 36 months after implantation. Results: Median follow-up time was 76 months. Eight-year Kaplan-Meier disease-free survival (DFS) rates were 100% vs 73.4% for patients with 48mPSA ≤0.2 vs those with >0.2 ng/mL; 99.1% versus 53.8% for a 48mPSA threshold of ≤0.4 versus >0.4 ng/mL, respectively; and 97.3% versus 0% for a threshold of ≤1.0 versus >1.0 ng/mL, respectively. On multivariate analysis, the only factor predictive of DFS was 48mPSA (P<.0001). On subset analysis (n=585), 29 patients had a PSA rise (defined as >0.2 ng/mL) between 24 and 36 months, 24 patients had a rise between 36 and 48 months, and 11 patients had rises over both intervals. Failure rates in these patients were 52%, 79%, and 100%, respectively. On multivariate analysis, initial PSA, androgen deprivation therapy, and dose to 90% of the prostate significantly correlated with 48mPSA but together accounted for only ∼5% of its total variance. Conclusions: The 48mPSA after LDR-PB is highly predictive of long-term DFS. Patients with 48mPSA ≤0.4 ng/mL had a <1% risk of disease relapse at 8 years, whereas all patients with 48mPSA >1.0 ng/mL relapsed. Consecutive PSA rises of >0.2 ng/mL from 24 to 36 months and from 36 to 48 months were also highly predictive of subsequent failure.

  3. Functional impairment of activated protein C in breast cancer - relationship to survival outcomes

    PubMed Central

    Roselli, Mario; Ferroni, Patrizia; Riondino, Silvia; Mariotti, Sabrina; Portarena, Ilaria; Alessandroni, Jhessica; Ialongo, Cristiano; Massoud, Renato; Costarelli, Leopoldo; Cavaliere, Francesco; Bernardini, Sergio; Guadagni, Fiorella

    2016-01-01

    An impairment of the activated protein C (APC) system has been occasionally reported in breast cancer (BC). However, the clinical significance and prognostic value of an impaired APC functionality in BC patients is still poorly understood. Thus, the present study was aimed at investigating the prognostic value of altered APC functionality for progression-free (PFS) and overall survival (OS) in a cohort study of BC patients. APC functionality was retrospectively analyzed by a coagulation inhibition assay (ThromboPath) in 290 consecutive patients with primary (n=246) or relapsing/recurrent (n=44) BC. All patients were prospectively followed for a median time of 3.5 years (14% recurrence rate). As control group, 145 age-matched healthy women were also investigated. The results obtained demonstrated that APC function was impaired in roughly 20% of all BC at baseline. BC women with stage I/II had a significantly lower rate of APC impairment (13%) than women with stage III (22%) or distant metastases (44%, p=0.001). At univariate analyses, an impairment of APC function had a negative prognostic impact in terms of PFS (5-year PFS rates 53% vs. 70%; HR=2.5; p<0.001) and OS (5-year OS rates 79% vs. 93%; HR=3.9; p=0.005). However, prognostic significance was retained in multivariate models only for PFS (HR=2.0; p=0.017). We may, thus, conclude that BC patients are in a prothrombotic condition, which could play a role in the progression of the disease. Monitoring coagulation changes in BC women could provide important prognostic information especially in patients with advanced stages. PMID:27429857

  4. Functional impairment of activated protein C in breast cancer - relationship to survival outcomes.

    PubMed

    Roselli, Mario; Ferroni, Patrizia; Riondino, Silvia; Mariotti, Sabrina; Portarena, Ilaria; Alessandroni, Jhessica; Ialongo, Cristiano; Massoud, Renato; Costarelli, Leopoldo; Cavaliere, Francesco; Bernardini, Sergio; Guadagni, Fiorella

    2016-01-01

    An impairment of the activated protein C (APC) system has been occasionally reported in breast cancer (BC). However, the clinical significance and prognostic value of an impaired APC functionality in BC patients is still poorly understood. Thus, the present study was aimed at investigating the prognostic value of altered APC functionality for progression-free (PFS) and overall survival (OS) in a cohort study of BC patients. APC functionality was retrospectively analyzed by a coagulation inhibition assay (ThromboPath) in 290 consecutive patients with primary (n=246) or relapsing/recurrent (n=44) BC. All patients were prospectively followed for a median time of 3.5 years (14% recurrence rate). As control group, 145 age-matched healthy women were also investigated. The results obtained demonstrated that APC function was impaired in roughly 20% of all BC at baseline. BC women with stage I/II had a significantly lower rate of APC impairment (13%) than women with stage III (22%) or distant metastases (44%, p=0.001). At univariate analyses, an impairment of APC function had a negative prognostic impact in terms of PFS (5-year PFS rates 53% vs. 70%; HR=2.5; p<0.001) and OS (5-year OS rates 79% vs. 93%; HR=3.9; p=0.005). However, prognostic significance was retained in multivariate models only for PFS (HR=2.0; p=0.017). We may, thus, conclude that BC patients are in a prothrombotic condition, which could play a role in the progression of the disease. Monitoring coagulation changes in BC women could provide important prognostic information especially in patients with advanced stages. PMID:27429857

  5. Developmental milestones record - 5 years

    MedlinePlus

    Normal childhood growth milestones - 5 years; Childhood growth milestones - 5 years; Growth milestones for children - 5 years ... Physical and motor skill milestones for a typical 5-year-old child include: Gains about 4 - 5 ...

  6. Breast cancer survival disparity between African American and Caucasian women in Arkansas: A race-by-grade analysis

    PubMed Central

    Monzavi-Karbassi, Behjatolah; Siegel, Eric R.; Medarametla, Srikanth; Makhoul, Issam; Kieber-Emmons, Thomas

    2016-01-01

    Despite progress in breast cancer treatment, disparity persists in survival time between African American (AA) and Caucasian women in the US. Tumor stage and tumor grade are the major prognostic factors that define tumor aggressiveness and contribute to racial disparity between AA and Caucasian women. Studying the interaction of race with tumor grade or stage may provide further insights into the role of intrinsic biological aggressiveness in disecting the AA-Caucasian survival disparity. Therefore, the current study was performed to evaluate the interaction of race with tumor grade and stage at diagnosis regarding survival in a cohort of patients treated at the Winthrop P. Rockefeller Cancer Institute of the University of Arkansas for Medical Sciences (Little Rock, AR, USA). The cohort included 1,077 patients, 208 (19.3%) AA and 869 (80.7%) Caucasian, diagnosed with breast cancer between January 1997 and December 2005. Kaplan-Meier survival plots were generated and Cox regressions were performed to analyze the associations of race with breast cancer-specific survival time. Over a mean follow-up time of 1.5 years, AA women displayed increased mortality risk due to breast cancer-specific causes [hazard ratio (HR), 1.74; 95% confidence interval (CI), 1.23–2.46]. The magnitude of racial disparity varied strongly with tumor grade (race-x-grade interaction; P<0.001). No significant interaction was observed between race and tumor stage or race and age at diagnosis. Among women diagnosed with grade I tumors, the race disparity in survival time after controlling for tumor stage and age was strong (HR, 9.07; 95% CI, 2.11–38.95), but no significant AA-Caucasian disparity was observed among women with higher-grade tumors. The data suggest that, when diagnosed with grade I breast cancer, AA may experience poorer survival outcomes compared with Caucasian patients, regardless of tumor stage or age. The findings potentially provide significant clinical and public health

  7. Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial

    PubMed Central

    Davies, Christina; Pan, Hongchao; Godwin, Jon; Gray, Richard; Arriagada, Rodrigo; Raina, Vinod; Abraham, Mirta; Alencar, Victor Hugo Medeiros; Badran, Atef; Bonfill, Xavier; Bradbury, Joan; Clarke, Michael; Collins, Rory; Davis, Susan R; Delmestri, Antonella; Forbes, John F; Haddad, Peiman; Hou, Ming-Feng; Inbar, Moshe; Khaled, Hussein; Kielanowska, Joanna; Kwan, Wing-Hong; Mathew, Beela S; Müller, Bettina; Nicolucci, Antonio; Peralta, Octavio; Pernas, Fany; Petruzelka, Lubos; Pienkowski, Tadeusz; Rajan, Balakrishnan; Rubach, Maryna T; Tort, Sera; Urrútia, Gerard; Valentini, Miriam; Wang, Yaochen; Peto, Richard

    2013-01-01

    Summary Background For women with oestrogen receptor (ER)-positive early breast cancer, treatment with tamoxifen for 5 years substantially reduces the breast cancer mortality rate throughout the first 15 years after diagnosis. We aimed to assess the further effects of continuing tamoxifen to 10 years instead of stopping at 5 years. Methods In the worldwide Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) trial, 12 894 women with early breast cancer who had completed 5 years of treatment with tamoxifen were randomly allocated to continue tamoxifen to 10 years or stop at 5 years (open control). Allocation (1:1) was by central computer, using minimisation. After entry (between 1996 and 2005), yearly follow-up forms recorded any recurrence, second cancer, hospital admission, or death. We report effects on breast cancer outcomes among the 6846 women with ER-positive disease, and side-effects among all women (with positive, negative, or unknown ER status). Long-term follow-up still continues. This study is registered, number ISRCTN19652633. Findings Among women with ER-positive disease, allocation to continue tamoxifen reduced the risk of breast cancer recurrence (617 recurrences in 3428 women allocated to continue vs 711 in 3418 controls, p=0·002), reduced breast cancer mortality (331 deaths vs 397 deaths, p=0·01), and reduced overall mortality (639 deaths vs 722 deaths, p=0·01). The reductions in adverse breast cancer outcomes appeared to be less extreme before than after year 10 (recurrence rate ratio [RR] 0·90 [95% CI 0·79–1·02] during years 5–9 and 0·75 [0·62–0·90] in later years; breast cancer mortality RR 0·97 [0·79–1·18] during years 5–9 and 0·71 [0·58–0·88] in later years). The cumulative risk of recurrence during years 5–14 was 21·4% for women allocated to continue versus 25·1% for controls; breast cancer mortality during years 5–14 was 12·2% for women allocated to continue versus 15·0% for controls (absolute mortality

  8. Triple-Negative Subtype Predicts Poor Overall Survival and High Locoregional Relapse in Inflammatory Breast Cancer

    PubMed Central

    Li, Jing; Gonzalez-Angulo, Ana M.; Allen, Pamela K.; Yu, Tse K.; Woodward, Wendy A.; Ueno, Naoto T.; Lucci, Anthony; Krishnamurthy, Savitri; Gong, Yun; Bondy, Melissa L.; Yang, Wei; Willey, Jie S.; Cristofanilli, Massimo; Valero, Vicente

    2011-01-01

    Background. Numerous studies have demonstrated that expression of estrogen/progesterone receptor (ER/PR) and human epidermal growth factor receptor (HER)-2 is important for predicting overall survival (OS), distant relapse (DR), and locoregional relapse (LRR) in early and advanced breast cancer patients. However, these findings have not been confirmed for inflammatory breast cancer (IBC), which has different biological features than non-IBC. Methods. We retrospectively analyzed the records of 316 women who presented to MD Anderson Cancer Center in 1989–2008 with newly diagnosed IBC without distant metastases. Most patients received neoadjuvant chemotherapy, mastectomy, and postmastectomy radiation. Patients were grouped according to receptor status: ER+ (ER+/PR+ and HER-2−; n = 105), ER+HER-2+ (ER+/PR+ and HER-2+; n = 37), HER-2+ (ER−/PR− and HER-2+; n = 83), or triple-negative (TN) (ER−PR−HER-2−; n = 91). Kaplan–Meier and Cox proportional hazards methods were used to assess LRR, DR, and OS rates and their associations with prognostic factors. Results. The median age was 50 years (range, 24–83 years). The median follow-up time and median OS time for all patients were both 33 months. The 5-year actuarial OS rates were 58.7% for the entire cohort, 69.7% for ER+ patients, 73.5% for ER+HER-2+ patients, 54.0% for HER=2+ patients, and 42.7% for TN patients (p < .0001); 5-year LRR rates were 20.3%, 8.0%, 12.6%, 22.6%, and 38.6%, respectively, for the four subgroups (p < .0001); and 5-year DR rates were 45.5%, 28.8%, 50.1%, 52.1%, and 56.7%, respectively (p < .001). OS and LRR rates were worse for TN patients than for any other subgroup (p < .0001–.03). Conclusions. TN disease is associated with worse OS, DR, and LRR outcomes in IBC patients, indicating the need for developing new locoregional and systemic treatment strategies for patients with this aggressive subtype. PMID:22147002

  9. Paget's disease of the breast.

    PubMed

    Freund, H; Maydovnik, M; Laufer, N; Durst, A L

    1977-01-01

    Twenty-nine histologically verified cases of Paget's disease of the breast treated at the Hadassah University Hospital in the years 1949-1972 were followed up and analyzed. Dividing this material into two groups according to the presence or absence of a palpable breast tumor revealed significant difference in behavior and survival. Patients with a breast mass (34%) had a 50% axillary lymph node involvement and behaved as with any other ordinary breast cancer, with a 5-year survival rate of 40% and a 10-year survival rate of 33%. Patients with no palpable breast mass (66%) had only a 10.5% lymph node involvement, the 5-year survival rate being 94% and the 10-year survival rate being 91%. Delay in diagnosis seems to play no significant factor in survival rates and outcome. We believe radical mastectomy to be the treatment of choice in all cases of Paget's disease of the breast. PMID:190481

  10. Quality of Life over 5 years after Breast Cancer Diagnosis among Low-Income Women: Effects of Race/Ethnicity and Patient-Physician Communication

    PubMed Central

    Maly, Rose C.; Liu, Yihang; Liang, Li-Jung; Ganz, Patricia A.

    2014-01-01

    Background To identify risk factors for lower quality of life (QOL) among low-income women with breast cancer (BC), with an emphasis on the impact of patient-physician communication. In addition, we examined ethnic/racial group differences in QOL change over time. Methods A longitudinal study was conducted among 921 low-income women with BC. Patients were interviewed at 6-, 18-, 36- and 60- months after BC diagnosis. Mixed-effect regression models were performed to investigate predictors for and time effects on QOL. The main outcomes included the Medical Outcomes Study Health Survey Short Form 36 Mental Component Summary score (SF-36 MCS), SF-36 Physical Component Summary score (SF-36 PCS) and the Ladder of Life scale. Chief independent variables included physician information-giving and patient self-efficacy in interacting with physicians. Results There were no significant changes over time in QOL except for physical functioning, with survivors reporting a significant decrease over time (P<0.0001). Mean SF-36 MCS and PCS scores were lower than national general population norms at all time points. Both patient self-efficacy in interacting with physicians and physician information-giving were positively associated with SF-36 MCS (P=0.03, P=0.02, respectively) and Ladder of Life (P=0.01, P=0.03, respectively). Less acculturated Latinas reported higher SF-36 MCS and PCS scores (P<0.0001, P=0.01, respectively) and better global QOL (P<0.0001) than whites. Conclusion Low-income women with BC experienced poor physical and mental health. The results suggest that QOL among low-income women with BC would be enhanced by interventions aimed at empowering patients in communicating with physicians and increasing physician information giving. PMID:25411008

  11. Copy number variation in glutathione-S-transferase T1 and M1 predicts incidence and 5-year survival from prostate and bladder cancer, and incidence of corpus uteri cancer in the general population.

    PubMed

    Nørskov, M S; Frikke-Schmidt, R; Bojesen, S E; Nordestgaard, B G; Loft, S; Tybjærg-Hansen, A

    2011-08-01

    Glutathione-S-transferase T1 (GSTT1) and GSTM1 detoxify carcinogens and thus potentially contribute to inter-individual susceptibility to cancer. We determined the ability of GST copy number variation (CNV) to predict the risk of cancer in the general population. Exact copy numbers of GSTT1 and GSTM1 were measured by real-time PCR in 10 247 individuals, of whom 2090 had cancer. In men, the cumulative incidence of prostate cancer increased and the cumulative 5-year survival decreased with decreasing GSTT1 copy numbers (trends=0.02). The hazard ratios (HRs) (95% CIs) for prostate cancer and for death after prostate cancer diagnosis were, respectively, 1.2 (0.8-1.8) and 1.2 (0.6-2.1) for GSTT1*1/0, and 1.8 (1.1-3.0) and 2.2 (1.1-4.4) for GSTT1*0/0 versus GSTT1*1/1. In women, the cumulative incidence of corpus uteri cancer increased with decreasing GSTT1 copy numbers (trend=0.04). The HRs for corpus uteri cancer were, respectively, 1.8 (1.0-3.2) and 2.2 (1.0-4.6) for GSTT1*1/0 and GSTT1*0/0 versus GSTT1*1/1. Finally, the cumulative incidence of bladder cancer increased, and the cumulative 5-year survival decreased, with decreasing GSTM1 copy numbers (P=0.03-0.05). The HRs for bladder cancer were, respectively, 1.5 (0.7-3.2) and 2.0 (0.9-4.3) for GSTM1*1/0 and GSTM1*0/0 versus GSTM1*1/1. The HR for death after bladder cancer diagnosis was 1.9 (1.0-3.7) for GSTM1*0/0 versus GSTM1*1/0. In conclusion, exact CNV in GSTT1 and GSTM1 predict incidence and 5-year survival from prostate and bladder cancer, and incidence of corpus uteri cancer.

  12. PPAR-delta promotes survival of breast cancer cells in harsh metabolic conditions.

    PubMed

    Wang, X; Wang, G; Shi, Y; Sun, L; Gorczynski, R; Li, Y-J; Xu, Z; Spaner, D E

    2016-01-01

    Expression of the nuclear receptor peroxisome proliferator activated receptor delta (PPARδ) in breast cancer cells is negatively associated with patient survival, but the underlying mechanisms are not clear. High PPARδ protein levels in rat breast adenocarcinomas were found to be associated with increased growth in soft agar and mice. Transgenic expression of PPARδ increased the ability of human breast cancer cell lines to migrate in vitro and form lung metastases in mice. PPARδ also conferred the ability to grow in exhausted tissue culture media and survive in low-glucose and other endoplasmic reticulum stress conditions such as hypoxia. Upregulation of PPARδ by glucocorticoids or synthetic agonists also protected human breast cancer cells from low glucose. Survival in low glucose was related to increased antioxidant defenses mediated in part by catalase and also to late AKT phosphorylation, which is associated with the prolonged glucose-deprivation response. Synthetic antagonists reversed the survival benefits conferred by PPARδ in vitro. These findings suggest that PPARδ conditions breast cancer cells to survive in harsh microenvironmental conditions by reducing oxidative stress and enhancing survival signaling responses. Drugs that target PPARδ may have a role in the treatment of breast cancer. PMID:27270614

  13. PPAR-delta promotes survival of breast cancer cells in harsh metabolic conditions

    PubMed Central

    Wang, X; Wang, G; Shi, Y; Sun, L; Gorczynski, R; Li, Y-J; Xu, Z; Spaner, D E

    2016-01-01

    Expression of the nuclear receptor peroxisome proliferator activated receptor delta (PPARδ) in breast cancer cells is negatively associated with patient survival, but the underlying mechanisms are not clear. High PPARδ protein levels in rat breast adenocarcinomas were found to be associated with increased growth in soft agar and mice. Transgenic expression of PPARδ increased the ability of human breast cancer cell lines to migrate in vitro and form lung metastases in mice. PPARδ also conferred the ability to grow in exhausted tissue culture media and survive in low-glucose and other endoplasmic reticulum stress conditions such as hypoxia. Upregulation of PPARδ by glucocorticoids or synthetic agonists also protected human breast cancer cells from low glucose. Survival in low glucose was related to increased antioxidant defenses mediated in part by catalase and also to late AKT phosphorylation, which is associated with the prolonged glucose-deprivation response. Synthetic antagonists reversed the survival benefits conferred by PPARδ in vitro. These findings suggest that PPARδ conditions breast cancer cells to survive in harsh microenvironmental conditions by reducing oxidative stress and enhancing survival signaling responses. Drugs that target PPARδ may have a role in the treatment of breast cancer. PMID:27270614

  14. The California Breast Cancer Survivorship Consortium (CBCSC): Prognostic factors associated with racial/ethnic differences in breast cancer survival

    PubMed Central

    Wu, Anna H.; Gomez, Scarlett Lin; Vigen, Cheryl; Kwan, Marilyn L.; Keegan, Theresa H.M.; Lu, Yani; Shariff-Marco, Salma; Monroe, Kristine R.; Kurian, Allison W.; Cheng, Iona; Caan, Bette J.; Lee, Valerie S.; Roh, Janise M.; Sullivan-Halley, Jane; Henderson, Brian E.; Bernstein, Leslie; John, Esther M.; Sposto, Richard

    2014-01-01

    Racial/ethnic disparities in mortality among US breast cancer patients are well-documented. Our knowledge of the contribution of lifestyle factors to disease prognosis is based primarily on non-Latina Whites and is limited for Latina, African American and Asian American women. To address this knowledge gap, the California Breast Cancer Survivorship Consortium (CBCSC) harmonized and pooled interview information (e.g., demographics, family history of breast cancer, parity, smoking, alcohol consumption) from six California-based breast cancer studies and assembled corresponding cancer registry data (clinical characteristics, mortality), resulting in 12,210 patients (6,501 non-Latina Whites, 2,060 African Americans, 2,032 Latinas, 1,505 Asian Americans, 112 other race/ethnicity) diagnosed with primary invasive breast cancer between 1993 and 2007. In total, 3,047 deaths (1,570 breast cancer-specific) were observed with a mean (SD) follow-up of 8.3 (3.5) years. Cox-proportional hazards regression models were fit to data to estimate hazards ratios (HR) and 95% confidence intervals (CI) for overall and breast cancer-specific mortality. Compared with non-Latina Whites, the HR of breast cancer-specific mortality was 1.13 (95% CI, 0.97-1.33) for African Americans, 0.84 (95% CI, 0.70-1.00) for Latinas, and 0.60 (95% CI, 0.37-0.97) for Asian Americans after adjustment for age, tumor characteristics, and select lifestyle factors. The CBCSC represents a large and racially/ethnically diverse cohort of breast cancer patients from California. This cohort will enable analyses to jointly consider a variety of clinical, lifestyle, and contextual factors in attempting to explain the long-standing disparities in breast cancer outcomes. PMID:23864487

  15. Impact of neighborhoods and body size on survival after breast cancer diagnosis.

    PubMed

    Shariff-Marco, Salma; Gomez, Scarlett L; Sangaramoorthy, Meera; Yang, Juan; Koo, Jocelyn; Hertz, Andrew; John, Esther M; Cheng, Iona; Keegan, Theresa H M

    2015-11-01

    With data from the Neighborhoods and Breast Cancer Study, we examined the associations between body size, social and built environments, and survival following breast cancer diagnosis among 4347 women in the San Francisco Bay Area. Lower neighborhood socioeconomic status and greater neighborhood crowding were associated with higher waist-to-hip ratio (WHR). After mutual adjustment, WHR, but not neighborhood characteristics, was positively associated with overall mortality and marginally with breast cancer-specific mortality. Our findings suggest that WHR is an important modifiable prognostic factor for breast cancer survivors. Future WHR interventions should account for neighborhood characteristics that may influence WHR. PMID:26606455

  16. Value of volume-based metabolic parameters for predicting survival in breast cancer patients treated with neoadjuvant chemotherapy

    PubMed Central

    Kim, Tae Hee; Yoon, Joon-Kee; Kang, Doo Kyoung; Kang, Seok Yun; Jung, Yong Sik; Han, Sehwan; Kim, Ji Young; Yim, Hyunee; An, Young-Sil

    2016-01-01

    Abstract We evaluated the role of metabolic parameters in the prediction of disease recurrence in operable invasive ductal breast cancer patients treated with neoadjuvant chemotherapy (NAC). We retrospectively evaluated 139 female patients (mean age, 46.5 years; range: 27–72 years) with invasive ductal breast cancer, treated with NAC followed by surgery. All patients underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography and magnetic resonance imaging at baseline and after completion of NAC before surgery. The prognostic significance of clinicopathological and imaging parameters for disease-free survival (DFS) was evaluated. Recurrence of cancer was detected in 31 of 139 patients (22.3%; follow-up period: 6–82 months). Baseline maximum standardized uptake value, metabolic tumor volume (MTV), and reduction rate (RR) of MTV after NAC were significant independent prognostic factors for DFS in a multivariate analysis (all P < 0.05). The survival functions differed significantly between low and high histological grades (P < 0.001). DFS of the patients with high baseline MTV (≥5.23 cm3) was significantly poorer than that of low MTV patients (P = 0.019). The survival function of the group with low RR of MTV after NAC (≤90.72%) was poorer than the higher RR of the MTV group (P = 0.008). Our findings suggest that breast cancer patients who have a high histological grade, large baseline MTV, or a small RR of MTV after NAC should receive great attention to check for possible recurrence. PMID:27741099

  17. Hereditary breast/ovarian cancer: clinicopathological characteristics and survival of BRCA2 positive and negative cases.

    PubMed

    Syamala, Vani; Syamala, Volga S; Sreeja, Leelakumari; Raveendran, Praveenkumar B; Vijayalekshmi, R V; Sheeja, V R; Santhi, S; Kuttan, Ratheesan; Abraham, Elizabeth K; Ankathil, Ravindran

    2008-01-01

    The clinical and pathological characteristics and prognostic outcome of patients with hereditary breast/ovarian cancer and BRCA2 mutations are poorly known. Hence, the present study aimed to correlate the BRCA2 mutation status with clinical characteristics and overall survival of 102 breast/ovarian cancer patients in Kerala, South India. All the coding regions of BRCA2 genes were PCR amplified and analyzed for mutations employing Conformation Sensitive Gel Electrophoresis and characterized by sequencing. The ORs with 95% Cls was computed to assess the association between BRCA2 gene mutation status and clinicopathologic characteristics of breast cancer patients. Survival curves were generated according to Kaplan-Meier method using Log Rank test and Cox proportional hazards regression method. Out of the 102 breast/ovarian cancer patients with known BRCA2 status, 19 were BRCA2 mutation positive. In survival analysis, BRCA2 gene mutation status (P = 0.02) and clinicopathologic parameters such as tumour size (p = 0.01), metastasis (P = 0.01), disease stage (P = 0.03) and laterality (P = 0.02) were significantly associated with poor prognosis of breast cancer patients. Patients with hereditary breast/ovarian cancer resulting from a BRCA2 mutation have been conclusively shown to have a worse survival prognosis compared to the non mutated group of patients. PMID:19066131

  18. Statin use and breast cancer survival and risk: a systematic review and meta-analysis.

    PubMed

    Wu, Qi-Jun; Tu, Chao; Li, Yuan-Yuan; Zhu, Jingjing; Qian, Ke-Qing; Li, Wen-Jing; Wu, Lang

    2015-12-15

    The purpose of this study is to determine the associations between statin use and breast cancer survival and risk by performing a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science up to August 2015 for identifying relevant prospective or case-control studies, or randomized clinical trials. Five prospective studies involving 60,911 patients reported the association between statin use and breast cancer mortality. Eleven prospective studies, 12 case-control studies and 9 randomized clinical trials involving 83,919 patients reported the association between statin use and breast cancer risk. After pooling estimates from all available studies, there was a significantly negative association between pre-diagnosis statin use and breast cancer mortality (for overall survival (OS): hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.54-0.84; for disease specific survival (DSS): HR = 0.72, 95% CI 0.53-0.99). There was also a significant inverse association between post-diagnosis statin use and breast cancer DSS (HR = 0.65, 95% CI 0.43-0.98), although the association with breast cancer OS did not reach statistical significance (HR = 0.71, 95% CI 0.48-1.07). Additionally, there was a non-linear relationship for the duration of post-diagnosis statin use with breast cancer specific mortality. On the other hand, with regards to the relationship between statin use and breast cancer risk, no significant association was detected. Our analyses suggest that although statin use may not influence breast cancer risk, the use of statin may be associated with decrease mortality of breast cancer patients. Further large-scale studies are warranted to validate our findings.

  19. Statin use and breast cancer survival and risk: a systematic review and meta-analysis

    PubMed Central

    Li, Yuan-Yuan; Zhu, Jingjing; Qian, Ke-Qing; Li, Wen-Jing; Wu, Lang

    2015-01-01

    The purpose of this study is to determine the associations between statin use and breast cancer survival and risk by performing a systematic review and meta-analysis. We searched PubMed, Embase and Web of Science up to August 2015 for identifying relevant prospective or case-control studies, or randomized clinical trials. Five prospective studies involving 60,911 patients reported the association between statin use and breast cancer mortality. Eleven prospective studies, 12 case-control studies and 9 randomized clinical trials involving 83,919 patients reported the association between statin use and breast cancer risk. After pooling estimates from all available studies, there was a significantly negative association between pre-diagnosis statin use and breast cancer mortality (for overall survival (OS): hazard ratio (HR) = 0.68, 95% confidence interval (CI) 0.54–0.84; for disease specific survival (DSS): HR = 0.72, 95% CI 0.53–0.99). There was also a significant inverse association between post-diagnosis statin use and breast cancer DSS (HR = 0.65, 95% CI 0.43–0.98), although the association with breast cancer OS did not reach statistical significance (HR = 0.71, 95% CI 0.48–1.07). Additionally, there was a non-linear relationship for the duration of post-diagnosis statin use with breast cancer specific mortality. On the other hand, with regards to the relationship between statin use and breast cancer risk, no significant association was detected. Our analyses suggest that although statin use may not influence breast cancer risk, the use of statin may be associated with decrease mortality of breast cancer patients. Further large-scale studies are warranted to validate our findings. PMID:26472026

  20. The optimal number of lymph nodes removed in maximizing the survival of breast cancer patients

    NASA Astrophysics Data System (ADS)

    Peng, Lim Fong; Taib, Nur Aishah; Mohamed, Ibrahim; Daud, Noorizam

    2014-07-01

    The number of lymph nodes removed is one of the important predictors for survival in breast cancer study. Our aim is to determine the optimal number of lymph nodes to be removed for maximizing the survival of breast cancer patients. The study population consists of 873 patients with at least one of axillary nodes involved among 1890 patients from the University of Malaya Medical Center (UMMC) breast cancer registry. For this study, the Chi-square test of independence is performed to determine the significant association between prognostic factors and survival status, while Wilcoxon test is used to compare the estimates of the hazard functions of the two or more groups at each observed event time. Logistic regression analysis is then conducted to identify important predictors of survival. In particular, Akaike's Information Criterion (AIC) are calculated from the logistic regression model for all thresholds of node involved, as an alternative measure for the Wald statistic (χ2), in order to determine the optimal number of nodes that need to be removed to obtain the maximum differential in survival. The results from both measurements are compared. It is recommended that, for this particular group, the minimum of 10 nodes should be removed to maximize survival of breast cancer patients.

  1. Disparities in Breast Cancer Treatment and Survival for Women with Disabilities

    PubMed Central

    McCarthy, Ellen P.; Ngo, Long H.; Roetzheim, Richard G.; Chirikos, Thomas N.; Li, Donglin; Drews, Reed E.; Iezzoni, Lisa I.

    2008-01-01

    Background Breast-conserving surgery combined with axillary lymph node dissection and radiotherapy or mastectomy are definitive treatments for women with early-stage breast cancer. Little is known about breast cancer treatment for women with disabilities. Objective To compare initial treatment for early-stage breast cancer between women with and without disabilities and to examine the association of treatment differences and survival. Design Retrospective cohort study. Setting 11 Surveillance, Epidemiology, and End Results (SEER) Program tumor registries. Participants 100 311 women who received a diagnosis of stage I to IIIA breast cancer at 21 to 64 years of age from 1988 to 1999. Women who qualified for Social Security Disability Insurance (SSDI) and Medicare at breast cancer diagnosis were considered disabled. Measurements Receipt of breast-conserving surgery versus mastectomy. For women who had breast-conserving surgery (n = 49 166), the authors examined receipt of radiotherapy and axillary lymph node dissection. Survival was measured from diagnosis until death or until 31 December 2001. Results Women with SSDI and Medicare coverage had lower rates of breast-conserving surgery than other women (43.2% vs. 49.2%; adjusted relative risk, 0.80 [95% CI, 0.76 to 0.84]). Among women who had breast-conserving surgery, women with SSDI and Medicare coverage were less likely than other women to receive radiotherapy (adjusted relative risk, 0.83 [CI, 0.77 to 0.90]) and axillary lymph node dissection (adjusted relative risk, 0.81 [CI, 0.74 to 0.90]). Women with SSDI and Medicare coverage had lower survival rates than those of other women in all-cause mortality (adjusted hazard ratio, 2.02 [CI, 1.88 to 2.16]) and breast cancer–specific mortality (adjusted hazard ratio, 1.31 [CI, 1.18 to 1.45]). Results were similar after adjustment for treatment differences. Limitations Findings are limited to women who qualified for SSDI and Medicare. No data on adjuvant chemotherapy and

  2. Cost-effectiveness analysis of anastrozole vs tamoxifen in adjuvant therapy for early stage breast cancer in the United Kingdom: the 5-year completed treatment analysis of the ATAC (‘Arimidex', Tamoxifen alone or in combination) trial

    PubMed Central

    Mansel, R; Locker, G; Fallowfield, L; Benedict, Á; Jones, D

    2007-01-01

    Results from the completed treatment analysis of the ATAC (Arimidex, Tamoxifen alone or in combination) trial indicated that anastrozole was significantly superior to tamoxifen in terms of efficacy and safety in the adjuvant treatment of postmenopausal women with hormone receptor-positive (HR+) early breast cancer. On the basis of these results, this study estimated the cost-effectiveness of anastrozole vs tamoxifen, from the perspective of the UK National Health Service (NHS). A Markov model was developed using the 5-year completed treatment analysis from the ATAC trial (ISRCTN18233230), as well as data obtained from published literature and expert opinion. Resource utilisation data and associated costs (2003–4 UK£) were compiled from standard sources and expert opinion. Utility scores for a number of health states were obtained from a cross-sectional study of 26 representative patients using the standard gamble technique. The utility scores were then inserted into the model to obtain cost per quality adjusted life-year (QALY) gained. Costs and benefits were discounted at recommended annual rates of the UK Treasury (3.5%). Modelled for 25 years, anastrozole, relative to generic tamoxifen, was estimated to result in 0.244 QALYs gained per patient at an additional cost of £4315 per patient). The estimated incremental cost-effectiveness of anastrozole compared with tamoxifen was £17 656 per QALY gained. There was a greater than 90% probability that the cost-effectiveness of anastrozole was below £30 000 per QALY gained and of the order of 65% that it was below £20 000 per QALY gained. The results were robust to all parameters tested in sensitivity analysis. Compared with commonly accepted thresholds, anastrozole is a cost-effective alternative to generic tamoxifen in adjuvant treatment of postmenopausal women with HR+ early breast cancer from the UK NHS perspective. PMID:17622238

  3. Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina Breast Cancer Study

    PubMed Central

    O’Brien, Katie M.; Cole, Stephen R.; Tse, Chiu-Kit; Perou, Charles M.; Carey, Lisa A.; Foulkes, William D.; Dressler, Lynn G.; Geradts, Joseph; Millikan, Robert C.

    2010-01-01

    Purpose Previous research identified differences in breast cancer-specific mortality across four "intrinsic" tumor subtypes: luminal A, luminal B, basal-like, and human epidermal growth factor receptor 2 positive/estrogen receptor negative (HER2+/ER−). Experimental Design We used immunohistochemical markers to subtype 1149 invasive breast cancer patients (518 African American, 631 white) in the Carolina Breast Cancer Study, a population-based study of women diagnosed with breast cancer. Vital status was determined through 2006 using the National Death Index, with median follow-up of 9 years. Results Cancer subtypes luminal A, luminal B, basal-like and HER2+/ER- were distributed as 64%, 11%, 11% and 5% for whites, and 48%, 8%, 22% and 7% for African Americans, respectively. Breast cancer mortality was higher for patients with HER2+/ER- and basal-like breast cancer compared to luminal A and B. African Americans had higher breast-cancer specific mortality than whites, but the effect of race was statistically significant only among women with luminal A breast cancer. However, when compared to the luminal A subtype within racial categories, mortality for patients with basal-like breast cancer was higher among whites (HR=2.0, 95% CI: 1.2, 3.4) than African Americans (HR=1.5, 95% CI: 1.0, 2.4), with the strongest effect seen in postmenopausal white women (HR=3.9, 95% CI: 1.5, 10.0). Conclusions Our results confirm the association of basal-like breast cancer with poor prognosis, and suggest that basal-like breast cancer is not an inherently more aggressive disease in African American women compared to whites. Additional analyses are needed in populations with known treatment profiles to understand the role of tumor subtypes and race in breast cancer mortality, and in particular our finding that among women with luminal A breast cancer, African Americans have higher mortality than whites. PMID:21169259

  4. LOXL2 expression is associated with invasiveness and negatively influences survival in breast cancer patients.

    PubMed

    Ahn, Sung Gwe; Dong, Seung Myung; Oshima, Akira; Kim, Woo Ho; Lee, Hak Min; Lee, Seung Ah; Kwon, Seung-Hyun; Lee, Ji-Hae; Lee, Jae Myun; Jeong, Joon; Lee, Hy-De; Green, Jeffrey E

    2013-08-01

    Lysyl oxidase-like 2 (LOXL2) is associated with invasiveness and metastasis in breast cancer. We analyzed the prognostic impact of LOXL2 for breast cancer patients and investigated the role of LOXL2 in breast cancer cell lines. Immunohistochemical study of LOXL2 expression was done in samples from 309 patients. Survival analysis was performed using log-rank test and Cox regression hazard model. After identification of LOXL2 expression in breast cancer cell lines, we performed matrigel invasion and wound-healing assays with LOXL2-silenced cell lines. In the human study, LOXL2 was expressed in 16.2 % of patients. Comparing the LOXL2-positive versus negative groups, there was a significantly higher proportion of estrogen receptor-negative patients (54.0 vs. 37.0 %, respectively; p = 0.029) and triple-negative patients (34.0 vs. 18.0 %; p = 0.022) in the positive group. In multivariate analysis for overall survival and metastasis-free survival, positive LOXL2 was demonstrated as a poor prognostic factor (HR 2.27 and 2.10, respectively). In vitro study indicated that LOXL2 silencing induces a mesenchymal-epithelial transition-like process in basal cell lines (MDA-MB-231 and BT549) associated with decreased invasive and migratory properties. These clinical and preclinical data confirm that higher LOXL2 expression is associated with invasiveness of basal-like breast cancer cells and lower survival of breast cancer patients. Our results suggest the clinical value of LOXL2 as a therapeutic target in breast cancer.

  5. [Survival of women with breast cancer, of a city in the south of Brazil].

    PubMed

    Ayala, Arlene Laurenti Monterrosa

    2012-01-01

    A retrospective cohort study was carried out aiming to evaluate the survival of 655 women with breast cancer, seen in the Single Health System, Joinville, Santa Catarina, Brazil. For the analysis of survival, the method of Kaplan-Meier and Cox model was applied. The survival according to the staging of women was significantly different in accordance with the results of the test of Log-rank Test. The rate of risk of instantaneous death between the stages I/II, I/III and I/IV was 3.26, 15.40 and 25.51, respectively. These findings are in consonance with literature data, and indicate that the staging is a variable that explains the differences in the survival among women with breast cancer.

  6. Are international differences in breast cancer survival between Australia and the UK present amongst both screen-detected women and non-screen-detected women? survival estimates for women diagnosed in West Midlands and New South Wales 1997-2006.

    PubMed

    Woods, Laura M; Rachet, Bernard; O'Connell, Dianne L; Lawrence, Gill; Coleman, Michel P

    2016-05-15

    We examined survival in screened-detected and non-screen-detected women diagnosed in the West Midlands (UK) and New South Wales (Australia) in order to evaluate whether international differences in survival are related to early diagnosis, or to other factors relating to the healthcare women receive. Data for women aged 50 - 65 years who had been eligible for screening from 50 years were examined. Data for 5,628 women in West Midlands and 6,396 women in New South Wales were linked to screening service records (mean age at diagnosis 53.7 years). We estimated net survival and modelled the excess hazard ratio of breast cancer death by screening status. Survival was lower for women in the West Midlands than in New South Wales (5-year net survival 90.9% [95% CI 89.9%-91.7%] compared with 93.4% [95% CI 92.6%-94.1%], respectively). The difference was greater between the two populations of non-screen-detected women (4.9%) compared to between screen-detected women, (1.8% after adjustment for lead-time and over-diagnosis). The adjusted excess hazard ratio of breast cancer death for West Midlands compared with New South Wales was greater in the non-screen-detected group (EHR 2.00, 95% CI 1.70 - 2.31) but not significantly different to that for women whose cancer had been screen-detected (EHR 1.72, 95% CI 0.87 - 2.56). In this study more than one in three breast cancer deaths in the West Midlands would have been avoided if survival had been the same as in New South Wales. The possibility that women in the UK receive poorer treatment is an important potential explanation which should be examined with care.

  7. Association of cyclin D1 genotype with breast cancer risk and survival.

    PubMed

    Shu, Xiao Ou; Moore, Derek B; Cai, Qiuyin; Cheng, Jiarong; Wen, Wanqing; Pierce, Larry; Cai, Hui; Gao, Yu-Tang; Zheng, Wei

    2005-01-01

    Cyclin D1 (CCND1) is a key cell cycle regulatory protein that governs cell cycle progression from the G(1) to S phase. A common polymorphism (A870G) in exon 4 of the CCND1 gene produces an alternate transcript (transcript-b) that preferentially encodes a protein with enhanced cell transformation activity and possible prolonged half-life. We evaluated the association of CCND1 A870G polymorphism with breast cancer risk and survival in 1,130 breast cancer cases and 1,196 controls who participated in the Shanghai Breast Cancer Study. Approximately 81% of cases and 79% of controls carried the A allele at A870G of the CCND1 gene [odds ratio, 1.1; 95% confidence interval (95% CI), 0.9-1.4]. As lightly stronger but nonsignificant association was found for the A allele among younger women (odds ratio, 1.3; 95% CI, 0.9-1.8). However, this polymorphism seems to modify the effect of hormonal exposures on postmenopausal breast cancer, as the positive associations of postmenopausal breast cancer with body mass index (Pfor interaction = 0.02) and waist-to-hip ratios (P for interaction < 0.03; all Ps are two sided) were only observed among women who carry the A allele at A870G of the CCND1 gene. Following up with this cohort of patients for an average of 4.84 years, we found that the CCND1 A870G polymorphism was inversely associated with overall and disease-free survival, particularly among women with late stage or estrogen/progesterone receptor-negative breast cancer. The adjusted hazard ratios for disease-free survival associated with GA and AA genotypes were 0.94 (95% CI, 0.49-1.82) and 0.41 (95% CI, 0.19-0.91) for tumor-node-metastasis stage III to IV breast cancer, and 0.35 (95% CI, 0.15-0.80) and 0.32 (95% CI, 0.13-0.79) for estrogen/progesterone receptor-negative breast cancer. This study suggests that CCND1 A870G polymorphism may modify the postmenopausal breast cancer risk associated with hormonal exposure and predict survival after breast cancer diagnosis. PMID:15668481

  8. Differences in IGF-axis protein expression and survival among multiethnic breast cancer patients

    PubMed Central

    Hernandez, Brenda Y; Wilkens, Lynne R; Le Marchand, Loïc; Horio, David; Chong, Clayton D; Loo, Lenora W M

    2015-01-01

    There is limited knowledge about the biological basis of racial/ethnic disparities in breast cancer outcomes. Aberrations in IGF signaling induced by obesity and other factors may contribute to these disparities. This study examines the expression profiles of the insulin-like growth factor (IGF)-axis proteins and the association with breast cancer survival across a multiethnic population. We examined the expression profiles of the IGF1, IGF1R, IGFBP2 (IGF-binding proteins), and IGFBP3 proteins in breast tumor tissue and their relationships with all-cause and breast cancer-specific survival up to 17 years postdiagnosis in a multiethnic series of 358 patients in Hawaii, USA. Native Hawaiians, Caucasians, and Japanese were compared. Covariates included demographic and clinical factors and ER/PR/HER2 (estrogen receptor/progesterone receptor/human epidermal growth factor receptor-2) status. In Native Hawaiian patients, IGFBP2 and IGFBP3 expression were each independently associated with overall and breast cancer mortality (IGFB2: HRmort = 10.96, 95% CI: 2.18–55.19 and HRmort = 35.75, 95% CI: 3.64–350.95, respectively; IGFBP3: HRmort = 5.16, 95% CI: 1.27–20.94 and HRmort = 8.60, 95% CI: 1.84–40.15, respectively). IGF1R expression was also positively associated with all-cause mortality in Native Hawaiians. No association of IGF-axis protein expression and survival was observed in Japanese or Caucasian patients. The interaction of race/ethnicity and IGFBP3 expression on mortality risk was significant. IGF-axis proteins may have variable influence on breast cancer progression across different racial/ethnic groups. Expression of binding proteins and receptors in breast tumors may influence survival in breast cancer patients by inducing aberrations in IGF signaling and/or through IGF-independent mechanisms. Additional studies to evaluate the role of the IGF-axis in breast cancer are critical to improve targeted breast cancer treatment strategies. PMID

  9. A mechanistic breast cancer survival modelling through the axillary lymph node chain.

    PubMed

    Cobre, Juliana; Castro Perdoná, Gleici S; Peria, Fernanda M; Louzada, Francisco

    2013-04-30

    In this paper, we proposed a mechanistic breast cancer survival model based on the axillary lymph node chain structure, considering lymph nodes as a potential dissemination arrangement. We assume a naive breast cancer treatment protocol consisting of exposing patients first to a chemotherapy treatment on r intervals at k-cycles separated by equal time intervals, and then they proceed to surgery. Our model, different from former ones, accommodates a quantity of contaminated lymph nodes, which is observed during surgery. We assume a generalised negative binomial survival distribution for the unknown number of contaminated lymph nodes after surgery, which, during an unknown period, may potentially propagate the disease. Estimation is based on a maximum likelihood approach. A simulation study assesses the coverage probability of asymptotic confidence intervals when small or moderate samples are considered. A Brazilian breast cancer data illustrate the applicability of our modelling.

  10. Modeling the Impact of Breast-Feeding by HIV-Infected Women on Child Survival.

    ERIC Educational Resources Information Center

    Heymann, Sally Jody

    1990-01-01

    Models the survival outcomes of children in developing countries born to women infected with human immunodeficiency virus (HIV) who are breast-fed, bottle-fed, and wet-nursed. Uses decision analysis to assess the relative risk of child mortality from HIV transmission and non-HIV causes associated with different methods of feeding. (FMW)

  11. Breast cancer survival in the US and Europe: a CONCORD high-resolution study

    PubMed Central

    Allemani, Claudia; Sant, Milena; Weir, Hannah K; Richardson, Lisa C; Baili, Paolo; Storm, Hans; Siesling, Sabine; Torrella-Ramos, Ana; Voogd, Adri C; Aareleid, Tiiu; Ardanaz, Eva; Berrino, Franco; Bielska-Lasota, Magdalena; Bolick, Susan; Cirilli, Claudia; Colonna, Marc; Contiero, Paolo; Cress, Rosemary; Crocetti, Emanuele; Fulton, John P; Grosclaude, Pascale; Hakulinen, Timo; Izarzugaza, M Isabel; Malmström, Per; Peignaux, Karin; Primic-Žakelj, Maja; Rachtan, Jadwiga; Diba, Chakameh Safaei; Sánchez, Maria-José; Schymura, Maria J; Shen, Tiefu; Traina, Adele; Tryggvadottir, Laufey; Tumino, Rosario; Velten, Michel; Vercelli, Marina; Wolf, Holly J; Woronoff, Anne-Sophie; Wu, Xiaocheng; Coleman, Michel P

    2015-01-01

    Breast cancer survival is reportedly higher in the US than in Europe. The first worldwide study (CONCORD) found wide international differences in age-standardised survival. The aim of this study is to explain these survival differences. Population-based data on stage at diagnosis, diagnostic procedures, treatment and follow-up were collected for about 20,000 women diagnosed with breast cancer aged 15–99 years during 1996–98 in 7 US states and 12 European countries. Age-standardised net survival and the excess hazard of death up to five years after diagnosis were estimated by jurisdiction (registry, country, European region), age and stage with flexible parametric models. Breast cancers were generally less advanced in the US than in Europe. Stage also varied less between US states than between European jurisdictions. Early, node-negative tumours were more frequent in the US (39%) than in Europe (32%), while locally advanced tumours were twice as frequent in Europe (8%), and metastatic tumours of similar frequency (5–6%). Net survival in Northern, Western and Southern Europe (82–85%) was similar to that in the US (84%), but lower in Eastern Europe (72%). For the first 3 years after diagnosis the mean excess hazard was higher in Eastern Europe than elsewhere: the difference was most marked for women aged 70–99 years, and mainly confined to women with locally advanced or metastatic tumours. Differences in breast cancer survival between Europe and the US in the late 1990s were mainly explained by lower survival in Eastern Europe, where low healthcare expenditure may have constrained the quality of treatment. PMID:22815141

  12. Prognostic factors and survival of patients with brain metastasis from breast cancer who underwent craniotomy.

    PubMed

    Leone, José Pablo; Lee, Adrian V; Brufsky, Adam M

    2015-07-01

    Brain metastasis (BM) in patients with breast cancer is a catastrophic event that results in poor prognosis. Identification of prognostic factors associated with breast cancer brain metastases (BCBM) could help to identify patients at risk. The aim of this study was to assess clinical characteristics, prognostic factors, and survival of patients with BCBM who had craniotomy and resection in a series of patients treated with modern multimodality therapy. We analyzed 42 patients with BCBM who underwent resection. Patients were diagnosed with breast cancer between April 1994 and May 2010. Cox proportional hazards regression was selected to describe factors associated with time to BM, survival from the date of first recurrence, and overall survival (OS). Median age was 51 years (range 24-74). Median follow-up was 4.2 years (range 0.6-18.5). The proportion of the biological subtypes of breast cancer was ER+/HER2- 25%, ER+/HER2+ 15%, ER-/HER2+ 30%, and ER-/HER2- 30%. Median OS from the date of primary diagnosis was 5.74 years. Median survival after diagnosis of BM was 1.33 years. In multivariate Cox regression analyses, stage was the only factor associated with shorter time to the development of BM (P = 0.033), whereas age was the only factor associated with survival from the date of recurrence (P = 0.027) and with OS (P = 0.037). Stage at primary diagnosis correlated with shorter time to the development of BM, while age at diagnosis was associated with shorter survival in BCBM. None of the other clinical factors had influence on survival.

  13. Method of Detection and Breast Cancer Survival Disparities in Hispanic Women

    PubMed Central

    Hill, Deirdre A.; Nibbe, Andrea; Royce, Melanie E.; Wallace, Anne Marie; Kang, Huining; Wiggins, Charles L.; Rosenberg, Robert D.

    2010-01-01

    Background Hispanic women in New Mexico (NM) are more likely to die of breast cancer-related causes than non-Hispanic women. We determined whether survival differences between Hispanic and non-Hispanic women might be attributable to the method of detection, an independent breast cancer prognostic factor in previous studies. Methods White women diagnosed with invasive breast cancer from 1995 through 2004 were identified from NM Surveillance Epidemiology End Results (SEER) files (n=5067), and matched to NM Mammography Project records. Method of cancer detection was categorized as “symptomatic” or “screen-detected”. The proportion of Hispanic survival disparity accounted for by included variables was assessed using Cox models. Results During 87 months median follow-up, 490 breast cancer deaths occurred. Symptomatic vs. screen-detection was classifiable for 3891 women (76.8%), and was independently related to breast cancer-specific survival (Hazard ratio (HR) 1.6; 95% confidence interval (CI) 1.3–2.0). Hispanic women had a 1.5-fold increased risk of breast cancer-related death, relative to non-Hispanic women (95% CI 1.2–1.8). After adjustment for detection method, the Hispanic HR declined from 1.50 to 1.45 (10%), but after inclusion of other prognostic indicators, the Hispanic HR=1.23 (95% CI 1.01–1.48). Conclusions Although the Hispanic HR declined 50% after adjustment, the decrease was largely due to adverse tumor prognostic characteristics. Impact Reduction of disparate survival in Hispanic women may rely not only on increased detection of tumors when asymptomatic but on development of greater understanding of biological factors that predispose to poor prognosis tumors. PMID:20841385

  14. Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer

    PubMed Central

    2012-01-01

    Introduction The presence of circulating tumor cells (CTC) is an independent prognostic factor for progression-free survival and breast cancer-related death (BRD) for patients with metastatic breast cancer beginning a new line of systemic therapy. The current study was undertaken to explore whether the presence of CTC at the time of diagnosis was associated with recurrence-free survival (RFS) and BRD. Methods In a prospective single center study, CTC were enumerated with the CellSearch system in 30 ml of peripheral blood of 602 patients before undergoing surgery for breast cancer. There were 97 patients with a benign tumor, 101 did not meet the inclusion criteria of which there were 48 patients with DCIS, leaving 404 stage I to III patients. Patients were stratified into unfavorable (CTC ≥1) and favorable (CTC = 0) prognostic groups. Results ≥1 CTC in 30 ml blood was detected in 15 (15%) benign tumors, in 9 DCIS (19%), in 28 (16%) stage I, 32 (18%) stage II and in 16 (31%) patients with stage III. In stage I to III patients 76 (19%) had ≥1 CTC of whom 16 (21.1%) developed a recurrence. In 328 patients with 0 CTC 38 (11.6%) developed a recurrence. Four-year RFS was 88.4% for favorable CTC and 78.9% for unfavorable CTC (P = 0.038). A total of 25 patients died of breast cancer-related causes and 11 (44%) had ≥1 CTC. BRD was 4.3% for favorable and 14.5% for unfavorable CTC (P = 0.001). In multivariate analysis ≥1 CTC was associated with distant disease-free survival, but not for overall recurrence-free survival. CTC, progesterone receptor and N-stage were independent predictors of BRD in multivariate analysis. Conclusions Presence of CTC in breast cancer patients before undergoing surgery with curative intent is associated with an increased risk for breast cancer-related death. PMID:23088337

  15. Surviving breast cancer: women's experiences with their changed bodies.

    PubMed

    Brunet, Jennifer; Sabiston, Catherine M; Burke, Shaunna

    2013-06-01

    In this study, we explored women's experiences with their bodies following treatment for breast cancer. Eleven women who had been treated for the disease (M(time since treatment)=4.45 years) were interviewed. Data were collected and analyzed using interpretative phenomenological analysis (Smith et al., 2009). Four main themes emerged from the data: changing visibly and invisibly; experiencing intense thoughts and emotions; meaning of the body: a vehicle of health, well-being, and social expression; and managing and dealing with physical changes. Overall, the women experienced various physical changes that shaped, mostly in a negative way, their perceptions, thoughts, attitudes, feelings, and beliefs about their bodies. The women described attempts to make positive lifestyle behavior choices (e.g., diet, participate in physical activity), and used other strategies (e.g., wigs, make-up, clothes) to manage their appearances and restore positive body-related experiences. Based on these findings, it is important to be cognizant of women's body image concerns following breast cancer given the poignant and lasting effects they can have on their psychosocial and emotional well-being.

  16. Factors affecting disease-free survival in patients with human epidermal growth factor receptor 2-positive breast cancer who receive adjuvant trastuzumab

    PubMed Central

    GÜNDÜZ, SEYDA; GÖKSU, SEMA SEZGIN; ARSLAN, DENIZ; TATLI, ALI MURAT; UYSAL, MÜKREMIN; GÜNDÜZ, UMUT RIZA; SEVINÇ, MERT MAHSUNI; COŞKUN, HASAN SENOL; BOZCUK, HAKAN; MUTLU, HASAN; SAVAS, BURHAN

    2015-01-01

    Breast cancer is the most frequently diagnosed cancer in women worldwide and the second cause of cancer-related mortality. A total of 20–30% of patients with early-stage breast cancer develop recurrence within the first 5 years following diagnosis. Trastuzumab significantly improves overall survival and disease-free survival (DFS) in women with human epidermal growth factor receptor 2 (HER2)-positive early and locally advanced breast cancer. This study aimed to determine the factors that affect DFS following adjuvant transtuzumab therapy. A total of 62 patients treated with trastuzumab for early and locally advanced breast cancer were included in our study. Data, including pathology, treatment and treatment outcome, rate of recurrence and laboratory tests, were retrospectively collected. There was no significant association between DFS and age, menopausal status, disease stage and hormone receptor status. The median follow-up was 48.4 months. The median DFS of patients treated with adjuvant trastuzumab was 64.1 months. In addition, the median DFS was 44.3 vs. 66.8 months in patients with platelet-lymphocyte ratio (PLR) ≤200 vs. >200, respectively (log-rank test; P=0.001), and 70 vs. 45 months in patients with eosinophil count ≤70 vs. >70×103/mm3 (log-rank test; P=0.001). Our data revealed the prognostic relevance of a decrease in the peripheral blood eosinophil count and PLR value following trastuzumab therapy in breast cancer. PLR and eosinophil count measurements are cost-effective, readily available worldwide, non-invasive and safe. Combined with other markers, such as patient age, tumor stage and tumor histology, may be effectively used for patients with breast cancer. PMID:26623060

  17. Breast malignant phyllodes tumor with rare pelvic metastases and long-term overall survival

    PubMed Central

    Shan, Jinlan; Zhang, Shizhen; Wang, Zhen; Fu, Yanbiao; Li, Ling; Wang, Xiaochen

    2016-01-01

    Abstract Background: Malignant phyllodes tumor (PT) is a rare fibro epithelial neoplasm of the breast, which is poor prognosis due to high risk of recurrence and distant metastasis. Methods: We report a case of malignant PT. It had recurred locally five times, and the sixth relapse was occurred 54 months after first diagnosis, presenting a huge pelvic mass (14 cm × 11 cm) by CT scan. Histopathological examination has demonstrated a metastatic phyllodes tumor. After postoperative chemotherapy treatment, a longer survival has been achieved, which is more than 72 months. Results: Our case report describes a breast PT with several local recurrences and a rare metastasis (pelvic cavity), but long-term overall survival was achieved after surgery and chemotherapy. Conclusion: We conclude that trustworthy prognosticators that identify patients with excessive potential of aggressive clinical course should be explored. Moreover, proper treatment could prolong overall survival of metastatic PT patients. PMID:27661051

  18. Female breast cancer incidence and survival in Utah according to religious preference, 1985–1999

    PubMed Central

    Merrill, Ray M; Folsom, Jeffrey A

    2005-01-01

    Background Female breast cancer incidence rates in Utah are among the lowest in the U.S. The influence of the Church of Jesus Christ of Latter-day Saint (LDS or Mormon) religion on these rates, as well as on disease-specific survival, will be explored for individuals diagnosed with breast cancer in Utah from 1985 through 1999. Methods Population-based records for incident female breast cancer patients were linked with membership records from the LDS Church to determine religious affiliation and, for LDS Church members, level of religiosity. Incidence rates were age-adjusted to the 2000 U.S. standard population using the direct method. Cox proportional hazards model was used to compare survival among religiously active LDS, less religiously active LDS, and non-LDS with simultaneous adjustment for prognostic factors. Results Age-adjusted breast cancer incidence rates were consistently lower for LDS than non-LDS in Utah from 1985 through 1999. Rates were lower among LDS compared with non-LDS across the age span. In 1995–99, the age-adjusted incidence rates were 107.6 (95% CI: 103.9 – 111.3) for LDS women and 130.5 (123.2 – 137.9) for non-LDS women. If non-LDS women in Utah had the same breast cancer risk profile as LDS women, an estimated 214 (4.8%) fewer malignant breast cancer cases would have occurred during 1995–99. With religiously active LDS serving as the reference group, the adjusted death hazard ratio for religiously less active LDS was 1.09 (0.94 – 1.27) and for non-LDS was 0.86 (0.75 – 0.98). Conclusion In Utah, LDS lifestyle is associated with lower incidence rates of female breast cancer. However, LDS experience poorer survivability from breast cancer than their non-LDS counterparts. Parity and breastfeeding, while protective factors against breast cancer, may contribute to poorer prognosis of female breast cancer in LDS women. PMID:15904509

  19. Neoadjuvant Chemotherapy Induces Expression Levels of Breast Cancer Resistance Protein That Predict Disease-Free Survival in Breast Cancer

    PubMed Central

    Kim, Baek; Fatayer, Hiba; Hanby, Andrew M.; Horgan, Kieran; Perry, Sarah L.; Valleley, Elizabeth M.A.; Verghese, Eldo T.; Williams, Bethany J.; Thorne, James L.; Hughes, Thomas A.

    2013-01-01

    Three main xenobiotic efflux pumps have been implicated in modulating breast cancer chemotherapy responses. These are P-glycoprotein (Pgp), Multidrug Resistance-associated Protein 1 (MRP1), and Breast Cancer Resistance Protein (BCRP). We investigated expression of these proteins in breast cancers before and after neoadjuvant chemotherapy (NAC) to determine whether their levels define response to NAC or subsequent survival. Formalin-fixed paraffin-embedded tissues were collected representing matched pairs of core biopsy (pre-NAC) and surgical specimen (post-NAC) from 45 patients with invasive ductal carcinomas. NAC regimes were anthracyclines +/− taxanes. Immunohistochemistry was performed for Pgp, MRP1 and BCRP and expression was quantified objectively using computer-aided scoring. Pgp and MRP1 were significantly up-regulated after exposure to NAC (Wilcoxon signed-rank p = 0.0024 and p<0.0001), while BCRP showed more variation in response to NAC, with frequent up- (59% of cases) and down-regulation (41%) contributing to a lack of significant difference overall. Pre-NAC expression of all markers, and post-NAC expression of Pgp and MRP1 did not correlate with NAC response or with disease-free survival (DFS). Post-NAC expression of BCRP did not correlate with NAC response, but correlated significantly with DFS (Log rank p = 0.007), with longer DFS in patients with low post-NAC BCRP expression. In multivariate Cox regression analyses, post-NAC BCRP expression levels proved to predict DFS independently of standard prognostic factors, with high expression associated with a hazard ratio of 4.04 (95% confidence interval 1.3–12.2; p = 0.013). We conclude that NAC-induced expression levels of BCRP predict survival after NAC for breast cancer, while Pgp and MRP1 expression have little predictive value. PMID:23658771

  20. Genetic polymorphisms in the MMP-7 gene and breast cancer survival

    PubMed Central

    Beeghly-Fadiel, Alicia; Shu, Xiao-ou; Long, Jirong; Li, Chun; Cai, Qiuyin; Cai, Hui; Gao, Yu-Tang; Zheng, Wei

    2008-01-01

    Matrix metalloproteinase-7 (MMP-7) is a small secreted proteolytic enzyme with broad substrate specificity. Its expression has been shown to be associated with tumor invasion, metastasis, and survival for a variety of cancers. We systematically evaluated single nucleotide polymorphisms (SNPs) in this gene in relation to breast cancer survival in a large follow-up study. This study included 1,079 breast cancer patients, recruited from 1996 to 1998, that were followed for a median of 7.1 years as part of the Shanghai Breast Cancer Study (SBCS). Eleven SNPs, including two known functional promoter SNPs, were analyzed using the Affymetrix Targeted Genotyping System. Associations with survival were evaluated by Cox proportional hazards regression and Kaplan-Meier functions. Statistically significant associations with disease-free (DFS) and/or overall survival (OS) were found for 5 polymorphisms; these associations were explained primarily by two SNPs (rs11568818 and rs11225297) that were in high linkage disequilibrium (LD) with the others. Patients homozygous for the rs11568818 rare allele (G) had a significantly worse prognosis (OS HR: 6.7, 95% CI: 2.4–18.6) than patients homozygous for the common allele (A). Significantly improved survival was seen for patients with the rs11225297 T allele, and this association occurred in a dose-response manner; patients with AT (OS HR: 0.7, 95% CI: 0.5–0.9) and TT (OS HR: 0.3, 95% CI: 0.1–0.8) fared better than patients with AA (p-value for trend: 0.001). Thus, common MMP-7 genetic polymorphisms were found to be significant determinants of survival among Chinese women with breast cancer. PMID:18798254

  1. Local therapy in metastatic breast cancer is associated with improved survival.

    PubMed

    Sofi, Aijaz A; Mohamed, Iman; Koumaya, Meghan; Kamaluddin, Zarine

    2013-01-01

    Patients presenting with stage-IV breast cancer are usually offered systemic chemotherapy to control metastatic tumor burden and palliative radiation therapy to manage the symptomatic primary tumor. The aim of this study was to assess the result of local therapy on the overall outcome of patients with metastatic breast cancer. We reviewed medical records of all patients with metastatic breast cancer that presented to our institution between 2000 and 2009. Based on the treatment received, the patients were grouped as follows: group 1 included patients who underwent surgery and also received radiotherapy and chemotherapy/hormonal therapy, group 2 included patients who received radiotherapy and chemotherapy/hormonal therapy only, and group 3 included patients who received chemotherapy/hormonal therapy alone. Of the 37 patients included in the study, 10 patients were placed in group 1, 17 patients in group 2, and 10 patients in group 3. About 38% had high to anaplastic tumor grade, and 48% had ≥2 metastatic sites in the body. Overall, the average survival time was 3.13 years (range: 0-17 years). A significant difference in survival estimates was noted between groups 1, 2, and 3 with mean survival times of 8.83, 4.9, and 2.26 years, respectively (log rank χ = 10.44, P = 0.005). In age-adjusted multivariate Cox regression model (χ = 21.729, P= 0.001), high/anaplastic tumor grade (P = 0.036), African American race (P = 0.009), central nervous system metastasis (P = 0.003), group 2 (P = 0.006), and group 3 (P = 0.002) were associated with poor survival. Survival was not associated with estrogen and progesterone receptor and visceral or bone metastases. We conclude that aggressive local control of primary tumor in patients presenting with stage-IV breast cancer is associated with improved survival.

  2. Physical Activity, Weight Control, and Breast Cancer Risk and Survival: Clinical Trial Rationale and Design Considerations

    PubMed Central

    Hunsberger, Sally; Alciati, Marianne H.; Blair, Steven N.; Goodwin, Pamela J.; McTiernan, Anne; Wing, Rena; Schatzkin, Arthur

    2009-01-01

    Substantial observational epidemiological evidence exists that physical activity and weight control are associated with decreased risk of postmenopausal breast cancer. Uncertainty remains regarding several aspects of these associations, including the effect of possible confounding factors on these associations. We present the rationale and design for two randomized controlled trials that can help resolve this uncertainty. In a 5-year prevention trial conducted among women at high risk of breast cancer, the primary endpoint would be breast cancer incidence. For a comparable survivorship trial, the primary endpoint would be the disease-free interval and secondary endpoints would be breast cancer recurrence–free interval, second primary breast cancer, and total invasive plus in situ breast cancer. A set of inclusion and exclusion criteria is proposed for both trials. Intervention goals are the same for both trials. Goals for the weight control intervention would be, for women whose body mass index (BMI) is greater than 25 kg/m2, to lose 10% of body weight and, for women whose BMI is less than or equal to 25 kg/m2, to avoid weight gain. The goal for the physical activity intervention would be to achieve and maintain regular participation in a moderate-intensity physical activity program for a total of 150–225 minutes over at least 5 days per week. Sample size calculations are based on alternative assumptions about hazard ratio, adherence, follow-up duration, and power and are presented for the primary prevention and survivorship trials. Although both studies could enhance our understanding of breast cancer etiology and benefit public health, practical considerations, including smaller sample size, ease of recruitment, and reduced likelihood of early termination, favor the survivorship trial at this time. PMID:19401543

  3. Semiparametric Bayesian estimation of quantile function for breast cancer survival data with cured fraction.

    PubMed

    Gupta, Cherry; Cobre, Juliana; Polpo, Adriano; Sinha, Debjayoti

    2016-09-01

    Existing cure-rate survival models are generally not convenient for modeling and estimating the survival quantiles of a patient with specified covariate values. This paper proposes a novel class of cure-rate model, the transform-both-sides cure-rate model (TBSCRM), that can be used to make inferences about both the cure-rate and the survival quantiles. We develop the Bayesian inference about the covariate effects on the cure-rate as well as on the survival quantiles via Markov Chain Monte Carlo (MCMC) tools. We also show that the TBSCRM-based Bayesian method outperforms existing cure-rate models based methods in our simulation studies and in application to the breast cancer survival data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database.

  4. Semiparametric Bayesian estimation of quantile function for breast cancer survival data with cured fraction.

    PubMed

    Gupta, Cherry; Cobre, Juliana; Polpo, Adriano; Sinha, Debjayoti

    2016-09-01

    Existing cure-rate survival models are generally not convenient for modeling and estimating the survival quantiles of a patient with specified covariate values. This paper proposes a novel class of cure-rate model, the transform-both-sides cure-rate model (TBSCRM), that can be used to make inferences about both the cure-rate and the survival quantiles. We develop the Bayesian inference about the covariate effects on the cure-rate as well as on the survival quantiles via Markov Chain Monte Carlo (MCMC) tools. We also show that the TBSCRM-based Bayesian method outperforms existing cure-rate models based methods in our simulation studies and in application to the breast cancer survival data from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. PMID:27162061

  5. EPH/ephrin profile and EPHB2 expression predicts patient survival in breast cancer

    PubMed Central

    Husa, Anna-Maria; Magić, Željana; Larsson, Malin; Fornander, Tommy; Pérez-Tenorio, Gizeh

    2016-01-01

    The EPH and ephrins function as both receptor and ligands and the output on their complex signaling is currently investigated in cancer. Previous work shows that some EPH family members have clinical value in breast cancer, suggesting that this family could be a source of novel clinical targets. Here we quantified the mRNA expression levels of EPH receptors and their ligands, ephrins, in 65 node positive breast cancer samples by RT-PCR with TaqMan® Micro Fluidics Cards Microarray. Upon hierarchical clustering of the mRNA expression levels, we identified a subgroup of patients with high expression, and poor clinical outcome. EPHA2, EPHA4, EFNB1, EFNB2, EPHB2 and EPHB6 were significantly correlated with the cluster groups and particularly EPHB2 was an independent prognostic factor in multivariate analysis and in four public databases. The EPHB2 protein expression was also analyzed by immunohistochemistry in paraffin embedded material (cohort 2). EPHB2 was detected in the membrane and cytoplasmic cell compartments and there was an inverse correlation between membranous and cytoplasmic EPHB2. Membranous EPHB2 predicted longer breast cancer survival in both univariate and multivariate analysis while cytoplasmic EPHB2 indicated shorter breast cancer survival in univariate analysis. Concluding: the EPH/EFN cluster analysis revealed that high EPH/EFN mRNA expression is an independent prognostic factor for poor survival. Especially EPHB2 predicted poor breast cancer survival in several materials and EPHB2 protein expression has also prognostic value depending on cell localization. PMID:26870995

  6. MRI breast screening in high-risk women: cancer detection and survival analysis.

    PubMed

    Evans, D Gareth; Gareth, Evans D; Kesavan, Nisha; Nisha, Kesavan; Lim, Yit; Yit, Lim; Gadde, Soujanye; Soujanye, Gadde; Hurley, Emma; Emma, Hurley; Massat, Nathalie J; Maxwell, Anthony J; Ingham, Sarah; Sarah, Ingham; Eeles, Rosalind; Rosalind, Eeles; Leach, Martin O; Howell, Anthony; Anthony, Howell; Duffy, Stephen W; Stephen, Duffy

    2014-06-01

    Women with a genetic predisposition to breast cancer tend to develop the disease at a younger age with denser breasts making mammography screening less effective. The introduction of magnetic resonance imaging (MRI) for familial breast cancer screening programs in recent years was intended to improve outcomes in these women. We aimed to assess whether introduction of MRI surveillance improves 5- and 10-year survival of high-risk women and determine the accuracy of MRI breast cancer detection compared with mammography-only or no enhanced surveillance and compare size and pathology of cancers detected in women screened with MRI + mammography and mammography only. We used data from two prospective studies where asymptomatic women with a very high breast cancer risk were screened by either mammography alone or with MRI also compared with BRCA1/2 carriers with no intensive surveillance. 63 cancers were detected in women receiving MRI + mammography and 76 in women receiving mammography only. Sensitivity of MRI + mammography was 93 % with 63 % specificity. Fewer cancers detected on MRI were lymph node positive compared to mammography/no additional screening. There were no differences in 10-year survival between the MRI + mammography and mammography-only groups, but survival was significantly higher in the MRI-screened group (95.3 %) compared to no intensive screening (73.7 %; p = 0.002). There were no deaths among the 21 BRCA2 carriers receiving MRI. There appears to be benefit from screening with MRI, particularly in BRCA2 carriers. Extended follow-up of larger numbers of high-risk women is required to assess long-term survival.

  7. Mitochondrial calcium uniporter activity is dispensable for MDA-MB-231 breast carcinoma cell survival.

    PubMed

    Hall, Duane D; Wu, Yuejin; Domann, Frederick E; Spitz, Douglas R; Anderson, Mark E

    2014-01-01

    Calcium uptake through the mitochondrial Ca2+ uniporter (MCU) is thought to be essential in regulating cellular signaling events, energy status, and survival. Functional dissection of the uniporter is now possible through the recent identification of the genes encoding for MCU protein complex subunits. Cancer cells exhibit many aspects of mitochondrial dysfunction associated with altered mitochondrial Ca2+ levels including resistance to apoptosis, increased reactive oxygen species production and decreased oxidative metabolism. We used a publically available database to determine that breast cancer patient outcomes negatively correlated with increased MCU Ca2+ conducting pore subunit expression and decreased MICU1 regulatory subunit expression. We hypothesized breast cancer cells may therefore be sensitive to MCU channel manipulation. We used the widely studied MDA-MB-231 breast cancer cell line to investigate whether disruption or increased activation of mitochondrial Ca2+ uptake with specific siRNAs and adenoviral overexpression constructs would sensitize these cells to therapy-related stress. MDA-MB-231 cells were found to contain functional MCU channels that readily respond to cellular stimulation and elicit robust AMPK phosphorylation responses to nutrient withdrawal. Surprisingly, knockdown of MCU or MICU1 did not affect reactive oxygen species production or cause significant effects on clonogenic cell survival of MDA-MB-231 cells exposed to irradiation, chemotherapeutic agents, or nutrient deprivation. Overexpression of wild type or a dominant negative mutant MCU did not affect basal cloning efficiency or ceramide-induced cell killing. In contrast, non-cancerous breast epithelial HMEC cells showed reduced survival after MCU or MICU1 knockdown. These results support the conclusion that MDA-MB-231 breast cancer cells do not rely on MCU or MICU1 activity for survival in contrast to previous findings in cells derived from cervical, colon, and prostate cancers and

  8. Survival of breast cancer patients with meningeal carcinomatosis treated by intrathecal thiotepa.

    PubMed

    Comte, A; Jdid, W; Guilhaume, M N; Kriegel, I; Piperno-Neumann, S; Dieras, V; Dorval, T; Pierga, J Y; Cottu, P H; Mignot, L; Bidard, F C

    2013-12-01

    Treatment of breast cancer meningeal carcinomatosis (MC) relies on intrathecal chemotherapy. Thiotepa is one of the few drugs approved in this setting, although no large cohort has been reported. The aim of our retrospective study is to describe survival and prognostic factors of breast cancer patients treated by intrathecal thiotepa. A search in the electronic database of the Institut Curie was performed and retrieved the patients diagnosed with breast cancer MC from 2000 to 2012 and who received at least one intrathecal injection of thiotepa. The standard regimen was intrathecal thiotepa (10 mg) and methylprednisolone (40 mg), repeated every other week. Clinical data were retrieved from the computerized medical file of each patient. Sixty-six patients have been treated with intrathecal thiotepa either as first line or second line of treatment for breast cancer MC. The median overall survival was 4.5 months (range 0.1-50). There was no significant survival difference between patients treated as first or second line. In multivariate analysis, main adverse prognostic factors at diagnosis were performance status >2 (p = 0.001, RR = 3.4, 95 % CI 1.6-7.2) and history of more than 3 previous systemic chemotherapy lines (p = 0.002, RR = 2.90, 95 % CI 1.50-5.65). After start of the treatment, high primary tumor grade, elevated Cyfra 21-1 levels in the cerebrospinal fluid, and lack of clinical improvement were also independent adverse prognostic factors in multivariate analysis. This is the largest retrospective cohort of breast cancer MC treated by intrathecal thiotepa ever reported. The median overall survival was short but some patients clearly benefited from this treatment, even used as second line. PMID:24043602

  9. Breast Cancer Characteristics and Survival in a Hispanic Population of Costa Rica

    PubMed Central

    Srur-Rivero, Nadia; Cartin-Brenes, Mayra

    2014-01-01

    BACKGROUND Breast cancer characteristics may vary according to the patient’s ethnic group. The goal of this cohort study was to evaluate the characteristics of a group of Costa Rican breast cancer patients and their relationship with survival. METHODS Age, stage, tumor grade, immunohistochemistry, lymphovascular invasion, recurrence, and survival data on 199 Hispanic patients with breast cancer diagnosis, treated between January 2009 and May 2010, were collected from a single institution in San Jose, Costa Rica. The data were statistically analyzed for significance. RESULTS Median age at diagnosis was 53 years. With a median follow-up of 46.5 months, there was an 88% overall survival rate. Thirty-seven percent of the patients (p < 0.001) were at stages III and IV during diagnosis. The hormone receptor human epidermal receptor negative phenotype (HR−HER2−) (p < 0.001) was present in 17% of the cases. In a multivariate analysis, local (risk ratio, RR: 7.2; confidence interval, CI 95%: 3.8–7.6; p = 0.06) and distant recurrence (RR: 14.9; CI 95%: 7.7–28.9; p = 0.01) showed the strongest association with the probability of death from the disease. Patients with HR−HER2− phenotype tumors reported more local recurrences (p = 0.04), a higher tumor grade (p < 0.01), and lower overall survival than patients with other breast cancer phenotypes (p = 0.01). CONCLUSIONS Although this study analyzes a modest number of cases, it is an initial insight into factors that may contribute to differences in breast cancer outcomes among Hispanic women in Costa Rica. The higher proportion of triple negative tumors, advanced stage, and younger median age at diagnosis could contribute to the inferior prognostic described among Hispanic women. There may be a different distribution of tumor subtypes compared to non-Hispanic white women. Further studies are necessary to confirm such findings. PMID:25125980

  10. The effects of soy consumption before diagnosis on breast cancer survival: the Multiethnic Cohort Study.

    PubMed

    Conroy, Shannon M; Maskarinec, Gertraud; Park, Song-Yi; Wilkens, Lynne R; Henderson, Brian E; Kolonel, Laurence N

    2013-01-01

    This study tested the hypothesis that prediagnostic soy intake was inversely associated with all-cause and breast cancer-specific mortality. The analyses included 3842 women in the Multiethnic Cohort (MEC) study of African Americans, Native Hawaiians, Japanese Americans, Latinos, and Caucasians, who completed a quantitative food frequency questionnaire, aged ≥50 yr at cohort entry, and diagnosed with primary invasive breast cancer following cohort entry (1993-2007). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated from Cox proportional hazards regression with adjustment for known clinical and lifestyle factors. During a mean follow-up after diagnosis of invasive breast cancer of 6.2 ± 3.8 yr, there were 804 deaths including 376 breast cancer-specific deaths. The HR (95%CI) for all-cause and breast cancer-specific morality comparing the highest versus lowest tertiles were 1.03 (0.81-1.33) and 1.03 (0.71-1.50) for soy products and 0.99 (0.82-1.20) and 0.95 (0.71-1.28) for total isoflavones, respectively (Ptrend > 0.60 for all). There was limited evidence of differences by hormone receptor status, tumor stage, or ethnic group. Prediagnostic soy intake was unrelated to mortality in postmenopausal women. Our findings are consistent with the literature that soy consumption does not adversely affect breast cancer survival in women.

  11. Defining the Survival Benchmark for Breast Cancer Patients with Systemic Relapse

    PubMed Central

    Zeichner, Simon B; Ambros, Tadeu; Zaravinos, John; Montero, Alberto J; Mahtani, Reshma L; Ahn, Eugene R; Mani, Aruna; Markward, Nathan J; Vogel, Charles L

    2015-01-01

    BACKGROUND Our original paper, published in 1992, reported a median overall survival after first relapse in breast cancer of 26 months. The current retrospective review concentrates more specifically on patients with first systemic relapse, recognizing that subsets of patients with local recurrence are potentially curable. METHODS Records of 5,168 patients from a largely breast-cancer-specific oncology practice were reviewed to identify breast cancer patients with their first relapse between 1996 and 2006 after primary treatment. There were 189 patients diagnosed with metastatic disease within 2 months of being seen by our therapeutic team and 101 patients diagnosed with metastatic disease greater than 2 months. The patients were divided in order to account for lead-time bias than could potentially confound the analysis of the latter 101 patients. RESULTS Median survival for our primary study population of 189 patients was 33 months. As expected, the median survival from first systemic relapse (MSFSR) for the 101 patients excluded because of the potential for lead-time bias was better at 46 months. Factors influencing prognosis included estrogen receptor (ER) status, disease-free interval (DFI), and dominant site of metastasis. Compared with our original series, even with elimination of local-regional recurrences in our present series, the median survival from first relapse has improved by 7 months over the past two decades. CONCLUSION The new benchmark for MSFSR approaches 3 years. PMID:25922577

  12. Similar Survival With Breast Conservation Therapy or Mastectomy in the Management of Young Women With Early-Stage Breast Cancer

    SciTech Connect

    Mahmood, Usama; Morris, Christopher; Neuner, Geoffrey; Koshy, Matthew; Kesmodel, Susan; Buras, Robert; Chumsri, Saranya; Bao Ting; Tkaczuk, Katherine; Feigenberg, Steven

    2012-08-01

    Purpose: To evaluate survival outcomes of young women with early-stage breast cancer treated with breast conservation therapy (BCT) or mastectomy, using a large, population-based database. Methods and Materials: Using the Surveillance, Epidemiology, and End Results (SEER) database, information was obtained for all female patients, ages 20 to 39 years old, diagnosed with T1-2 N0-1 M0 breast cancer between 1990 and 2007, who underwent either BCT (lumpectomy and radiation treatment) or mastectomy. Multivariable and matched pair analyses were performed to compare overall survival (OS) and cause-specific survival (CSS) of patients undergoing BCT and mastectomy. Results: A total of 14,764 women were identified, of whom 45% received BCT and 55% received mastectomy. Median follow-up was 5.7 years (range, 0.5-17.9 years). After we accounted for all patient and tumor characteristics, multivariable analysis found that BCT resulted in OS (hazard ratio [HR], 0.93; 95% confidence interval [CI], 0.83-1.04; p = 0.16) and CSS (HR, 0.93; CI, 0.83-1.05; p = 0.26) similar to that of mastectomy. Matched pair analysis, including 4,644 BCT and mastectomy patients, confirmed no difference in OS or CSS: the 5-, 10-, and15-year OS rates for BCT and mastectomy were 92.5%, 83.5%, and 77.0% and 91.9%, 83.6%, and 79.1%, respectively (p = 0.99), and the 5-, 10-, and 15-year CSS rates for BCT and mastectomy were 93.3%, 85.5%, and 79.9% and 92.5%, 85.5%, and 81.9%, respectively (p = 0.88). Conclusions: Our analysis of this population-based database suggests that young women with early-stage breast cancer have similar survival rates whether treated with BCT or mastectomy. These patients should be counseled appropriately regarding their treatment options and should not choose a mastectomy based on the assumption of improved survival.

  13. SNP-SNP interaction analysis of NF-κB signaling pathway on breast cancer survival

    PubMed Central

    Jamshidi, Maral; Fagerholm, Rainer; Khan, Sofia; Aittomäki, Kristiina; Czene, Kamila; Darabi, Hatef; Li, Jingmei; Andrulis, Irene L.; Chang-Claude, Jenny; Devilee, Peter; Fasching, Peter A.; Michailidou, Kyriaki; Bolla, Manjeet K.; Dennis, Joe; Wang, Qin; Guo, Qi; Rhenius, Valerie; Cornelissen, Sten; Rudolph, Anja; Knight, Julia A.; Loehberg, Christian R.; Burwinkel, Barbara; Marme, Frederik; Hopper, John L.; Southey, Melissa C.; Bojesen, Stig E.; Flyger, Henrik; Brenner, Hermann; Holleczek, Bernd; Margolin, Sara; Mannermaa, Arto; Kosma, Veli-Matti; Dyck, Laurien Van; Nevelsteen, Ines; Couch, Fergus J.; Olson, Janet E.; Giles, Graham G.; McLean, Catriona; Haiman, Christopher A.; Henderson, Brian E.; Winqvist, Robert; Pylkäs, Katri; Tollenaar, Rob A.E.M.; García-Closas, Montserrat; Figueroa, Jonine; Hooning, Maartje J.; Martens, John W.M.; Cox, Angela; Cross, Simon S.; Simard, Jacques; Dunning, Alison M.; Easton, Douglas F.; Pharoah, Paul D.P.; Hall, Per; Blomqvist, Carl; Schmidt, Marjanka K.; Nevanlinna, Heli

    2015-01-01

    In breast cancer, constitutive activation of NF-κB has been reported, however, the impact of genetic variation of the pathway on patient prognosis has been little studied. Furthermore, a combination of genetic variants, rather than single polymorphisms, may affect disease prognosis. Here, in an extensive dataset (n = 30,431) from the Breast Cancer Association Consortium, we investigated the association of 917 SNPs in 75 genes in the NF-κB pathway with breast cancer prognosis. We explored SNP-SNP interactions on survival using the likelihood-ratio test comparing multivariate Cox’ regression models of SNP pairs without and with an interaction term. We found two interacting pairs associating with prognosis: patients simultaneously homozygous for the rare alleles of rs5996080 and rs7973914 had worse survival (HRinteraction 6.98, 95% CI=3.3-14.4, P = 1.42E-07), and patients carrying at least one rare allele for rs17243893 and rs57890595 had better survival (HRinteraction 0.51, 95% CI=0.3-0.6, P = 2.19E-05). Based on in silico functional analyses and literature, we speculate that the rs5996080 and rs7973914 loci may affect the BAFFR and TNFR1/TNFR3 receptors and breast cancer survival, possibly by disturbing both the canonical and non-canonical NF-κB pathways or their dynamics, whereas, rs17243893-rs57890595 interaction on survival may be mediated through TRAF2-TRAIL-R4 interplay. These results warrant further validation and functional analyses. PMID:26317411

  14. Survival Prognostic Factors of Male Breast Cancer in Southern Iran: a LASSO-Cox Regression Approach.

    PubMed

    Shahraki, Hadi Raeisi; Salehi, Alireza; Zare, Najaf

    2015-01-01

    We used to LASSO-Cox method for determining prognostic factors of male breast cancer survival and showed the superiority of this method compared to Cox proportional hazard model in low sample size setting. In order to identify and estimate exactly the relative hazard of the most important factors effective for the survival duration of male breast cancer, the LASSO-Cox method has been used. Our data includes the information of male breast cancer patients in Fars province, south of Iran, from 1989 to 2008. Cox proportional hazard and LASSO-Cox models were fitted for 20 classified variables. To reduce the impact of missing data, the multiple imputation method was used 20 times through the Markov chain Mont Carlo method and the results were combined with Rubin's rules. In 50 patients, the age at diagnosis was 59.6 (SD=12.8) years with a minimum of 34 and maximum of 84 years and the mean of survival time was 62 months. Three, 5 and 10 year survival were 92%, 77% and 26%, respectively. Using the LASSO-Cox method led to eliminating 8 low effect variables and also decreased the standard error by 2.5 to 7 times. The relative efficiency of LASSO-Cox method compared with the Cox proportional hazard method was calculated as 22.39. The19 years follow of male breast cancer patients show that the age, having a history of alcohol use, nipple discharge, laterality, histological grade and duration of symptoms were the most important variables that have played an effective role in the patient's survival. In such situations, estimating the coefficients by LASSO-Cox method will be more efficient than the Cox's proportional hazard method. PMID:26434910

  15. Breast cancer among the oldest old: tumor characteristics, treatment choices, and survival.

    PubMed

    Schonberg, Mara A; Marcantonio, Edward R; Li, Donglin; Silliman, Rebecca A; Ngo, Long; McCarthy, Ellen P

    2010-04-20

    PURPOSE Few data are available on breast cancer characteristics, treatment, and survival for women age 80 years or older. PATIENTS AND METHODS We used the linked Surveillance, Epidemiology and End Results-Medicare data set from 1992 to 2003 to examine tumor characteristics, treatments (mastectomy, breast-conserving surgery [BCS] with radiation therapy or alone, or no surgery), and outcomes of women age 80 years or older (80 to 84, 85 to 89, > or = 90 years) with stage I/II breast cancer compared with younger women (age 67 to 79 years). We used Cox proportional hazard models to examine the impact of age on breast cancer-related and other causes of death. Analyses were performed within stage, adjusted for tumor and sociodemographic characteristics, treatments received, and comorbidities. Results In total, 49,616 women age 67 years or older with stage I/II disease were included. Tumor characteristics (grade, hormone receptivity) were similar across age groups. Treatment with BCS alone increased with age, especially after age 80. The risk of dying from breast cancer increased with age, significantly after age 80. For stage I disease, the adjusted hazard ratio of dying from breast cancer for women age > or = 90 years compared with women age 67 to 69 years was 2.6 (range, 2.0 to 3.4). Types of treatments received were significantly associated with age and comorbidity, with age as the stronger predictor (26% of women age > or = 80 years without comorbidity received BCS alone or no surgery compared with 6% of women age 67 to 79 years). CONCLUSION Women age > or = 80 years have breast cancer characteristics similar to those of younger women yet receive less aggressive treatment and experience higher mortality from early-stage breast cancer. Future studies should focus on identifying tumor and patient characteristics to help target treatments to the oldest women most likely to benefit.

  16. Clinical predictors of long-term survival in HER2-positive metastatic breast cancer.

    PubMed

    Murthy, Pooja; Kidwell, Kelley M; Schott, Anne F; Merajver, Sofia D; Griggs, Jennifer J; Smerage, Jeffrey D; Van Poznak, Catherine H; Wicha, Max S; Hayes, Daniel F; Henry, N Lynn

    2016-02-01

    Prior to availability of anti-HER2 therapies, HER2-positive metastatic breast cancer (MBC) was associated with a poor prognosis. Prospective randomized trials have demonstrated survival benefit from anti-HER2 treatments. Anecdotal observations have suggested that a small but meaningful fraction of patients with HER2-positive MBC may be "exceptional responders" with long survival. We hypothesized that demographic and/or clinicopathologic characteristics can be identified to distinguish short-term from long-term survivors. A retrospective, single-institution review of 168 patients with HER2-positive MBC who received treatment with anti-HER2 therapy in the metastatic setting was performed. Cox proportional hazards analysis was used to assess factors associated with long-term survival. Median overall survival from the time of breast cancer recurrence was 3.9 years (95 % CI 3.4-5.2). From the time of diagnosis of MBC, 56 (33 %) survived for 5 or more years and 12 (7 %) survived more than 10 years. Of the 66 patients diagnosed with central nervous system metastases, 9 (14 %) survived more than 5 years following that diagnosis. Younger age at diagnosis, lower stage, hormone receptor positive status, and only having one organ involved at diagnosis were associated with longer survival. Four patients discontinued anti-HER2 therapy and are without evidence of progression of disease after a median 7.4 years (0.2-12.0) since stopping therapy. In a cohort of patients with HER2-positive MBC treated primarily with trastuzumab and lapatinib, 7 % of patients were "exceptional responders." Combining these clinical factors with molecular determinants of prolonged survival may provide insights for individualizing treatment selection. PMID:26875184

  17. Neoadjuvant chemotherapy of breast cancer: tumor markers as predictors of pathologic response, recurrence, and survival.

    PubMed

    Precht, Lisa M; Lowe, Kimberly A; Atwood, Mary; Beatty, J David

    2010-01-01

    This study reports the value of the tumor markers estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) in predicting the response of breast cancer to neoadjuvant chemotherapy. A community cancer center prospectively maintained breast cancer database containing over 8,000 patient records was used. Since 1989, 464 patients were treated with neoadjuvant chemotherapy followed by surgical resection and were tested for ER and PR. Estrogen receptor and/or PR positive patients were considered hormone receptor (HR) positive. Human epidermal growth factor receptor 2 status was available on 368 patients. Total, breast, and nodal pathologic complete response (pCR) rates, recurrence, and overall survival were assessed. Total and breast pCR rates were higher in HR negative (HR-) patients (26% and 32%, respectively) than in HR positive (HR+) patients (4% and 7%, respectively; p < 0.001). Compared to HR+ patients, HR- patients had higher recurrence rates (38% versus 22%; p < 0.001), a shorter time to recurrence (1.28 versus 2.14 years; p < 0.001), and decreased overall survival (67% versus 81%; p < 0.001). Human epidermal growth factor receptor 2 positive patients treated with neoadjuvant trastuzumab (NAT) demonstrated higher total pCR (34% versus 13%; p = 0.008), breast pCR (37% versus 17%; p = 0.02), and nodal pCR rates (47% versus 23%; p = 0.05) compared to HER2+ patients not treated with NAT. Furthermore, HER2+ patients who received NAT had lower recurrence rates (5% versus 42%; p < 0.001) and increased overall survival (97% versus 68%; p < 0.001). In conclusion, breast cancer HR status is predictive of total and breast pCR rates after neoadjuvant chemotherapy. Although HR- patients derive greater benefit from neoadjuvant chemotherapy in terms of pathologic response, they have worse outcomes in terms of recurrence and survival. Hormone receptor positive patients demonstrate significantly less response to neoadjuvant

  18. Molecular phenotype is associated with survival in breast cancer patients with spinal bone metastases.

    PubMed

    Bollen, L; Wibmer, C; Wang, M; van der Linden, Y M; Leithner, A; Bünger, C E; Jensen, A B; Fiocco, M; Bratschitsch, G; Pondaag, W; Bovée, J V M G; Dijkstra, P D S

    2015-01-01

    To aid in therapy selection for patients with spinal bone metastases (SBM), predictive models have been developed. These models consider SBM from breast cancer a positive predictive factor, but do not take phenotypes based on estrogen (ER), progesterone (PR) and human epidermal growth factor 2 (HER2) receptors into account. The aim of this study was to ascertain whether receptors are associated with survival, when the disease has progressed up to SBM. All patients who were treated for SBM from breast cancer between 2005 and 2012 were included in this international multi-center retrospective study (n = 111). Reports were reviewed for ER, PR and HER2 status and subsequently subdivided into one of four categories; luminal A, luminal B, HER2 and triple negative. Survival time was calculated as the difference between start of treatment for SBM and date of death. Analysis was performed using the Kaplan-Meier method and log-rank tests. Median follow-up was 3.7 years. Survival times in the luminal B and HER2 categories were not significantly different to the luminal A category and were joined into a single receptor positive category. Eighty-five patients (77 %) had a receptor positive phenotype and 25 (23 %) had a triple negative phenotype. Median survival time was 22.5 months (95 %CI 18.0-26.9) for the receptor positive category and 6.7 months (95 %CI 2.4-10.9) for the triple negative category (p < 0.001). Patients with SBM from breast cancer with a triple negative phenotype have a shorter survival time than patients with a receptor positive phenotype. Models estimating survival should be adjusted accordingly. PMID:25359620

  19. Do signal transduction cascades influence survival in triple-negative breast cancer? A preliminary study

    PubMed Central

    Mumm, Jan-Niclas; Kölbl, Alexandra C; Jeschke, Udo; Andergassen, Ulrich

    2016-01-01

    Background Triple-negative breast cancer (TNBC) is a rather aggressive form of breast cancer, comprised by early metastasis formation and reduced overall survival of the affected patients. Steroid hormone receptors and the human epidermal growth factor receptor 2 are not overexpressed, limiting therapeutic options. Therefore, new treatment options have to be investigated. The aim of our preliminary study was to detect coherences between some molecules of intracellular signal transduction pathways and survival of patients with TNBC, in order to obtain some hints for new therapeutical solutions. Methods Thirty-one paraffin-embedded tumor tissue samples, which were determined to be negative for steroid hormone receptors as well as human epidermal growth factor receptor 2, were immunohistochemically stained for a number of signal transduction molecules from several signaling pathways. β-Catenin, HIF1α, MCL, Notch1, LRP6, XBP1, and FOXP3 were stained with specific antibodies, and their staining was correlated with patient survival by Kaplan–Meier analyses. Results Only two of the investigated molecules have shown correlation with overall survival. Cytoplasmic staining of HIF1α and centro-tumoral lymphocyte FOXP3 staining showed statistically significant correlations with survival. Conclusion The coherence of signal transduction molecules with survival of patients with TNBC is still controversially discussed in the literature. Our study comprises one more mosaic stone in the elucidation of these intracellular processes and their influences on patient outcome. Lots of research still has to be done in this field, but it would be worthwhile as it may offer new therapeutic targets for a group of patients with breast cancer, which is still hard to treat. PMID:27307757

  20. Infused Therapy and Survival in Older Patients Diagnosed with Metastatic Breast Cancer who Received Trastuzumab

    PubMed Central

    Griffiths, Robert I; Lalla, Deepa; Herbert, Robert J; Doan, Justin F; Brammer, Melissa G; Danese, Mark D

    2011-01-01

    We used Surveillance, Epidemiology, and End Results-Medicare data (2000-2006) to describe treatment and survival in women diagnosed with metastatic breast cancer (MBC) who received trastuzumab. There were 610 patients with a mean age of 74 years. Overall, 32% received trastuzumab alone and 47% received trastuzumab plus a taxane. In multivariate analysis, trastuzumab plus chemotherapy was associated with a lower adjusted cancer mortality rate (Hazard Ratio [HR] 0.54; 95% Confidence Interval [CI] 0.39-0.74; p < .001) than trastuzumab alone among patients who received trastuzumab as part of first-line therapy. Adding chemotherapy to first-line trastuzumab for metastatic breast cancer is associated with improved cancer survival. PMID:21929325

  1. Impact of a prior diagnosis of DCIS on survival from invasive breast cancer.

    PubMed

    Sopik, Victoria; Iqbal, Javaid; Sun, Ping; Narod, Steven A

    2016-07-01

    A diagnosis of invasive breast cancer after DCIS can be described as a new primary cancer or as a local invasive recurrence. It is of interest to determine if, among women with early-stage breast cancer, a past history of DCIS influences survival. We retrieved the records of 306,249 women diagnosed with stage I or stage II breast cancer between 2004 and 2012, in the surveillance, epidemiology, and end results registries database, of whom 5395 had a previous diagnosis of DCIS. For each patient, we extracted information on the year of diagnosis, age at diagnosis, tumor size, nodal status, grade, estrogen receptor status, type of surgery (lumpectomy/mastectomy), use of radiotherapy (no/yes), prior DCIS (no/yes), cause of death, and follow-up time. For each case with prior DCIS, we recorded information on the year of diagnosis of DCIS, laterality of DCIS, and treatments received for DCIS. We matched 3979 patients with a prior DCIS to 3979 patients without a prior DCIS, according to the various prognostic features of the invasive cancer. We estimated the risk of death from breast cancer for patients with invasive ductal carcinoma, with and without a prior diagnosis of DCIS. We identified 306,249 women with stage I/II breast cancer, of whom 2335 had a prior ipsilateral DCIS and 3060 had a prior contralateral DCIS. Breast cancer-specific survival at 9 years was 94.6 % for patients with a prior DCIS (ipsilateral or contralateral) and was 95.2 % for patients with no prior DCIS (p = 0.32). In a matched analysis (3979 matched pairs), the hazard ratio for death from breast cancer for patients with a prior ipsilateral DCIS, compared to patients with no prior DCIS, was 0.91 (95 % CI = 0.49-1.68; p = 0.75). A prior diagnosis of ipsilateral DCIS does not impact upon the prognosis of women with early-stage invasive breast cancer. This suggests that primary breast cancers and local invasive recurrences following DCIS are similar conditions and should be treated in the same

  2. FOXM1 targets XIAP and Survivin to modulate breast cancer survival and chemoresistance.

    PubMed

    Nestal de Moraes, Gabriela; Delbue, Deborah; Silva, Karina L; Robaina, Marcela Cristina; Khongkow, Pasarat; Gomes, Ana R; Zona, Stefania; Crocamo, Susanne; Mencalha, André Luiz; Magalhães, Lídia M; Lam, Eric W-F; Maia, Raquel C

    2015-12-01

    Drug resistance is a major hurdle for successful treatment of breast cancer, the leading cause of deaths in women throughout the world. The FOXM1 transcription factor is a potent oncogene that transcriptionally regulates a wide range of target genes involved in DNA repair, metastasis, cell invasion, and migration. However, little is known about the role of FOXM1 in cell survival and the gene targets involved. Here, we show that FOXM1-overexpressing breast cancer cells display an apoptosis-resistant phenotype, which associates with the upregulation of expression of XIAP and Survivin antiapoptotic genes. Conversely, FOXM1 knockdown results in XIAP and Survivin downregulation as well as decreased binding of FOXM1 to the promoter regions of XIAP and Survivin. Consistently, FOXM1, XIAP, and Survivin expression levels were higher in taxane and anthracycline-resistant cell lines when compared to their sensitive counterparts and could not be downregulated in response to drug treatment. In agreement with our in vitro findings, we found that FOXM1 expression is significantly associated with Survivin and XIAP expression in samples from patients with IIIa stage breast invasive ductal carcinoma. Importantly, patients co-expressing FOXM1, Survivin, and nuclear XIAP had significantly worst overall survival, further confirming the physiological relevance of the regulation of Survivin and XIAP by FOXM1. Together, these findings suggest that the overexpression of FOXM1, XIAP, and Survivin contributes to the development of drug-resistance and is associated with poor clinical outcome in breast cancer patients.

  3. Cellular growth and survival are mediated by beta 1 integrins in normal human breast epithelium but not in breast carcinoma

    SciTech Connect

    Howlett, Anthony R; Bailey, Nina; Damsky, Caroline; Petersen, Ole W; Bissell, Mina J

    1994-11-28

    We previously established a rapid three-dimensional assay for discrimination of normal and malignant human breast epithelial cells using a laminin-rich reconstituted basement membrane. In this assay, normal epithelial cells differentiate into well-organized acinar structures whereas tumor cells fail to recapitulate this process and produce large, disordered colonies. The data suggest that breast acinar morphogenesis and differentiation is regulated by cell-extracellular matrix (ECM) interactions and that these interactions are altered in malignancy. Here, we investigated the role of ECM receptors (integrins) in these processes and report on the expression and function of potential laminin receptors in normal and tumorigenic breast epithelial cells. Immmunocytochemical analysis showed that normal and carcinoma cells in a three-dimensional substratum express profiles of integrins similar to normal and malignant breast tissues in situ. Normal cells express {alpha}1, {alpha}2, {alpha}3, {alpha}6, {beta}1 and {beta}4 integrin subunits, whereas breast carcinoma cells show variable losses, disordered expression, or down regulation of these subunits. Function-blocking experiments using inhibitory antiintegrin subunit antibodies showed a >5-fold inhibition of the formation of acinar structures by normal cells in the presence of either anti-{beta}1 or anti-{alpha}3 antibodies, whereas anti-{alpha}2 or -{alpha}6 had little or no effect. In experiments where collagen type I gels were used instead of basement membrane, acinar morphogenesis was blocked by anti-{beta}1 and -{alpha}2 antibodies but not by anti-{alpha}3. These data suggest a specificity of integrin utilization dependent on the ECM ligands encountered by the cell. The interruption of normal acinar morphogenesis by anti-integrin antibodies was associated with an inhibition of cell growth and induction of apoptosis. Function-blocking antibodies had no inhibitory effect on the rate of tumor cell growth, survival or

  4. Transcriptome sequencing uncovers a three–long noncoding RNA signature in predicting breast cancer survival

    PubMed Central

    Guo, Wenna; Wang, Qiang; Zhan, Yueping; Chen, Xijia; Yu, Qi; Zhang, Jiawei; Wang, Yi; Xu, Xin-jian; Zhu, Liucun

    2016-01-01

    Long noncoding RNAs (lncRNAs) play a crucial role in tumorigenesis. The aim of this study is to identify lncRNA signature that can predict breast cancer patient survival. RNA expression data from 1064 patients were downloaded from The Cancer Genome Atlas project. Cox regression, Kaplan–Meier, and receiver operating characteristic (ROC) analyses were performed to construct a model for predicting the overall survival (OS) of patients and evaluate it. A model consisting of three lncRNA genes (CAT104, LINC01234, and STXBP5-AS1) was identified. The Kaplan–Meier analysis and ROC curves proved that the model could predict the prognostic survival with good sensitivity and specificity in both the validation set (AUC = 0.752, 95% confidence intervals (CI): 0.651–0.854) and the microarray dataset (AUC = 0.714, 95%CI: 0.615–0.814). Further study showed the three-lncRNA signature was not only pervasive in different breast cancer stages, subtypes and age groups, but also provides more accurate prognostic information than some widely known biomarkers. The results suggested that RNA-seq transcriptome profiling provides that the three-lncRNA signature is an independent prognostic biomarker, and have clinical significance. In addition, lncRNA, miRNA, and mRNA interaction network indicated lncRNAs may intervene in breast cancer pathogenesis by binding to miR-190b, acting as competing endogenous RNAs. PMID:27338266

  5. Application of Cox and Parametric Survival Models to Assess Social Determinants of Health Affecting Three-Year Survival of Breast Cancer Patients.

    PubMed

    Mohseny, Maryam; Amanpour, Farzaneh; Mosavi-Jarrahi, Alireza; Jafari, Hossein; Moradi-Joo, Mohammad; Davoudi Monfared, Esmat

    2016-01-01

    Breast cancer is one of the most common causes of cancer mortality in Iran. Social determinants of health are among the key factors affecting the pathogenesis of diseases. This cross-sectional study aimed to determine the social determinants of breast cancer survival time with parametric and semi-parametric regression models. It was conducted on male and female patients diagnosed with breast cancer presenting to the Cancer Research Center of Shohada-E-Tajrish Hospital from 2006 to 2010. The Cox proportional hazard model and parametric models including the Weibull, log normal and log-logistic models were applied to determine the social determinants of survival time of breast cancer patients. The Akaike information criterion (AIC) was used to assess the best fit. Statistical analysis was performed with STATA (version 11) software. This study was performed on 797 breast cancer patients, aged 25-93 years with a mean age of 54.7 (±11.9) years. In both semi-parametric and parametric models, the three-year survival was related to level of education and municipal district of residence (P<0.05). The AIC suggested that log normal distribution was the best fit for the three-year survival time of breast cancer patients. Social determinants of health such as level of education and municipal district of residence affect the survival of breast cancer cases. Future studies must focus on the effect of childhood social class on the survival times of cancers, which have hitherto only been paid limited attention. PMID:27165244

  6. Unilateral and Bilateral Breast Cancer in Women Surviving Pediatric Hodgkin's Disease

    SciTech Connect

    Basu, Swati K.; Schwartz, Cindy; Fisher, Susan G.; Hudson, Melissa M.; Tarbell, Nancy; Muhs, Ann; Marcus, Karen J.; Mendenhall, Nancy; Mauch, Peter; Kun, Larry E.; Constine, Louis S.

    2008-09-01

    Purpose: To define demographic and therapeutic associations with the risk of breast cancer in children treated for Hodgkin's disease (HD), particularly the frequency and interval to the development of contralateral breast cancer. Methods and Materials: All 398 female patients (<19 years) treated for HD in five institutions during the accrual period were evaluated. Mean follow-up was 16.9 years. The standardized incidence ratio (SIR) was calculated as the ratio of the observed number of cases to the expected number of cases, estimated using age-matched controls from the Surveillance, Epidemiology, and End Results database. Results: A total of 29 women developed breast cancer (25 invasive, 4 ductal carcinoma in situ; SIR, 37.25; 95% confidence interval, 24.96-53.64). Time to diagnosis was 9.4 to 36.1 years. Cumulative incidence was 24% at 30 years. Ten patients (34%) had bilateral disease (9 metachronous, 1 synchronous). The interval to contralateral breast cancer was 12 to 34 months. On univariate analysis, significant variables included stage of HD, mantle radiation dose, pelvic radiation (protective), and follow-up time. On multivariate analysis, early stage and older age at diagnosis of HD ({<=}12 vs. >12 years) were significant predictors of secondary breast cancer. Conclusions: Women surviving pediatric HD were found to have a 37-fold increase in the risk of breast cancer and a high likelihood of rapidly developing bilateral disease. Early-stage HD and age greater than 12 years at diagnosis of HD were independent risk factors. Higher radiation doses may augment risk, and pelvic radiation may be protective. Breast cancer screening methodology and frequency, plus the role of prophylaxis in patients with unilateral disease, require definition.

  7. African American Race is an Independent Risk Factor in Survival from Initially Diagnosed Localized Breast Cancer

    PubMed Central

    Wieder, Robert; Shafiq, Basit; Adam, Nabil

    2016-01-01

    BACKGROUND: African American race negatively impacts survival from localized breast cancer but co-variable factors confound the impact. METHODS: Data sets were analyzed from the Surveillance, Epidemiology and End Results (SEER) directories from 1973 to 2011 consisting of patients with designated diagnosis of breast adenocarcinoma, race as White or Caucasian, Black or African American, Asian, American Indian or Alaskan Native, Native Hawaiian or Pacific Islander, age, stage I, II or III, grade 1, 2 or 3, estrogen receptor or progesterone receptor positive or negative, marital status as single, married, separated, divorced or widowed and laterality as right or left. The Cox Proportional Hazards Regression model was used to determine hazard ratios for survival. Chi square test was applied to determine the interdependence of variables found significant in the multivariable Cox Proportional Hazards Regression analysis. Cells with stratified data of patients with identical characteristics except African American or Caucasian race were compared. RESULTS: Age, stage, grade, ER and PR status and marital status significantly co-varied with race and with each other. Stratifications by single co-variables demonstrated worse hazard ratios for survival for African Americans. Stratification by three and four co-variables demonstrated worse hazard ratios for survival for African Americans in most subgroupings with sufficient numbers of values. Differences in some subgroupings containing poor prognostic co-variables did not reach significance, suggesting that race effects may be partly overcome by additional poor prognostic indicators. CONCLUSIONS: African American race is a poor prognostic indicator for survival from breast cancer independent of 6 associated co-variables with prognostic significance.

  8. African American Race is an Independent Risk Factor in Survival from Initially Diagnosed Localized Breast Cancer

    PubMed Central

    Wieder, Robert; Shafiq, Basit; Adam, Nabil

    2016-01-01

    BACKGROUND: African American race negatively impacts survival from localized breast cancer but co-variable factors confound the impact. METHODS: Data sets were analyzed from the Surveillance, Epidemiology and End Results (SEER) directories from 1973 to 2011 consisting of patients with designated diagnosis of breast adenocarcinoma, race as White or Caucasian, Black or African American, Asian, American Indian or Alaskan Native, Native Hawaiian or Pacific Islander, age, stage I, II or III, grade 1, 2 or 3, estrogen receptor or progesterone receptor positive or negative, marital status as single, married, separated, divorced or widowed and laterality as right or left. The Cox Proportional Hazards Regression model was used to determine hazard ratios for survival. Chi square test was applied to determine the interdependence of variables found significant in the multivariable Cox Proportional Hazards Regression analysis. Cells with stratified data of patients with identical characteristics except African American or Caucasian race were compared. RESULTS: Age, stage, grade, ER and PR status and marital status significantly co-varied with race and with each other. Stratifications by single co-variables demonstrated worse hazard ratios for survival for African Americans. Stratification by three and four co-variables demonstrated worse hazard ratios for survival for African Americans in most subgroupings with sufficient numbers of values. Differences in some subgroupings containing poor prognostic co-variables did not reach significance, suggesting that race effects may be partly overcome by additional poor prognostic indicators. CONCLUSIONS: African American race is a poor prognostic indicator for survival from breast cancer independent of 6 associated co-variables with prognostic significance. PMID:27698895

  9. Survival of patients with metastatic breast cancer: a single-centre experience.

    PubMed

    D'hondt, R; Spoormans, I; Neyens, N; Mortier, N; Van Aelst, F

    2014-06-01

    Metastatic breast cancer (MBC) remains an incurable disease, despite major advances in the treatment in the past 10-12 years. Data on real life overall survival in a non-selected group containing all metastatic breast cancer patients are hard to find in the literature, as is the correlation of their survival with prognostic factors and treatment. This article provides overall survival data for all patients treated for MBC in a single-centre non-academic hospital. Survival data have been correlated with frequently used prognostic factors (subtype, age at diagnosis, M-status at diagnosis, metastases-free interval, and grade). It also gives an insight in the treatments given to and response rates in this population of MBC patients without selection bias representing the real life situation. A total of 169 patients were analysed. Mean survival from metastases is 31·8 months. Overall survival is better for the luminal subtypes, for younger age, for patients with a longer metastases-free interval, and for a lower grade. A small difference in survival has been seen in favour of the patients who represent immediately with metastases. With a larger sample size, we expect these factors to be prognostic significant. The luminal subtypes have a clear predisposition to metastasize in the bone, whereas visceral metastases occur more frequently and earlier in the hormone receptor-negative tumours. Brain metastases do occur in about half of the triple negative tumours and Her2/neu-positive tumours. Overall response rate to first-line chemotherapy was 56% in consecutive lines of treatment, a continuous clinical benefit exceeding 50% when selecting fit patients. This article represents a unique and valuable description of medical oncologists' real-life daily practice in MBC patients, with a clinical outcome that certainly compares to the sparse data provided in the literature. PMID:24641516

  10. Predicting response and survival in chemotherapy-treated triple-negative breast cancer

    PubMed Central

    Prat, A; Lluch, A; Albanell, J; Barry, W T; Fan, C; Chacón, J I; Parker, J S; Calvo, L; Plazaola, A; Arcusa, A; Seguí-Palmer, M A; Burgues, O; Ribelles, N; Rodriguez-Lescure, A; Guerrero, A; Ruiz-Borrego, M; Munarriz, B; López, J A; Adamo, B; Cheang, M C U; Li, Y; Hu, Z; Gulley, M L; Vidal, M J; Pitcher, B N; Liu, M C; Citron, M L; Ellis, M J; Mardis, E; Vickery, T; Hudis, C A; Winer, E P; Carey, L A; Caballero, R; Carrasco, E; Martín, M; Perou, C M; Alba, E

    2014-01-01

    Background: In this study, we evaluated the ability of gene expression profiles to predict chemotherapy response and survival in triple-negative breast cancer (TNBC). Methods: Gene expression and clinical–pathological data were evaluated in five independent cohorts, including three randomised clinical trials for a total of 1055 patients with TNBC, basal-like disease (BLBC) or both. Previously defined intrinsic molecular subtype and a proliferation signature were determined and tested. Each signature was tested using multivariable logistic regression models (for pCR (pathological complete response)) and Cox models (for survival). Within TNBC, interactions between each signature and the basal-like subtype (vs other subtypes) for predicting either pCR or survival were investigated. Results: Within TNBC, all intrinsic subtypes were identified but BLBC predominated (55–81%). Significant associations between genomic signatures and response and survival after chemotherapy were only identified within BLBC and not within TNBC as a whole. In particular, high expression of a previously identified proliferation signature, or low expression of the luminal A signature, was found independently associated with pCR and improved survival following chemotherapy across different cohorts. Significant interaction tests were only obtained between each signature and the BLBC subtype for prediction of chemotherapy response or survival. Conclusions: The proliferation signature predicts response and improved survival after chemotherapy, but only within BLBC. This highlights the clinical implications of TNBC heterogeneity, and suggests that future clinical trials focused on this phenotypic subtype should consider stratifying patients as having BLBC or not. PMID:25101563

  11. μ-Opioid Receptor Gene A118G Polymorphism Predicts Survival in Patients with Breast Cancer

    PubMed Central

    Bortsov, Andrey V.; Millikan, Robert C.; Belfer, Inna; Boortz-Marx, Richard L.; Arora, Harendra; McLean, Samuel A.

    2012-01-01

    Background Preclinical studies suggest that opioids may promote tumor growth. Genetic polymorphisms have been shown to affect opioid receptor function and to modify the clinical effects of morphine. In this study we assessed the association between six common polymorphisms in the μ-opioid receptor gene, including the well known A118G polymorphism, and breast cancer survival. Methods A total of 2,039 women ages 23–74 yr (38% African American, 62% European American, 55% postmenopausal) diagnosed with breast cancer between 1993 – 2001 were followed through 2006. Genotyping was performed using the TaqMan platform (Applied Biosystems Inc., Foster City, CA). Kaplan-Meyer curves, log-rank tests, and Cox proportional hazard models were used to examine the association between each genotype and survival. Results After Bonferroni adjustment for multiple testing, patient genotype at A118G was associated with breast cancer-specific mortality at 10 yr. Women with one or more copies of the G allele had decreased breast cancer-specific mortality (p < .001). This association was limited to invasive cases only; effect size appeared to increase with clinical stage. Cox regression model adjusted for age and ethnicity also showed decreased mortality in A/G and G/G genotypes compared to A/A genotype (hazard ratio = 0.57 [0.38, 0.85] and 0.32 [0.22, 0.49], respectively; p = .006). Conclusions These results suggest that opioid pathways may be involved in tumor growth. Further studies examining the association between genetic variants influencing opioid system function and cancer survival are warranted. PMID:22433205

  12. Survival and disease-free benefits with mastectomy versus breast conservation therapy for early breast cancer: a meta-analysis.

    PubMed

    Chen, Yan; Jiang, Lei; Gao, Bo; Cheng, Zhi-Yuan; Jin, Jiaxin; Yang, Ke-Hu

    2016-06-01

    The objective of the present meta-analysis was to estimate the magnitude of survival and disease-free benefits from mastectomy compared with breast conservation therapy (BCT) in patients with early breast cancer. We searched PubMed, Embase, the Cochrane Library, Web of Science, and Chinese biomedical literature database from their inception to May 2015. All the data were independently extracted from the publications by two reviewers. Results regarding the overall survival (OS) and disease-free survival (DFS) in the meta-analysis were expressed as hazard ratios (HRs) with 95 % confidence intervals (CIs). Nine randomized control trials were eligible for final meta-analysis. Meta-analysis showed that mastectomy provided significant benefit in OS compared with BCT (HR 1.09, 95 % CI 1.01-1.19; P = 0.03). Sensitivity analysis gives similar OS estimates (HR 1.12, 95 % CI 1.01-1.25). In the subgroup analysis of patients according to tumor size, the pooled HRs for OS indicated that there is a borderline statistical difference between two arms in the subgroup with tumor size ranging between ≥2 cm and <5 cm (HR 1.09, 95 % CI 1.00-1.19), but subgroup analysis of tumor size <2 cm showed no statistically significant difference in OS (HR 1.08, 95 % CI 0.88-1.33) when comparing the BCT arm with the mastectomy arm. There was no significant difference in DFS between BCT and mastectomy groups (HR 1.08, 95 % CI 0.99-1.18; P = 0.08). Sensitivity analysis also gives similar DFS estimates (HR 1.11, 95 % CI 0.96-1.27). Subgroup analysis indicated that the pooled HRs for DFS did not favor mastectomy arm or BCT arm either in the subgroup with tumor size <2 cm (HR 1.09, 95 % CI 0.78-1.52) or in the subgroup with tumor size ranging between ≥2 cm and <5 cm (HR 1.08, 95 % CI 0.99-1.18) according to tumor size. Five-year OS decreased from 70 to 68 % with BCT. The present meta-analysis indicated that mastectomy might provide slight OS benefit compared with BCT in early

  13. Spatially Varying Coefficient Inequalities: Evaluating How the Impact of Patient Characteristics on Breast Cancer Survival Varies by Location

    PubMed Central

    Hsieh, Jeff Ching-Fu; Cramb, Susanna M.; McGree, James M.; Dunn, Nathan A. M.; Baade, Peter D.; Mengersen, Kerrie L.

    2016-01-01

    An increasing number of studies have identified spatial differences in breast cancer survival. However little is known about whether the structure and dynamics of this spatial inequality are consistent across a region. This study aims to evaluate the spatially varying nature of predictors of spatial inequality in relative survival for women diagnosed with breast cancer across Queensland, Australia. All Queensland women aged less than 90 years diagnosed with invasive breast cancer from 1997 to 2007 and followed up to the end of 2008 were extracted from linked Queensland Cancer Registry and BreastScreen Queensland data. Bayesian relative survival models were fitted using various model structures (a spatial regression model, a varying coefficient model and a finite mixture of regressions model) to evaluate the relative excess risk of breast cancer, with the use of Markov chain Monte Carlo computation. The spatially varying coefficient models revealed that some covariate effects may not be constant across the geographic regions of the study. The overall spatial patterns showed lower survival among women living in more remote areas, and higher survival among the urbanised south-east corner. Notwithstanding this, the spatial survival pattern for younger women contrasted with that for older women as well as single women. This complex spatial interplay may be indicative of different factors impacting on survival patterns for these women. PMID:27149274

  14. RACIAL DISPARITIES IN BREAST CANCER SURVIVAL: AN ANALYSIS BY AGE AND STAGE

    PubMed Central

    Deshpande, Anjali D.; Jeffe, Donna B.; Gnerlich, Jennifer; Iqbal, Ayesha Z.; Thummalakunta, Abhishek; Margenthaler, Julie A.

    2011-01-01

    Background Black women often present with advanced-stage breast cancer compared with White women, which may result in the observed higher mortality among Black women. Age-related factors (e.g., comorbidity) also affect mortality. Whether racial disparities in mortality are evident within age and/or stage groups has not been reported, and risk factors for greater mortality among Black women are not well defined. Methods Using the 1988–2003 Surveillance, Epidemiology, and End Results (SEER) Program data, we conducted a retrospective, population-based cohort study to compare overall and stage-specific breast-cancer mortality between Black and White women within each age (<40, 40–49, 50–64, and 65+) and stage (stage 0–IV and unstaged) group at diagnosis. Cox regression models calculated unadjusted and adjusted hazard ratios (HR) and 95% confidence intervals (CI), the latter controlling for potential confounders of the relationship between race and survival. Results In the 1988–2003 SEER data, 20,424 Black and 204,506 White women were diagnosed with first primary breast cancer. In unadjusted models, Black women were more likely than White women to die from breast cancer (HR: 1.90, 95% CI: 1.83–1.96) and from all causes (HR: 1.52, 95% CI: 1.48–1.55) during follow-up. In models stratified by age and stage, Black women were at increased risk of breast-cancer-specific mortality within each stage group among women <65 years. Conclusion Racial disparities in breast-cancer-specific mortality were predominantly observed within each stage at diagnosis among women <65 years old. This greater mortality risk for Black women was largely not observed among women ≥65 years of age. PMID:19084242

  15. Genetic variants in the vitamin D pathway and breast cancer disease-free survival

    PubMed Central

    Brewster, Abenaa M.

    2013-01-01

    Epidemiological studies have investigated the association between vitamin D pathway genes and breast cancer risk; however, little is known about the association between vitamin D pathway genes and breast cancer prognosis. In a retrospective cohort of 1029 patients with early-stage breast cancer, we analyzed the association between 106 tagging single nucleotide polymorphisms (SNPs) in eight vitamin D pathway genes and breast cancer disease-free survival (DFS) using Cox regression analysis adjusted for known prognostic variables. Using a false discovery rate of 10%, six intronic SNPs were significantly associated with poorer DFS: retinoid-X receptor alpha (RXRA) SNPs (rs881658, rs11185659, rs10881583, rs881657 and rs7864987) and plasminogen activator and urokinase receptor (PLAUR) SNP (rs4251864). Treatment received (no systemic therapy, hormone therapy alone or chemotherapy) was an effect modifier of the RXRA SNPs association with DFS (P < 0.05); therefore, we stratified further analysis by treatment group. Among patients who did not receive systemic therapy, RXRA SNP [rs10881583 (P = 0.02)] was associated with poorer DFS, and among patients who received chemotherapy, RXRA SNPs (rs881658, rs11185659, rs10881583, rs881657 and rs7864987) were associated with poorer DFS (P < 0.001 for all SNPs). However, RXRA SNPs: rs10881583 (P < 0.001) and rs881657 (P = 0.02) were associated with improved DFS in patients treated with hormone therapy alone. Our results suggest that SNPs in the RXRA and PLAUR genes in the vitamin D pathway may contribute to breast cancer DFS. In particular, SNPs in RXRA may predict for poorer or improved DFS in patients, according to type of systemic treatment received. If validated, these markers could be used for risk stratification of breast cancer patients. PMID:23180655

  16. Population-based survival-cure analysis of ER-negative breast cancer.

    PubMed

    Huang, Lan; Johnson, Karen A; Mariotto, Angela B; Dignam, James J; Feuer, Eric J

    2010-08-01

    This study investigated the trends over time in age and stage specific population-based survival of estrogen receptor negative (ER-) breast cancer patients by examining the fraction of cured patients and the median survival time for uncured patients. Cause-specific survival data from the Surveillance, Epidemiology, and End Results program for cases diagnosed during 1992-1998 were used in mixed survival cure models to evaluate the cure fraction and the extension in survival for uncured patients. Survival trends were compared with adjuvant chemotherapy data available from an overlapping patterns-of-care study. For stage II N+ disease, the largest increase in cure fraction was 44-60% (P = 0.0257) for women aged >or=70 in contrast to a 7-8% point increase for women aged <50 or 50-69 (P = 0.056 and 0.038, respectively). For women with stage III disease, the increases in the cure fraction were not statistically significant, although women aged 50-69 had a 10% point increase (P = 0.103). Increases in cure fraction correspond with increases in the use of adjuvant chemotherapy, particularly for the oldest age group. In this article, for the first time, we estimate the cure fraction for ER- patients. We notice that at age >o5r=70, the accelerated increase in cure fraction from 1992 to 1998 for women with stage II N+ compared with stage III suggests a selective benefit for chemotherapy in the lower stage group.

  17. Breast cancer survival is associated with telomere length in peripheral blood cells.

    PubMed

    Svenson, Ulrika; Nordfjäll, Katarina; Stegmayr, Birgitta; Manjer, Jonas; Nilsson, Peter; Tavelin, Björn; Henriksson, Roger; Lenner, Per; Roos, Göran

    2008-05-15

    Telomeres are essential for maintaining chromosomal stability. Previous studies have indicated that individuals with shorter blood telomeres may be at higher risk of developing various types of cancer, such as in lung, bladder, and kidney. We have analyzed relative telomere length (RTL) of peripheral blood cells in relation to breast cancer incidence and prognosis. The study included 265 newly diagnosed breast cancer patients and 446 female controls. RTL was measured by real-time PCR, and our results show that the patient group displayed significantly longer telomeres compared with controls (P < 0.001). Age-adjusted odds ratios (OR) for breast cancer risk increased with increasing telomere length, with a maximal OR of 5.17 [95% confidence interval (95% CI), 3.09-8.64] for the quartile with the longest telomeres. Furthermore, RTL carried prognostic information for patients with advanced disease. Node positive (N+) patients with short telomeres (survival compared with N+ patients with long telomeres (P = 0.001). For patients with ages <50 years with tumors >16 mm (median tumor diameter), short telomeres were associated with a significantly better outcome than longer telomeres (P = 0.006). Cox regression analysis showed that long RTL was a significant independent negative prognostic factor (hazards ratio, 2.92; 95% CI, 1.33-6.39; P = 0.007). Our results indicate that blood RTL may serve as a prognostic indicator in breast cancer patients with advanced disease.

  18. Selective Estrogen Receptor Modulator-Associated Nonalcoholic Fatty Liver Disease Improved Survival in Patients With Breast Cancer: A Retrospective Cohort Analysis.

    PubMed

    Zheng, Qiufan; Xu, Fei; Nie, Man; Xia, Wen; Qin, Tao; Qin, Ge; An, Xin; Xue, Cong; Peng, Roujun; Yuan, Zhongyu; Shi, Yanxia; Wang, Shusen

    2015-10-01

    Selective estrogen receptor modulator (SERM)-associated nonalcoholic fatty liver disease (NAFLD) might be related to treatment efficacy in patients with breast cancer because of circulating estrogen antagonism. The aim of the study was to investigate the relationship between NAFLD and survival outcomes in patients with breast cancer who were treated with tamoxifen or toremifene. This single-center, retrospective, cohort study included 785 eligible patients who received tamoxifen or toremifene, after curative resection for breast cancer, at the Sun Yat-sen University Cancer Center between January 2005 and December 2009. Data were extracted from patient medical records. All patients underwent abdominal ultrasonography, at least once, at baseline and at the annual follow-up. Patients who were diagnosed with NAFLD on ultrasonography were classified into the NAFLD or the non-NAFLD arm at the 3-year follow-up visit. Univariate and multivariate Cox regression analyses were conducted to evaluate any associations between NAFLD and disease-free survival (DFS) or overall survival (OS). One hundred fifty-eight patients were diagnosed with NAFLD. Patients who developed NAFLD had better DFS and OS compared with those who did not. Univariate analyses revealed that the 5-year DFS rates were 91.56% and 85.01% for the NAFLD and non-NAFLD arms, respectively (hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.37-0.96; log-rank P = 0.032). The 5-year OS rates were 96.64% and 93.31% for the NAFLD and non-NAFLD arms, respectively (HR, 0.39; 95% CI, 0.16-0.99; log-rank P = 0.039). Multivariate analysis revealed that NAFLD was an independent prognostic factor for DFS, improving the DFS rate by 41% compared with that in the non-NAFLD arm (HR, 0.59; 95% CI, 0.36-0.96; P = 0.033). SERM-associated NAFLD was independently associated with improved DFS and might be useful for predicting treatment responses in breast cancer patients treated with SERMs. PMID:26448028

  19. The Extent of Axillary Surgery Is Associated With Breast Cancer-specific Survival in T1-2 Breast Cancer Patients With 1 or 2 Positive Lymph Nodes: A SEER-Population Study.

    PubMed

    Li, Shunrong; Liu, Fengtao; Chen, Kai; Rao, Nanyan; Xie, Yufen; Su, Fengxi; Zhu, Liling

    2016-04-01

    This study aimed to compare the breast cancer-specific survival (BCSS) of a nonclinical trial population of T1-2 breast cancer patients with 1 to 2 positive lymph nodes who received breast-conserving surgery and either sentinel lymph node biopsy (SLNB) or axillary lymph node dissection (ALND).We used the Surveillance, Epidemiology and End Results (SEER) database to identify 17,028 patients with a median follow-up of 7.1 years. We assigned the patients into a SLNB-cohort (≤5 nodes) and an ALND-cohort (>5 nodes) based on the number of removed lymph nodes. We used Kaplan-Meier analysis to estimate the cumulative BCSS and used Cox-regression analysis to study the risk factors. We also performed subgroup analysis by the patients' age and hormonal receptor (HR) status.The cumulative BCSS and Overall Survival (OS) of the entire population were 94.4% and 91.4% at 5 years and 88.2% and 79.9% at 10 years, respectively. Axillary surgery (ALND vs SLNB) had no association with BCSS when adjusted for stage, HR status, tumor grade, or other factors. In subgroup analysis by age and HR status, ALND was associated with a significantly improved BCSS relative to SNLB (HR = 0.70, HR = 0.026, 95% confidence interval 0.51-0.96) only in patients younger than 50 years with HR- disease (N = 1281), but not in other subgroup of patients.In early-stage breast cancer patients with limited lymph node metastasis, ALND had better BCSS than SLNB only in patients younger than 50 years and with HR- disease. More studies are needed to confirm our findings. PMID:27057872

  20. Differences in Breast Cancer Survival between Public and Private Care in New Zealand: Which Factors Contribute?

    PubMed Central

    Tin Tin, Sandar; Elwood, J. Mark; Lawrenson, Ross; Campbell, Ian; Harvey, Vernon; Seneviratne, Sanjeewa

    2016-01-01

    Background Patients who received private health care appear to have better survival from breast cancer compared to those who received public care. This study investigated if this applied to New Zealand women and identified factors that could explain such disparities. Methods This study involved all women who were diagnosed with primary breast cancer in two health regions in New Zealand, covering about 40% of the national population, between June 2000 and May 2013. Patients who received public care for primary treatment, mostly surgical treatment, were compared with those who received private care in terms of demographics, mode of presentation, disease factors, comorbidity index and treatment factors. Cox regression modelling was performed with stepwise adjustments, and hazards of breast cancer specific mortality associated with the type of health care received was assessed. Results Of the 14,468 patients, 8,916 (61.6%) received public care. Compared to patients treated in private care facilities, they were older, more likely to be Māori, Pacifika or Asian and to reside in deprived neighbourhoods and rural areas, and less likely to be diagnosed with early staged cancer and to receive timely cancer treatments. They had a higher risk of mortality from breast cancer (hazard ratio: 1.95; 95% CI: 1.75, 2.17), of which 80% (95% CI: 63%, 100%) was explained by baseline differences, particularly related to ethnicity, stage at diagnosis and type of loco-regional therapy. After controlling for these demographic, disease and treatment factors, the risk of mortality was still 14% higher in the public sector patients. Conclusions Ethnicity, stage at diagnosis and type of loco-regional therapy were the three key contributors to survival disparities between patients treated in public and private health care facilities in New Zealand. The findings underscore the need for more efforts to improve the quality, timeliness and equitability of public cancer care services. PMID:27054698

  1. Hedgehog Related Protein Expression in Breast Cancer: Gli-2 Is Associated with Poor Overall Survival

    PubMed Central

    Im, Soyoung; Yoo, Changyoung; Jung, Ji-Han; Jeon, Ye-Won; Suh, Young Jin; Kang, Chang Suk

    2013-01-01

    Background The hedgehog (Hh) signaling pathway is known to play a critical role in various malignancies, but its clinicopathologic role in breast cancer is yet to be established. Methods Tissue microarray blocks from 334 cases of breast cancer were prepared. The expression of six Hh signaling proteins including sonic hedgehog (Shh), patched (Ptch), smoothened (Smo), and the glioma-associated oncogene (Gli)-1, Gli-2, and Gli-3 were analyzed immunohistochemically. Results The expression of Hh signaling proteins was significantly correlated with some prognostic factors including the correlation of lymph node metastasis with the expression of Shh (p=0.001) and Ptch (p=0.064), the correlation of the stages with Shh and Gli-3 expression (p=0.007 and p=0.024, respectively), the correlation of the nuclear grade with the Smo (p=0.004) and Gli-3 (p=0.000), and the correlation of the histologic grade with the Ptch (p=0.016), Smo (p=0.007), and Gli-3 (p=0.000). The Shh, Ptch, Smo, Gli-1, and Gli-2 expression was significantly different between the phenotypes (p=0.000, p=0.001, p=0.004, p=0.039, and p=0.031, respectively). Gli-2 expression was correlated with a worse overall survival outcome (p=0.012). Conclusions Hh pathway activation is correlated with a more aggressive clinical behavior in breast carcinomas. The comparison of phenotypes suggested that the Hh pathway may be a useful therapeutic target for breast carcinoma. Patients with Gli-2 expression had a significantly lower overall survival rate and, therefore, it showed promise as a prognostic marker. PMID:23667370

  2. The BMP inhibitor DAND5 in serum predicts poor survival in breast cancer

    PubMed Central

    Huang, Sheng; Huang, Naisi; Li, Shan; Shao, Zhiming; Wu, Jiong

    2016-01-01

    Background & Aims Breast cancer (BC) is prevalent worldwide malignant cancer. Improvements in timely and effective diagnosis and prediction are needed. As reported, secreted DAND5 is contributed to BC metastasis. We aim to assess whether DAND5 in peripheral blood serum could determine BC-specific mortality. Methods We used immunohistochemistry staining to detect DAND5 expression in our BC tissue array including 250 samples. Angiogenesis assay and xenograft mice model were used to examine the secreted DAND5 function in BC progression. Serum concentration of DAND5 was examined by ELISA in 1730 BC patients. Kaplan-Meier and adjusted Cox proportional hazards models were utilized to analyze the prognosis and survival of BC patients. Results Tissue array results showed that positive DAND5 staining cases displayed a higher likelihood of occurrence of disease events (HR=5.494; 95% CI: 1.008-2.353; P=0.048) in univariate analysis and remained the same trend in multivariate analysis (HR=2.537; 95% CI: 1.056-6.096; P=0.037). DAND5 positive patients exerted generally poor DFS (P=0.041) in the Kaplan-Meier survival analysis. Furthermore, secreted DAND5 promoted tumor growth and angiogenesis in vitro and in vivo. In addition, positive DAND5 in BC patients serum was associated with increased risk of disease events occurrence (univariate: HR=1.58; 95% CI: 1.206-2.070; P=0.001; multivariate: HR=1.4; 95% CI: 1.003-1.954; P=0.048) in univariate and multivariate survival analysis. In the Kaplan-Meier analysis, serum DAND5 positively correlated with poor DFS (P=0.001) and DDFS (P=0.002). Conclusions DAND5 was correlated with poor survival and could serve as an easily detectable serum biomarker to predict the survival of breast cancer. PMID:26908452

  3. Delay in initiating adjuvant radiotherapy following breast conservation surgery and its impact on survival

    SciTech Connect

    Hershman, Dawn L. . E-mail: dlh23@columbia.edu; Wang Xiaoyan; McBride, Russell

    2006-08-01

    Purpose: Delays in the diagnosis of breast cancer are associated with advanced stage and poor survival, but the importance of the time interval between lumpectomy and initiation of radiation therapy (RT) has not been well studied. We investigated factors that influence the time interval between lumpectomy and RT, and the association between that interval and survival. Patients and Methods: We used data from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database on women aged 65 years and older, diagnosed with Stages I-II breast cancer, between 1991 and 1999. Among patients who did not receive chemotherapy, we studied factors associated with the time interval between lumpectomy and the initiation of RT, and the association of delay with survival, using linear regression and Cox proportional hazards modeling. Results: Among 24,833 women with who underwent lumpectomy, 13,907 (56%) underwent RT. Among those receiving RT, 97% started treatment within 3 months; older age, black race, advanced stage, more comorbidities, and being unmarried were associated with longer time intervals between surgery and RT. There was no benefit to earlier initiation of RT; however, delays >3 months were associated with higher overall mortality (hazard ratio, 1.92; 95% confidence interval, 1.64-2.24) and cancer-specific mortality (hazard ratio, 3.84; 95% confidence interval 3.01-4.91). Conclusions: Reassuringly, early initiation of RT was not associated with survival. Although delays of >3 months are uncommon, they are associated with poor survival. Whether this association is causal or due to confounding factors, such as poor health behaviors, is unknown; until it is better understood, efforts should be made to initiate RT in a timely fashion.

  4. CIB1 depletion impairs cell survival and tumor growth in triple-negative breast cancer

    PubMed Central

    Black, Justin L.; Harrell, J. Chuck; Leisner, Tina M.; Fellmeth, Melissa J.; George, Samuel D.; Reinhold, Dominik; Baker, Nicole M.; Jones, Corbin D.; Der, Channing J.; Perou, Charles M.

    2015-01-01

    Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype with generally poor prognosis and no available targeted therapies, highlighting a critical unmet need to identify and characterize novel therapeutic targets. We previously demonstrated that CIB1 is necessary for cancer cell survival and proliferation via regulation of two oncogenic signaling pathways, RAF–MEK–ERK and PI3K–AKT. Because these pathways are often upregulated in TNBC, we hypothesized that CIB1 may play a broader role in TNBC cell survival and tumor growth. Methods utilized include inducible RNAi depletion of CIB1 in vitro and in vivo, immunoblotting, clonogenic assay, flow cytometry, RNA-sequencing, bioinformatics analysis, and Kaplan–Meier survival analysis. CIB1 depletion resulted in significant cell death in 8 of 11 TNBC cell lines tested. Analysis of components related to PI3K–AKT and RAF–MEK–ERK signaling revealed that elevated AKT activation status and low PTEN expression were key predictors of sensitivity to CIB1 depletion. Furthermore, CIB1 knockdown caused dramatic shrinkage of MDA-MB-468 xenograft tumors in vivo. RNA sequence analysis also showed that CIB1 depletion in TNBC cells activates gene programs associated with decreased proliferation and increased cell death. CIB1 expression levels per se did not predict TNBC susceptibility to CIB1 depletion, and CIB1 mRNA expression levels did not associate with TNBC patient survival. Our data are consistent with the emerging theory of non-oncogene addiction, where a large subset of TNBCs depend on CIB1 for cell survival and tumor growth, independent of CIB1 expression levels. Our data establish CIB1 as a novel therapeutic target for TNBC. PMID:26105795

  5. Association of germline microRNA SNPs in pre-miRNA flanking region and breast cancer risk and survival: the Carolina Breast Cancer Study

    PubMed Central

    Bensen, Jeannette T.; Tse, Chiu Kit; Nyante, Sarah J.; Barnholtz-Sloan, Jill S.; Cole, Stephen R.; Millikan, Robert C.

    2013-01-01

    Purpose Common germline variation in the 5′ region proximal to precursor (pre-) miRNA gene sequences is evaluated for association with breast cancer risk and survival among African Americans and Caucasians. Methods We genotyped 9 single nucleotide polymorphisms (SNPs) within 6 miRNA gene regions previously associated with breast cancer, in 1972 cases and 1776 controls. In a race-stratified analysis using unconditional logistic regression, odds ratios (OR) and 95% confidence intervals (CI) were calculated to evaluate SNP association with breast cancer risk. Additionally, hazard ratios (HR) for breast cancer-specific mortality were estimated. Results 2 miR-185 SNPs provided suggestive evidence of an inverse association with breast cancer risk (rs2008591, OR = 0.72 (95% CI = 0.53 – 0.98, p-value = 0.04) and rs887205, OR = 0.71 (95% CI = 0.52 – 0.96, p-value = 0.03), respectively) among African Americans. Two SNPs, miR-34b/34c (rs4938723, HR = 0.57 (95% CI = 0.37 – 0.89, p-value = 0.01)) and miR-206 (rs6920648, HR = 0.77 (95% CI = 0.61 – 0.97, p-value = 0.02)), provided evidence of association with breast cancer survival. Further adjustment for stage resulted in more modest associations with survival (HR = 0.65 (95% CI = 0.42 – 1.02, p-value = 0.06 and HR = 0.79 (95% CI = 0.62 – 1.00, p-value = 0.05, respectively). Conclusions Our results suggest that germline variation in the 5' region proximal to pre-miRNA gene sequences may be associated with breast cancer risk among African Americans and breast cancer-specific survival generally, however further validation is needed to confirm these findings. PMID:23526039

  6. Survival of women with inflammatory breast cancer: a large population-based study†

    PubMed Central

    Dawood, S.; Lei, X.; Dent, R.; Gupta, S.; Sirohi, B.; Cortes, J.; Cristofanilli, M.; Buchholz, T.; Gonzalez-Angulo, A. M.

    2014-01-01

    Background Our group has previously reported that women with inflammatory breast cancer (IBC) continue to have worse outcome compared with those with non-IBC. We undertook this population-based study to see if there have been improvements in survival among women with stage III IBC, over time. Patient and methods We searched the Surveillance, Epidemiology and End Results Registry to identify female patients diagnosed with stage III IBC between 1990 and 2010. Patients were divided into four groups according to year of diagnosis: 1990–1995, 1996–2000, 2001–2005, and 2006–2010. Breast cancer-specific survival (BCSS) was estimated using the Kaplan–Meier method and compared across groups using the log-rank test. Cox models were then fit to determine the association of year of diagnosis and BCSS after adjusting for patient and tumor characteristics. Results A total of 7679 patients with IBC were identified of whom 1084 patients (14.1%) were diagnosed between 1990 and 1995, 1614 patients (21.0%) between 1996 and 2000, 2683 patients (34.9%) between 2001 and 2005, and 2298 patients (29.9%) between 2006 and 2010. The 2-year BCSS for the whole cohort was 71%. Two-year BCSS were 62%, 67%, 72%, and 76% for patients diagnosed between 1990–1995, 1996–2000, 2001–2005, and 2006–2010, respectively (P < 0.0001). In the multivariable analysis, increasing year of diagnosis (modeled as a continuous variable) was associated with decreasing risks of death from breast cancer (HR = 0.98, 95% confidence interval 0.97–0.99, P < 0.0001). Conclusion There has been a significant improvement in survival of patients diagnosed with IBC over a two-decade time span in this large population-based study. This suggests that therapeutic strategies researched and evolved in the context of non-IBC have also had a positive impact in women with IBC. PMID:24669011

  7. Group X secreted phospholipase A2 induces lipid droplet formation and prolongs breast cancer cell survival

    PubMed Central

    2013-01-01

    Background Alterations in lipid metabolism are inherent to the metabolic transformations that support tumorigenesis. The relationship between the synthesis, storage and use of lipids and their importance in cancer is poorly understood. The human group X secreted phospholipase A2 (hGX sPLA2) releases fatty acids (FAs) from cell membranes and lipoproteins, but its involvement in the regulation of cellular FA metabolism and cancer is not known. Results Here we demonstrate that hGX sPLA2 induces lipid droplet (LD) formation in invasive breast cancer cells, stimulates their proliferation and prevents their death on serum deprivation. The effects of hGX sPLA2 are shown to be dependent on its enzymatic activity, are mimicked by oleic acid and include activation of protein kinase B/Akt, a cell survival signaling kinase. The hGX sPLA2-stimulated LD biogenesis is accompanied by AMP-activated protein kinase (AMPK) activation, up-regulation of FA oxidation enzymes and the LD-coating protein perilipin 2, and suppression of lipogenic gene expression. Prolonged activation of AMPK inhibited hGX sPLA2-induced LD formation, while etomoxir, an inhibitor of FA oxidation, abrogated both LD formation and cell survival. The hGX sPLA2-induced changes in lipid metabolism provide a minimal immediate proliferative advantage during growth under optimal conditions, but they confer to the breast cancer cells a sustained ability to resist apoptosis during nutrient and growth factor limitation. Conclusion Our results identify hGX sPLA2 as a novel modulator of lipid metabolism that promotes breast cancer cell growth and survival by stimulating LD formation and FA oxidation. PMID:24070020

  8. Survival of patients with structurally-grouped TP53 mutations in ovarian and breast cancers

    PubMed Central

    Seagle, Brandon-Luke L.; Eng, Kevin H.; Dandapani, Monica; Yeh, Judy Y.; Odunsi, Kunle; Shahabi, Shohreh

    2015-01-01

    The objective of this study was to determine if ovarian cancer patients with a TP53 mutation grouped by location of the mutation within the p53 protein structure exhibit differential survival outcomes. Data from patients with high grade serous ovarian cancer (HGS OvCa) (N = 316) or breast cancer (BrCa) (N = 981) sequenced by The Cancer Genome Atlas (TCGA) was studied by Kaplan-Meier and Cox proportional hazards survival analysis. A TP53 DNA binding domain (BD) missense mutation (MM) occurred in 58.5% (185/316) of HGS OvCas and 16.8% (165/981) of BrCas. Patients with a TP53 DNA BD MM grouped by structural location had significantly different overall survival (OS) and progression free survival (PFS). Median OS (months) of HGS OvCa patients by structural group were: Sheet-loop-helix stabilizers, 31.1; DNA minor groove residue R248, 33.6; Wild-type, 34.2; all other MMs, 44.5; DNA major groove residues, 84.1, and zinc ion coordinating residues, 87.0 (log-rank p = 0.006). PFS of DNA major groove MM cases was longer than TP53 wild-type cases (19.1 versus 10.1 months, log-rank p = 0.038). HGS OvCa and BrCa patients with structurally-grouped TP53 DNA BD MMs have different survival outcomes. PMID:26215675

  9. Determination of a Change Point in the Age at Diagnosis of Breast Cancer Using a Survival Model.

    PubMed

    Abdollahi, Mahbubeh; Hajizadeh, Ebrahim; Baghestani, Ahmad Reza; Haghighat, Shahpar

    2016-01-01

    Breast cancer, the second cause of cancer-related death after lung cancer and the most common cancer in women after skin cancer, is curable if detected in early stages of clinical presentation. Knowledge as to any age cut-off points which might have significance for prognostic groups is important in screening and treatment planning. Therefore, determining a change-point could improve resource allocation. This study aimed to determine if a change point for survival might exist in the age of breast cancer diagnosis. This study included 568 cases of breast cancer that were registered in Breast Cancer Research Center, Tehran, Iran, during the period 1986-2006 and were followed up to 2012. In the presence of curable cases of breast cancer, a change point in the age of breast cancer diagnosis was estimated using a mixture survival cure model. The data were analyzed using SPSS (versions 20) and R (version 2.15.0) software. The results revealed that a change point in the age of breast cancer diagnosis was at 50 years age. Based on our estimation, 35% of the patients diagnosed with breast cancer at age less than or equal to 50 years of age were cured while the figure was 57% for those diagnosed after 50 years of age. Those in the older age group had better survival compared to their younger counterparts during 12 years of follow up. Our results suggest that it is better to estimate change points in age for cancers which are curable in early stages using survival cure models, and that the cure rate would increase with timely screening for breast cancer.

  10. Biomarker discovery to improve prediction of breast cancer survival: using gene expression profiling, meta-analysis, and tissue validation

    PubMed Central

    Meng, Liwei; Xu, Yingchun; Xu, Chaoyang; Zhang, Wei

    2016-01-01

    Purpose Breast cancer is the leading cause of cancer death worldwide in women. The molecular mechanism for human breast cancer is unknown. Gene microarray has been widely used in breast cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis survival. So far, the valuable multigene signatures in clinical practice are unclear, and the biological importance of individual genes is difficult to detect, as the described signatures virtually do not overlap. Early prognosis of this disease, breast invasive ductal carcinoma (IDC) and breast ductal carcinoma in situ (DCIS), is vital in breast surgery. Methods Thus, this study reports gene expression profiling in large breast cancer cohorts from Gene Expression Omnibus, including GSE29044 (N=138) and GSE10780 (N=185) test series and four independent validation series GSE21653 (N=266), GSE20685 (N=327), GSE26971 (N=276), and GSE12776 (N=204). Significantly differentially expressed genes in human breast IDC and breast DCIS were detected by transcriptome microarray analysis. Results We created a set of three genes (MAMDC2, TSHZ2, and CLDN11) that were significantly correlated with disease-free survival of breast cancer patients using a univariate Cox regression model (significance level P<0.01) in a meta-analysis. Based on the risk score of the three genes, the test series patients could be separated into low-risk and high-risk groups with significantly different survival times. This signature was validated in the other three cohorts. The prognostic value of this three-gene signature was confirmed in the internal validation series and another four independent breast cancer data sets. The prognostic impact of one of the three genes, CLDN11, was confirmed by immunohistochemistry. CLDN11 was significantly overexpressed in human breast IDC as compared with normal breast tissues and breast DCIS. Conclusion Using novel gene expression profiling together with a meta-analysis validation

  11. Trends in presentation, management and survival of patients with de novo metastatic breast cancer in a Southeast Asian setting.

    PubMed

    Bhoo-Pathy, Nirmala; Verkooijen, Helena Marieke; Tan, Ern-Yu; Miao, Hui; Taib, Nur Aishah Mohd; Brand, Judith S; Dent, Rebecca A; See, Mee-Hoong; Subramaniam, ShriDevi; Chan, Patrick; Lee, Soo-Chin; Hartman, Mikael; Yip, Cheng-Har

    2015-11-05

    Up to 25% of breast cancer patients in Asia present with de novo metastatic disease. We examined the survival trends of Asian patients with metastatic breast cancer over fifteen years. The impact of changes in patient's demography, tumor characteristics, tumor burden, and treatment on survival trend were examined. Patients with de novo metastatic breast cancer from three hospitals in Malaysia and Singapore (N = 856) were grouped by year of diagnosis: 1996-2000, 2001-2005 and 2006-2010. Step-wise multivariable Poisson regression was used to estimate the contribution of above-mentioned factors on the survival trend. Proportions of patients presenting with metastatic breast cancer were 10% in 1996-2000, 7% in 2001-2005, and 9% in 2006-2010. Patients in 2006-2010 were significantly older, appeared to have higher disease burden, and received more chemotherapy, endocrine therapy, and surgery of primary tumor. The three-year relative survival in the above periods were 20·6% (95% CI: 13·9%-28·2%), 28·8% (95% CI: 23·4%-34·2%), and 33·6% (95% CI: 28·8%-38·5%), respectively. Adjustment for treatment considerably attenuated the relative excess risk of mortality in recent years, compared to other factors. Substantial improvements in survival were observed in patients with de novo metastatic breast cancer in this study.

  12. CD4+ follicular helper T cell infiltration predicts breast cancer survival

    PubMed Central

    Gu-Trantien, Chunyan; Loi, Sherene; Garaud, Soizic; Equeter, Carole; Libin, Myriam; de Wind, Alexandre; Ravoet, Marie; Le Buanec, Hélène; Sibille, Catherine; Manfouo-Foutsop, Germain; Veys, Isabelle; Haibe-Kains, Benjamin; Singhal, Sandeep K.; Michiels, Stefan; Rothé, Françoise; Salgado, Roberto; Duvillier, Hugues; Ignatiadis, Michail; Desmedt, Christine; Bron, Dominique; Larsimont, Denis; Piccart, Martine; Sotiriou, Christos; Willard-Gallo, Karen

    2013-01-01

    CD4+ T cells are critical regulators of immune responses, but their functional role in human breast cancer is relatively unknown. The goal of this study was to produce an image of CD4+ T cells infiltrating breast tumors using limited ex vivo manipulation to better understand the in vivo differences associated with patient prognosis. We performed comprehensive molecular profiling of infiltrating CD4+ T cells isolated from untreated invasive primary tumors and found that the infiltrating T cell subpopulations included follicular helper T (Tfh) cells, which have not previously been found in solid tumors, as well as Th1, Th2, and Th17 effector memory cells and Tregs. T cell signaling pathway alterations included a mixture of activation and suppression characterized by restricted cytokine/chemokine production, which inversely paralleled lymphoid infiltration levels and could be reproduced in activated donor CD4+ T cells treated with primary tumor supernatant. A comparison of extensively versus minimally infiltrated tumors showed that CXCL13-producing CD4+ Tfh cells distinguish extensive immune infiltrates, principally located in tertiary lymphoid structure germinal centers. An 8-gene Tfh signature, signifying organized antitumor immunity, robustly predicted survival or preoperative response to chemotherapy. Our identification of CD4+ Tfh cells in breast cancer suggests that they are an important immune element whose presence in the tumor is a prognostic factor. PMID:23778140

  13. Impact of Diabetes and Hyperglycemia on Survival in Advanced Breast Cancer Patients

    PubMed Central

    Villarreal-Garza, Cynthia; Shaw-Dulin, Robin; Lara-Medina, Fernando; Bacon, Ludwing; Rivera, Daniel; Urzua, Lorena; Aguila, Christian; Ramirez-Morales, Rebeca; Santamaria, Julieta; Bargallo, Enrique; Mohar, Alejandro; Herrera, Luis A.

    2012-01-01

    Purpose. We examined the impact of diabetes and hyperglycemia on cancer-specific survival of patients with metastatic or recurrent breast cancer (BC). Methods. We performed a retrospective analysis of 265 patients with advanced BC receiving palliative chemotherapy. BC-specific mortality was compared for diabetic and nondiabetic patients as well as for patients that presented hyperglycemia during treatment. Results. No difference was observed between the diabetic and nondiabetic patients in terms of overall survival (OS). A difference in OS was observed between nondiabetic patients and diabetic patients who had hyperglycemia. The OS was greater in diabetic patients with proper metabolic control than diabetic patients with hyperglycemia. The risk of death was higher in patients with mean glucose levels >130 mg/dL during treatment. Several factors were associated with poor OS: tumor stage, hormone-receptor-negative tumors, HER2 negative disease, multiple metastatic sites, presence of visceral metastases, and mean glucose >130 mg/dL. Conclusion. Elevated glucose levels are associated with a poor outcome in diabetic and nondiabetic patients in contrast to patients with normoglycemic levels, conferring an elevated risk of death. According to these results, clinicians should monitor glucose levels during treatment for advanced breast cancer disease and take action to maintain normal glucose levels. PMID:22919369

  14. Modelling circulating tumour cells for personalised survival prediction in metastatic breast cancer.

    PubMed

    Ascolani, Gianluca; Occhipinti, Annalisa; Liò, Pietro

    2015-05-01

    Ductal carcinoma is one of the most common cancers among women, and the main cause of death is the formation of metastases. The development of metastases is caused by cancer cells that migrate from the primary tumour site (the mammary duct) through the blood vessels and extravasating they initiate metastasis. Here, we propose a multi-compartment model which mimics the dynamics of tumoural cells in the mammary duct, in the circulatory system and in the bone. Through a branching process model, we describe the relation between the survival times and the four markers mainly involved in metastatic breast cancer (EPCAM, CD47, CD44 and MET). In particular, the model takes into account the gene expression profile of circulating tumour cells to predict personalised survival probability. We also include the administration of drugs as bisphosphonates, which reduce the formation of circulating tumour cells and their survival in the blood vessels, in order to analyse the dynamic changes induced by the therapy. We analyse the effects of circulating tumour cells on the progression of the disease providing a quantitative measure of the cell driver mutations needed for invading the bone tissue. Our model allows to design intervention scenarios that alter the patient-specific survival probability by modifying the populations of circulating tumour cells and it could be extended to other cancer metastasis dynamics.

  15. Modelling Circulating Tumour Cells for Personalised Survival Prediction in Metastatic Breast Cancer

    PubMed Central

    2015-01-01

    Ductal carcinoma is one of the most common cancers among women, and the main cause of death is the formation of metastases. The development of metastases is caused by cancer cells that migrate from the primary tumour site (the mammary duct) through the blood vessels and extravasating they initiate metastasis. Here, we propose a multi-compartment model which mimics the dynamics of tumoural cells in the mammary duct, in the circulatory system and in the bone. Through a branching process model, we describe the relation between the survival times and the four markers mainly involved in metastatic breast cancer (EPCAM, CD47, CD44 and MET). In particular, the model takes into account the gene expression profile of circulating tumour cells to predict personalised survival probability. We also include the administration of drugs as bisphosphonates, which reduce the formation of circulating tumour cells and their survival in the blood vessels, in order to analyse the dynamic changes induced by the therapy. We analyse the effects of circulating tumour cells on the progression of the disease providing a quantitative measure of the cell driver mutations needed for invading the bone tissue. Our model allows to design intervention scenarios that alter the patient-specific survival probability by modifying the populations of circulating tumour cells and it could be extended to other cancer metastasis dynamics. PMID:25978366

  16. Pre-diagnostic polyphenol intake and breast cancer survival: the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    PubMed

    Kyrø, Cecilie; Zamora-Ros, Raul; Scalbert, Augustin; Tjønneland, Anne; Dossus, Laure; Johansen, Christoffer; Bidstrup, Pernille Envold; Weiderpass, Elisabete; Christensen, Jane; Ward, Heather; Aune, Dagfinn; Riboli, Elio; His, Mathilde; Clavel-Chapelon, Françoise; Baglietto, Laura; Katzke, Verena; Kühn, Tilman; Boeing, Heiner; Floegel, Anna; Overvad, Kim; Lasheras, Cristina; Travier, Noémie; Sánchez, Maria-José; Amiano, Pilar; Chirlaque, Maria-Dolores; Ardanaz, Eva; Khaw, Kay-Tee; Wareham, Nick; Perez-Cornago, Aurora; Trichopoulou, Antonia; Lagiou, Pagona; Vasilopoulou, Effie; Masala, Giovanna; Grioni, Sara; Berrino, Franco; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Bueno-de-Mesquita, H Bas; Peeters, Petra H; van Gils, Carla; Borgquist, Signe; Butt, Salma; Zeleniuch-Jacquotte, Anne; Sund, Malin; Hjartåker, Anette; Skeie, Guri; Olsen, Anja; Romieu, Isabelle

    2015-11-01

    The aim was to investigate the association between pre-diagnostic intakes of polyphenol classes (flavonoids, lignans, phenolic acids, stilbenes, and other polyphenols) in relation to breast cancer survival (all-cause and breast cancer-specific mortality). We used data from the European Prospective Investigation into Cancer and Nutrition cohort. Pre-diagnostic usual diet was assessed using dietary questionnaires, and polyphenol intakes were estimated using the Phenol-Explorer database. We followed 11,782 breast cancer cases from time of diagnosis until death, end of follow-up or last day of contact. During a median of 6 years, 1482 women died (753 of breast cancer). We related polyphenol intake to all-cause and breast cancer-specific mortality using Cox proportional hazard models with time since diagnosis as underlying time and strata for age and country. Among postmenopausal women, an intake of lignans in the highest versus lowest quartile was related to a 28 % lower risk of dying from breast (adjusted model: HR, quartile 4 vs. quartile 1, 0.72, 95 % CI 0.53; 0.98). In contrast, in premenopausal women, a positive association between lignan intake and all-cause mortality was found (adjusted model: HR, quartile 4 vs. quartile 1, 1.63, 95 % CI 1.03; 2.57). We found no association for other polyphenol classes. Intake of lignans before breast cancer diagnosis may be related to improved survival among postmenopausal women, but may on the contrary worsen the survival for premenopausal women. This suggests that the role of phytoestrogens in breast cancer survival is complex and may be dependent of menopausal status.

  17. Pre-diagnostic polyphenol intake and breast cancer survival: the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort.

    PubMed

    Kyrø, Cecilie; Zamora-Ros, Raul; Scalbert, Augustin; Tjønneland, Anne; Dossus, Laure; Johansen, Christoffer; Bidstrup, Pernille Envold; Weiderpass, Elisabete; Christensen, Jane; Ward, Heather; Aune, Dagfinn; Riboli, Elio; His, Mathilde; Clavel-Chapelon, Françoise; Baglietto, Laura; Katzke, Verena; Kühn, Tilman; Boeing, Heiner; Floegel, Anna; Overvad, Kim; Lasheras, Cristina; Travier, Noémie; Sánchez, Maria-José; Amiano, Pilar; Chirlaque, Maria-Dolores; Ardanaz, Eva; Khaw, Kay-Tee; Wareham, Nick; Perez-Cornago, Aurora; Trichopoulou, Antonia; Lagiou, Pagona; Vasilopoulou, Effie; Masala, Giovanna; Grioni, Sara; Berrino, Franco; Tumino, Rosario; Sacerdote, Carlotta; Mattiello, Amalia; Bueno-de-Mesquita, H Bas; Peeters, Petra H; van Gils, Carla; Borgquist, Signe; Butt, Salma; Zeleniuch-Jacquotte, Anne; Sund, Malin; Hjartåker, Anette; Skeie, Guri; Olsen, Anja; Romieu, Isabelle

    2015-11-01

    The aim was to investigate the association between pre-diagnostic intakes of polyphenol classes (flavonoids, lignans, phenolic acids, stilbenes, and other polyphenols) in relation to breast cancer survival (all-cause and breast cancer-specific mortality). We used data from the European Prospective Investigation into Cancer and Nutrition cohort. Pre-diagnostic usual diet was assessed using dietary questionnaires, and polyphenol intakes were estimated using the Phenol-Explorer database. We followed 11,782 breast cancer cases from time of diagnosis until death, end of follow-up or last day of contact. During a median of 6 years, 1482 women died (753 of breast cancer). We related polyphenol intake to all-cause and breast cancer-specific mortality using Cox proportional hazard models with time since diagnosis as underlying time and strata for age and country. Among postmenopausal women, an intake of lignans in the highest versus lowest quartile was related to a 28 % lower risk of dying from breast (adjusted model: HR, quartile 4 vs. quartile 1, 0.72, 95 % CI 0.53; 0.98). In contrast, in premenopausal women, a positive association between lignan intake and all-cause mortality was found (adjusted model: HR, quartile 4 vs. quartile 1, 1.63, 95 % CI 1.03; 2.57). We found no association for other polyphenol classes. Intake of lignans before breast cancer diagnosis may be related to improved survival among postmenopausal women, but may on the contrary worsen the survival for premenopausal women. This suggests that the role of phytoestrogens in breast cancer survival is complex and may be dependent of menopausal status. PMID:26531755

  18. Effect on Survival of Longer Intervals Between Confirmed Diagnosis and Treatment Initiation Among Low-Income Women With Breast Cancer

    PubMed Central

    McLaughlin, John M.; Anderson, Roger T.; Ferketich, Amy K.; Seiber, Eric E.; Balkrishnan, Rajesh; Paskett, Electra D.

    2012-01-01

    Purpose To determine the impact of longer periods between biopsy-confirmed breast cancer diagnosis and the initiation of treatment (Dx2Tx) on survival. Patients and Methods This study was a noninterventional, retrospective analysis of adult female North Carolina Medicaid enrollees diagnosed with breast cancer from January 1, 2000, through December, 31, 2002, in the linked North Carolina Central Cancer Registry–Medicaid Claims database. Follow-up data were available through July 31, 2006. Cox proportional hazards regression models were constructed to evaluate the impact on survival of delaying treatment ≥ 60 days after a confirmed diagnosis of breast cancer. Results The study cohort consisted of 1,786 low-income, adult women with a mean age of 61.6 years. A large proportion of the patients (44.3%) were racial minorities. Median time from biopsy-confirmed diagnosis to treatment initiation was 22 days. Adjusted Cox proportional hazards regression showed that although Dx2Tx length did not affect survival among those diagnosed at early stage, among late-stage patients, intervals between diagnosis and first treatment ≥ 60 days were associated with significantly worse overall survival (hazard ratio [HR], 1.66; 95% CI, 1.00 to 2.77; P = .05) and breast cancer–specific survival (HR, 1.85; 95% CI, 1.04 to 3.27; P = .04). Conclusion One in 10 women waited ≥ 60 days to initiate treatment after a diagnosis of breast cancer. Waiting ≥ 60 days to initiate treatment was associated with a significant 66% and 85% increased risk of overall and breast cancer–related death, respectively, among late-stage patients. Interventions designed to increase the timeliness of receiving breast cancer treatments should target late-stage patients, and clinicians should strive to promptly triage and initiate treatment for patients diagnosed at late stage. PMID:23169521

  19. Exclusive breast feeding is the strongest predictor of infant survival in Northwest Ethiopia: a longitudinal study.

    PubMed

    Biks, Gashaw Andargie; Berhane, Yemane; Worku, Alemayehu; Gete, Yigzaw Kebede

    2015-01-01

    Despite the overall national success in reducing infant mortality rate in Ethiopia, infant mortality rate is still high in northwest Amhara region. This study is conducted in one of the high mortality areas with the aim of identifying risk factors that are associated with infant mortality in Northwest Amhara Region, Ethiopia. A prospective open cohort study involving 1752 infants (1472.4518 person years of follow-up) was undertaken from November 2009 to August 2011. Kaplan-Meier Survival analysis was used to estimate infant mortality rate. Risk factors associated with infant mortality were assessed using multivariate Poisson regression. The overall infant mortality rate was 88 per 1000 person-years (95% CI: 74.3, 104.9). After controlling other important predictors in multivariate Poisson regression, infants not exclusively breastfed [IRR = 7.86, 95% CI: (5.11, 12.10), )], breast milk initiated after 24 hours of birth [IRR = 4.84,95% CI: (2.94,7.99)], mothers not washing hands with soap after visiting toilet and before feeding child [IRR = 4.61, 95% CI: (2.24, 9.48)], being rural residents [IRR = 2.33, 95% CI: (1.12, 4.88)], infants born within 24 months for the previous birth [IRR = 2.79, 95%CI: (1.88, 4.15)], have increased the risk of infant mortality. In conclusion, exclusive breast feeding is the strongest predictor of infant survival in this predominantly rural setting where hygienic standards are poor. Supporting mothers to exclusively breast feeding which is cost effective, safe and feasible strategy, can help reduce infant mortality in the study setting. PMID:26825334

  20. Associations among ancestry, geography and breast cancer incidence, mortality, and survival in Trinidad and Tobago

    PubMed Central

    Warner, Wayne A; Morrison, Robert L; Lee, Tammy Y; Williams, Tanisha M; Ramnarine, Shelina; Roach, Veronica; Slovacek, Simeon; Maharaj, Ravi; Bascombe, Nigel; Bondy, Melissa L; Ellis, Matthew J; Toriola, Adetunji T; Roach, Allana; Llanos, Adana A M

    2015-01-01

    Breast cancer (BC) is the most common newly diagnosed cancer among women in Trinidad and Tobago (TT) and BC mortality rates are among the highest in the world. Globally, racial/ethnic trends in BC incidence, mortality and survival have been reported. However, such investigations have not been conducted in TT, which has been noted for its rich diversity. In this study, we investigated associations among ancestry, geography and BC incidence, mortality and survival in TT. Data on 3767 incident BC cases, reported to the National Cancer Registry of TT, from 1995 to 2007, were analyzed in this study. Women of African ancestry had significantly higher BC incidence and mortality rates (Incidence: 66.96; Mortality: 30.82 per 100,000) compared to women of East Indian (Incidence: 41.04, Mortality: 14.19 per 100,000) or mixed ancestry (Incidence: 36.72, Mortality: 13.80 per 100,000). Geographically, women residing in the North West Regional Health Authority (RHA) catchment area followed by the North Central RHA exhibited the highest incidence and mortality rates. Notable ancestral differences in survival were also observed. Women of East Indian and mixed ancestry experienced significantly longer survival than those of African ancestry. Differences in survival by geography were not observed. In TT, ancestry and geographical residence seem to be strong predictors of BC incidence and mortality rates. Additionally, disparities in survival by ancestry were found. These data should be considered in the design and implementation of strategies to reduce BC incidence and mortality rates in TT. PMID:26338451

  1. Cytochrome P450 1A1 Regulates Breast Cancer Cell Proliferation and Survival

    PubMed Central

    Rodriguez, Mariangellys; Potter, David A.

    2013-01-01

    Cytochrome P450 1A1 (CYP1A1) is an extrahepatic phase I metabolizing enzyme whose expression is suppressed under physiologic conditions, but can be induced by substrates via the aryl hydrocarbon receptor (AhR). Nonetheless, recent studies show that the majority of breast tumors constitutively express CYP1A1. These findings led us to test the hypothesis that CYP1A1 promotes breast cancer progression by evaluating the effects of CYP1A1 knock down on the proliferation and survival of the MCF7 and MDA-MB-231 lines. Independently of estrogen receptor status, CYP1A1 knock down decreases cell proliferation, decreases colony formation, blocks the cell cycle at G0/G1 associated with reduction of cyclin D1, and increases apoptosis associated with reduction of survivin. CYP1A1 knock down markedly increases phosphorylation of AMP-activated protein kinase (AMPK) and decreases phosphorylation of AKT, extracellular signal-regulated kinases 1 and 2 (ERK1/2), and 70kDa ribosomal protein S6 kinase (P70S6K). AMPK inhibition by compound C partially abrogates the pro-apoptotic effects of CYP1A1siRNA, suggesting that CYP1A1siRNA effects are mediated, in part, through AMPK signaling. Consistent with CYP1A1 knock down results, pharmacologic reduction of CYP1A1 levels by the phytopolyphenol carnosol also correlates with impaired proliferation and induced AMPK phosphorylation. These results indicate that reduction of basal CYP1A1 expression is critical for inhibition of proliferation, which is not affected by alpha-naphthoflavone-mediated inhibition of CYP1A1 activity nor modulated by AhR silencing. This study supports that CYP1A1 may promote breast cancer proliferation and survival, at least in part, through AMPK signaling and that reduction of CYP1A1 levels is a potential strategy for breast cancer therapeutics. PMID:23576571

  2. Breast Cancer. Patients' Survival. Report to the Chairman, Subcommittee on Health and Environment, Committee on Energy and Commerce. House of Representatives.

    ERIC Educational Resources Information Center

    General Accounting Office, Washington, DC.

    This monograph examines the effectiveness of adjuvant chemotherapy in premenopausal women with breast cancer that has spread to the lymph nodes under the arm. The review focuses on the issue of how the survival of node-positive breast cancer patients has changed over time. It concludes that the survivability benefits from this treatment need…

  3. p70S6 kinase mediates breast cancer cell survival in response to surgical wound fluid stimulation.

    PubMed

    Segatto, Ilenia; Berton, Stefania; Sonego, Maura; Massarut, Samuele; Fabris, Linda; Armenia, Joshua; Mileto, Mario; Colombatti, Alfonso; Vecchione, Andrea; Baldassarre, Gustavo; Belletti, Barbara

    2014-05-01

    In early breast cancer, local relapses represent a determinant and not simply an indicator of risk for distant relapse and death. Notably, 90% of local recurrences occur at or close to the same quadrant of the primary cancer. Relevance of PI3K/mTOR/p70S6K signaling in breast tumorigenesis is very well documented. However, the pathway/s involved in the process of breast cancer local relapse are not well understood. The ribosomal protein p70S6K has been implicated in breast cancer cell response to post-surgical inflammation, supporting the hypothesis that it may be crucial also for breast cancer recurrence. Here, we show that p70S6K activity is required for the survival of breast cancer cells challenged in "hostile" microenvironments. We found that impairment of p70S6K activity in breast cancer cells strongly decreased their tumor take rate in nude mice. In line with this observation, if cells were challenged to grow in anchorage independence or in clonogenic assay, growth of colonies was strongly dependent on an intact p70S6K signaling. This in vitro finding was particularly evident when breast cancer cells were grown in the presence of wound fluids harvested following surgery from breast cancer patients, suggesting that the stimuli present in the post-surgical setting at least partially relied on activity of p70S6K to stimulate breast cancer relapse. From a mechanistic point of view, our results indicated that p70S6K signaling was able to activate Gli1 and up-regulate the anti-apoptotic protein Bcl2, thereby activating a survival response in breast cancer cells challenged in hostile settings. Our work highlights a previously poorly recognized function of p70S6K in preserving breast cancer cell survival, which could eventually be responsible for local relapse and opens the way to the design of new and more specific therapies aiming to restrain the deleterious effects of wound response.

  4. Variation in the survival of women with breast cancer in Scotland. The Scottish Breast Cancer Focus Group and The Scottish Cancer Therapy Network.

    PubMed Central

    Twelves, C. J.; Thomson, C. S.; Gould, A.; Dewar, J. A.

    1998-01-01

    We have investigated factors influencing the survival of women with early breast cancer in Scotland. In a retrospective study, clinical, treatment and 'service' factors, e.g. surgical case load, deprivation and geographical area (health board of first treatment) were recorded from hospital records. A total of 2148 women with invasive breast cancer diagnosed in 1987 were identified from the Scottish Cancer Registry, of whom 1619 without metastases at diagnosis underwent surgery as part of their primary treatment. In a multivariate analysis, clinical factors (age, clinical stage, pathological tumour size, node status and oestrogen receptor status) all influenced survival. After allowing for these clinical factors, surgical case load and deprivation did not have statistically significant effects on survival. By contrast, health board did affect survival. This was explained in part by the selection of patients for surgery. There appeared, however, to be a residual effect that may be related to differences in the use of adjuvant systemic treatment among the different health boards. We conclude that, in Scotland, geographical variation in both surgical and non-surgical treatment has a greater effect on variability in survival for women with breast cancer than surgical case load and deprivation. PMID:9744492

  5. Yap1 promotes the survival and self-renewal of breast tumor initiating cells via inhibiting Smad3 signaling

    PubMed Central

    Sun, Jian-Guo; Chen, Xie-Wan; Zhang, Lu-Ping; Wang, Jiang; Diehn, Max

    2016-01-01

    Tumor initiating cells (TICs) serve as the root of tumor growth. After identifying TICs in spontaneous breast tumors of the MMTV-Wnt1 mouse model, we confirmed the specific expression and activation of Yes-associated protein 1 (Yap1) within TICs. To investigate the role of Yap1 in the self-renewal of breast TICs and the underlying mechanism, we sorted CD49fhighEpCAMlow cells as breast TICs. Active Yap1 with ectopic expression in breast TICs promoted their colony formation in vitro (p< 0.01) and self-renewal in vivo (p< 0.01), and led to a 4-fold increase in TIC frequency (p< 0.05). A conditional knock-out mouse was reconstructed to generate Yap1 knock-out breast tumors. The loss of Yap1 led to a dramatic growth disadvantage of breast TICs in vitro (p< 0.01) and in vivo (p< 0.01), and it also led to an over 200-fold decrease in TIC frequency (p< 0.01). The expression of active Yap1 was negatively correlated with that of phosphorylated Smad3 (p-Smad3). Transforming growth factor β (TGF-β) served as a strong enhancer of Smad3 and an inhibitor of clonogenesis of TICs. The presence of SIS3, a specific inhibitor of Smad3, could rescue the TGF-β -induced growth inhibition and reverse the Smad3 inhibition by Yap1. Analysis of a database containing 2,072 human breast cancer samples showed that higher expressions of Yap1 correlated with a poorer outcome of a 15-year survival rate and median overall survival (mOS)in patients, especially in those with basal breast tumors without estrogen receptor 1 (ER) expression. The findings indicate that active Yap1 promotes the self-renewal of breast TICs by inhibiting Smad3 signaling. PMID:26695440

  6. MicroRNA-155 Regulates Cell Survival, Growth, and Chemosensitivity by Targeting FOXO3a in Breast Cancer*

    PubMed Central

    Kong, William; He, Lili; Coppola, Marc; Guo, Jianping; Esposito, Nicole N.; Coppola, Domenico; Cheng, Jin Q.

    2010-01-01

    Breast cancer is the second leading cause of cancer death in women. Despite improvement in treatment over the past few decades, there is an urgent need for development of targeted therapies. miR-155 (microRNA-155) is frequently up-regulated in breast cancer. In this study, we demonstrate the critical role of miR-155 in regulation of cell survival and chemosensitivity through down-regulation of FOXO3a in breast cancer. Ectopic expression of miR-155 induces cell survival and chemoresistance to multiple agents, whereas knockdown of miR-155 renders cells to apoptosis and enhances chemosensitivity. Further, we identified FOXO3a as a direct target of miR-155. Sustained overexpression of miR-155 resulted in repression of FOXO3a protein without changing mRNA levels, and knockdown of miR-155 increases FOXO3a. Introduction of FOXO3a cDNA lacking the 3′-untranslated region abrogates miR-155-induced cell survival and chemoresistance. Finally, inverse correlation between miR-155 and FOXO3a levels were observed in a panel of breast cancer cell lines and tumors. In conclusion, our study reveals a molecular link between miR-155 and FOXO3a and presents evidence that miR-155 is a critical therapeutic target in breast cancer. PMID:20371610

  7. Protein Kinase CK2 Expression Predicts Relapse Survival in ERα Dependent Breast Cancer, and Modulates ERα Expression in Vitro

    PubMed Central

    Williams, Marlon D.; Nguyen, Thu; Carriere, Patrick P.; Tilghman, Syreeta L.; Williams, Christopher

    2015-01-01

    The heterotetrameric protein kinase CK2 has been associated with oncogenic transformation, and our previous studies have shown that it may affect estrogenic signaling. Here, we investigate the role of the protein kinase CK2 in regulating ERα (estrogen receptor α) signaling in breast cancer. We determined the correlation of CK2α expression with relapse free breast cancer patient survival utilizing Kaplan Meier Plotter (kmplot.com/analysis/) to mine breast cancer microarrays repositories. Patients were stratified according to ERα status, histological grade, and hormonal therapy. Luciferase reporter assays and flow cytometry were implemented to determine the impact of CK2 inhibition on ERE-mediated gene expression and expression of ERα protein. CK2α expression is associated with shorter relapse free survival among ERα (+) patients with grade 1 or 2 tumors, as well as among those patients receiving hormonal therapy. Biochemical inhibition of CK2 activity results in increased ER-transactivation as well as increased expression among ERα (+) and ERα (−) breast cancer cell lines. These findings suggest that CK2 may contribute to estrogen-independent cell proliferation and breast tumor progression, and may potentially serve as a biomarker and pharmacological target in breast cancer. PMID:26703694

  8. Surrogate end points for overall survival in breast cancer trials: A review.

    PubMed

    Fiteni, Frédéric; Bonnetain, Franck

    2016-10-01

    Our aim was to review the studies which assessed potential surrogate endpoints for overall survival (OS) in breast cancer trials. A Literature search in PubMed database of studies which assessed potential surrogate endpoints for OS in breast cancer trials was conducted. The surrogacy was assessed with the German institute of Quality and efficiency in Health Care's (IWQiG) framework and the Fleming hierarchy. Thirteen studies were identified. At the neoadjuvant setting, two individual patient data (IPD) meta-analyses and one aggregate data meta-analysis assessing surrogacy of pathological complete response (PCR) were identified. Trial-level association was calculated in one study and the squared correlation was 0.24. Therefore PCR was not judged to be valid surrogate for OS at the neoadjuvant setting according to the IWQiG framework and Fleming hierarchy. At the adjuvant setting, one meta-analysis on aggregate data was identified. 2-year DFS was not judged to be valid surrogate for OS at the neoadjuvant setting according to the IWQiG framework and Fleming hierarchy. At the metastatic setting, six meta-analyses based on aggregate data, three IPD meta-analyses and one retrospective study were identified. Within the IPD meta-analyses, at the trial-level association the squared correlation between the potential surrogates and OS ranged from 0.10 to 0.57 and no endpoint was judged to be valid surrogate for OS at the metastatic setting. The level of evidence available supporting a relationship between OS and potential surrogate endpoints in breast cancer trials is low. PMID:27400447

  9. Retrospective study of reasons for improved survival in patients with breast cancer in east Anglia: earlier diagnosis or better treatment.

    PubMed Central

    Stockton, D.; Davies, T.; Day, N.; McCann, J.

    1997-01-01

    OBJECTIVES: To investigate the recent fall in mortality from breast cancer in England and Wales, and to determine the relative contributions of improvements in treatment and earlier detection of tumours. DESIGN: Retrospective study of all women with breast cancer registered by the East Anglian cancer registry and diagnosed between 1982 and 1989. SUBJECTS: 3965 patients diagnosed 1982-5 compared with 4665 patients diagnosed 1986-9, in three age groups 0-49, 50-64, > or = 65 years, with information on stage at diagnosis and survival. MAIN OUTCOME MEASURES: Three year relative survival rates by time period, age group, and stage; relative hazard ratios for each time period and age group derived from Cox's proportional hazards model, adjusted for single year of age and stage. RESULTS: Survival improved in the later time period, although there was little stage specific improvement. The proportion of early stage tumours increased especially in the 50-64 year age group, and adjustment for stage accounted for over half of the improvement in survival in women aged under 65 years. CONCLUSION: Over half of the drop in mortality in women aged under 65 years seems to be attributable to earlier detection of tumours, which has been observed since the mid-1980s. This could have resulted from an increase in breast awareness predating the start of the breast screening programme. PMID:9056796

  10. Elevation of Soluble Guanylate Cyclase Suppresses Proliferation and Survival of Human Breast Cancer Cells

    PubMed Central

    Chen, Chen-Yu; Shiah, Shine-Gwo; Kung, Hsing-Jien; King, Kuang-Liang; Su, Liang-Chen; Chang, Shi-Chuan; Chang, Chung-Ho

    2015-01-01

    Nitric oxide (NO) is an essential signaling molecule in biological systems. Soluble guanylate cyclase (sGC), composing of α1 and β1 subunit, is the receptor for NO. Using radioimmunoassay, we discovered that activation of sGC by treatment with bradykinin or sodium nitroprusside (SNP) is impaired in MCF-7 and MDA-MB-231 breast cancer cells as compared to normal breast epithelial 184A1 cells. The 184A1 cells expressed both sGC α1 and sGCβ1 mRNAs. However, levels of sGCβ1 mRNAs were relatively lower in MCF-7 cells while both mRNA of sGC subunits were absent in MDA-MB-231 cells. Treatment with DNA methyltransferase inhibitor 5-aza-2’-deoxycytidine (5-aza-dC) increased mRNA levels of both sGCα1 and sGCβ1 in MDA-MB-231 cells but only sGCβ1 mRNAs in MCF-7 cells. The 5-aza-dC treatment increased the SNP-induced cGMP production in MCF-7 and MDA-MB-231, but not in 184A1 cells. Bisulfite sequencing revealed that the promoter of sGCα1 in MDA-MB-231 cells and promoter of sGCβ1 in MCF-7 cells were methylated. Promoter hypermethylation of sGCα1 and sGCβ1 was found in 1 out of 10 breast cancer patients. Over-expression of both sGC subunits in MDA-MB-231 cells induced apoptosis and growth inhibition in vitro as well as reduced tumor incidence and tumor growth rate of MDA-MB-231 xenografts in nude mice. Elevation of sGC reduced protein abundance of Bcl-2, Bcl-xL, Cdc2, Cdc25A, Cyclin B1, Cyclin D1, Cdk6, c-Myc, and Skp2 while increased protein expression of p53. Our study demonstrated that down-regulation of sGC, partially due to promoter methylation, provides growth and survival advantage in human breast cancer cells. PMID:25928539

  11. A naringenin–tamoxifen combination impairs cell proliferation and survival of MCF-7 breast cancer cells

    SciTech Connect

    Hatkevich, Talia; Ramos, Joseph; Santos-Sanchez, Idalys; Patel, Yashomati M.

    2014-10-01

    Since over 60% of breast cancers are estrogen receptor positive (ER+), many therapies have targeted the ER. The ER is activated by both estrogen binding and phosphorylation. While anti-estrogen therapies, such as tamoxifen (Tam) have been successful they do not target the growth factor promoting phosphorylation of the ER. Other proliferation pathways such as the phosphatidylinositol-3 kinase, (PI3K) and the mitogen-activated protein kinase (MAPK) pathways are activated in breast cancer cells and are associated with poor prognosis. Thus targeting multiple cellular proliferation and survival pathways at the onset of treatment is critical for the development of more effective therapies. The grapefruit flavanone naringenin (Nar) is an inhibitor of both the PI3K and MAPK pathways. Previous studies examining either Nar or Tam used charcoal-stripped serum which removed estrogen as well as other factors. We wanted to use serum containing medium in order to retain all the potential inducers of cell proliferation so as not to exclude any targets of Nar. Here we show that a Nar–Tam combination is more effective than either Tam alone or Nar alone in MCF-7 breast cancer cells. We demonstrate that a Nar–Tam combination impaired cellular proliferation and viability to a greater extent than either component alone in MCF-7 cells. Furthermore, the use of a Nar–Tam combination requires lower concentrations of both compounds to achieve the same effects on proliferation and viability. Nar may function by inhibiting both PI3K and MAPK pathways as well as localizing ERα to the cytoplasm in MCF-7 cells. Our results demonstrate that a Nar–Tam combination induces apoptosis and impairs proliferation signaling to a greater extent than either compound alone. These studies provide critical information for understanding the molecular mechanisms involved in cell proliferation and apoptosis in breast cancer cells. - Highlights: • Nar–Tam impairs cell viability more effectively than

  12. Macrophage binding to receptor VCAM-1 transmits survival signals in breast cancer cells that invade the lungs

    PubMed Central

    Chen, Qing; Zhang, Xiang H.-F.; Massagué, Joan

    2012-01-01

    SUMMARY Aberrant expression of vascular cell adhesion molecule-1 (VCAM-1) in breast cancer cells is associated with lung relapse, but the role of VCAM-1 as a mediator of metastasis has remained unknown. We report that VCAM-1 provides a survival advantage to breast cancer cells that infiltrate leukocyte-rich microenvironments such as the lungs. VCAM-1 tethers metastasis-associated macrophages to cancer cells via counter-receptor α4 integrins. Clustering of cell surface VCAM-1, acting through Ezrin, triggers Akt activation and protects cancer cells from pro-apoptotic cytokines such as TRAIL. This pro-survival function of VCAM-1 can be blocked by antibodies against α4 integrins. Thus, newly disseminated cancer cells expressing VCAM-1 can thrive in leukocyte-rich microenvironments through juxtacrine activation of a VCAM-1–Ezrin-PI3K/Akt survival pathway. PMID:22014578

  13. Lunar phases and survival of breast cancer patients--a statistical analysis of 3,757 cases.

    PubMed

    Peters-Engl, C; Frank, W; Kerschbaum, F; Denison, U; Medl, M; Sevelda, P

    2001-11-01

    The potential influence of lunar phases on human life has been widely discussed by the lay press. The purpose of this study was to find out whether the timing of surgery during particular lunar phases influences the survival of breast cancer patients. It has been postulated that breast cancer surgery performed during the waxing moon, or particularly at full moon, is associated with a poorer outcome. We tested this hypothesis by evaluating the overall survival for 3,757 consecutive patients with invasive breast cancer. All patients underwent either modified radical mastectomy or breast conserving surgery plus radiotherapy, followed by adjuvant cytotoxic or hormonal therapy. The date of definitive surgery was allocated to the lunar phases. 1,904 (50.7%) patients were operated on during the waxing moon and 1,853 (47.3%) during the waning moon. The median follow-up was 74 months (range 1-372 months). The mean age at primary surgery did not differ significantly in the two groups 58.39 (SD 13.14) versus 58.34 (12.75) (p >0.05, t-test). Breast cancer stages at initial diagnosis were evenly distributed according to the lunar phases (p = 0.325; chi-square). Survival curves were plotted according to the method of Kaplan-Meier. No significant differences were observed when timing of surgery was allocated to the lunar phases (p = 0.4841, log-rank). Subgroup analysis of premenopausal patients revealed similar results (p = 0.2950, log-rank; n = 1072). Using multivariate Cox modelling, we found a significant association between the patient's age, stage of disease and survival, whereas no association with survival was observed for the timing of surgery (RR= 1.062; 95% CI, 0.970-1.163; p = 0.1937). No significant differences in overall survival of breast cancer patients were observed when timing of breast cancer surgery during the lunar cycle was considered. Although this was not a prospective randomized trial, the statistical magnitude of the results do not support any

  14. Survival in patients with metastatic breast cancer: analysis of randomized studies comparing oral aromatase inhibitors versus megestrol.

    PubMed

    Messori, A; Cattel, F; Trippoli, S; Vaiani, M

    2000-10-01

    In patients with metastatic breast cancer, second-line therapy with aromatase inhibitors can improve survival in comparison with megestrol. We conducted a meta-analysis to assess the effectiveness of aromatase inhibitors versus megestrol. After a Medline search, three trials (evaluating letrozole, anastrozole or exemestane versus megestrol) were included in the survival meta-analysis. Our methodology retrieved patient-level information on survival. In comparison with megestrol, aromatase inhibitors prolonged survival at levels of statistical significance (relative death risk for oral aromatase inhibitors=0.79, 95% confidence interval 0.69-0.91; p=0.0011). A lifetime analysis of the pooled survival curves of aromatase inhibitors versus megestrol found a mean survival gain of 4.1 months per patient. Aromatase inhibitors confer a significant survival benefit to patients with metastatic breast cancer as compared with megestrol. A preliminary calculation of the cost per life year gained shows that the pharmacoeconomic profile of these drugs is favorable. PMID:11129731

  15. An improved survivability prognosis of breast cancer by using sampling and feature selection technique to solve imbalanced patient classification data

    PubMed Central

    2013-01-01

    Background Breast cancer is one of the most critical cancers and is a major cause of cancer death among women. It is essential to know the survivability of the patients in order to ease the decision making process regarding medical treatment and financial preparation. Recently, the breast cancer data sets have been imbalanced (i.e., the number of survival patients outnumbers the number of non-survival patients) whereas the standard classifiers are not applicable for the imbalanced data sets. The methods to improve survivability prognosis of breast cancer need for study. Methods Two well-known five-year prognosis models/classifiers [i.e., logistic regression (LR) and decision tree (DT)] are constructed by combining synthetic minority over-sampling technique (SMOTE) ,cost-sensitive classifier technique (CSC), under-sampling, bagging, and boosting. The feature selection method is used to select relevant variables, while the pruning technique is applied to obtain low information-burden models. These methods are applied on data obtained from the Surveillance, Epidemiology, and End Results database. The improvements of survivability prognosis of breast cancer are investigated based on the experimental results. Results Experimental results confirm that the DT and LR models combined with SMOTE, CSC, and under-sampling generate higher predictive performance consecutively than the original ones. Most of the time, DT and LR models combined with SMOTE and CSC use less informative burden/features when a feature selection method and a pruning technique are applied. Conclusions LR is found to have better statistical power than DT in predicting five-year survivability. CSC is superior to SMOTE, under-sampling, bagging, and boosting to improve the prognostic performance of DT and LR. PMID:24207108

  16. Enhanced Survival with Implantable Scaffolds That Capture Metastatic Breast Cancer Cells In Vivo.

    PubMed

    Rao, Shreyas S; Bushnell, Grace G; Azarin, Samira M; Spicer, Graham; Aguado, Brian A; Stoehr, Jenna R; Jiang, Eric J; Backman, Vadim; Shea, Lonnie D; Jeruss, Jacqueline S

    2016-09-15

    The onset of distant organ metastasis from primary breast cancer marks the transition to a stage IV diagnosis. Standard imaging modalities often detect distant metastasis when the burden of disease is high, underscoring the need for improved methods of detection to allow for interventions that would impede disease progression. Here, microporous poly(ε-caprolactone) scaffolds were developed that capture early metastatic cells and thus serve as a sentinel for early detection. These scaffolds were used to characterize the dynamic immune response to the implant spanning the acute and chronic foreign body response. The immune cell composition had stabilized at the scaffold after approximately 1 month and changed dramatically within days to weeks after tumor inoculation, with CD11b(+)Gr1(hi)Ly6C(-) cells having the greatest increase in abundance. Implanted scaffolds recruited metastatic cancer cells that were inoculated into the mammary fat pad in vivo, which also significantly reduced tumor burden in the liver and brain. Additionally, cancer cells could be detected using a label-free imaging modality termed inverse spectroscopic optical coherence tomography, and we tested the hypothesis that subsequent removal of the primary tumor after early detection would enhance survival. Surgical removal of the primary tumor following cancer cell detection in the scaffold significantly improved disease-specific survival. The enhanced disease-specific survival was associated with a systemic reduction in the CD11b(+)Gr1(hi)Ly6C(-) cells as a consequence of the implant, which was further supported by Gr-1 depletion studies. Implementation of the scaffold may provide diagnostic and therapeutic options for cancer patients in both the high-risk and adjuvant treatment settings. Cancer Res; 76(18); 5209-18. ©2016 AACR. PMID:27635043

  17. Breast Cancer Laterality Does Not Influence Survival in a Large Modern Cohort: Implications for Radiation-Related Cardiac Mortality

    SciTech Connect

    Rutter, Charles E.; Chagpar, Anees B.; Evans, Suzanne B.

    2014-10-01

    Objectives: Radiation therapy for left-sided breast cancer has been associated with an elevated risk of cardiac mortality, based on studies predating treatment planning based on computed tomography. This study assessed the impact of tumor laterality on overall survival (OS) in a large cohort treated with modern techniques, to indirectly determine whether left-sided treatment remains associated with increased cardiac mortality. Methods and Materials: Patients treated for breast cancer with breast conserving surgery and adjuvant external beam radiation therapy were identified in the National Cancer Database, and OS was compared based on tumor laterality using Kaplan-Meier analysis. Separate analyses were performed for noninvasive and invasive carcinoma and for breast-only and breast plus regional nodal radiation therapy. Multivariate regression analysis of OS was performed with demographic, pathologic, and treatment variables as covariates to adjust for factors associated with breast cancer–specific survival. Results: We identified 344,831 patients whose cancer was diagnosed from 1998 to 2006 with a median follow-up time of 6.04 years (range, 0-14.17 years). Clinical, tumor, and treatment characteristics were similar between laterality groups. Regional nodal radiation was used in 14.2% of invasive cancers. No OS difference was noted based on tumor laterality for patients treated with breast-only (hazard ratio [HR] 0.984, P=.132) and breast plus regional nodal radiation therapy (HR 1.001, P=.957). In multivariate analysis including potential confounders, OS was identical between left and right sided cancers (HR 1.002, P=.874). No significant OS difference by laterality was observed when analyses were restricted to patients with at least 10 years of follow-up (n=27,725), both in patients treated with breast-only (HR 0.955, P=.368) and breast plus regional nodal radiation therapy (HR 0.859, P=.155). Conclusions: Radiation therapy for left-sided breast cancer does

  18. Effect of Tumor Subtype on Survival and the Graded Prognostic Assessment for Patients With Breast Cancer and Brain Metastases

    SciTech Connect

    Sperduto, Paul W.; Kased, Norbert; Roberge, David; Xu Zhiyuan; Shanley, Ryan; Luo, Xianghua; Sneed, Penny K.; Chao, Samuel T.; Weil, Robert J.; Suh, John; Bhatt, Amit; Jensen, Ashley W.; Brown, Paul D.; Shih, Helen A.; Kirkpatrick, John; Gaspar, Laurie E.; Fiveash, John B.; and others

    2012-04-01

    Purpose: The diagnosis-specific Graded Prognostic Assessment (GPA) was published to clarify prognosis for patients with brain metastases. This study refines the existing Breast-GPA by analyzing a larger cohort and tumor subtype. Methods and Materials: A multi-institutional retrospective database of 400 breast cancer patients treated for newly diagnosed brain metastases was generated. Prognostic factors significant for survival were analyzed by multivariate Cox regression and recursive partitioning analysis (RPA). Factors were weighted by the magnitude of their regression coefficients to define the GPA index. Results: Significant prognostic factors by multivariate Cox regression and RPA were Karnofsky performance status (KPS), HER2, ER/PR status, and the interaction between ER/PR and HER2. RPA showed age was significant for patients with KPS 60 to 80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0 to 1.0, 1.5 to 2.0, 2.5 to 3.0, and 3.5 to 4.0 were 3.4 (n = 23), 7.7 (n = 104), 15.1 (n = 140), and 25.3 (n = 133) months, respectively (p < 0.0001). Among HER2-negative patients, being ER/PR positive improved MST from 6.4 to 9.7 months, whereas in HER2-positive patients, being ER/PR positive improved MST from 17.9 to 20.7 months. The log-rank statistic (predictive power) was 110 for the Breast-GPA vs. 55 for tumor subtype. Conclusions: The Breast-GPA documents wide variation in prognosis and shows clear separation between subgroups of patients with breast cancer and brain metastases. This tool will aid clinical decision making and stratification in clinical trials. These data confirm the effect of tumor subtype on survival and show the Breast-GPA offers significantly more predictive power than the tumor subtype alone.

  19. Guidelines are advantageous, though not essential for improved survival among breast cancer patients.

    PubMed

    Wolters, Regine; Wischhusen, Jörg; Stüber, Tanja; Weiss, Claire Rachel; Krockberger, Mathias; Bartmann, Catharina; Blettner, Maria; Janni, Wolfgang; Kreienberg, Rolf; Schwentner, Lukas; Novopashenny, Igor; Wischnewsky, Manfred; Wöckel, Achim; Diessner, Joachim

    2015-07-01

    The purpose of this retrospective multicenter study was to resolve the pseudo-paradox that the clinical outcome of women affected by breast cancer has improved during the last 20 years irrespective of whether they were treated in accordance with clinical guidelines or not. This retrospective German multicenter study included 9061 patients with primary breast cancer recruited from 1991 to 2009. We formed subgroups for the time intervals 1991-2000 (TI1) and 2001-2009 (TI2). In these subgroups, the risk of recurrence (RFS) and overall survival (OS) were compared between patients whose treatment was either 100% guideline-conforming or, respectively, non-guideline-conforming. The clinical outcome of all patients significantly improved in TI2 compared to TI1 [RFS: p < 0.001, HR = 0.57, 95% CI (0.49-0.67); OS: p < 0.001, HR = 0.76, 95% (CI 0.66-0.87)]. OS and RFS of guideline non-adherent patients also improved in TI2 compared to TI. Comparing risk profiles, determined by Nottingham Prognostic Score reveals a significant (p = 0.001) enhancement in the time cohort TI2. Furthermore, the percentage of guideline-conforming systemic therapy (endocrine therapy and chemotherapy) significantly increased (p < 0.001) in the time cohort TI2 to TI for the non-adherent group. The general improvement of clinical outcome of patients during the last 20 years is also valid in the subgroup of women who received treatments, which deviated from the guidelines. The shift in risk profiles as well as medical advances are major reasons for this improvement. Nevertheless, patients with 100% guideline-conforming therapy always had a better outcome compared to patients with guideline non-adherent therapy.

  20. The Metastasis-Associated Anterior Gradient 2 Protein Is Correlated with Poor Survival of Breast Cancer Patients

    PubMed Central

    Barraclough, Dong L.; Platt-Higgins, Angela; de Silva Rudland, Suzete; Barraclough, Roger; Winstanley, John; West, Christopher R.; Rudland, Philip S.

    2009-01-01

    The secreted metastasis-inducing protein, human anterior gradient 2 (AGR2), has been independently reported to be associated with either a reduced or an increased survival of different groups of patients with breast cancer. We now aim to analyze the expression of AGR2 in a third completely independent group of patients using a specific AGR2 monoclonal antibody (mAb). Primary tumors from a group of 315 patients suffering from operable (stage I and II) breast cancer with 20-years follow-up were immunocytochemically stained with a specific mAb to AGR2 and associations with prognostic factors and patient survival were analyzed. The mAb specifically recognized AGR2 in Western blots, and positive staining for AGR2 was significantly associated with involved lymph nodes and staining for estrogen receptor α, progesterone receptor, and the metastasis-inducing proteins osteopontin, S100P, and S100A4. After 20 years of follow-up, only 26% of patients with AGR2-positive carcinomas survived compared with 96% of those with AGR2 negative carcinomas, with the highly significant difference in median survival times of 68 and >216 months, respectively (P < 0.0001). Cox’s multivariate regression analysis showed that staining for AGR2 was one of the most significant independent prognostic indicators, with a corrected relative risk of 9.4. The presence of AGR2 in the primary tumor is therefore a possible prognostic indicator of poor patient outcome in breast cancer. PMID:19834055

  1. Late breast recurrence after lumpectomy and irradiation

    SciTech Connect

    Kurtz, J.M.; Spitalier, J.M.; Amalric, R.

    1983-08-01

    For 276 patients with early breast cancer followed from 10 to 21 years after lumpectomy and radiotherapy, the recurrence rate in the treated breast was 15.6%, and 7.2% developed contralateral breast cancer. Only 63% of breast recurrences occurred within 5 years, and the remainder were late failures, with 5 of the 43 recurrences observed after 10 years. The proportion of failures occurring late was greater for T/sub 1/ than for T/sub 2/ tumors (53% vs 25%). Twenty-six percent of early recurrences were inoperable, and an adverse impact of early recurrence on 10-year survival was clearly demonstrable. Late recurrences were all operable and did not appear to be associated with decreased survival. Only 16 of the 36 patients (44%) with operable breast recurrence ever developed metastatic disease, and 5 year survival following salvage therapy was 62%. Although the treated breast remains at continuous cancer risk even beyond 5 years, the prognosis of late recurrence appears quite similar to that of contralateral breast cancer.

  2. Immortalised breast epithelia survive prolonged DNA replication stress and return to cycle from a senescent-like state

    PubMed Central

    Maya-Mendoza, A; Merchut-Maya, J M; Bartkova, J; Bartek, J; Streuli, C H; Jackson, D A

    2014-01-01

    Mammalian cells have mechanisms to counteract the effects of metabolic and exogenous stresses, many of that would be mutagenic if ignored. Damage arising during DNA replication is a major source of mutagenesis. The extent of damage dictates whether cells undergo transient cell cycle arrest and damage repair, senescence or apoptosis. Existing dogma defines these alternative fates as distinct choices. Here we show that immortalised breast epithelial cells are able to survive prolonged S phase arrest and subsequently re-enter cycle after many days of being in an arrested, senescence-like state. Prolonged cell cycle inhibition in fibroblasts induced DNA damage response and cell death. However, in immortalised breast epithelia, efficient S phase arrest minimised chromosome damage and protected sufficient chromatin-bound replication licensing complexes to allow cell cycle re-entry. We propose that our observation could have implications for the design of drug therapies for breast cancer. PMID:25058425

  3. Obesity and its impact on breast cancer: tumor incidence, recurrence, survival, and possible interventions.

    PubMed

    Ligibel, Jennifer A; Strickler, Howard D

    2013-01-01

    A positive association between obesity and the risk of incident postmenopausal breast cancer has been consistently observed in epidemiologic studies. Although most studies of premenopausal women have not found a similar relationship between breast cancer and obesity, the prognosis for both pre- and postmenopausal breast cancer is substantially worse among obese than normal-weight individuals. Increasing evidence suggests that these associations may be mechanistically related to sex hormones, insulin, and certain adipokines. Insulin, for example, has important mitogenic/antiapoptotic activity in addition to its metabolic effects, and many breast tumors express high levels of the insulin receptor (IR)-A isoform. Further, the use of metformin, a diabetes medication that reduces insulin levels, has been epidemiologically associated with reduced breast cancer risk among patients with diabetes, and a recent observational study found a higher rate of pathologic complete responses among patients with diabetes and breast cancer who were using metformin. Formal clinical trials of metformin as adjuvant breast cancer therapy have been initiated and are ongoing. Similarly, the effect of lifestyle changes on breast cancer outcomes is actively being investigated. Several lifestyle intervention studies have demonstrated that weight loss, increased physical activity, and dietary changes are feasible in breast cancer populations, and that individuals who make lifestyle changes after breast cancer diagnosis experience several physical and psychologic benefits. In this article, the authors review the evidence linking obesity with breast cancer risk and outcomes and provide an overview of lifestyle intervention studies in patients with breast cancer.

  4. Associations of intakes of magnesium and calcium and survival among women with breast cancer: results from Western New York Exposures and Breast Cancer (WEB) Study

    PubMed Central

    Tao, Meng-Hua; Dai, Qi; Millen, Amy E; Nie, Jing; Edge, Stephen B; Trevisan, Maurizio; Shields, Peter G; Freudenheim, Jo L

    2016-01-01

    Magnesium (Mg) and calcium (Ca) antagonizes each other in (re) absorption, cell cycle regulation, inflammation, and many other physiologic activities. However, few studies have investigated the association between magnesium and calcium intakes and breast cancer survival, and the interaction between calcium and magnesium intake. In a cohort of 1,170 women with primary, incident, and histologically confirmed breast cancer from Western New York State, we examined the relationship between intakes of these two minerals and survival. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Mean follow-up time was 87.4 months after breast cancer diagnosis; there were 170 deaths identified. After adjustment for known prognostic factors, and intakes of energy, total vitamin D and total calcium, higher dietary intake of magnesium was inversely associated with risk of all-cause mortality (HR = 0.50, 95% CI, 0.28-0.90 for highest vs. lowest tertile; p trend = 0.02). Likewise, a marginal association was found for total Magnesium intake from foods and supplements combined (HR = 0.58, 95% CI, 0.31-1.08; p trend = 0.09). The inverse association of higher total magnesium intake with all-cause mortality was primarily presented among postmenopausal women and was stronger among women who had a high Ca:Mg intake ratio (>2.59). There were no clear associations for prognosis with intake of calcium. We found that magnesium intake alone may improve overall survival following breast cancer, and the association may be stronger among those with high Ca:Mg intake ratio. PMID:27073728

  5. Associations of intakes of magnesium and calcium and survival among women with breast cancer: results from Western New York Exposures and Breast Cancer (WEB) Study.

    PubMed

    Tao, Meng-Hua; Dai, Qi; Millen, Amy E; Nie, Jing; Edge, Stephen B; Trevisan, Maurizio; Shields, Peter G; Freudenheim, Jo L

    2016-01-01

    Magnesium (Mg) and calcium (Ca) antagonizes each other in (re) absorption, cell cycle regulation, inflammation, and many other physiologic activities. However, few studies have investigated the association between magnesium and calcium intakes and breast cancer survival, and the interaction between calcium and magnesium intake. In a cohort of 1,170 women with primary, incident, and histologically confirmed breast cancer from Western New York State, we examined the relationship between intakes of these two minerals and survival. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Mean follow-up time was 87.4 months after breast cancer diagnosis; there were 170 deaths identified. After adjustment for known prognostic factors, and intakes of energy, total vitamin D and total calcium, higher dietary intake of magnesium was inversely associated with risk of all-cause mortality (HR = 0.50, 95% CI, 0.28-0.90 for highest vs. lowest tertile; p trend = 0.02). Likewise, a marginal association was found for total Magnesium intake from foods and supplements combined (HR = 0.58, 95% CI, 0.31-1.08; p trend = 0.09). The inverse association of higher total magnesium intake with all-cause mortality was primarily presented among postmenopausal women and was stronger among women who had a high Ca:Mg intake ratio (>2.59). There were no clear associations for prognosis with intake of calcium. We found that magnesium intake alone may improve overall survival following breast cancer, and the association may be stronger among those with high Ca:Mg intake ratio. PMID:27073728

  6. Associations of intakes of magnesium and calcium and survival among women with breast cancer: results from Western New York Exposures and Breast Cancer (WEB) Study.

    PubMed

    Tao, Meng-Hua; Dai, Qi; Millen, Amy E; Nie, Jing; Edge, Stephen B; Trevisan, Maurizio; Shields, Peter G; Freudenheim, Jo L

    2016-01-01

    Magnesium (Mg) and calcium (Ca) antagonizes each other in (re) absorption, cell cycle regulation, inflammation, and many other physiologic activities. However, few studies have investigated the association between magnesium and calcium intakes and breast cancer survival, and the interaction between calcium and magnesium intake. In a cohort of 1,170 women with primary, incident, and histologically confirmed breast cancer from Western New York State, we examined the relationship between intakes of these two minerals and survival. Cox regression models were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI). Mean follow-up time was 87.4 months after breast cancer diagnosis; there were 170 deaths identified. After adjustment for known prognostic factors, and intakes of energy, total vitamin D and total calcium, higher dietary intake of magnesium was inversely associated with risk of all-cause mortality (HR = 0.50, 95% CI, 0.28-0.90 for highest vs. lowest tertile; p trend = 0.02). Likewise, a marginal association was found for total Magnesium intake from foods and supplements combined (HR = 0.58, 95% CI, 0.31-1.08; p trend = 0.09). The inverse association of higher total magnesium intake with all-cause mortality was primarily presented among postmenopausal women and was stronger among women who had a high Ca:Mg intake ratio (>2.59). There were no clear associations for prognosis with intake of calcium. We found that magnesium intake alone may improve overall survival following breast cancer, and the association may be stronger among those with high Ca:Mg intake ratio.

  7. Racial and Ethnic Differences in Breast Cancer Survival: Mediating Effect of Tumor Characteristics and Sociodemographic and Treatment Factors

    PubMed Central

    Warner, Erica T.; Tamimi, Rulla M.; Hughes, Melissa E.; Ottesen, Rebecca A.; Wong, Yu-Ning; Edge, Stephen B.; Theriault, Richard L.; Blayney, Douglas W.; Niland, Joyce C.; Winer, Eric P.; Weeks, Jane C.; Partridge, Ann H.

    2015-01-01

    Purpose To evaluate the relationship between race/ethnicity and breast cancer–specific survival according to subtype and explore mediating factors. Patients and Methods Participants were women presenting with stage I to III breast cancer between January 2000 and December 2007 at National Comprehensive Cancer Network centers with survival follow-up through December 2009. Cox proportional hazards regression was used to compare breast cancer–specific survival among Asians (n = 533), Hispanics (n = 1,122), and blacks (n = 1,345) with that among whites (n = 14,268), overall and stratified by subtype (luminal A like, luminal B like, human epidermal growth factor receptor 2 type, and triple negative). Model estimates were used to derive mediation proportion and 95% CI for selected risk factors. Results In multivariable adjusted models, overall, blacks had 21% higher risk of breast cancer–specific death (hazard ratio [HR], 1.21; 95% CI, 1.00 to 1.45). For estrogen receptor–positive tumors, black and white survival differences were greatest within 2 years of diagnosis (years 0 to 2: HR, 2.65; 95% CI, 1.34 to 5.24; year 2 to end of follow-up: HR, 1.50; 95% CI, 1.12 to 2.00). Blacks were 76% and 56% more likely to die as a result of luminal A–like and luminal B–like tumors, respectively. No disparities were observed for triple-negative or human epidermal growth factor receptor 2–type tumors. Asians and Hispanics were less likely to die as a result of breast cancer compared with whites (Asians: HR, 0.56; 95% CI, 0.37 to 0.85; Hispanics: HR, 0.74; 95% CI, 0.58 to 0.95). For blacks, tumor characteristics and stage at diagnosis were significant disparity mediators. Body mass index was an important mediator for blacks and Asians. Conclusion Racial disparities in breast cancer survival vary by tumor subtype. Interventions are needed to reduce disparities, particularly in the first 2 years after diagnosis among black women with estrogen receptor–positive tumors. PMID

  8. A tumor DNA complex aberration index is an independent predictor of survival in breast and ovarian cancer.

    PubMed

    Vollan, Hans Kristian Moen; Rueda, Oscar M; Chin, Suet-Feung; Curtis, Christina; Turashvili, Gulisa; Shah, Sohrab; Lingjærde, Ole Christian; Yuan, Yinyin; Ng, Charlotte K; Dunning, Mark J; Dicks, Ed; Provenzano, Elena; Sammut, Stephen; McKinney, Steven; Ellis, Ian O; Pinder, Sarah; Purushotham, Arnie; Murphy, Leigh C; Kristensen, Vessela N; Brenton, James D; Pharoah, Paul D P; Børresen-Dale, Anne-Lise; Aparicio, Samuel; Caldas, Carlos

    2015-01-01

    Complex focal chromosomal rearrangements in cancer genomes, also called "firestorms", can be scored from DNA copy number data. The complex arm-wise aberration index (CAAI) is a score that captures DNA copy number alterations that appear as focal complex events in tumors, and has potential prognostic value in breast cancer. This study aimed to validate this DNA-based prognostic index in breast cancer and test for the first time its potential prognostic value in ovarian cancer. Copy number alteration (CNA) data from 1950 breast carcinomas (METABRIC cohort) and 508 high-grade serous ovarian carcinomas (TCGA dataset) were analyzed. Cases were classified as CAAI positive if at least one complex focal event was scored. Complex alterations were frequently localized on chromosome 8p (n = 159), 17q (n = 176) and 11q (n = 251). CAAI events on 11q were most frequent in estrogen receptor positive (ER+) cases and on 17q in estrogen receptor negative (ER-) cases. We found only a modest correlation between CAAI and the overall rate of genomic instability (GII) and number of breakpoints (r = 0.27 and r = 0.42, p < 0.001). Breast cancer specific survival (BCSS), overall survival (OS) and ovarian cancer progression free survival (PFS) were used as clinical end points in Cox proportional hazard model survival analyses. CAAI positive breast cancers (43%) had higher mortality: hazard ratio (HR) of 1.94 (95%CI, 1.62-2.32) for BCSS, and of 1.49 (95%CI, 1.30-1.71) for OS. Representations of the 70-gene and the 21-gene predictors were compared with CAAI in multivariable models and CAAI was independently significant with a Cox adjusted HR of 1.56 (95%CI, 1.23-1.99) for ER+ and 1.55 (95%CI, 1.11-2.18) for ER- disease. None of the expression-based predictors were prognostic in the ER- subset. We found that a model including CAAI and the two expression-based prognostic signatures outperformed a model including the 21-gene and 70-gene signatures but excluding CAAI. Inclusion of CAAI in the

  9. The role of histological subtype in hormone receptor positive metastatic breast cancer: similar survival but different therapeutic approaches

    PubMed Central

    Lobbezoo, Dorien; Truin, Wilfred; Voogd, Adri; Roumen, Rudi; Vreugdenhil, Gerard; Dercksen, Marcus Wouter; van den Berkmortel, Franchette; Smilde, Tineke; van de Wouw, Agnes; van Kampen, Roel; van Riel, Johanna; Peters, Natascha; Peer, Petronella; Tjan-Heijnen, Vivianne C.G.

    2016-01-01

    Introduction This study describes the differences between the two largest histological breast cancer subtypes (invasive ductal carcinoma (IDC) and invasive (mixed) lobular carcinoma (ILC) with respect to patient and tumor characteristics, treatment-choices and outcome in metastatic breast cancer. Results Patients with ILC were older at diagnosis of primary breast cancer and had more often initial bone metastasis (46.5% versus 34.8%, P = 0.01) and less often multiple metastatic sites compared to IDC (23.7% versus 30.9%, P = 0.11). Six months after diagnosis of metastatic breast cancer, 28.1% of patients with ILC and 39.8% of patients with IDC had received chemotherapy with a longer median time to first chemotherapy for those with ILC (P = 0.001). After six months 84.8% of patients with ILC had received endocrine therapy versus 72.5% of patients with IDC (P = 0.0001). Median overall survival was 29 months for ILC and 25 months for IDC (P = 0.53). Materials and Methods We included 437 patients with hormone receptor-positive IDC and 131 patients with hormone receptor-positive ILC, all diagnosed with metastatic breast cancer between 2007–2009, irrespective of date of the primary diagnosis. Patient and tumor characteristics and data on treatment and outcome were collected. Survival curves were obtained using the Kaplan-Meier method. Conclusions Treatment strategies of hormone receptor-positive metastatic breast cancer were remarkably different for patients with ILC and IDC. Further research is required to understand tumor behavior and treatment-choices in real-life. PMID:27121067

  10. Angiopoietin-2 promotes ER+ breast cancer cell survival in bone marrow niche

    PubMed Central

    Han, Hyun Ho; Kim, Baek Gil; Lee, Joo Hyun; Kang, Suki; Kim, Ji Eun

    2016-01-01

    In estrogen receptor-positive (ER+) breast cancer, it is recognized that metastases may develop after a long period of dormancy. Bone marrow (BM) vascular niche is where the dormant tumor cells are most likely to reside. So far, it is not fully understood why the dormant tumor cells become proliferative and eventually generate tumor. We hypothesized that therapeutic or menopause-related estrogen depletion may be the switch behind dormant ER+ tumor cell awakening in BM. We utilized an existing experimental model of BM endothelial niche that can simulate ER+ tumor cell dormancy to test our hypothesis. In results, estrogen depletion paradoxically promoted ER+ tumor cell proliferation in the BM endothelial niche, and their molecular phenotype shifted from dormant to awaken. Following estrogen depletion, the BM niche cells produced angiopoietin-2 (ANGPT2), which destabilized niche endothelium by interfering ANGPT1/Tie2 signaling, and promoted ER+ tumor cell survival under estrogen deficiency via cell surface integrin &1. Knockdown of ANGPT2 completely negated ER+ tumor cell awakening in the niche. Furthermore, ANGPT2 expression in ER+ tumor human samples was associated with increased risk of distant metastasis only in those who underwent adjuvant estrogen depletion therapy, not in those who did not undergo adjuvant therapy. In conclusion, we demonstrate that ANGPT2 signaling activated after estrogen depletion paradoxically triggers ER+ tumor cell awakening from dormancy in their BM niche, partly indirectly via endothelial Tie2 receptor and partly directly via tumor cell surface integrin &1. PMID:27353038

  11. Impact of Screening and Risk Factors for Local Recurrence and Survival After Conservative Surgery and Radiotherapy for Early Breast Cancer: Results From a Large Series With Long-Term Follow-Up

    SciTech Connect

    Kunkler, Ian H.; Kerr, Gillian R.; Thomas, Jeremy S.; Jack, Wilma J.L.; Bartlett, John M.S.; Pedersen, Hans C.; Cameron, David A.; Dixon, J. Michael; Chetty, Udi

    2012-07-01

    Purpose: To investigate conventional prognostic factors for ipsilateral breast tumor recurrence (IBTR), distant metastasis (DM), and survival after breast-conserving therapy (BCT) in screen-detected and symptomatic cases on surveillance up to 25 years. Patients and Methods: A total of 1812 consecutive patients in three cohorts (1981-1989, 1990-1992, and 1993-1998) with T12N01M0 invasive breast cancer were treated with BCT (median follow-up, 14 years). Tumor type and grade were reviewed by a single pathologist. Hormone receptor status was measured by immunohistochemistry on tissue microarrays. A Cox proportional hazards model was used to assess independent prognostic variables for relapse and survival. Results: A total of 205 IBTR occurred, with 5-, 10-, 15-, and 20-year actuarial relapse rates of 4.5% (95% confidence interval [CI] 3.35-5.5%), 8.4% (95% CI 7.1-9.8%), 14.1% (95% CI 12.0-16%), and 17.4% (95% CI 14.5-20.2%). Number of nodes, young age, pathologic tumor size, and multifocality were significant factors for IBTR. Three hundred seventy-eight patients developed DM. The actuarial metastatic rate was 12% at 5 years and 17.9% at 10 years. Young age, number of positive nodes, pathologic tumor size, and tumor grade were significant factors for DM relapse. When conventional prognostic indices were taken into account screen-detected cancers showed no improvement in overall relapse or survival rate compared with symptomatic cases but did show a reduced risk of DM after IBTR. After 10 years IBTR relapse continued at a constant rate of 0.87% per annum. Conclusions: The Edinburgh BCT series has shown that screen-detected invasive breast cancers do not have significantly different clinical outcomes compared with symptomatic cases when pathologic risk factors are taken into account. This suggests that these patients be managed in a similar way.

  12. Cure frailty models for survival data: application to recurrences for breast cancer and to hospital readmissions for colorectal cancer.

    PubMed

    Rondeau, Virginie; Schaffner, Emmanuel; Corbière, Fabien; Gonzalez, Juan R; Mathoulin-Pélissier, Simone

    2013-06-01

    Owing to the natural evolution of a disease, several events often arise after a first treatment for the same subject. For example, patients with a primary invasive breast cancer and treated with breast conserving surgery may experience breast cancer recurrences, metastases or death. A certain proportion of subjects in the population who are not expected to experience the events of interest are considered to be 'cured' or non-susceptible. To model correlated failure time data incorporating a surviving fraction, we compare several forms of cure rate frailty models. In the first model already proposed non-susceptible patients are those who are not expected to experience the event of interest over a sufficiently long period of time. The other proposed models account for the possibility of cure after each event. We illustrate the cure frailty models with two data sets. First to analyse time-dependent prognostic factors associated with breast cancer recurrences, metastases, new primary malignancy and death. Second to analyse successive rehospitalizations of patients diagnosed with colorectal cancer. Estimates were obtained by maximization of likelihood using SAS proc NLMIXED for a piecewise constant hazards model. As opposed to the simple frailty model, the proposed methods demonstrate great potential in modelling multivariate survival data with long-term survivors ('cured' individuals).

  13. Greater Survival After Breast Cancer in Physically Active Women With High Vegetable-Fruit Intake Regardless of Obesity

    PubMed Central

    Pierce, John P.; Stefanick, Marcia L.; Flatt, Shirley W.; Natarajan, Loki; Sternfeld, Barbara; Madlensky, Lisa; Al-Delaimy, Wael K.; Thomson, Cynthia A.; Kealey, Sheila; Hajek, Richard; Parker, Barbara A.; Newman, Vicky A.; Caan, Bette; Rock, Cheryl L.

    2007-01-01

    Purpose Single-variable analyses have associated physical activity, diet, and obesity with survival after breast cancer. This report investigates interactions among these variables. Patients and Methods A prospective study was performed of 1,490 women diagnosed and treated for early-stage breast cancer between 1991 and 2000. Enrollment was an average of 2 years postdiagnosis. Only seven women were lost to follow-up through December 2005. Results In univariate analysis, reduced mortality was weakly associated with higher vegetable-fruit consumption, increased physical activity, and a body mass index that was neither low weight nor obese. In a multivariate Cox model, only the combination of consuming five or more daily servings of vegetables-fruits, and accumulating 540+ metabolic equivalent tasks-min/wk (equivalent to walking 30 minutes 6 d/wk), was associated with a significant survival advantage (hazard ratio, 0.56; 95% CI, 0.31 to 0.98). The approximate 50% reduction in risk associated with these healthy lifestyle behaviors was observed in both obese and nonobese women, although fewer obese women were physically active with a healthy dietary pattern (16% v 30%). Among those who adhered to this healthy lifestyle, there was no apparent effect of obesity on survival. The effect was stronger in women who had hormone receptor–positive cancers. Conclusion A minority of breast cancer survivors follow a healthy lifestyle that includes both recommended intakes of vegetables-fruits and moderate levels of physical activity. The strong protective effect observed suggests a need for additional investigation of the effect of the combined influence of diet and physical activity on breast cancer survival. PMID:17557947

  14. Identification of Gene Expression Pattern Related to Breast Cancer Survival Using Integrated TCGA Datasets and Genomic Tools

    PubMed Central

    Huang, Zhenzhen; Duan, Huilong; Li, Haomin

    2015-01-01

    Several large-scale human cancer genomics projects such as TCGA offered huge genomic and clinical data for researchers to obtain meaningful genomics alterations which intervene in the development and metastasis of the tumor. A web-based TCGA data analysis platform called TCGA4U was developed in this study. TCGA4U provides a visualization solution for this study to illustrate the relationship of these genomics alternations with clinical data. A whole genome screening of the survival related gene expression patterns in breast cancer was studied. The gene list that impacts the breast cancer patient survival was divided into two patterns. Gene list of each of these patterns was separately analyzed on DAVID. The result showed that mitochondrial ribosomes play a more crucial role in the cancer development. We also reported that breast cancer patients with low HSPA2 expression level had shorter overall survival time. This is widely different to findings of HSPA2 expression pattern in other cancer types. TCGA4U provided a new perspective for the TCGA datasets. We believe it can inspire more biomedical researchers to study and explain the genomic alterations in cancer development and discover more targeted therapies to help more cancer patients. PMID:26576432

  15. Design and Multiseries Validation of a Web-Based Gene Expression Assay for Predicting Breast Cancer Recurrence and Patient Survival

    PubMed Central

    Van Laar, Ryan K.

    2011-01-01

    Gene expression analysis is a valuable tool for determining the risk of disease recurrence and overall survival of an individual patient with breast cancer. The purpose of this study was to create and validate a robust prognostic algorithm and implement it within an online analysis environment. Genomic and clinical data from 477 clinically diverse patients with breast cancer were analyzed with Cox regression models to identify genes associated with outcome, independent of standard prognostic factors. Percentile-ranked expression data were used to train a “metagene” algorithm to stratify patients as having a high or low risk of recurrence. The classifier was applied to 1016 patients from five independent series. The 200-gene algorithm stratifies patients into risk groups with statistically and clinically significant differences in recurrence-free and overall survival. Multivariate analysis revealed the classifier to be the strongest predictor of outcome in each validation series. In untreated node-negative patients, 88% sensitivity and 44% specificity for 10-year recurrence-free survival was observed, with positive and negative predictive values of 32% and 92%, respectively. High-risk patients appear to significantly benefit from systemic adjuvant therapy. A 200-gene prognosis signature has been developed and validated using genomic and clinical data representing a range of breast cancer clinicopathological subtypes. It is a strong independent predictor of patient outcome and is available for research use. PMID:21458382

  16. Design and multiseries validation of a web-based gene expression assay for predicting breast cancer recurrence and patient survival.

    PubMed

    Van Laar, Ryan K

    2011-05-01

    Gene expression analysis is a valuable tool for determining the risk of disease recurrence and overall survival of an individual patient with breast cancer. The purpose of this study was to create and validate a robust prognostic algorithm and implement it within an online analysis environment. Genomic and clinical data from 477 clinically diverse patients with breast cancer were analyzed with Cox regression models to identify genes associated with outcome, independent of standard prognostic factors. Percentile-ranked expression data were used to train a "metagene" algorithm to stratify patients as having a high or low risk of recurrence. The classifier was applied to 1016 patients from five independent series. The 200-gene algorithm stratifies patients into risk groups with statistically and clinically significant differences in recurrence-free and overall survival. Multivariate analysis revealed the classifier to be the strongest predictor of outcome in each validation series. In untreated node-negative patients, 88% sensitivity and 44% specificity for 10-year recurrence-free survival was observed, with positive and negative predictive values of 32% and 92%, respectively. High-risk patients appear to significantly benefit from systemic adjuvant therapy. A 200-gene prognosis signature has been developed and validated using genomic and clinical data representing a range of breast cancer clinicopathological subtypes. It is a strong independent predictor of patient outcome and is available for research use.

  17. Breast Cancer in Young Women: Research Priorities. A Report of the Young Survival Coalition Research Think Tank Meeting.

    PubMed

    Korde, Larissa A; Partridge, Ann H; Esser, Michelle; Lewis, Stacy; Simha, Joy; Johnson, Rebecca H

    2015-03-01

    Breast cancer in young women is a significant issue-7% of all female breast cancer is diagnosed in women under 40 years of age. Young women with breast cancer (YWBC) face significant and unique challenges, including a higher likelihood of biologically aggressive disease and metastatic disease at diagnosis, leading to poorer prognosis, more aggressive treatment and long-term treatment-related toxicities, and unique psychosocial concerns. This article summarizes the Young Survival Coalition (YSC) Research Think Tank Meeting, held in Arlington, Virginia, in February 2013, and presents the process that led to YSC's priorities for YWBC research. The meeting's participants focused on six broad categories of investigation in which additional advancements in research on YWBC are crucial: risk factors; treatment; fertility; pregnancy-associated breast cancer; quality of life and survivorship; and metastasis. Several key themes emerged from this meeting. Researchers and advocates felt that a large-scale data registry focused on YWBC is necessary to collect quality information to guide future research for YWBC. This database should include clinical data, genomic profiling of primary tumor and metastatic sites, and an increased focus on fertility and pregnancy following breast cancer treatment. The participants also felt that more must be done to elucidate how and why YWBC develop more aggressive tumors, and to what degree treatment should be modified for young women. The discussions summarized here led to the formulation of YSC's Research Agenda, published in May 2014.

  18. Breast Cancer in Young Women: Research Priorities. A Report of the Young Survival Coalition Research Think Tank Meeting.

    PubMed

    Korde, Larissa A; Partridge, Ann H; Esser, Michelle; Lewis, Stacy; Simha, Joy; Johnson, Rebecca H

    2015-03-01

    Breast cancer in young women is a significant issue-7% of all female breast cancer is diagnosed in women under 40 years of age. Young women with breast cancer (YWBC) face significant and unique challenges, including a higher likelihood of biologically aggressive disease and metastatic disease at diagnosis, leading to poorer prognosis, more aggressive treatment and long-term treatment-related toxicities, and unique psychosocial concerns. This article summarizes the Young Survival Coalition (YSC) Research Think Tank Meeting, held in Arlington, Virginia, in February 2013, and presents the process that led to YSC's priorities for YWBC research. The meeting's participants focused on six broad categories of investigation in which additional advancements in research on YWBC are crucial: risk factors; treatment; fertility; pregnancy-associated breast cancer; quality of life and survivorship; and metastasis. Several key themes emerged from this meeting. Researchers and advocates felt that a large-scale data registry focused on YWBC is necessary to collect quality information to guide future research for YWBC. This database should include clinical data, genomic profiling of primary tumor and metastatic sites, and an increased focus on fertility and pregnancy following breast cancer treatment. The participants also felt that more must be done to elucidate how and why YWBC develop more aggressive tumors, and to what degree treatment should be modified for young women. The discussions summarized here led to the formulation of YSC's Research Agenda, published in May 2014. PMID:26812429

  19. Contribution of the Neighborhood Environment and Obesity to Breast Cancer Survival: The California Breast Cancer Survivorship Consortium

    PubMed Central

    Cheng, Iona; Shariff-Marco, Salma; Koo, Jocelyn; Monroe, Kristine R.; Yang, Juan; John, Esther M.; Kurian, Allison W.; Kwan, Marilyn L.; Henderson, Brian E.; Bernstein, Leslie; Lu, Yani; Sposto, Richard; Vigen, Cheryl; Wu, Anna H.; Gomez, Scarlett Lin; Keegan, Theresa H.M.

    2015-01-01

    Little is known about neighborhood attributes that may influence opportunities for healthy eating and physical activity in relation to breast cancer mortality. We used data from the California Breast Cancer Survivorship Consortium and the California Neighborhoods Data System to examine the neighborhood environment, body mass index, and mortality after breast cancer. We studied 8,995 African American, Asian American, Latina, and non-Latina White women with breast cancer. Residential addresses were linked to the CNDS to characterize neighborhoods. We used multinomial logistic regression to evaluate the associations between neighborhood factors and obesity, and Cox proportional hazards regression to examine associations between neighborhood factors and mortality. For Latinas, obesity was associated with more neighborhood crowding (Quartile 4 (Q4) vs. Q1: Odds Ratio (OR)=3.24; 95% Confidence Interval (CI): 1.50-7.00); breast cancer-specific mortality was inversely associated with neighborhood businesses (Q4 vs. Q1: Hazard Ratio (HR)=0.46; 95% CI: 0.25-0.85) and positively associated with multi-family housing (Q3 vs. Q1: HR=1.98; 95% CI: 1.20-3.26). For non-Latina Whites, lower neighborhood socioeconomic status (SES) was associated with obesity (Quintile 1 (Q1) vs. Q5: OR=2.52; 95% CI: 1.31-4.84), breast cancer-specific (Q1 vs. Q5: HR=2.75; 95% CI: 1.47-5.12), and all-cause (Q1 vs. Q5: HR=1.75; 95% CI: 1.17-2.62) mortality. For Asian Americans, no associations were seen. For African Americans, lower neighborhood SES was associated with lower mortality in a nonlinear fashion. Attributes of the neighborhood environment were associated with obesity and mortality following breast cancer diagnosis, but these associations differed across racial/ethnic groups. PMID:26063477

  20. Contribution of the neighborhood environment and obesity to breast cancer survival: the California Breast Cancer Survivorship Consortium.

    PubMed

    Cheng, Iona; Shariff-Marco, Salma; Koo, Jocelyn; Monroe, Kristine R; Yang, Juan; John, Esther M; Kurian, Allison W; Kwan, Marilyn L; Henderson, Brian E; Bernstein, Leslie; Lu, Yani; Sposto, Richard; Vigen, Cheryl; Wu, Anna H; Gomez, Scarlett Lin; Keegan, Theresa H M

    2015-08-01

    Little is known about neighborhood attributes that may influence opportunities for healthy eating and physical activity in relation to breast cancer mortality. We used data from the California Breast Cancer Survivorship Consortium and the California Neighborhoods Data System (CNDS) to examine the neighborhood environment, body mass index, and mortality after breast cancer. We studied 8,995 African American, Asian American, Latina, and non-Latina white women with breast cancer. Residential addresses were linked to the CNDS to characterize neighborhoods. We used multinomial logistic regression to evaluate the associations between neighborhood factors and obesity and Cox proportional hazards regression to examine associations between neighborhood factors and mortality. For Latinas, obesity was associated with more neighborhood crowding [quartile 4 (Q4) vs. Q1: OR, 3.24; 95% confidence interval (CI), 1.50-7.00]; breast cancer-specific mortality was inversely associated with neighborhood businesses (Q4 vs. Q1: HR, 0.46; 95% CI, 0.25-0.85) and positively associated with multifamily housing (Q3 vs. Q1: HR, 1.98; 95% CI, 1.20-3.26). For non-Latina whites, lower neighborhood socioeconomic status (SES) was associated with obesity [quintile 1 (Q1) vs. Q5: OR, 2.52; 95% CI, 1.31-4.84], breast cancer-specific (Q1 vs. Q5: HR, 2.75; 95% CI, 1.47-5.12), and all-cause (Q1 vs. Q5: HR, 1.75; 95% CI, 1.17-2.62) mortality. For Asian Americans, no associations were seen. For African Americans, lower neighborhood SES was associated with lower mortality in a nonlinear fashion. Attributes of the neighborhood environment were associated with obesity and mortality following breast cancer diagnosis, but these associations differed across racial/ethnic groups.

  1. Impact of immunohistochemistry-based molecular subtype on chemosensitivity and survival in Hispanic breast cancer patients following neoadjuvant chemotherapy

    PubMed Central

    Gómez, Rodolfo; Ossa, Carlos Andrés; Montoya, María Elvira; Echeverri, Carolina; Ángel, Gonzalo; Ascuntar, Johana; Borrero, Mauricio; Gil, Mónica; Herrera, Sabrina; Gutiérrez, Eduardo; Herazo, Fernando; Jiménez, Alejo; Madrid, Jorge; Reyes, Pedro Alejandro; Zuluaga, Lina; García, Héctor

    2015-01-01

    Background Neoadjuvant chemotherapy (NAC) is the standard treatment for patients with locally advanced breast cancer, showing improvement in disease-free survival (DFS) and overall survival (OS) rates in patients achieving pathological complete response (pCR). The relationship between immunohistochemistry-based molecular subtyping (IMS), chemo sensitivity and survival is currently a matter of interest. We explore this relationship in a Hispanic cohort of breast cancer patients treated with NAC. Methods A retrospective survival analysis was performed on Colombian females with breast cancer treated at Instituto de Cancerología-Clinica Las Américas between January 2009 and December 2011. Patients were classified according to immunohistochemistry-based subtyping into the following five groups: Luminal A, Luminal B, Luminal B/HER 2+, HER2-enriched, and triple-negative breast cancer. Demographic characteristics, recurrence pattern, and survival rate were reviewed by bivariate and multivariate analysis. Results A total of 328 patients fulfilled the study’s inclusion parameters and the distribution of subtypes were as follows: Luminal A: 73 (22.3%), Luminal B/HER2−: 110 (33.5%), Luminal B/HER2+: 75 (22.9%), HER2-enriched: 30 (9.1%), and triple-negative: 40 (12.2%). The median follow-up was 41 months (interquartile range: 31–52). Pathological response to NAC was as follows: complete pathological response (pCR) in 28 (8.5%) patients, partial 247 (75.3%); stable disease 47 (14.3%), and progression 6 (1.8%) patients. The presence of pCR had a significant DFS and OS in the entire group (p = 0.01) but subtypes had different DFS in Luminal B (p = 0.01) and triple negative (p = 0.02) and also OS in Luminal B (p = 0.01) and triple negative (p = 0.01). Conclusions pCR is associated with an improved overall survival and disease-free survival rates in this group of Hispanics patients. Advanced stages, Luminal B subtypes, triple-negative tumours and non-pCR showed lower DFS

  2. Racial and ethnic disparities in the impact of obesity on breast cancer risk and survival: a global perspective.

    PubMed

    Bandera, Elisa V; Maskarinec, Gertraud; Romieu, Isabelle; John, Esther M

    2015-11-01

    Obesity is a global concern, affecting both developed and developing countries. Although there are large variations in obesity and breast cancer rates worldwide and across racial/ethnic groups, most studies evaluating the impact of obesity on breast cancer risk and survival have been conducted in non-Hispanic white women in the United States or Europe. Given the known racial/ethnic differences in tumor hormone receptor subtype distribution, obesity prevalence, and risk factor profiles, we reviewed published data for women of African, Hispanic, and Asian ancestry in the United States and their countries of origin. Although the data are limited, current evidence suggests a stronger adverse effect of obesity on breast cancer risk and survival in women of Asian ancestry. For African Americans and Hispanics, the strength of the associations appears to be more comparable to that of non-Hispanic whites, particularly when accounting for subtype and menopausal status. Central obesity seems to have a stronger impact in African-American women than general adiposity as measured by body mass index. International data from countries undergoing economic transition offer a unique opportunity to evaluate the impact of rapid weight gain on breast cancer. Such studies should take into account genetic ancestry, which may help elucidate differences in associations between ethnically admixed populations. Overall, additional large studies that use a variety of adiposity measures are needed, because the current evidence is based on few studies, most with limited statistical power. Future investigations of obesity biomarkers will be useful to understand possible racial/ethnic biological differences underlying the complex association between obesity and breast cancer development and progression. PMID:26567202

  3. Racial and ethnic disparities in the impact of obesity on breast cancer risk and survival: a global perspective.

    PubMed

    Bandera, Elisa V; Maskarinec, Gertraud; Romieu, Isabelle; John, Esther M

    2015-11-01

    Obesity is a global concern, affecting both developed and developing countries. Although there are large variations in obesity and breast cancer rates worldwide and across racial/ethnic groups, most studies evaluating the impact of obesity on breast cancer risk and survival have been conducted in non-Hispanic white women in the United States or Europe. Given the known racial/ethnic differences in tumor hormone receptor subtype distribution, obesity prevalence, and risk factor profiles, we reviewed published data for women of African, Hispanic, and Asian ancestry in the United States and their countries of origin. Although the data are limited, current evidence suggests a stronger adverse effect of obesity on breast cancer risk and survival in women of Asian ancestry. For African Americans and Hispanics, the strength of the associations appears to be more comparable to that of non-Hispanic whites, particularly when accounting for subtype and menopausal status. Central obesity seems to have a stronger impact in African-American women than general adiposity as measured by body mass index. International data from countries undergoing economic transition offer a unique opportunity to evaluate the impact of rapid weight gain on breast cancer. Such studies should take into account genetic ancestry, which may help elucidate differences in associations between ethnically admixed populations. Overall, additional large studies that use a variety of adiposity measures are needed, because the current evidence is based on few studies, most with limited statistical power. Future investigations of obesity biomarkers will be useful to understand possible racial/ethnic biological differences underlying the complex association between obesity and breast cancer development and progression.

  4. Racial and Ethnic Disparities in the Impact of Obesity on Breast Cancer Risk and Survival: A Global Perspective123

    PubMed Central

    Bandera, Elisa V; Maskarinec, Gertraud; Romieu, Isabelle; John, Esther M

    2015-01-01

    Obesity is a global concern, affecting both developed and developing countries. Although there are large variations in obesity and breast cancer rates worldwide and across racial/ethnic groups, most studies evaluating the impact of obesity on breast cancer risk and survival have been conducted in non-Hispanic white women in the United States or Europe. Given the known racial/ethnic differences in tumor hormone receptor subtype distribution, obesity prevalence, and risk factor profiles, we reviewed published data for women of African, Hispanic, and Asian ancestry in the United States and their countries of origin. Although the data are limited, current evidence suggests a stronger adverse effect of obesity on breast cancer risk and survival in women of Asian ancestry. For African Americans and Hispanics, the strength of the associations appears to be more comparable to that of non-Hispanic whites, particularly when accounting for subtype and menopausal status. Central obesity seems to have a stronger impact in African-American women than general adiposity as measured by body mass index. International data from countries undergoing economic transition offer a unique opportunity to evaluate the impact of rapid weight gain on breast cancer. Such studies should take into account genetic ancestry, which may help elucidate differences in associations between ethnically admixed populations. Overall, additional large studies that use a variety of adiposity measures are needed, because the current evidence is based on few studies, most with limited statistical power. Future investigations of obesity biomarkers will be useful to understand possible racial/ethnic biological differences underlying the complex association between obesity and breast cancer development and progression. PMID:26567202

  5. Clinicopathologic study associated with long-term survival in Japanese patients with node-negative breast cancer

    PubMed Central

    Kato, T; Kimura, T; Miyakawa, R; Fujii, A; Yamamoto, K; Kameoka, S; Nishikawa, T; Kasajima, T

    2000-01-01

    This study was undertaken to determine the absolute and relative value of blood vessel invasion (BVI) using both factor VIII-related antigen and elastica van Gieson staining, proliferating cell nuclear antigen (PCNA), p53, c- erb B-2, and conventional prognostic factors in predicting relapse-free survival (RFS) and overall survival (OS) rates associated with long-term survival in Japanese patients with node-negative breast cancer. Two hundred patients with histological node-negative breast cancer were studied. We investigated nine clinicopathological factors, including PCNA, p53, c- erb B-2 using permanent-section immunohistochemistry, clinical tumour size (T), histological grade (HG), mitotic index (MI), tumour necrosis (TN), lymphatic vessel invasion (LVI) and BVI, followed for a median of 10 years (range 1–20). Twenty-one patients (10.5%) had recurrence and 15 patients (7.5%) died of breast cancer. Univariate analysis showed that BVI, PCNA, T, HG, MI, p53, c- erb B-2 and LVI were significantly predictive of 20-year RFS or OS. Multivariate analysis showed that BVI (P = 0.0159, P = 0.0368), proliferating cell nuclear antigen (PCNA) (P = 0.0165, P = 0.0001), and T (P = 0.0190, P = 0.0399) were significantly independent prognostic factors for RFS or OS respectively. BVI, PCNA and T were independent prognostic indicators for RFS or OS in Japanese patients with node-negative breast cancer and are useful in selecting high-risk patients who may be eligible to receive strong adjuvant therapies. © 2000 Cancer Research Campaign PMID:10646896

  6. Expression of ribosome-binding protein 1 correlates with shorter survival in Her-2 positive breast cancer

    PubMed Central

    Liang, Xiaoshuan; Sun, Shanshan; Zhang, Xianyu; Wu, Hao; Tao, Weiyang; Liu, Tong; Wei, Wei; Geng, Jingshu; Pang, Da

    2015-01-01

    The aim of this study is to investigate the expression of ribosome-binding protein 1 (RRBP1) in invasive breast cancer and to analyze its relationship to clinical features and prognosis. RRBP1 expression was studied using real-time quantitative PCR and western blotting using pair-matched breast samples and immunohistochemical staining using a tissue microarray. Then the correlation between RRBP1 expression and clinicopathologic features was analyzed. RRBP1 mRNA and protein expression were significantly increased in breast cancer tissues compared with normal tissues. The protein level of RRBP1 is proved to be positively related to histological grade (P = 0.02), molecular subtype (P = 0.048) and status of Her-2 (P = 0.026) and P53 (P = 0.015). We performed a grade-stratified analysis of all patients according to the level of RRBP1 expression and found that RRBP1 overexpression highly affected overall survival in patients with early-stage (I and II) tumors (P = 0.042). Furthermore, Her-2 positive patients with negative RRBP1 expression had longer overall survival rates than those with positive RRBP1 expression (P = 0.031). Using multivariate analysis, it was determined that lymph node metastasis (LNM, P = 0.002) and RRBP1 expression (P = 0.005) were independent prognosis factors for overall survival. RRBP1 is a valuable prognostic factor in Her-2-positive breast cancer patients, indicating that RRBP1 is a potentially important target for the prediction of prognosis. PMID:25845758

  7. Loss of membranous VEGFR1 expression is associated with an adverse phenotype and shortened survival in breast cancer

    PubMed Central

    Lebok, Patrick; Huber, Julia; Burandt, Eike-Christian; Lebeau, Annette; Marx, Andreas Holger; Terracciano, Luigi; Heilenkötter, Uwe; Jänicke, Fritz; Müller, Volkmar; Paluchowski, Peter; Geist, Stefan; Wilke, Christian; Simon, Ronald; Sauter, Guido; Quaas, Alexander

    2016-01-01

    Angiogenesis is a key process in tumor growth and progression, which is controlled by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs). In order to better understand the prevalence and prognostic value of VEGFR1 expression in breast cancer, a tissue microarray containing >2,100 breast cancer specimens, with clinical follow-up data, was analyzed by immunohistochemistry using an antibody directed against the membrane-bound full-length receptor protein. The results demonstrated that membranous VEGFR1 staining was detected in all (5 of 5) normal breast specimens. In carcinoma specimens, membranous staining was negative in 3.1%, weak in 6.3%, moderate in 10.9%, and strong in 79.7% of the 1,630 interpretable tissues. Strong staining was significantly associated with estrogen receptor and progesterone receptor expression, but was inversely associated with advanced tumor stage (P=0.0431), high Bloom-Richardson-Ellis Score for Breast Cancer grade and low Ki67 labeling index (both P<0.0001). Cancers with moderate to strong (high) VEGFR1 expression were associated with significantly improved overall survival, as compared with tumors exhibiting negative or weak (low) expression (P=0.0015). This association was also detected in the subset of nodal-positive cancers (P=0.0018), and in the subset of 185 patients who had received tamoxifen as the sole therapy (P=0.001). In conclusion, these data indicated that membrane-bound VEGFR1 is frequently expressed in normal and cancerous breast epithelium. In addition, reduced or lost VEGFR1 expression may serve as a marker for poor prognosis in patients with breast cancer, who might not optimally benefit from endocrine therapy. PMID:27357606

  8. γKlotho is a novel marker and cell survival factor in a subset of triple negative breast cancers

    PubMed Central

    Trošt, Nuša; Peña-Llopis, Samuel; Koirala, Sajjan; Stojan, Jurij; Potts, Patrick Ryan; Tacer, Klementina Fon; Martinez, Elisabeth D.

    2016-01-01

    Over the last decade, breast cancer mortality has declined. However, triple negative breast cancer (TNBC) remains a challenging problem mostly due to early recurrence and lack of molecularly driven treatments. There is a critical need to identify subgroups of TNBC with common molecular features that can be therapeutically targeted. Here we show that in contrast to Klotho and βKlotho, the third member of the Klotho protein family, γKlotho, is overexpressed in more than 60% of TNBCs and correlates with poorer disease progression. Furthermore, we find that γKlotho is expressed in a subset of TNBC cell lines promoting cell growth. Importantly, we demonstrate that in these cells γKlotho is necessary for cell survival and that its depletion leads to constitutive ERK activation, cell cycle arrest and apoptosis. Interestingly, we observe increased oxidative stress in γKlotho-depleted cells suggesting that γKlotho enables cancer cells to cope with an oxidative environment and that cells become dependent on its expression to maintain this survival advantage. These findings indicate that γKlotho might be a potential marker for patients that would benefit from treatments that alter oxidative stress and constitutes a novel drug target for a subset of TN breast cancers. PMID:26556877

  9. African American Women: Surviving Breast Cancer Mortality against the Highest Odds.

    PubMed

    White-Means, Shelley; Rice, Muriel; Dapremont, Jill; Davis, Barbara; Martin, Judy

    2016-01-01

    Among the country's 25 largest cities, the breast cancer mortality disparity is highest in Memphis, Tennessee, where African American women are twice as likely to die from breast cancer as White women. This qualitative study of African-American breast cancer survivors explores experiences during and post treatment that contributed to their beating the high odds of mortality. Using a semi-structured interview guide, a focus group session was held in 2012 with 10 breast cancer survivors. Thematic analysis and a deductive a priori template of codes were used to analyze the data. Five main themes were identified: family history, breast/body awareness and preparedness to manage a breast cancer event, diagnosis experience and reaction to the diagnosis, family reactions, and impact on life. Prayer and family support were central to coping, and survivors voiced a cultural acceptance of racial disparities in health outcomes. They reported lack of provider sensitivity regarding pain, financial difficulties, negative responses from family/friends, and resiliency strategies for coping with physical and mental limitations. Our research suggested that a patient-centered approach of demystifying breast cancer (both in patient-provider communication and in community settings) would impact how women cope with breast cancer and respond to information about its diagnosis. PMID:26703655

  10. African American Women: Surviving Breast Cancer Mortality against the Highest Odds.

    PubMed

    White-Means, Shelley; Rice, Muriel; Dapremont, Jill; Davis, Barbara; Martin, Judy

    2016-01-01

    Among the country's 25 largest cities, the breast cancer mortality disparity is highest in Memphis, Tennessee, where African American women are twice as likely to die from breast cancer as White women. This qualitative study of African-American breast cancer survivors explores experiences during and post treatment that contributed to their beating the high odds of mortality. Using a semi-structured interview guide, a focus group session was held in 2012 with 10 breast cancer survivors. Thematic analysis and a deductive a priori template of codes were used to analyze the data. Five main themes were identified: family history, breast/body awareness and preparedness to manage a breast cancer event, diagnosis experience and reaction to the diagnosis, family reactions, and impact on life. Prayer and family support were central to coping, and survivors voiced a cultural acceptance of racial disparities in health outcomes. They reported lack of provider sensitivity regarding pain, financial difficulties, negative responses from family/friends, and resiliency strategies for coping with physical and mental limitations. Our research suggested that a patient-centered approach of demystifying breast cancer (both in patient-provider communication and in community settings) would impact how women cope with breast cancer and respond to information about its diagnosis.

  11. African American Women: Surviving Breast Cancer Mortality against the Highest Odds

    PubMed Central

    White-Means, Shelley; Rice, Muriel; Dapremont, Jill; Davis, Barbara; Martin, Judy

    2015-01-01

    Among the country’s 25 largest cities, the breast cancer mortality disparity is highest in Memphis, Tennessee, where African American women are twice as likely to die from breast cancer as White women. This qualitative study of African-American breast cancer survivors explores experiences during and post treatment that contributed to their beating the high odds of mortality. Using a semi-structured interview guide, a focus group session was held in 2012 with 10 breast cancer survivors. Thematic analysis and a deductive a priori template of codes were used to analyze the data. Five main themes were identified: family history, breast/body awareness and preparedness to manage a breast cancer event, diagnosis experience and reaction to the diagnosis, family reactions, and impact on life. Prayer and family support were central to coping, and survivors voiced a cultural acceptance of racial disparities in health outcomes. They reported lack of provider sensitivity regarding pain, financial difficulties, negative responses from family/friends, and resiliency strategies for coping with physical and mental limitations. Our research suggested that a patient-centered approach of demystifying breast cancer (both in patient-provider communication and in community settings) would impact how women cope with breast cancer and respond to information about its diagnosis. PMID:26703655

  12. Smoking and Survival After Breast Cancer Diagnosis: A Prospective Observational Study and Systematic Review

    PubMed Central

    Braithwaite, Dejana; Izano, Monika; Moore, Dan H.; Kwan, Marilyn L.; Tammemagi, Martin C.; Hiatt, Robert A.; Kerlikowske, Karla; Kroenke, Candyce H.; Sweeney, Carol; Habel, Laurel; Castillo, Adrienne; Weltzien, Erin; Caan, Bette

    2012-01-01

    Background The association of smoking with outcomes following breast cancer prognosis is not well understood. Method In a cohort study called Life After Cancer Epidemiology (LACE), 2265 women diagnosed with breast cancer were followed for a median of twelve years. We used multivariable proportional-hazards models to determine whether smoking, assessed approximately two years post-diagnosis, was associated with risk of death among these women. We also undertook a systematic review of all cohort studies to date that have examined the association between smoking and breast cancer mortality. Results Compared with never smokers, women who were current smokers had a two-fold higher rate of dying from breast cancer [hazard ratio (HR)=2.01, 95% confidence interval (CI) 1.27–3.18] and an approximately four-fold higher rate of dying from competing (non-breast cancer) causes (HR=3.84, 95%CI 2.50–5.89). Among seven studies that met the inclusion criteria in the systematic review, three studies and our own reported significantly increased risk of breast cancer death with current smoking. We found little evidence of an association between former smoking and breast cancer mortality (HR=1.24, 95% CI 0.94–1.64). Conclusions Consistent with findings from our prospective observational study, the systematic review of seven additional studies indicates positive association of current smoking with breast cancer mortality, but weak association with former smoking. Impact Women who smoke following breast cancer diagnosis and treatment are at higher risk of death both from breast cancer and other causes. PMID:23053660

  13. Stemness of the hybrid Epithelial/Mesenchymal State in Breast Cancer and Its Association with Poor Survival

    PubMed Central

    Grosse-Wilde, Anne; Fouquier d’Hérouël, Aymeric; McIntosh, Ellie; Ertaylan, Gökhan; Skupin, Alexander; Kuestner, Rolf E.; del Sol, Antonio; Walters, Kathie-Anne; Huang, Sui

    2015-01-01

    /M heterogeneity by eliminating hybrid E/M cells and cooperation between E and M cell-types could improve breast cancer patient survival independent of breast cancer-subtype. PMID:26020648

  14. Sodium channel-inhibiting drugs and survival of breast, colon and prostate cancer: a population-based study

    PubMed Central

    Fairhurst, Caroline; Watt, Ian; Martin, Fabiola; Bland, Martin; Brackenbury, William J.

    2015-01-01

    Metastasis is the leading cause of cancer-related deaths. Voltage-gated sodium channels (VGSCs) regulate invasion and metastasis. Several VGSC-inhibiting drugs reduce metastasis in murine cancer models. We aimed to test the hypothesis that patients taking VGSC-inhibiting drugs who developed cancer live longer than those not taking these drugs. A cohort study was performed on primary care data from the QResearch database, including patients with breast, bowel or prostate cancer. Cox proportional hazards regression was used to compare the survival from cancer diagnosis of patients taking VGSC-inhibiting drugs with those not exposed to these drugs. Median time to death was 9.7 years in the exposed group and 18.4 years in the unexposed group, and exposure to these medications significantly increased mortality. Thus, exposure to VGSC-inhibiting drugs associates with reduced survival in breast, bowel and prostate cancer patients. This finding is not consistent with the preclinical data. Despite the strengths of this study including the large sample size, the study is limited by missing information on potentially important confounders such as cancer stage, co-morbidities and cause of death. Further research, which is able to account for these confounding issues, is needed to investigate the relationship between VGSC-inhibiting drugs and cancer survival. PMID:26577038

  15. Effect of BRCA2 mutation on familial breast cancer survival: A systematic review and meta-analysis.

    PubMed

    Shao, Jun; Yang, Jie; Wang, Jun-nai; Qiao, Long; Fan, Wei; Gao, Qing-lei; Feng, Yao-jun

    2015-10-01

    Reports of BRCA2 genetic mutations on the prognosis of familial breast cancer (BC) patients have been contradictory. True difference in survival, if it exists, would have important implications for genetic counseling and in treatment of hereditary BC. The purpose of this study was to compare overall survival rate (OSR) among BRCA2 mutation carriers, non-carriers and sporadic BC patients. We searched the PUBMED and EMBASE databases and retrieved 4529 articles using keywords that included breast cancer, BRCA, prognosis and survival. Nine articles were selected for systematic review and among them 6 were included in our meta-analysis. We used the fixed and random effect models to calculate the summary odds ratio (OR) and corresponding 95% confidence interval (CI). BRCA2 mutation carriers had significantly higher long-term OSR than non-carriers (OR=0.69 [95% CI=0.5-0.95]), while both short-term and long-term OSR of BRCA2 mutation carriers did not differ from those of patients with sporadic disease (OR=1.11 [95% CI=0.74-1.65]; 0.85 [95% CI=0.38-1.94], respectively). For BC-specific survival rate (BCSSR), BRCA2 mutation carriers had a similar BCSSR to the non-carriers (OR=0.61 [95% CI=0.28-1.34]). There was no significant difference in disease-free survival (DFS) between BRCA2 mutation carriers and patients with sporadic disease. Our results suggest that BRCA2 mutation increases long-term OSR in hereditary BC, which reminds us a new prospect of management of the disease.

  16. Breast cancer and bone metastases: the association of axial skeleton MRI findings with skeletal-related events and survival.

    PubMed

    van der Pol, Christian B; Schweitzer, Mark E; Di Primio, Gina; Sampaio, Marcos L; Kielar, Ania; Clemons, Mark; Jaberi, Arash

    2014-08-01

    The purpose of this study was to determine if bone metastasis characteristics on axial skeleton MRI are associated with either skeletal-related events (SREs) or survival in breast cancer patients. A retrospective review was performed on 247 breast cancer patients with bone metastases identified on axial skeleton MRI. MRI studies were reviewed for metastases T1 signal, signal uniformity, complete vertebral metastatic marrow replacement, metastases quantity, and distribution. Odds ratio (OR) and hazard ratios (HR) were calculated, with 95 % confidence intervals (95 % CI), to determine association with either future SREs or survival. At the time of analysis, 174 (70 %) patients had developed SREs and 176 (71 %) patients were dead. Features of skeletal metastases associated with SREs included the presence of complete metastatic marrow replacement within any vertebra; OR 2.363 (95 % CI 1.240-4.504, P = 0.0090), and more widely distributed metastases; OR 1.239 (95 % CI 1.070-1.435, P = 0.0040). Features associated with shorter survival included the presence of complete metastatic marrow replacement within any vertebra; HR 1.500 (95 % CI 1.105-2.036, P = 0.0093), and more widely distributed metastases; HR 1.141 (95 % CI 1.047-1.243, P = 0.0027). Metastases T1 signal, signal uniformity, and surprisingly quantity were not associated with SREs or survival. Axial skeleton MRI was able to identify characteristics predictive of future SREs and survival. These characteristics could be used for risk stratification for future trials if prospectively validated.

  17. Clinicopathological Characteristics and Survival Outcomes of Invasive Cribriform Carcinoma of Breast: A SEER Population-Based Study.

    PubMed

    Liu, Xi-Yu; Jiang, Yi-Zhou; Liu, Yi-Rong; Zuo, Wen-Jia; Shao, Zhi-Ming

    2015-08-01

    Invasive cribriform carcinoma (ICC) is a rare histologic subtype of breast cancer. We aimed to investigate the clinicopathological characteristics and survival outcomes of ICC.Using the Surveillance, Epidemiology, and End Results (SEER) database, we identified 233,337 female patients diagnosed with ICC (n = 618) or infiltrating ductal carcinoma (IDC) (n = 232,719). Univariate and multivariate survival analyses were utilized to calculate and compare disease-specific survival (DSS) and overall survival (OS). A 1:1 paired match was carried out on age, tumor stage, tumor grade, estrogen receptor (ER) status, and progesterone receptor (PR) status. Baseline characteristics and survival outcomes were also analyzed in ER-positive tumors. Subgroup analyses summarized the hazard ratio (HR) of IDC versus ICC using a forest plot.ICCs presented smaller size, lower grade, higher ER and PR positive rate, less nodal metastasis, and were less likely to be treated with mastectomy compared to IDCs. Five-year DSS rates were significantly better for patients with ICC than for patients with IDC (98.8% vs. 93%, P < 0.001). Five-year OS rates were 95.3% versus 90.1% (P < 0.001). After adjustment for common clinicopathological factors in the multivariate analysis, patients with ICC showed limited DSS advantage over the IDC group (HR = 0.75, 95% CI: 0.38-1.51, P = 0.421). No significant difference in DSS nor OS was observed in matched groups between ICC and IDC. Analysis among ER-positive patients revealed similar prognostic factors as among all patients. Survival analysis in different tumor grade subgroups showed no significant difference between ICC and IDC.ICCs have unique clinicopathological characteristics, higher rates of breast-conserving surgery, and more favorable prognosis compared to the overall IDC population. Difference in tumor grade between the 2 groups may partially explain the different outcome. Improved clinical and biological understanding of ICC

  18. Functional SNP in stem of mir-146a affects Her2 status and breast cancer survival.

    PubMed

    Meshkat, Mahboobeh; Tanha, Hamzeh Mesrian; Naeini, Marjan Mojtabavi; Ghaedi, Kamran; Sanati, Mohammad H; Meshkat, Marzieh; Bagheri, Fatemeh

    2016-07-01

    In-silico investigation suggested a common variant within stem of miR-146a-5p precursor (rs2910164, n.60C>G) associated with breast cancer (BC) phenotypes. Our aim was computationally predicting possible targets of miR-146a-5p and probable rs2910164 mechanism of action in expression of phenotypes in BC. Additionally, a case-control study was designated to examine experimentally the correlation of mir-146a rs2910164 variant and BC phenotypes. In this study, 152 BC subjects and healthy controls were genotyped using RFLP-PCR. Allelic and genotypic association and Armitage's trend tests were run to investigate the correlation between the alleles and genotypes and expressed phenotypes of BC. Bioinformatics analyses introduce regulatory function of miR-146a-5p in numerous signaling pathways and impact of allele substitution upon mir-146a stem-loop stability. Logistic regression data represented the C allele of rs2910164 (OR = 4.00, p= 0.0037) as the risk allele and associated with Her2-positive phenotype. In a similar vein, data revealed the correlation of the C allele and cancer death less than two years in BC patients (OR = 2.65, p= 0.0217). Ultimately, unconditional logistical regression models suggested log-additive model for inheritance manner of rs2910164 in either Her2 status or BC survival (OR = 5.64, p= 0.0025 and OR = 3.13, p= 0.019, respectively). Using bioinformatics connected association of Her2 status to altered function of miR-146a-5p in regulation of focal adhesion and Ras pathway. Furthermore, computations inferred the association between death phenotype and studied SNP upon specific target genes of miR-146a-5p involved in focal adhesion, EGF receptor, Ras, ErbB, interleukin, Toll-like receptor, NGF, angiogenesis, and p53 feedback loops 2 signaling pathways. These verdicts may enhance our perceptions of how mir-146a rs2910164 affect expressed phenotypes in BC, and might have potential implications to develop BC treatment in future. PMID:27434289

  19. G-CSF regulates macrophage phenotype and associates with poor overall survival in human triple-negative breast cancer

    PubMed Central

    Hollmén, Maija; Karaman, Sinem; Schwager, Simon; Lisibach, Angela; Christiansen, Ailsa J.; Maksimow, Mikael; Varga, Zsuzsanna; Jalkanen, Sirpa; Detmar, Michael

    2016-01-01

    ABSTRACT Tumor-associated macrophages (TAMs) have been implicated in the promotion of breast cancer growth and metastasis, and a strong infiltration by TAMs has been associated with estrogen receptor (ER)-negative tumors and poor prognosis. However, the molecular mechanisms behind these observations are unclear. We investigated macrophage activation in response to co-culture with several breast cancer cell lines (T47D, MCF-7, BT-474, SKBR-3, Cal-51 and MDA-MB-231) and found that high granulocyte colony-stimulating factor (G-CSF) secretion by the triple-negative breast cancer (TNBC) cell line MDA-MB-231 gave rise to immunosuppressive HLA-DRlo macrophages that promoted migration of breast cancer cells via secretion of TGF-α. In human breast cancer samples (n = 548), G-CSF was highly expressed in TNBC (p < 0.001) and associated with CD163+ macrophages (p < 0.0001), poorer overall survival (OS) (p = 0.021) and significantly increased numbers of TGF-α+ cells. While G-CSF blockade in the 4T1 mammary tumor model promoted maturation of MHCIIhi blood monocytes and TAMs and significantly reduced lung metastasis, anti-CSF-1R treatment promoted MHCIIloF4/80hiMRhi anti-inflammatory TAMs and enhanced lung metastasis in the presence of high G-CSF levels. Combined anti-G-CSF and anti-CSF-1R therapy significantly increased lymph node metastases, possibly via depletion of the so-called “gate-keeper” subcapsular sinus macrophages. These results indicate that G-CSF promotes the anti-inflammatory phenotype of tumor-induced macrophages when CSF-1R is inhibited and therefore caution against the use of M-CSF/CSF-1R targeting agents in tumors with high G-CSF expression. PMID:27141367

  20. Comparative study of joint analysis of microarray gene expression data in survival prediction and risk assessment of breast cancer patients.

    PubMed

    Yasrebi, Haleh

    2016-09-01

    Microarray gene expression data sets are jointly analyzed to increase statistical power. They could either be merged together or analyzed by meta-analysis. For a given ensemble of data sets, it cannot be foreseen which of these paradigms, merging or meta-analysis, works better. In this article, three joint analysis methods, Z-score normalization, ComBat and the inverse normal method (meta-analysis) were selected for survival prognosis and risk assessment of breast cancer patients. The methods were applied to eight microarray gene expression data sets, totaling 1324 patients with two clinical endpoints, overall survival and relapse-free survival. The performance derived from the joint analysis methods was evaluated using Cox regression for survival analysis and independent validation used as bias estimation. Overall, Z-score normalization had a better performance than ComBat and meta-analysis. Higher Area Under the Receiver Operating Characteristic curve and hazard ratio were also obtained when independent validation was used as bias estimation. With a lower time and memory complexity, Z-score normalization is a simple method for joint analysis of microarray gene expression data sets. The derived findings suggest further assessment of this method in future survival prediction and cancer classification applications.

  1. Affluence and Breast Cancer.

    PubMed

    Lehrer, Steven; Green, Sheryl; Rosenzweig, Kenneth E

    2016-09-01

    High income, high socioeconomic status, and affluence increase breast cancer incidence. Socioeconomic status in USA breast cancer studies has been assessed by block-group socioeconomic measures. A block group is a portion of a census tract with boundaries that segregate, as far as possible, socioeconomic groups. In this study, we used US Census income data instead of block groups to gauge socioeconomic status of breast cancer patients in relationship with incidence, prognostic markers, and survival. US state breast cancer incidence and mortality data are from the U.S. Cancer Statistics Working Group, United States Cancer Statistics: 1999-2011. Three-Year-Average Median Household Income by State, 2010 to 2012, is from the U.S. Census Bureau, Current Population Survey, 2011 to 2013 Annual Social and Economic Supplements. County incomes are from the 2005-2009 American Community Survey of the U.S. Census Bureau. The American Community Survey is an ongoing statistical survey that samples a small percentage of the population yearly. Its purpose is to provide communities the information they need to plan investments and services. Breast cancer county incidence and survival data are from the National Cancer Institute's Surveillance, Epidemiology and End Results Program (SEER) data base. We analyzed SEER data from 198 counties in California, Connecticut, Georgia, Hawaii, Iowa, New Mexico, Utah, and Washington. SEER uses the Collaborative Stage (CS) Data Collection System. We have retained the SEER CS variables. There was a significant relationship of income with breast cancer incidence in 50 USA states and the District of Columbia in White women (r = 0.623, p < 0.001). There was a significant relationship between node involvement and income in Whites in 198 USA counties. Income was significantly correlated with 5-year relative survival in Whites with localized breast cancer. Income was not correlated with 5-year survival of Black race (p = 0.364) or other races (p = 0

  2. Cyclooxygenase-2 in tumor-associated macrophages promotes breast cancer cell survival by triggering a positive-feedback loop between macrophages and cancer cells

    PubMed Central

    Li, Hongzhong; Yang, Bing; Huang, Jing; Lin, Yong; Xiang, Tingxiu; Wan, Jingyuan; Li, Hongyuan; Chouaib, Salem; Ren, Guosheng

    2015-01-01

    Tumor-associated macrophages (TAMs) play an important role in cancer cell survival, however, the mechanism of which remains elusive. In this study, we found that COX-2 was abundantly expressed in breast TAMs, which was correlated to poor prognosis in breast cancer patients. Ectopic over-expression of COX-2 in TAMs enhanced breast cancer cell survival both in vitro and in vivo. COX-2 in TAMs was determined to be essential for the induction and maintenance of M2-phenotype macrophage polarity. COX-2+ TAMs promoted breast cancer cell proliferation and survival by increasing Bcl-2 and P-gp and decreasing Bax in cancer cells. Furthermore, COX-2 in TAMs induced the expression of COX-2 in breast cancer cells, which in turn promoted M2 macrophage polarization. Inhibiting PI3K/Akt pathway in cancer cells suppressed COX-2+ TAMs-induced cancer cell survival. These findings suggest that COX-2, functions as a key cancer promoting factor by triggering a positive-feedback loop between macrophages and cancer cells, which could be exploited for breast cancer prevention and therapy. PMID:26359357

  3. Survival of patients with operable breast cancer (Stages I-III) at a Brazilian public hospital - a closer look into cause-specific mortality

    PubMed Central

    2013-01-01

    Background Breast cancer incidence is increasing. The survival rate varies and is longer in high-income countries. In Brazil, lower-income populations rely on the Unified Public Health System (Sistema Único de Saude, SUS) for breast cancer care. The goal of our study is to evaluate the survival of patients with operable breast cancer stages I-III at a Brazilian public hospital that treats mostly patients from the SUS. Methods A cohort study of patients who underwent surgery for breast cancer treatment at the Clinical Hospital of the Federal University of Minas Gerais from 2001 to 2008 was performed, with a population of 897 cases. Information on tumor pathology and staging, as well as patients’ age and type of health coverage (SUS or private system) was collected. A probabilistic record linkage was performed with the database of the Mortality Information System to identify patients who died by December 31th, 2011. The basic cause of death was retrieved, and breast cancer-specific survival rates were estimated with the Kaplan-Meier method. The Cox proportional hazards model was used for univariate and multivariate analysis of factors related to survival. Results A total of 282 deaths occurred during the study’s period, 228 of them due to breast cancer. Five-year breast cancer-specific survival rates were 95.5% for stage I, 85.1% for stage II and 62.1% for stage III disease. Patients from the SUS had higher stages at diagnosis (42% was in stage III, and from the private system only 17.6% was in this stage), and in the univariate but not multivariate analysis, being treated by the SUS was associated with shorter survival (hazard ratio, HR = 2.22, 95% CI 1.24-3.98). In the multivariate analysis, larger tumor size, higher histologic grade, higher number of positive nodes and age older than 70 years were associated with a shorter breast cancer-specific survival. Conclusions Five-year breast cancer survival was comparable to other Brazilian cohorts. Patients

  4. A tumor DNA complex aberration index is an independent predictor of survival in breast and ovarian cancer

    PubMed Central

    Vollan, Hans Kristian Moen; Rueda, Oscar M.; Chin, Suet-Feung; Curtis, Christina; Turashvili, Gulisa; Shah, Sohrab; Lingjærde, Ole Christian; Yuan, Yinyin; Ng, Charlotte K.; Dunning, Mark J.; Dicks, Ed; Provenzano, Elena; Sammut, Stephen; McKinney, Steven; Ellis, Ian O.; Pinder, Sarah; Purushotham, Arnie; Murphy, Leigh C.; Kristensen, Vessela N.; Brenton, James D.; Pharoah, Paul D.P.; Børresen-Dale, Anne-Lise; Aparicio, Samuel; Caldas, Carlos

    2015-01-01

    Complex focal chromosomal rearrangements in cancer genomes, also called “firestorms”, can be scored from DNA copy number data. The complex arm-wise aberration index (CAAI) is a score that captures DNA copy number alterations that appear as focal complex events in tumors, and has potential prognostic value in breast cancer. This study aimed to validate this DNA-based prognostic index in breast cancer and test for the first time its potential prognostic value in ovarian cancer. Copy number alteration (CNA) data from 1950 breast carcinomas (METABRIC cohort) and 508 high-grade serous ovarian carcinomas (TCGA dataset) were analyzed. Cases were classified as CAAI positive if at least one complex focal event was scored. Complex alterations were frequently localized on chromosome 8p (n = 159), 17q (n = 176) and 11q (n = 251). CAAI events on 11q were most frequent in estrogen receptor positive (ER+) cases and on 17q in estrogen receptor negative (ER−) cases. We found only a modest correlation between CAAI and the overall rate of genomic instability (GII) and number of breakpoints (r = 0.27 and r = 0.42, p < 0.001). Breast cancer specific survival (BCSS), overall survival (OS) and ovarian cancer progression free survival (PFS) were used as clinical end points in Cox proportional hazard model survival analyses. CAAI positive breast cancers (43%) had higher mortality: hazard ratio (HR) of 1.94 (95%CI, 1.62–2.32) for BCSS, and of 1.49 (95%CI, 1.30–1.71) for OS. Representations of the 70-gene and the 21-gene predictors were compared with CAAI in multivariable models and CAAI was independently significant with a Cox adjusted HR of 1.56 (95%CI, 1.23–1.99) for ER+ and 1.55 (95%CI, 1.11–2.18) for ER− disease. None of the expression-based predictors were prognostic in the ER− subset. We found that a model including CAAI and the two expression-based prognostic signatures outperformed a model including the 21-gene and 70-gene signatures but excluding CAAI

  5. Decrease in Depression Symptoms Is Associated With Longer Survival in Patients With Metastatic Breast Cancer: A Secondary Analysis

    PubMed Central

    Giese-Davis, Janine; Collie, Kate; Rancourt, Kate M.S.; Neri, Eric; Kraemer, Helena C.; Spiegel, David

    2011-01-01

    Purpose Numerous studies have examined the comorbidity of depression with cancer, and some have indicated that depression may be associated with cancer progression or survival. However, few studies have assessed whether changes in depression symptoms are associated with survival. Methods In a secondary analysis of a randomized trial of supportive-expressive group therapy, 125 women with metastatic breast cancer (MBC) completed a depression symptom measure (Center for Epidemiologic Studies–Depression Scale [CES-D]) at baseline and were randomly assigned to a treatment group or to a control group that received educational materials. At baseline and three follow-up points, 101 of 125 women completed a depression symptom measure. We used these data in a Cox proportional hazards analysis to examine whether decreasing depression symptoms over the first year of the study (the length of the intervention) would be associated with longer survival. Results Median survival time was 53.6 months for women with decreasing CES-D scores over 1 year and 25.1 months for women with increasing CES-D scores. There was a significant effect of change in CES-D over the first year on survival out to 14 years (P = .007) but no significant interaction between treatment condition and CES-D change on survival. Neither demographic nor medical variables explained this association. Conclusion Decreasing depression symptoms over the first year were associated with longer subsequent survival for women with MBC in this sample. Further research is necessary to confirm this hypothesis in other samples, and causation cannot be assumed based on this analysis. PMID:21149651

  6. Factors associated with local recurrence and cause-specific survival in patients with ductal carcinoma in situ of the breast treated with breast-conserving therapy or mastectomy

    SciTech Connect

    Vargas, Carlos; Kestin, Larry; Go, Nel; Krauss, Daniel; Chen, Peter; Goldstein, Neal; Martinez, Alvaro; Vicini, Frank A. . E-mail: fvicini@beaumont.edu

    2005-12-01

    Purpose: We reviewed our institution's experience treating patients with ductal carcinoma in situ (DCIS) of the breast to determine risk factors for ipsilateral breast tumor recurrence (IBTR) and cause-specific survival (CSS) after breast-conserving therapy (BCT) or mastectomy. Materials and Methods: Between 1981 and 1999, 410 cases of DCIS (405 patients) were treated at our institution; 367 were managed with breast-conserving surgery (54 with lumpectomy alone and 313 with adjuvant radiation therapy (RT) [median dose, 45 Gy]). Of these 313 patients, 298 received also a supplemental boost of RT to the lumpectomy cavity (median dose, 16 Gy). Forty-three patients underwent mastectomy; 2 (5%) received adjuvant RT to the chest wall. A true recurrence/marginal miss (TR/MM) IBTR was defined as failure within or adjacent to the tumor bed in patients undergoing BCT. Median follow-up for all patients was 7 years (mean: 6.1 years). Results: Thirty patients (8.2%) experienced an IBTR after BCT (25 [8%] after RT, 5 [9.3%] after no RT), and 2 patients (4.7%) developed a chest wall recurrence after mastectomy. Of the 32 local failures, 20 (63%) were invasive (18/30 [60%] after BCT and 2/2 [100%] after mastectomy), and 37% were DCIS alone. Twenty-four (80%) of the IBTRs were classified as TR/MM. The 10-year freedom from local failure, CSS, and overall survival after BCT or mastectomy were 89% vs. 90% (p = 0.4), 98% vs. 100% (p = 0.7), and 89% vs. 100% (p = 0.3), respectively. Factors associated with IBTR on Cox multivariate analysis were younger age (p = 0.02, hazard ratio [HR] 1.06 per year), electron boost energy {<=}9 MeV (p = 0.03, HR 1.41), final margins {<=}2 mm (p = 0.007; HR, 3.65), and no breast radiation (p = 0.002, HR 5.56). On Cox univariate analysis for BCT patients, IBTR, TR/MM failures, and predominant nuclear Grade 3 were associated with an increased risk of distant metastases and a reduced CSS. Conclusions: After treatment for DCIS, 10-year rates of local control

  7. Randomised trial: survival benefit and safety of adjuvant dose-dense chemotherapy for node-positive breast cancer

    PubMed Central

    Kümmel, S; Krocker, J; Kohls, A; Breitbach, G-P; Morack, G; Budner, M; Blohmer, J-U; Elling, D

    2006-01-01

    We evaluated the survival benefit, safety, feasibility, and tolerability of dose-dense (DD) adjuvant chemotherapy with epirubicin and paclitaxel for women with node-positive primary breast cancer. Randomised patients (n=216) received DD or conventional-schedule (CS) chemotherapy. Dose-dense regimen patients (n=108) received epirubicin 90 mg m−2 plus paclitaxel 175 mg m−2 in four 14-day cycles, then cyclophosphamide 600 mg m−2, methotrexate 40 mg m−2, and fluorouracil 600 mg m−2 (CMF 600/40/600) in three 14-day cycles, plus filgrastim 5 μg kg day−1 as growth support in every cycle. Conventional-schedule regimen patients (n=108) received epirubicin 90 mg m−2 plus cyclophosphamide 600 mg m−2 in four 21-day cycles, then CMF 600/40/600 in three 21-day cycles, plus filgrastim if required. After a median follow-up of 38.4 months, 71 patients (33%) relapsed or died: DD, 33 patients (15 deaths); CS, 38 patients (22 deaths). Dose dense showed a trend for improved disease-free survival (DFS) and overall survival (OS). Four-year rates of DFS and OS were 64 and 85% for DD, and 58 and 75% for CS. All seven cycles were administered to 208 patients (96%). Rates of cycle delay, discontinuation, dose reduction, and adverse events were similar in both groups. Dose-dense sequential chemotherapy with epirubicin/paclitaxel then CMF, supported by filgrastim, is safe and improves survival for patients with node-positive breast cancer. PMID:16622463

  8. Influence of germline polymorphisms of GSTT1, GSTM1, and GSTP1 in familial versus sporadic breast cancer susceptibility and survival.

    PubMed

    Syamala, Volga S; Sreeja, Leelakumari; Syamala, Vani; Raveendran, Praveenkumar B; Balakrishnan, Rajan; Kuttan, Ratheesan; Ankathil, Ravindran

    2008-01-01

    Identifying genes associated with familial inheritance of breast cancer continues to be a major goal of current research as the known high penetrance genes could be attributable for only a small percentage of the risk. So, it is hypothesized that the low penetrance genes may also modify the risk for familial breast cancer. In the present case-control study, undertaken to examine the influence of polymorphisms of GSTs in familial and sporadic breast cancer susceptibility, 597 women including 222 sporadic breast cancer patients, 125 familial breast cancer patients and 250 females with no history of cancer as controls were genotyped by PCR based methods. Odds Ratios (ORs) and 95% Confidence Intervals (95%CIs) were calculated by unconditional logistic regression adjusted to age. Interestingly, GSTM1 deletion was found to be significantly associated only with familial breast cancer (OR = 2.0; 95%CI = 1.252-3.128) while GSTT1 was associated only with sporadic breast cancer (OR = 2.3; 95%CI = 1.336-3.970). GSTP1 Ile105Val polymorphism was associated neither with sporadic nor familial breast cancer susceptibility (P value > 0.05). The GST genotypes did not have any effect on the survival of both familial and sporadic breast cancer patients. However, familial breast cancer patients with GSTM1 null genotype had a relative risk of 0.42 (95%CI = 0.18-0.97) for an advanced disease stage. The results indicate that, in addition to the known high penetrance genes, certain low penetrance genes may also play a role, in the familial inheritance of breast cancer. It is also noticed that all the polymorphisms associated with sporadic breast cancer are not associated with familial breast cancer. PMID:18080216

  9. Impact of Bone-Targeted Treatments on Skeletal Morbidity and Survival in Breast Cancer.

    PubMed

    Coleman, Robert E

    2016-08-01

    Bone health is of increasing clinical importance throughout the clinical course of breast cancer. First, many breast cancer treatments have effects on reproductive hormones that are critical for bone health. This endocrine disturbance results in accelerated bone loss and an increased risk of fractures that can have a significant negative impact on cancer survivors. Second, the bone marrow microenvironment is intimately involved in the metastatic processes required for cancer dissemination, and may be modified by agents that influence bone cell physiology; there is now strong clinical trial evidence that the use of adjuvant bisphosphonates reduces metastasis to bone by one-third and reduces breast cancer mortality by one-sixth in postmenopausal or premenopausal women undergoing ovarian function suppression. Finally, bone metastases are common in advanced breast cancer, and may be associated with serious morbidity, including fractures, pain, nerve compression, and hypercalcemia. Through optimum multidisciplinary management and the use of bone-targeted treatments such as bisphosphonates or denosumab, patients with advanced breast cancer have experienced a major reduction in skeletal complications, less bone pain, and an improved quality of life.

  10. Impact of Bone-Targeted Treatments on Skeletal Morbidity and Survival in Breast Cancer.

    PubMed

    Coleman, Robert E

    2016-08-01

    Bone health is of increasing clinical importance throughout the clinical course of breast cancer. First, many breast cancer treatments have effects on reproductive hormones that are critical for bone health. This endocrine disturbance results in accelerated bone loss and an increased risk of fractures that can have a significant negative impact on cancer survivors. Second, the bone marrow microenvironment is intimately involved in the metastatic processes required for cancer dissemination, and may be modified by agents that influence bone cell physiology; there is now strong clinical trial evidence that the use of adjuvant bisphosphonates reduces metastasis to bone by one-third and reduces breast cancer mortality by one-sixth in postmenopausal or premenopausal women undergoing ovarian function suppression. Finally, bone metastases are common in advanced breast cancer, and may be associated with serious morbidity, including fractures, pain, nerve compression, and hypercalcemia. Through optimum multidisciplinary management and the use of bone-targeted treatments such as bisphosphonates or denosumab, patients with advanced breast cancer have experienced a major reduction in skeletal complications, less bone pain, and an improved quality of life. PMID:27528238

  11. Haptoglobin phenotype is not a predictor of recurrence free survival in high-risk primary breast cancer patients

    PubMed Central

    Gast, Marie-Christine W; van Tinteren, Harm; Bontenbal, Marijke; van Hoesel, René QGCM; Nooij, Marianne A; Rodenhuis, Sjoerd; Span, Paul N; Tjan-Heijnen, Vivianne CG; de Vries, Elisabeth GE; Harris, Nathan; Twisk, Jos WR; Schellens, Jan HM; Beijnen, Jos H

    2008-01-01

    Background Better breast cancer prognostication may improve selection of patients for adjuvant therapy. We conducted a retrospective follow-up study in which we investigated sera of high-risk primary breast cancer patients, to search for proteins predictive of recurrence free survival. Methods Two sample sets of high-risk primary breast cancer patients participating in a randomised national trial investigating the effectiveness of high-dose chemotherapy were analysed. Sera in set I (n = 63) were analysed by surface enhanced laser desorption ionisation time-of-flight mass spectrometry (SELDI-TOF MS) for biomarker finding. Initial results were validated by analysis of sample set II (n = 371), using one-dimensional gel-electrophoresis. Results In sample set I, the expression of a peak at mass-to-charge ratio 9198 (relative intensity ≤ 20 or > 20), identified as haptoglobin (Hp) alpha-1 chain, was strongly associated with recurrence free survival (global Log-rank test; p = 0.0014). Haptoglobin is present in three distinct phenotypes (Hp 1-1, Hp 2-1, and Hp 2-2), of which only individuals with phenotype Hp 1-1 or Hp 2-1 express the haptoglobin alpha-1 chain. As the expression of the haptoglobin alpha-1 chain, determined by SELDI-TOF MS, corresponds to the phenotype, initial results were validated by haptoglobin phenotyping of the independent sample set II by native one-dimensional gel-electrophoresis. With the Hp 1-1 phenotype as the reference category, the univariate hazard ratio for recurrence was 0.87 (95% CI: 0.56 – 1.34, p = 0.5221) and 1.03 (95% CI: 0.65 – 1.64, p = 0.8966) for the Hp 2-1 and Hp 2-2 phenotypes, respectively, in sample set II. Conclusion In contrast to our initial results, the haptoglobin phenotype was not identified as a predictor of recurrence free survival in high-risk primary breast cancer in our validation set. Our initial observation in the discovery set was probably the result of a type I error (i.e. false positive). This study

  12. Oestrogen receptors β1 and βcx have divergent roles in breast cancer survival and lymph node metastasis

    PubMed Central

    Rosin, G; de Boniface, J; Karthik, G M; Frisell, J; Bergh, J; Hartman, J

    2014-01-01

    Background: The expression of oestrogen receptor (ER) α characterises a subset of breast cancers associated with good response to endocrine therapy. However, the clinical significance of the second ER, ERβ1, and its splice variant ERβcx is still unclear. Methods: We here report an assessment of ERα, ERβ1 and ERβcx by immunohistochemistry using quantitative digital image analysis of 340 primary tumours and corresponding sentinel lymph nodes. Results: No differences were seen in ER levels in primary tumours vs lymph node metastases. ERβ1 and ERβcx were equally distributed among age groups and tumour histological grades. Loss of ERβ1 in the primary tumour was strongly associated with poor survival. Its prognostic impact was particularly evident in young patients and in high-grade tumours. The worst outcome was seen in the tumours lacking both ERα and ERβ1. ERβcx expression in the primary tumour correlated with a higher risk of lymph node metastasis, and with poor survival when expressed in sentinel node lymphocytes. Conclusions: Our study reveals highly significant although antagonising roles of ERβ1 and ERβcx in breast cancer. Consequently, we suggest that the histopathological assessment of ERβ1 is of value as a prognostic and potentially predictive biomarker. PMID:25025959

  13. Oligosaccharide Composition of Breast Milk Influences Survival of Uninfected Children Born to HIV-Infected Mothers in Lusaka, Zambia12

    PubMed Central

    Kuhn, Louise; Kim, Hae-Young; Hsiao, Lauren; Nissan, Caroline; Kankasa, Chipepo; Mwiya, Mwiya; Thea, Donald M; Aldrovandi, Grace M; Bode, Lars

    2015-01-01

    Background: Human milk oligosaccharides (HMOs) have multiple immunomodulatory functions that influence child health. Objective: In this study we investigated whether HMO composition influences survival to 2 y of age in HIV-infected and HIV-exposed, uninfected (HEU) children during and after breastfeeding. Methods: In the context of an early weaning trial in 958 HIV-infected women in Lusaka, Zambia, we conducted a nested case-cohort analysis of mortality to 2 y of age among 103 HIV-infected and 143 HEU children. Breast-milk samples collected at 1 mo postpartum were analyzed for HMO content. Samples were selected to include mothers of all HIV-infected children detected by 6 wk of age, of whom 63 died at <2 y of age; mothers of all HEU children who died at <2 y of age (n = 66); and a random sample of 77 HEU survivors. Associations before and after weaning in HIV-infected and HEU infants separately were investigated by using Cox models. Results: Among HEU children, higher maternal breast-milk concentrations of 2-linked fucosylated HMOs [2′-fucosyllactose and lacto-N-fucopentaose (LNFP) I] (HR: 0.33; 95% CI: 0.14, 0.74) as well as non–2-linked fucosylated HMOs (3-fucosyllactose and LNFP II/III; HR: 0.28; 95% CI: 0.13, 0.67) were significantly associated with reduced mortality during, but not after, breastfeeding after adjustment for confounders. Breastfeeding was protective against mortality only in HEU children with high concentrations of fucosylated HMOs. Among HIV-infected children, no consistent associations between HMOs and mortality were observed, but breastfeeding was protective against mortality. Conclusions: The oligosaccharide composition of breast milk may explain some of the benefits of breastfeeding in HEU children. HIV infection may modulate some of the consequences of HMOs on child survival. PMID:25527660

  14. Prognostic value of protein tyrosine kinase 6 (PTK6) for long-term survival of breast cancer patients.

    PubMed

    Aubele, M; Walch, A K; Ludyga, N; Braselmann, H; Atkinson, M J; Luber, B; Auer, G; Tapio, S; Cooke, T; Bartlett, J M S

    2008-10-01

    The cytoplasmic tyrosine kinase PTK6 (BRK) shows elevated expression in approximately two-thirds of primary breast tumours, and is implicated in EGF receptor-dependent signalling and epithelial tumorigenesis. Using immunohistochemistry, we performed a retrospective study on 426 archival breast cancer samples from patients with long-term follow-up and compared the protein expression levels of PTK6, the HER receptors, Sam68 (a substrate of PTK6), and signalling proteins including MAP kinase (MAPK), phosphorylated MAPK (P-MAPK), and PTEN. We show that PTK6 expression is of significant prognostic value in the outcome of breast carcinomas. In multivariate analysis, the disease-free survival of patients of >or=240 months was directly associated with the protein expression level of PTK6 (Pbreast cancer.

  15. Prognostic value of protein tyrosine kinase 6 (PTK6) for long-term survival of breast cancer patients

    PubMed Central

    Aubele, M; Walch, A K; Ludyga, N; Braselmann, H; Atkinson, M J; Luber, B; Auer, G; Tapio, S; Cooke, T; Bartlett, J M S

    2008-01-01

    The cytoplasmic tyrosine kinase PTK6 (BRK) shows elevated expression in approximately two-thirds of primary breast tumours, and is implicated in EGF receptor-dependent signalling and epithelial tumorigenesis. Using immunohistochemistry, we performed a retrospective study on 426 archival breast cancer samples from patients with long-term follow-up and compared the protein expression levels of PTK6, the HER receptors, Sam68 (a substrate of PTK6), and signalling proteins including MAP kinase (MAPK), phosphorylated MAPK (P-MAPK), and PTEN. We show that PTK6 expression is of significant prognostic value in the outcome of breast carcinomas. In multivariate analysis, the disease-free survival of patients of ⩾240 months was directly associated with the protein expression level of PTK6 (P⩽0.001), but was also inversely associated with nodal status (P⩽0.001) and tumour size (P⩽0.01). PTK6 expression in tumour tissue significantly correlated (P⩽0.05) with the expression of PTEN, MAPK, P-MAPK, and Sam68. To investigate whether these correlations may be due to molecular interactions between PTK6 and these proteins, we used protein extracts from the T47D cell line for immunoprecipitation and western blot analysis. By this, interactions could be demonstrated between PTK6 and MAPK, P-MAPK, HER2/neu, HER3, HER4, PTEN, and Sam68. On the basis of these results, we suggest that PTK6 may serve as a future target for the development of novel treatments in breast cancer. PMID:18781181

  16. Radiotherapy Can Decrease Locoregional Recurrence and Increase Survival in Mastectomy Patients With T1 to T2 Breast Cancer and One to Three Positive Nodes With Negative Estrogen Receptor and Positive Lymphovascular Invasion Status

    SciTech Connect

    Yang, P.S.; Chen, C.M.; Liu, M.C.; Jian, J.M.; Horng, C.F.; Liu, M.J.; Yu, B.L.; Lee, M.Y.; Chi, C.W.

    2010-06-01

    Purpose: To define a subgroup of patients at high risk of locoregional recurrence (LRR) who might be benefit from postmastectomy radiotherapy in invasive breast cancer and tumor size <5 cm with one to three involved axillary lymph nodes (T1-2 N1). Methods and Materials: Between April 1991 and December 2005, 544 patients with T1-2 N1 invasive breast cancer were treated with modified radical mastectomy. Of the 544 patients, 383 patients (70.4%) had no radiotherapy, and 161 patients (29.6%) received radiotherapy. We retrospectively compared these two patient groups. Results: With a median follow-up of 40.3 months, LRR occurred in 40 (7.4%) of 544 patients. On univariate analysis, high nuclear grade (p = 0.04), negative estrogen receptor (ER) status (p = 0.001), presence of lymphovascular invasion (LVI) (p = 0.003), and no radiotherapy (p = 0.0015) were associated with a significantly higher rate of LRR. Negative ER status (hazard ratio = 5.1) and presence of LVI (hazard ratio = 2.5) were the risk factors for LRR with statistical significance in the multivariate analysis. Radiotherapy reduced the LRR in patients with the following characteristics: age <40 years, T2 stage, high nuclear grade, negative ER status, and presence of LVI. For 41 patients with negative ER and positive LVI status, radiotherapy can reduce LRR from 10 of 25 (40%) to 2 of 16 (12.5%) and increase the 5-year overall survival from 43.7% to 87.1%. Conclusion: Radiotherapy can reduce LRR and increase survival in T1-2 N1 breast cancer patients with negative ER status and presence of LVI.

  17. Loss of PTPN12 Stimulates Progression of ErbB2-Dependent Breast Cancer by Enhancing Cell Survival, Migration, and Epithelial-to-Mesenchymal Transition.

    PubMed

    Li, Juan; Davidson, Dominique; Martins Souza, Cleiton; Zhong, Ming-Chao; Wu, Ning; Park, Morag; Muller, William J; Veillette, André

    2015-12-01

    PTPN12 is a cytoplasmic protein tyrosine phosphatase (PTP) reported to be a tumor suppressor in breast cancer, through its capacity to dephosphorylate oncogenic receptor protein tyrosine kinases (PTKs), such as ErbB2. However, the precise molecular and cellular impact of PTPN12 deficiency in breast cancer progression remains to be fully clarified. Here, we addressed this issue by examining the effect of PTPN12 deficiency on breast cancer progression in vivo, in a mouse model of ErbB2-dependent breast cancer using a conditional PTPN12-deficient mouse. Our studies showed that lack of PTPN12 in breast epithelial cells accelerated breast cancer development and lung metastases in vivo. PTPN12-deficient breast cancer cells displayed enhanced tyrosine phosphorylation of the adaptor Cas, the adaptor paxillin, and the kinase Pyk2. They exhibited no detectable increase in ErbB2 tyrosine phosphorylation. PTPN12-deficient cells were more resistant to anoikis and had augmented migratory and invasive properties. Enhanced migration was corrected by inhibiting Pyk2. PTPN12-deficient breast cancer cells also acquired partial features of epithelial-to-mesenchymal transition (EMT), a feature of more aggressive forms of breast cancer. Hence, loss of PTPN12 promoted tumor progression in a mouse model of breast cancer, supporting the notion that PTPN12 is a tumor suppressor in human breast cancer. This function was related to the ability of PTPN12 to suppress cell survival, migration, invasiveness, and EMT and to inhibit tyrosine phosphorylation of Cas, Pyk2, and paxillin. These findings enhance our understanding of the role and mechanism of action of PTPN12 in the control of breast cancer progression.

  18. Treatment-Associated Musculoskeletal and Vasomotor Symptoms and Relapse-Free Survival in the NCIC CTG MA.27 Adjuvant Breast Cancer Aromatase Inhibitor Trial

    PubMed Central

    Stearns, Vered; Chapman, Judith-Anne W.; Ma, Cynthia X.; Ellis, Matthew J.; Ingle, James N.; Pritchard, Kathleen I.; Budd, G. Thomas; Rabaglio, Manuela; Sledge, George W.; Le Maitre, Aurélie; Kundapur, Jessica; Liedke, Pedro E.R.; Shepherd, Lois E.; Goss, Paul E.

    2015-01-01

    Purpose Treatment-emergent symptoms with adjuvant tamoxifen and aromatase inhibitors (AIs) have been associated with superior recurrence-free survival (RFS). We hypothesized that MA.27 anastrozole- or exemestane-treated patients with new or worsening vasomotor and/or joint symptoms would have improved RFS. Patients and Methods MA.27 randomly assigned 7,576 postmenopausal women with breast cancer to 5 years of anastrozole or exemestane. Patient-reported symptoms were collected using the Common Terminology Criteria for Adverse Events version 3.0 at protocol-specified baseline and 6- and 12-month clinical visits. Symptoms were considered present with either vasomotor and/or joint complaints. Associations between symptoms and baseline patient characteristics were examined with χ2 and Fisher's exact tests. Subsequent effects of new or worsening symptoms on RFS were examined with landmark analyses and stratified univariable and multivariable Cox models. We examined the effects of 3-month symptoms arising from unplanned clinic visits as a result of severe toxicity. Results Patients were assessable if eligible for the MA.27 trial, received some trial therapy, and had no disease recurrence at the end of a symptom assessment period; 96% of patients (n = 7,306 patients) were included at 6 months, and 96% (n = 7,246) were included at 12 months. Thirty-four percent of patients had baseline symptoms. For patients without baseline symptoms, 25% and 52% had new symptoms by 6 and 12 months, respectively. Neither treatment-emergent nor baseline symptoms significantly impacted RFS (P > .10) in patients with or without baseline symptoms. Conclusion In MA.27, anastrozole or exemestane treatment-emergent symptoms were not associated with improved RFS. Women should be supported through treatment and encouraged to remain on their AI regardless of their symptoms. PMID:25512454

  19. Modeling Malignant Breast Cancer Occurrence and Survival in Black and White Women

    ERIC Educational Resources Information Center

    Gleason, Michael

    2013-01-01

    Background: Breast cancer (BC), the most common cancer diagnosed in women in the United States, is a heterogeneous disease in which age-specific incidence rates (ASIRs) differ by race and mortality rates are higher in blacks than whites. Goals: (i) understand the reasons for the black-to-white ethnic crossover in the ASIRs; (ii) formulate a…

  20. Vitamin supplement use during breast cancer treatment and survival: a prospective cohort study

    PubMed Central

    Nechuta, Sarah; Lu, Wei; Chen, Zhi; Zheng, Ying; Gu, Kai; Cai, Hui; Zheng, Wei; Shu, Xiao Ou

    2011-01-01

    Background Antioxidants may protect normal cells from the oxidative damage that occurs during radiotherapy and certain chemotherapy regimens, however, the same mechanism could protect tumor cells and potentially reduce effectiveness of cancer treatments. We evaluated the association of vitamin supplement use in the first six-months after breast cancer diagnosis and during cancer treatment with total mortality and recurrence. Methods We conducted a population-based prospective cohort study of 4,877 women aged 20–75 years diagnosed with invasive breast cancer in Shanghai, China between March 2002 and April 2006. Women were interviewed approximately six-months after diagnosis and followed-up by in-person interviews and record linkage with the vital statistics registry. Results During a mean follow-up of 4.1 years, 444 deaths and 532 recurrences occurred. Vitamin use shortly after breast cancer diagnosis was associated with reduced mortality and recurrence risk, adjusted for multiple lifestyle factors, sociodemographics, and known clinical prognostic factors. Women who used antioxidants (vitamin E, vitamin C, multivitamins) had 18% reduced mortality risk (hazard ratio (HR) = 0.82, 95% confidence interval (CI): 0.65–1.02) and 22% reduced recurrence risk (HR = 0.78, 95% CI: 0.63–0.95). The inverse association was found regardless of whether vitamin use was concurrent or non-concurrent with chemotherapy, but was only present among patients who did not receive radiotherapy. Conclusions Vitamin supplement use in the first six months after breast cancer diagnosis may be associated with reduced risk of mortality and recurrence. Impact Our results do not support the current recommendation that breast cancer patients should avoid use of vitamin supplements. PMID:21177425

  1. HMG-CoAR expression in male breast cancer: relationship with hormone receptors, Hippo transducers and survival outcomes

    PubMed Central

    Di Benedetto, Anna; Mottolese, Marcella; Sperati, Francesca; Ercolani, Cristiana; Di Lauro, Luigi; Pizzuti, Laura; Vici, Patrizia; Terrenato, Irene; Shaaban, Abeer M.; Sundara-Rajan, Sreekumar; Humphries, Matthew P.; Barba, Maddalena; Speirs, Valerie; De Maria, Ruggero; Maugeri-Saccà, Marcello

    2016-01-01

    Male breast cancer (MBC) is a rare hormone-driven disease often associated with obesity. HMG-CoAR is the central enzyme of the mevalonate pathway, a molecular route deputed to produce cholesterol and steroid-based hormones. HMG-CoAR regulates the oncogenic Hippo transducers TAZ/YAP whose expression was previously associated with shorter survival in MBC. 225 MBC samples were immunostained for HMG-CoAR and 124 were considered eligible for exploring its relationship with hormone receptors (ER, PgR, AR), Hippo transducers and survival outcomes. HMG-CoAR was positively associated with the expression of hormone receptors (ER, PgR, AR) and Hippo transducers. Overall survival was longer in patients with HMG-CoAR-positive tumors compared with their negative counterparts (p = 0.031). Five- and 10-year survival outcomes were better in patients whose tumors expressed HMG-CoAR (p = 0.044 and p = 0.043). Uni- and multivariate analyses for 10-year survival suggested that HMG-CoAR expression is a protective factor (HR 0.50, 95% CI: 0.25–0.99, p = 0.048 and HR 0.53, 95% CI: 0.26–1.07, p = 0.078). Results were confirmed in a sensitivity analysis by excluding uncommon histotypes (multivariate Cox: HR 0.45, 95% CI: 0.21–0.97, p = 0.043). A positive relationship emerged between HMG-CoAR, hormone receptors and TAZ/YAP, suggesting a connection between the mevalonate pathway, the hormonal milieu and Hippo in MBC. Moreover, HMG-CoAR expression may be a favorable prognostic indicator. PMID:27713571

  2. How much survival benefit is necessary for breast cancer patients to opt for adjuvant chemotherapy? Results from a Chilean survey

    PubMed Central

    Acevedo, Francisco; Sanchez, Cesar; Jans, Jaime; Rivera, Solange; Camus, Mauricio; Besa, Pelayo

    2014-01-01

    Background: Breast cancer (BC) is the leading cause of cancer death in Chilean women. Adjuvant chemotherapy decreases recurrence and death from BC. The recommendation to indicate chemotherapy is complex. Adjuvant! Online is a valuable computational tool to predict survival benefit obtained with adjuvant systemic therapy. Previous studies in Caucasian patients with BC showed that they are willing to receive chemotherapy for a small benefit. No studies, to our knowledge, have been done in the Hispanic or Latino populations. Methods: We interviewed females with BC who had previously received adjuvant chemotherapy. Age, stage at presentation, time since last chemotherapy, type of chemotherapy, marital status, number of children, and level of education were recorded. We used the graphic representation from Adjuvant! Online to question each patient on how much survival benefit she required to accept chemotherapy. Results: There were 101 women surveyed. The average age was 55.9 (±10.2), 54.5% had involved lymph nodes, 59.4% were married, and 15.8% did not have parity; 62.3% of females accepted chemotherapy for an absolute survival benefit of 1% or less. In a multivariate analysis, younger (p = 0.02) and less-educated patients (p = 0.018) were associated with lower survival benefit required to opt for chemotherapy. Conclusion: In our study, the acceptance of chemotherapy by the Hispanic population requires minimal survival benefit and is in agreement with the Caucasian population reported elsewhere. To our knowledge, our report is the first study that evaluates the perception of Latino patients regarding the benefit of chemotherapy in early BC. PMID:24678346

  3. A randomized controlled trial of cognitive-behavioral stress management in breast cancer: survival and recurrence at 11-year follow-up.

    PubMed

    Stagl, Jamie M; Lechner, Suzanne C; Carver, Charles S; Bouchard, Laura C; Gudenkauf, Lisa M; Jutagir, Devika R; Diaz, Alain; Yu, Qilu; Blomberg, Bonnie B; Ironson, Gail; Glück, Stefan; Antoni, Michael H

    2015-11-01

    Non-metastatic breast cancer patients often experience psychological distress which may influence disease progression and survival. Cognitive-behavioral stress management (CBSM) improves psychological adaptation and lowers distress during breast cancer treatment and long-term follow-ups. We examined whether breast cancer patients randomized to CBSM had improved survival and recurrence 8-15 years post-enrollment. From 1998 to 2005, women (N = 240) 2-10 weeks post-surgery for non-metastatic Stage 0-IIIb breast cancer were randomized to a 10-week, group-based CBSM intervention (n = 120) or a 1-day psychoeducational seminar control (n = 120). In 2013, 8-15 years post-study enrollment (11-year median), recurrence and survival data were collected. Cox Proportional Hazards Models and Weibull Accelerated Failure Time tests were used to assess group differences in all-cause mortality, breast cancer-specific mortality, and disease-free interval, controlling for biomedical confounders. Relative to the control, the CBSM group was found to have a reduced risk of all-cause mortality (HR = 0.21; 95 % CI [0.05, 0.93]; p = .040). Restricting analyses to women with invasive disease revealed significant effects of CBSM on breast cancer-related mortality (p = .006) and disease-free interval (p = .011). CBSM intervention delivered post-surgery may provide long-term clinical benefit for non-metastatic breast cancer patients in addition to previously established psychological benefits. Results should be interpreted with caution; however, the findings contribute to the limited evidence regarding physical benefits of psychosocial intervention post-surgery for non-metastatic breast cancer. Additional research is necessary to confirm these results and investigate potential explanatory mechanisms, including physiological pathways, health behaviors, and treatment adherence changes.

  4. Absence of Gamma-Interferon-Inducible Lysosomal Thiol Reductase (GILT) Is Associated with Poor Disease-Free Survival in Breast Cancer Patients

    PubMed Central

    Zhou, Cheng-Jun; Liu, Lu; Han, Bo; Kong, Ling-Yu; Gao, Zhong-Cheng; Ma, Zhong-Bing; Wang, Lu; Feng, Man; Chen, Hai-Ying; Jia, Guo-Tao; Gao, De-Zong; Zhang, Qiang; Li, Liang; Li, Yu-Yang; Yu, Zhi-Gang

    2014-01-01

    Tumor immunosurveillance is known to be of critical importance in controlling tumorigenesis and progression in various cancers. The role of gamma-interferon-inducible lysosomal thiol reductase (GILT) in tumor immunosurveillance has recently been studied in several malignant diseases, but its role in breast cancer remains to be elucidated. In the present study, we found GILT as a significant different expressed gene by cDNA microarray analysis. To further determine the role of GILT in breast cancer, we examined GILT expression in breast cancers as well as noncancerous breast tissues by immunohistochemistry and real-time PCR, and assessed its association with clinicopathologic characteristics and patient outcome. The absence of GILT expression increased significantly from 2.02% (2/99) in noncancerous breast tissues to 15.6% (34/218) in breast cancer tissues (P<0.001). In accordance with its proliferation inhibiting function, GILT expression was inversely correlated with Ki67 index (P<0.05). In addition, absence of GILT was positively correlated with adverse characteristics of breast cancers, such as histological type, tumor size, lymph nodes status, and pTNM stage (P<0.05). Consistently, breast cancers with reduced GILT expression had poorer disease-free survival (P<0.005). Moreover, significantly decreased expression of GILT was found in both primary and metastatic breast cancer cells, in contrast to normal epithelial cells. These findings indicate that GILT may act as a tumor suppressor in breast cancer, in line with its previously suggested role in anti-tumor immunity. Thus, GILT has the potential to be a novel independent prognostic factor in breast cancer and further studies are needed to illustrate the underlying mechanism of this relationship. PMID:25333930

  5. High EZH2 Protein Expression Is Associated with Poor Overall Survival in Patients with Luminal A Breast Cancer

    PubMed Central

    Jang, Si-Hyong; Lee, Jong Eun; Oh, Mee-Hye; Lee, Ji-Hye; Cho, Hyun Deuk; Kim, Kyung-Ju; Kim, Sung Yong; Han, Sun Wook; Kim, Han Jo; Bae, Sang Byung

    2016-01-01

    Purpose The enhancer of zeste homologue 2 (EZH2) is a catalytic subunit of the polycomb repressive complex 2, a highly conserved histone methyltransferase. EZH2 overexpression has been implicated in various malignancies, including breast cancer, where is associated with poor outcomes. This study aims to clarify nuclear EZH2 expression levels in breast cancers using immunohistochemistry (IHC) and correlate these findings with clinicopathologic variables, including prognostic significance. Methods IHC was performed on tissue microarrays of 432 invasive ductal carcinoma (IDC) tumors. Associations between EZH2 expression, clinicopathologic characteristics, and molecular subtype were retrospectively analyzed. The relationship between EZH2 protein expression in normal breast tissue and ductal carcinoma in situ (DCIS) was also assessed. Results High EZH2 expression was demonstrated in 215 of 432 tumors (49.8%). EZH2 was more frequently expressed in DCIS and IDC than in normal breast tissue (p=0.001). High EZH2 expression significantly correlated with high histologic grade (p<0.001), large tumor size (p=0.014), advanced pathologic stage (p=0.006), negative estrogen receptor status (p<0.001), positive human epidermal growth factor receptor 2 (HER2) status (p<0.001), high Ki-67 staining index (p<0.001), positive cytokeratin 5/6 status (p=0.003), positive epidermal growth factor receptor status (p<0.001), and positive p53 status (p<0.001). Based on molecular subtypes, high EZH2 expression was significantly associated with HER2-negative luminal B, HER2-positive luminal B, and HER2 type and triple-negative basal cancers (p<0.001). In patients with luminal A, there was a significant trend toward shorter overall survival for those with tumors having high EZH2 expression compared to those with tumors having low EZH2 expression (p=0.045). Conclusion EZH2 is frequently upregulated in breast malignancies, and it may play an important role in cancer development and progression

  6. Correlation between progression-free survival and overall survival in metastatic breast cancer patients receiving anthracyclines, taxanes, or targeted therapies: a trial-level meta-analysis

    PubMed Central

    Adunlin, George; Cyrus, John W. W.; Dranitsaris, George

    2016-01-01

    Over the past decade, several new drugs have received regulatory approval for metastatic breast cancer (MBC). However, some of these approvals were based on improvement in progression-free survival (PFS), without a concomitant increase in overall survival (OS). This has led some to question the utility of using PFS as a measure for drug approval. To address the uncertainty of using PFS as a surrogate for OS in MBC, a systematic literature review followed by a trial-level correlative analysis was conducted in patients receiving anthracyclines, taxanes, or targeted therapies. Electronic databases were searched to identify randomized trials published between January 1990 and August 2015. Data extraction included hazard ratios for PFS (HRPFS) and OS (HROS) between comparative arms as well as trial-level parameters. Weighted multivariate regression analysis was then used to test the strength of the association between HRPFS and HROS. 72 trials providing 84 comparative arms met the inclusion criteria. HRPFS was a significant predictor of HROS (model coefficient = 0.18, p = 0.04). However, only 31 % (i.e., model R2) of the variability between the PFS–OS association was accounted for. When trials were limited to ≥2nd-line setting, the strength of the association improved (model coefficient = 0.40, p < 0.001) and the model R2 increased to 55 %. However, the HRPFS–HROS association was no longer significant when only 1st-line trials were considered (p = 0.90). HRPFS is a predictor for HROS in MBC randomized trials. However, the effect was driven by trials in the ≥2nd-line setting. Therefore, PFS can be a suitable surrogate for OS in trials evaluating new treatments in the 2nd setting and beyond. The use of PFS alone as a primary trial endpoint in the 1st-line setting is not recommended. PMID:26596731

  7. Microbiological monitoring of endoscopes: 5-year review.

    PubMed

    Gillespie, Elizabeth E; Kotsanas, Despina; Stuart, Rhonda L

    2008-07-01

    Periodic microbiological monitoring of endoscopes is a recommendation of the Gastroenterological Society of Australia (GENSA). The aim of monitoring has been to provide quality assurance of the cleaning and disinfection of endoscopes; however, there is controversy regarding its frequency. This lack of consensus stimulated a review of the experience within our health service. At Southern Health, routine microbiological sampling has involved 4-weekly monitoring of bronchoscopes, duodenoscopes and automated flexible endoscope reprocessors (AFER), and 3-monthly monitoring of all other gastrointestinal endoscopes. Records of testing were reviewed from 1 January 2002 until 31 December 2006. A literature review was conducted, cost analysis performed and positive cultures investigated. There were 2374 screening tests performed during the 5-year period, including 287 AFER, 631 bronchoscopes for mycobacteria and 1456 endoscope bacterial screens. There were no positive results of the AFER or bronchoscopes for mycobacteria. Of the 1456 endoscopic bacterial samples, six were positive; however, retesting resulted in no growth. The overall cost of tests performed and cost in time for nursing staff to collect the samples was estimated at $AUD 100,400. Periodic monitoring of endoscopes is both time-consuming and costly. Our review demonstrates that AFER (Soluscope) perform well in cleaning endoscopes. Based on our 5-year experience, assurance of quality for endoscopic use could be achieved through process control as opposed to product control. Maintenance of endoscopes and AFER should be in accordance with the manufacturer's instructions and microbiological testing performed on commissioning, annually and following repair. Initial prompt manual leak testing and manual cleaning followed by mechanical leak testing, cleaning and disinfection should be the minimum standard in reprocessing of endoscopes. PMID:18086113

  8. Intratumoral expression of CCR3 in breast cancer is associated with improved relapse-free survival in luminal-like disease

    PubMed Central

    Chen, Hai-Yan; Ding, Ke-Feng; Yu, Ke-Da

    2016-01-01

    Purpose The association chemokine receptor CCR3 with breast cancer subtypes and relapse-free survival is unknown. Results The overall expression (either intratumoral or peritumoral) of CCR3 was not associated with tumor size, lymph node status, age, and subtype. When we confined the analysis in samples without peritumoral stromal CCR3 expression, intratumoral expression of CCR3 was associated with breast cancer subtype (P=0.04). Tumors with high expression of CCR3 were more likely to be luminal-like rather than TNBC or HER2-enriched cancers. Moreover, high mRNA expression of CCR3 was related with improved relapse-free survival in luminal-A/B (P<0.001). The subsequent sensitivity analysis using the systemically untreated patients confirmed that higher mRNA expression of CCR3 was a robust prognostic factor for luminal-A (P=0.0025) and luminal-B (P=0.088), but not for HER2-enriched (P=0.21) and TNBC (P=0.86). In the independent cohort, the positive association between increased expression of CCR3 and improved distant relapse-free survival was also observed. Methods We determined the expression level of CCR3 in 150 cases with breast cancer by using immunohistochemistry (IHC) assay, for both intratumoral and peritumoral stroma, and investigated the effect of CCR3 expression on relapse-free survival according to subtype using cases from publicly available datasets, in the whole group (N=3557) and in the patients without adjuvant systemic treatment (N=1005), respectively. Moreover, the survival outcomes were validated in another independent cohort including 508 breast cancer patients treated with neoadjuvant chemotherapy. Conclusions Our data indicate that intratumoral expression of CCR3 in breast cancer is associated with improved relapse-free survival in patients with luminal-like disease. PMID:27086913

  9. A perfect storm: How tumor biology, genomics, and health care delivery patterns collide to create a racial survival disparity in breast cancer and proposed interventions for change.

    PubMed

    Daly, Bobby; Olopade, Olufunmilayo I

    2015-01-01

    It is well known that there is a significant racial divide in breast cancer incidence and mortality rates. African American women are less likely to be diagnosed with breast cancer than white women but are more likely to die from it. This review explores the factors that may contribute to the racial survival disparity. Consideration is paid to what is known about the role of differences in tumor biology, genomics, cancer screening, and quality of cancer care. It is argued that it is the collision of 2 forces, tumor biology and genomics, with patterns of care that leads to the breast cancer mortality gap. The delays, misuse, and underuse of treatment for African American patients are of increased significance when these patients are presenting with more aggressive forms of breast cancer. In the current climate of health care reform ushered in by the Affordable Care Act, this article also evaluates interventions to close the disparity gap. Prior interventions have been too narrowly focused on the patient rather than addressing the system and improving care across the continuum of breast cancer evaluation and treatment. Lastly, areas of future investigation and policy initiatives aimed at reducing the racial survival disparity in breast cancer are discussed. PMID:25960198

  10. A perfect storm: How tumor biology, genomics, and health care delivery patterns collide to create a racial survival disparity in breast cancer and proposed interventions for change.

    PubMed

    Daly, Bobby; Olopade, Olufunmilayo I

    2015-01-01

    It is well known that there is a significant racial divide in breast cancer incidence and mortality rates. African American women are less likely to be diagnosed with breast cancer than white women but are more likely to die from it. This review explores the factors that may contribute to the racial survival disparity. Consideration is paid to what is known about the role of differences in tumor biology, genomics, cancer screening, and quality of cancer care. It is argued that it is the collision of 2 forces, tumor biology and genomics, with patterns of care that leads to the breast cancer mortality gap. The delays, misuse, and underuse of treatment for African American patients are of increased significance when these patients are presenting with more aggressive forms of breast cancer. In the current climate of health care reform ushered in by the Affordable Care Act, this article also evaluates interventions to close the disparity gap. Prior interventions have been too narrowly focused on the patient rather than addressing the system and improving care across the continuum of breast cancer evaluation and treatment. Lastly, areas of future investigation and policy initiatives aimed at reducing the racial survival disparity in breast cancer are discussed.

  11. Timing of Adjuvant Surgical Oophorectomy in the Menstrual Cycle and Disease-Free and Overall Survival in Premenopausal Women With Operable Breast Cancer

    PubMed Central

    Laudico, Adriano V.; Van Dinh, Nguyen; Allred, D. Craig; Uy, Gemma B.; Quang, Le Hong; Salvador, Jonathan Disraeli S.; Siguan, Stephen Sixto S.; Mirasol-Lumague, Maria Rica; Tung, Nguyen Dinh; Benjaafar, Noureddine; Navarro, Narciso S.; Quy, Tran Tu; De La Peña, Arturo S.; Dofitas, Rodney B.; Bisquera, Orlino C.; Linh, Nguyen Dieu; To, Ta Van; Young, Gregory S.; Hade, Erinn M.; Jarjoura, David

    2015-01-01

    Background: For women with hormone receptor–positive, operable breast cancer, surgical oophorectomy plus tamoxifen is an effective adjuvant therapy. We conducted a phase III randomized clinical trial to test the hypothesis that oophorectomy surgery performed during the luteal phase of the menstrual cycle was associated with better outcomes. Methods: Seven hundred forty premenopausal women entered a clinical trial in which those women estimated not to be in the luteal phase of their menstrual cycle for the next one to six days (n = 509) were randomly assigned to receive treatment with surgical oophorectomy either delayed to be during a five-day window in the history-estimated midluteal phase of the menstrual cycles, or in the next one to six days. Women who were estimated to be in the luteal phase of the menstrual cycle for the next one to six days (n = 231) were excluded from random assignment and received immediate surgical treatments. All patients began tamoxifen within 6 days of surgery and continued this for 5 years. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess differences in five-year disease-free survival (DFS) between the groups. All statistical tests were two-sided. Results: The randomized midluteal phase surgery group had a five-year DFS of 64%, compared with 71% for the immediate surgery random assignment group (hazard ratio [HR] = 1.24, 95% confidence interval [CI] = 0.91 to 1.68, P = .18). Multivariable Cox regression models, which included important prognostic variables, gave similar results (aHR = 1.28, 95% CI = 0.94 to 1.76, P = .12). For overall survival, the univariate hazard ratio was 1.33 (95% CI = 0.94 to 1.89, P = .11) and the multivariable aHR was 1.43 (95% CI = 1.00 to 2.06, P = .05). Better DFS for follicular phase surgery, which was unanticipated, proved consistent across multiple exploratory analyses. Conclusions: The hypothesized benefit of adjuvant luteal phase oophorectomy was

  12. Long-term cardiovascular outcomes and overall survival of early-stage breast cancer patients with early discontinuation of trastuzumab: a population-based study.

    PubMed

    Gong, Inna Y; Verma, Sunil; Yan, Andrew T; Ko, Dennis T; Earle, Craig C; Tomlinson, George A; Trudeau, Maureen E; Krahn, Murray D; Krzyzanowska, Monika K; Brezden-Masley, Christine B; Gavura, Scott; Peacock, Stuart; Chan, Kelvin K W

    2016-06-01

    We critically examined long-term cardiovascular (CV) outcomes and overall survival (OS) of breast cancer (BC) patients who had cardiotoxicity during adjuvant trastuzumab treatment requiring discontinuation in a population-based sample. This was a retrospective cohort of early-stage BC patients diagnosed before 2010 and treated with trastuzumab in Ontario. Patients were stratified based on trastuzumab doses received: 1-8, 9-15, ≥16 (therapy completion). Time-dependent multivariable Cox models were used to analyze primary endpoint OS, and the following composite endpoints: hospitalization/emergency room visit for heart failure (HF) or death; non-HF CV (myocardial infarction, stroke) or death; and clinically significant relapse (palliative systemic therapy initiation >90 days after last trastuzumab dose) or death. Of the 3134 women, 6, 10, and 85 % received 1-8, 9-15, and ≥16 doses, respectively. Over 5-year median follow-up, early trastuzumab discontinuation was associated with more HF/death [1-8 doses hazard ratio (HR) 4.0, 95 % confidence interval (CI) 2.7-6.0; 9-15 doses HR 2.97, 95 % CI 2.1-4.3], non-HF/death (1-8 doses HR 4.3, 95 % CI 3.0-6.1; 9-15 doses HR 3.1, 95 % CI 2.2-4.4), clinically significant relapse/death (1-8 doses HR 3.1, 95 % CI 2.2-4.4; 9-15 doses HR 2.4, 95 % CI 1.8-3.3), and importantly lower OS (77, 80, 93 %; P < 0.001). Early discontinuation (1-8 doses HR 2.41, 95 % CI 1.5-3.8; 9-15 doses HR 2.9, 95 % CI 2.0-4.1) and clinically significant relapse (HR 34.0, 95 % CI 24.9-46.6) were both independent predictors of mortality. Of note, early discontinuation remained a critical independent predictor of OS even after adjusting for incident HF. Early trastuzumab discontinuation is a powerful independent predictor of cardiac events and clinically significant relapse, and both may contribute to poor survival. Both adequate cancer control and optimal CV management are required to improve long-term outcomes. PMID:27271767

  13. Negative association between GATA3 and fascin could predict relapse-free and overall survival in patients with breast cancer.

    PubMed

    Min, Kyueng-Whan; Kim, Dong-Hoon; Do, Sung-Im; Chae, Seoung Wan; Kim, Kyungeun; Sohn, Jin Hee; Pyo, Jung-Soo; Lee, Hyun Joo; Kim, Dong Hyun; Oh, Sukjoong; Choi, Seon Hyeong; Park, Yong Lai; Park, Chan Heun; Kim, Eun-Kyung; Kwon, Mi Jung; Seo, Jinwon; Moon, Kyoung Min

    2016-04-01

    GATA3 and fascin proteins are known prognostic markers in several cancers. GATA3 is a key regulator of mammary gland morphogenesis and luminal cell differentiation, whereas fascin is a pro-metastatic actin-bundling protein. In this study, we analyzed and compared the predictive abilities of GATA3 and fascin for clinical outcomes of patients with breast cancer. The combined expression pattern based on GATA3-/+ and fascin-/+ was evaluated by immunostaining using a tissue microarray, and relationships between protein expression and several clinicopathological parameters were analyzed. GATA3 expression was associated with good prognostic parameters, but fascin was correlated with poor prognostic parameters. On comparing GATA3 and fascin, we found an inverse relationship between fascin and GATA3 expressions. On analysis of combined markers, GATA3+/fascin- was correlated with improved clinical outcomes compared to GATA3-/fascin+. Univariate and multivariate analyses revealed significant differences in relapse-free and overall survival between GATA3+/fascin- and GATA3-/fascin+. Combined marker analysis of GATA3/fascin showed an inverse association and improved prognostic information for patients with breast cancer. PMID:26719157

  14. S100A9 expressed in ER−PgR− breast cancers induces inflammatory cytokines and is associated with an impaired overall survival

    PubMed Central

    Bergenfelz, Caroline; Gaber, Alexander; Allaoui, Roni; Mehmeti, Meliha; Jirström, Karin; Leanderson, Tomas; Leandersson, Karin

    2015-01-01

    Background: Breast cancer is the most common cancer form among women today. Depending on hormone receptor status, breast cancers are divided into different subtypes with vastly varying prognosis. S100A9 is a calcium-binding protein that is associated with inflammation and expressed not only in myeloid cells but also in some tumours. The role for S100A9 in the malignant cells is not well characterised; however, previous studies have shown that the protein could have important immune-modulating properties. Methods: Using a human breast cancer cohort consisting of 144 tumour samples and in vitro analysis of human breast cancer cell lines, we investigated the expression and function of S100A9 in human breast cancer. Results: We show that S100A9 expression in breast cancer correlated with the ER−PgR− breast tumour subtype (P<0.001) and with Ki67 (P=0.024) and was expressed both in the malignant cells and in the tumour-infiltrating anti-inflammatory CD163+ myeloid cells (P<0.001). Stromal expression of S100A9 also correlated to nodal stage, tumour size and Her2 positivity. Within the ER−PgR− subgroup, all Her2+ and EGFR+ tumours expressed S100A9 in the cytoplasm. Both cytoplasmic staining in the malignant cells as well as stromal S100A9 expression in myeloid cells correlated with a decreased overall survival in breast cancer patients. Furthermore, rS100A9 homodimers induced expression of pro-inflammatory cytokines (IL-6, IL-8 and IL-1β) in a TLR4- and EGFR-dependent manner in human breast cancer cells in vitro. Conclusion: We suggest that S100A9 could be viewed as a novel therapeutic target for patients with ER−PgR− breast cancers. PMID:26448179

  15. Radiation Use and Long-Term Survival in Breast Cancer Patients With T1, T2 Primary Tumors and One to Three Positive Axillary Lymph Nodes

    SciTech Connect

    Buchholz, Thomas A. Woodward, Wendy A.; Duan Zhigang; Fang Shenying; Oh, Julia L.; Tereffe, Welela; Strom, Eric A.; Perkins, George H.; Yu, T.-K.; Hunt, Kelly K.; Meric-Bernstam, Funda; Hortobagyi, Gabriel N.; Giordano, Sharon H.

    2008-07-15

    Background: For patients with Stage II breast cancer with one to three positive lymph nodes, controversy exists about whether radiation as a component of treatment provides a survival benefit. Methods and Materials: We analyzed data from patients with Stage II breast cancer with one to three positive lymph nodes diagnosed from 1988-2002 in the Surveillance, Epidemiology, and End Results registry and compared the outcome of 12,693 patients treated with breast-conservation therapy with radiation (BCT + XRT) with the 18,902 patients treated with mastectomy without radiation (MRM w/o XRT). Results: Patients treated with BCT + XRT were younger, were more likely to be treated in recent years of the study period, more commonly had T1 primary tumors, and had fewer involved nodes compared with those treated with MRM w/o XRT (p < 0.001 for all differences). The 15-year breast cancer-specific survival rate for the BCT + XRT group was 80% vs. 72% for the MRM w/o XRT group (p < 0.001). Cox regression analysis showed that MRM w/o XRT was associated with a hazard ratio for breast cancer death of 1.19 (p < 0.001) and for overall death of 1.25 (p < 0.001). The survival benefit in the BCT + XRT group was not limited to subgroups with high-risk disease features. Conclusions: Radiation use was independently associated with improved survival for patients with Stage II breast cancer with one to three positive lymph nodes. Because multivariate analyses of retrospective data cannot account for all potential biases, these data require confirmation in randomized clinical trials.

  16. Methyl Binding Domain Protein 2 (MBD2) dependent proliferation and survival of breast cancer cells

    PubMed Central

    Mian, Omar Y.; Wang, Shou Zhen; Zhu, Sheng Zu; Gnanapragasam, Merlin N.; Graham, Laura; Bear, Harry D.; Ginder, Gordon D.

    2011-01-01

    Methyl Cytosine Binding Domain Protein 2 (MBD2) has been shown to bind to and mediate repression of methylated tumor suppressor genes in cancer cells, where re-patterning of CpG methylation and associated gene silencing is common. We have investigated the role of MBD2 in breast cancer cell growth and tumor suppressor gene expression. We show that stable shRNA mediated knockdown of MBD2 leads to growth suppression of cultured human mammary epithelial cancer lines, SK-BR-3, MDA-MB-231, and MDA-MB-435. The peak anti-proliferative occurs only after sustained, stable MBD2 knockdown. Once established, the growth inhibition persists over time and leads to a markedly decreased propensity for aggressive breast cancer cell lines to form in vivo xenograft tumors in BALB/C nu/nu mice. The growth effects of MBD2 knockdown are accompanied by de-repression of tumor suppressor genes including DAPK1 and KLK10. Chromatin immunoprecipitation assays and bisulfite sequencing demonstrate MBD2 binding directly to the hyper-methylated and CpG-rich promoters of both DAPK1 and KLK10. Remarkably, the promoter CpG-island associated methylation of these genes remained stable despite robust transcriptional activation in MBD2 knockdown cells. Expression of a shRNA-resistant MBD2 protein resulted in restoration of growth and re-silencing of the MBD2 dependent tumor suppressor genes. Our data suggest that uncoupling CpG-methylation from repressive chromatin remodeling and histone modifications by removing MBD2 is sufficient to initiate and maintain tumor suppressor gene transcription and suppress neoplastic cell growth. These results demonstrate a role for MBD2 in cancer progression and provide support for the prospect of targeting MBD2 therapeutically in aggressive breast cancers. PMID:21693597

  17. African Breast Cancer—Disparities in Outcomes (ABC-DO): protocol of a multicountry mobile health prospective study of breast cancer survival in sub-Saharan Africa

    PubMed Central

    McKenzie, Fiona; Zietsman, Annelle; Galukande, Moses; Anele, Angelica; Adisa, Charles; Cubasch, Herbert; Parham, Groesbeck; Anderson, Benjamin O; Abedi-Ardekani, Behnoush; Schuz, Joachim; dos Santos Silva, Isabel; McCormack, Valerie

    2016-01-01

    Introduction Sub-Saharan African (SSA) women with breast cancer (BC) have low survival rates from this potentially treatable disease. An understanding of context-specific societal, health-systems and woman-level barriers to BC early detection, diagnosis and treatment are needed. Methods The African Breast Cancer—Disparities in Outcomes (ABC-DO) is a prospective hospital-based study of overall survival, impact on quality of life (QOL) and delays along the journey to diagnosis and treatment of BC in SSA. ABC-DO is currently recruiting in Namibia, Nigeria, South Africa, Uganda and Zambia. Women aged 18 years or older who present at participating secondary and tertiary hospitals with a new clinical or histocytological diagnosis of primary BC are invited to participate. For consented women, tumour characteristics, specimen and treatment data are obtained. Over a 2-year enrolment period, we aim to recruit 2000 women who, in the first instance, will be followed for between 1 and 3 years. A face-to-face baseline interview obtains information on socioeconomic, cultural and demographic factors, QOL, health and BC attitudes/knowledge, and timing of all prediagnostic contacts with caregivers in orthodox health, traditional and spiritual systems. Responses are immediately captured on mobile devices that are fed into a tailored mobile health (mHealth) study management system. This system implements the study protocol, by prompting study researchers to phone women on her mobile phone every 3 months and, failing to reach her, prompts contact with her next-of-kin. At follow-up calls, women provide updated information on QOL, care received and disease impacts on family and working life; date of death is asked of her next-of-kin when relevant. Ethics and dissemination The study was approved by ethics committees of all involved institutions. All participants provide written informed consent. The findings from the study will be published in peer-reviewed scientific journals

  18. Clinicopathological Characteristics and Survival Outcomes in Invasive Papillary Carcinoma of the Breast: A SEER Population-Based Study.

    PubMed

    Zheng, Yi-Zi; Hu, Xin; Shao, Zhi-Ming

    2016-01-01

    To investigate the clinicopathological characteristics and survival outcomes of invasive papillary carcinoma (IPC), we identified 233,171 female patients in the Surveillance, Epidemiology, and End Results (SEER) database who had IPC (n = 524) or infiltrating ductal carcinoma (IDC) (n = 232,647). Generally, IPCs occurred in older women (≥ 50 years old) and presented with smaller sizes, lower grades, higher rates of oestrogen receptor (ER) and progesterone receptor (PR) positivity, and reduced lymph node (LN) involvement and were less likely to be treated with mastectomy than patients with IDC. The five-year disease-specific survival (DSS) rates were significantly better in IPC than in IDC (97.5% vs. 93%, respectively; P < 0.001). In the multivariate analysis, patients with IPC showed a DSS that was similar to that of IDC (hazard ratio = 0.556, 95% confidence interval 0.289-1.070, P = 0.079). No significant difference was observed in DSS between matched IPC and IDC groups (P = 0.085). Differences in outcomes may be partially explained by differences in tumour grade, LN status, and ER and PR status between the 2 groups. Gaining an improved clinical and biological understanding of IPC might result in more tailored and effective therapies in breast cancer patients. PMID:27053333

  19. EUROCARE-4. Survival of cancer patients diagnosed in 1995-1999. Results and commentary.

    PubMed

    Sant, Milena; Allemani, Claudia; Santaquilani, Mariano; Knijn, Arnold; Marchesi, Francesca; Capocaccia, Riccardo

    2009-04-01

    EUROCARE-4 analysed about three million adult cancer cases from 82 cancer registries in 23 European countries, diagnosed in 1995-1999 and followed to December 2003. For each cancer site, the mean European area-weighted observed and relative survival at 1-, 3-, and 5-years by age and sex are presented. Country-specific 1- and 5-year relative survival is also shown, together with 5-year relative survival conditional to surviving 1-year. Within-country variation in survival is analysed for selected cancers. Survival for most solid cancers, whose prognosis depends largely on stage at diagnosis (breast, colorectum, stomach, skin melanoma), was highest in Finland, Sweden, Norway and Iceland, lower in the UK and Denmark, and lowest in the Czech Republic, Poland and Slovenia. France, Switzerland and Italy generally had high survival, slightly below that in the northern countries. There were between-region differences in the survival for haematologic malignancies, possibly due to differences in the availability of effective treatments. Survival of elderly patients was low probably due to advanced stage at diagnosis, comorbidities, difficult access or lack of availability of appropriate care. For all cancers, 5-year survival conditional to surviving 1-year was higher and varied less with region, than the overall relative survival.

  20. Pyrosequencing quantified methylation level of BRCA1 promoter as prognostic factor for survival in breast cancer patient

    PubMed Central

    Lin, Xiao-Yan; Zhang, Lian; Zhang, Jia-Xin; Wang, Lian-Xin; Yang, Jun; Ding, Jin-Hua; Pan, Xin; Shao, Zhi-Ming; Biskup, Ewelina

    2016-01-01

    BRCA1 promoter methylation is an essential epigenetic transcriptional silencing mechanism, related to breast cancer (BC) occurrence and progression. We quantified the methylation level of BRCA1 promoter and evaluated its significance as prognostic and predictive factor. BRCA1 promoter methylation level was quantified by pyrosequencing in surgical cancerous and adjacent normal specimens from 154 BC patients. A follow up of 98 months was conducted to assess the correlation between BRCA1-methylation level vs. overall survival (OS) and disease free survival (DFS). The mean methylation level in BC tissues was significantly higher (mean 32.6%; median 31.9%) than in adjacent normal samples (mean 16.2%; median 13.0%) (P < 0.0001). Tumor stage (R = 0.6165, P < 0.0001) and size (R = 0.7328, P < 0.0001) were significantly correlated with the methylation level. Patients with unmethylated BRCA1 had a better OS and DFS compared to the methylated group (each P < 0.0001). BRCA1 promoter methylation level has a statistically significance on survival in BC patients (HazR = 1.465, P = 0.000) and is an independent prognostic factor for OS in BC patients (HazR = 2.042, P = 0.000). Patients with ductal type, HER2 negative, lymph node negative stage 1+2 tumors had a better OS and DFS. Classification of grades and molecular subtypes did not show any prognostic significance. Pyrosequencing is a precise and efficient method to quantify BRCA1 promoter methylation level, with a high potential for future clinical implication, as it identifies subgroups of patients with poorer prognosis. PMID:27027444

  1. Pyrosequencing quantified methylation level of BRCA1 promoter as prognostic factor for survival in breast cancer patient.

    PubMed

    Cai, Feng-Feng; Chen, Su; Wang, Ming-Hong; Lin, Xiao-Yan; Zhang, Lian; Zhang, Jia-Xin; Wang, Lian-Xin; Yang, Jun; Ding, Jin-Hua; Pan, Xin; Shao, Zhi-Ming; Biskup, Ewelina

    2016-05-10

    BRCA1 promoter methylation is an essential epigenetic transcriptional silencing mechanism, related to breast cancer (BC) occurrence and progression. We quantified the methylation level of BRCA1 promoter and evaluated its significance as prognostic and predictive factor. BRCA1 promoter methylation level was quantified by pyrosequencing in surgical cancerous and adjacent normal specimens from 154 BC patients. A follow up of 98 months was conducted to assess the correlation between BRCA1-methylation level vs. overall survival (OS) and disease free survival (DFS). The mean methylation level in BC tissues was significantly higher (mean 32.6%; median 31.9%) than in adjacent normal samples (mean 16.2%; median 13.0%) (P < 0.0001). Tumor stage (R = 0.6165, P < 0.0001) and size (R = 0.7328, P < 0.0001) were significantly correlated with the methylation level. Patients with unmethylated BRCA1 had a better OS and DFS compared to the methylated group (each P < 0.0001). BRCA1 promoter methylation level has a statistically significance on survival in BC patients (HazR = 1.465, P = 0.000) and is an independent prognostic factor for OS in BC patients (HazR = 2.042, P = 0.000). Patients with ductal type, HER2 negative, lymph node negative stage 1+2 tumors had a better OS and DFS. Classification of grades and molecular subtypes did not show any prognostic significance. Pyrosequencing is a precise and efficient method to quantify BRCA1 promoter methylation level, with a high potential for future clinical implication, as it identifies subgroups of patients with poorer prognosis. PMID:27027444

  2. Treatment and survival patterns of Chinese patients diagnosed with breast cancer between 2005 and 2009 in Southwest China: An observational, population-based cohort study.

    PubMed

    Peng, Zuxiang; Wei, Jia; Lu, Xuesong; Zheng, Hong; Zhong, Xiaorong; Gao, Weiguo; Chen, Yunqin; Jing, Jing

    2016-06-01

    Breast cancer is a significant health issue both globally and within China. Here, we present epidemiological data for female patients diagnosed with breast cancer and treated at West China Hospital, Sichuan University, between 2005 and 2009. Patients who were diagnosed with breast cancer between 2005 and 2009 were enrolled. Data cut-off in this analysis was October 2013, allowing a minimum of 3 years' follow-up, or follow-up until death. Data were collected and subject to statistical analyses to assess relationships between patient and cancer characteristics, treatment patterns and long-term outcomes. A total of 2252 women with breast cancer were included in the analyses. Luminal B was the most common subtype of breast cancer and human epidermal growth factor 2 (HER2)-positive (nonluminal) was the least common. Most patients had early-stage disease (stage ≤IIIa) at diagnosis. Patients with luminal A appeared to have the best overall survival (OS), compared with other subtypes. Hormone-receptor positivity was associated with improved prognosis, compared with negativity (OS hazard ratio [HR] 0.5). Late-stage compared with early-stage disease at diagnosis was associated with much poorer OS across all patients and tumor subtypes. Clear differences were apparent between breast cancer subtypes and the response to treatment. The interaction of breast cancer subtypes, treatments and disease stage is complex. One of the most important factors for improved prognosis is diagnosis and treatment at an early-stage of disease. With breast cancer becoming an increasingly important health concern, this highlights the importance of establishing systems and protocols to identify and treat patients with breast cancer as early as possible. PMID:27336872

  3. A novel truncated form of S100P predicts disease-free survival in patients with lymph node positive breast cancer.

    PubMed

    Chung, Liping; Phillips, Leo; Lin, Mike Z; Moore, Katrina; Marsh, Deborah J; Boyle, Frances M; Baxter, Robert C

    2015-11-01

    The calcium-binding protein S100P is overexpressed in various cancers and may contribute to the oncogenic phenotype. This study used mass spectrometry to characterize a novel 9.2-kDa C-terminally truncated form of S100P (t-S100P), and to investigate its potential prognostic value in breast cancer. Univariate analysis demonstrated the association between breast tissue t-S100P levels (n = 148) and conventional pathological markers. Across all tumor samples, high t-S100P was strongly prognostic for poor disease-free survival (P = 0.005), its efficacy confined to lymph node-positive tumors (n = 74, P = 0.007). Matrix-assisted laser desorption/ionization imaging mass spectrometry confirmed differential t-S100P abundance between breast cancer and unaffected adjacent tissue. t-S100P was exclusively located in the cell nucleus of breast cancer tissue, and full-length S100P was essentially undetectable by mass spectrometry. We conclude that t-S100P is the predominant form of S100P in breast cancer tissue and is strongly prognostic for disease-free survival in women with lymph node-positive disease.

  4. A novel truncated form of S100P predicts disease-free survival in patients with lymph node positive breast cancer.

    PubMed

    Chung, Liping; Phillips, Leo; Lin, Mike Z; Moore, Katrina; Marsh, Deborah J; Boyle, Frances M; Baxter, Robert C

    2015-11-01

    The calcium-binding protein S100P is overexpressed in various cancers and may contribute to the oncogenic phenotype. This study used mass spectrometry to characterize a novel 9.2-kDa C-terminally truncated form of S100P (t-S100P), and to investigate its potential prognostic value in breast cancer. Univariate analysis demonstrated the association between breast tissue t-S100P levels (n = 148) and conventional pathological markers. Across all tumor samples, high t-S100P was strongly prognostic for poor disease-free survival (P = 0.005), its efficacy confined to lymph node-positive tumors (n = 74, P = 0.007). Matrix-assisted laser desorption/ionization imaging mass spectrometry confirmed differential t-S100P abundance between breast cancer and unaffected adjacent tissue. t-S100P was exclusively located in the cell nucleus of breast cancer tissue, and full-length S100P was essentially undetectable by mass spectrometry. We conclude that t-S100P is the predominant form of S100P in breast cancer tissue and is strongly prognostic for disease-free survival in women with lymph node-positive disease. PMID:26276712

  5. Association of Estrogen Receptor Alpha and Interleukin 6 Polymorphisms with Lymphovascular Invasion, Extranodal Extension, and Lower Disease-Free Survival in Thai Breast Cancer Patients.

    PubMed

    Sa-Nguanraksa, Doonyapat; Suntiparpluacha, Monthira; Kulprom, Anchalee; Kummalue, Tanawan; Chuangsuwanich, Tuenjai; Avirutnan, Panissadee; O-Charoenrat, Pornchai

    2016-01-01

    Breast cancer is the most frequent type of cancer diagnosed among women worldwide and also in Thailand. Estrogen and estrogen receptors exert important roles in its genesis and progression. Several cytokines have been reported to be involved in the microenvironment that promotes distant metastasis via modulation of immune and inflammatory responses to tumor cells. Estrogen receptor genetic polymorphisms and several cytokines have been reported to be associated with breast cancer susceptibility and aggressiveness. To investigate roles of genetic polymorphisms in estrogen receptor alpha (ESR1) and interleukin 6 (IL6), breast cancer patients and control subjects were recruited from the Division of Head, Neck and Breast Surgery (Siriraj Hospital, Bangkok, Thailand). Polymorphisms in ESR1 (rs3798577) and IL6 (rs1800795 and rs1800797) were evaluated by real-time PCR in 391 breast cancer patients and 79 healthy controls. Associations between genetic polymorphisms and clinicopathological data were determined. There was no association between genetic polymorphisms and breast cancer susceptibility. However the ESR1 rs3798577 CT genotype was associated with presence of lymphovascular invasion (OR=2.07, 95%CI 1.20-3.56, p=0.009) when compared to the TT genotype. IL6 rs1800795 CC genotype was associated with presence of extranodal extension (OR= 2.30, 95%CI 1.23-4.31, p=0.009) when compared to the GG genotype. Survival analysis showed that IL6 rs1800797 AG or AA genotypes were associated with lower disease-free survival. These findings indicate that polymorphisms in ESR1 and IL6 contribute to aggressiveness of breast cancer and may be used to identify high risk patients. PMID:27356714

  6. Effect of the tyrosine kinase inhibitor lapatinib on CUB-domain containing protein (CDCP1)-mediated breast cancer cell survival and migration

    SciTech Connect

    Seidel, Jeanette; Kunc, Klaudia; Possinger, Kurt; Jehn, Christian; Lueftner, Diana

    2011-10-14

    Highlights: {yields} CDCP1 downregulation reduces anchorage free survival of breast cancer cells. {yields} Anoikis of CDCP1-positive breast cancer cells is increased after CDCP1 downregulation. {yields} CDCP1 knockdown decreases migration and extensively reduces invasiveness in vitro. {yields} Proliferation rate does not correlate with CDCP1 expression. {yields} Lapatinib does not influence tyrosine kinases of CDCP1 signal transduction. -- Abstract: The surface receptor CUB domain-containing protein 1 (CDCP1) is highly expressed in several adenocarcinomas and speculated to participate in anchorage-independent cell survival and cell motility. Tyrosine kinase phosphorylation seems to be crucial for intracellular signaling of CDCP1. Lapatinib, a tyrosine kinase inhibitor (TKI), is approved for treatment of HER-2/neu overexpressing metastatic breast cancer and functions by preventing autophosphorylation following HER-2/neu receptor activation. This study aimed to investigate the effect of CDCP1 expression on anchorage-independent growth and cell motility of breast cancer cells. Moreover, studies were performed to examine if lapatinib provided any beneficial effect on HER-2/neu{sup (+)/-}/CDCP1{sup +} breast cancer cell lines. In our studies, we affirmed that CDCP1 prevents cells from undergoing apoptosis when cultured in the absence of cell-substratum anchorage and that migratory and invasive properties of these cells were decreased when CDCP1 was down-regulated. However, only HER-2/neu{sup +}, but not HER-2/neu{sup (+)/-} cells showed decreased proliferation and invasion and an enhanced level of apoptosis towards loss of anchorage when treated with lapatinib. Therefore, we conclude that CDCP1 might be involved in regulating adhesion and motility of breast cancer cells but that lapatinib has no effect on tyrosine kinases regulating CDCP1. Nonetheless, other TKIs might offer therapeutic approaches for CDCP1-targeted breast cancer therapy and should be studied

  7. Body mass index and survival in women with breast cancer—systematic literature review and meta-analysis of 82 follow-up studies

    PubMed Central

    Chan, D. S. M.; Vieira, A. R.; Aune, D.; Bandera, E. V.; Greenwood, D. C.; McTiernan, A.; Navarro Rosenblatt, D.; Thune, I.; Vieira, R.; Norat, T.

    2014-01-01

    Background Positive association between obesity and survival after breast cancer was demonstrated in previous meta-analyses of published data, but only the results for the comparison of obese versus non-obese was summarised. Methods We systematically searched in MEDLINE and EMBASE for follow-up studies of breast cancer survivors with body mass index (BMI) before and after diagnosis, and total and cause-specific mortality until June 2013, as part of the World Cancer Research Fund Continuous Update Project. Random-effects meta-analyses were conducted to explore the magnitude and the shape of the associations. Results Eighty-two studies, including 213 075 breast cancer survivors with 41 477 deaths (23 182 from breast cancer) were identified. For BMI before diagnosis, compared with normal weight women, the summary relative risks (RRs) of total mortality were 1.41 [95% confidence interval (CI) 1.29–1.53] for obese (BMI >30.0), 1.07 (95 CI 1.02–1.12) for overweight (BMI 25.0–<30.0) and 1.10 (95% CI 0.92–1.31) for underweight (BMI <18.5) women. For obese women, the summary RRs were 1.75 (95% CI 1.26–2.41) for pre-menopausal and 1.34 (95% CI 1.18–1.53) for post-menopausal breast cancer. For each 5 kg/m2 increment of BMI before, <12 months after, and ≥12 months after diagnosis, increased risks of 17%, 11%, and 8% for total mortality, and 18%, 14%, and 29% for breast cancer mortality were observed, respectively. Conclusions Obesity is associated with poorer overall and breast cancer survival in pre- and post-menopausal breast cancer, regardless of when BMI is ascertained. Being overweight is also related to a higher risk of mortality. Randomised clinical trials are needed to test interventions for weight loss and maintenance on survival in women with breast cancer. PMID:24769692

  8. Evaluating the Survival Benefit Following Ovarian Function Suppression in Premenopausal Patients with Hormone Receptor Positive Early Breast Cancer

    PubMed Central

    Qiu, Lin; Fu, Fangmeng; Huang, Meng; Lin, Yuxiang; chen, Yazhen; Chen, Minyan; Wang, Chuan

    2016-01-01

    There are divergent opinions regarding the use of ovarian function suppression or ablation (hereafter, OFS) in hormone receptor positive early breast cancer patients. In order to clarify the survival benefit of OFS, a meta-analysis was performed. The result is that use of OFS was more effective than no OFS on DFS (the pooled relative risk (pRR) = 0.86; 95% CI: 0.75–0.96) and on OS (pRR = 0.79; 95% CI: 0.70–0.89). In subgroup analysis, we found that increased DFS was positively associated with patients who had received chemotherapy (pRR = 0.85; 95% CI: 0.74–0.96), who were lymph node negative (pRR = 0.74; 95% CI: 0.61–0.91) and were less than 40 years old (pRR = 0.71; 95% CI: 0.59–0.83). There was a significant difference in OS between the groups receiving chemotherapy (pRR = 0.73; 95% CI: 0.58–0.89) or for patients less than 40 years old (pRR = 0.52; 95% CI: 0.18–0.87). The use of OFS also produces statistical differences in the occurrence of the side-effects; severe hot flashes (pRR = 2.32; 95% CI: 1.36–3.97), and hypertension (pRR = 1.54; 95% CI: 1.12–2.12). In general, OFS should be considered as one treatment for hormone receptor positive premenopausal early breast cancer patients who have received chemotherapy and are less than 40 years old. We also should pay attention to the side-effects and weigh the advantages and disadvantages before deciding on using OFS. PMID:27230285

  9. Impact of modifiable lifestyle factors on outcomes after breast cancer diagnosis: the Setouchi Breast Cancer Cohort Study.

    PubMed

    Taira, Naruto; Akiyama, Ichiro; Ishihara, Setsuko; Ishibe, Youichi; Kawasaki, Kensuke; Saito, Makoto; Shien, Tadahiko; Nomura, Tsunehisa; Hara, Fumikata; Mizoo, Taeko; Mizota, Yuri; Yamamoto, Seiichiro; Ohsumi, Shozo; Doihara, Hiroyoshi

    2015-06-01

    The primary purpose of this large cohort study is to investigate the effects on breast cancer outcomes of modifiable lifestyle factors after breast cancer diagnosis. These factors include physical activity, smoking, alcohol consumption, obesity and weight gain after diagnosis, alternative medicine and dietary factors. Women diagnosed with Stage 0 to III breast cancer are eligible for participation to this study. Lifestyle, use of alternative medicine, psychosocial factors, reproductive factors and health-related quality of life will be assessed using a questionnaire at the time of breast cancer diagnosis (baseline), and 1, 2, 3 and 5 years after diagnosis. Clinical information and breast cancer outcomes will be obtained from a breast cancer database. The primary endpoint will be disease-free survival. Secondary endpoints are overall survival, health-related quality of life, breast cancer-related symptoms and adverse events. Patient recruitment commenced in February 2013. Enrollment of 2000 breast cancer patients is planned during the 5-year recruitment period. The concept of the study is described in this article.

  10. Impact of deprivation on breast cancer survival among women eligible for mammographic screening in the West Midlands (UK) and New South Wales (Australia): Women diagnosed 1997-2006.

    PubMed

    Woods, Laura M; Rachet, Bernard; O'Connell, Dianne; Lawrence, Gill; Coleman, Michel P

    2016-05-15

    Women diagnosed with breast cancer in the UK display marked differences in survival between categories defined by socio-economic deprivation. Timeliness of diagnosis is one of the possible explanations for these patterns. Women whose cancer is screen-detected are more likely to be diagnosed at an earlier stage. We examined deprivation and screening-specific survival in order to evaluate the role of early diagnosis upon deprivation-specific survival differences in the West Midlands (UK) and New South Wales (Australia). We estimated net survival for women aged 50-65 years at diagnosis and whom had been continuously eligible for screening from the age of 50. Records for 5,628 women in West Midlands (98.5% of those eligible, mean age at diagnosis 53.7 years) and 6,396 women in New South Wales (99.9% of those eligible, mean age at diagnosis 53.8 years). In New South Wales, survival was similar amongst affluent and deprived women, regardless of whether their cancer was screen-detected or not. In the West Midlands, there were large and persistent differences in survival between affluent and deprived women. Deprivation differences were similar between the screen-detected and non-screen detected groups. These differences are unlikely to be solely explained by artefact, or by patient or tumour factors. Further investigations into the timeliness and appropriateness of the treatments received by women with breast cancer across the social spectrum in the UK are warranted.

  11. Tumour-targeted delivery of TRAIL using Salmonella typhimurium enhances breast cancer survival in mice

    PubMed Central

    Ganai, S; Arenas, R B; Forbes, N S

    2009-01-01

    Background: An effective cancer therapeutic must selectively target tumours with minimal systemic toxicity. Expression of a cytotoxic protein using Salmonella typhimurium would enable spatial and temporal control of delivery because these bacteria preferentially target tumours over normal tissue. Methods: We engineered non-pathogenic S. typhimurium to secrete murine TNF-related apoptosis-inducing ligand (TRAIL) under the control of the prokaryotic radiation-inducible RecA promoter. The response of the RecA promoter to radiation was measured using fluorometry and immunoblotting. TRAIL toxicity was determined using flow cytometry and by measuring caspase-3 activation. A syngeneic murine tumour model was used to determine bacterial accumulation and the response to expressed TRAIL. Results: After irradiation, engineered S. typhimurium secreted TRAIL, which caused caspase-3-mediated apoptosis and death in 4T1 mammary carcinoma cells in culture. Systemic injection of Salmonella and induction of TRAIL expression using 2 Gy γ-irradiation caused a significant delay in mammary tumour growth and reduced the risk of death by 76% when compared with irradiated controls. Repeated dosing with TRAIL-bearing Salmonella in conjunction with radiation improved the 30-day survival from 0 to 100%. Conclusion: These results show the pre-clinical utility of S. typhimurium as a TRAIL expression vector that effectively reduces tumour growth and extends host survival. PMID:19861961

  12. [How can breast-conserving surgery be improved even more?].

    PubMed

    Rutgers, Emiel J T

    2012-01-01

    Due to population-wide screening and increased awareness of breast cancer by women, more early-stage diagnoses are being made. Breast-conserving surgery, performed according to well-established guidelines, results in the same level of local control and long-term survival as mastectomy for the same indication. The Dutch Cancer Registry has demonstrated an average local relapse rate at 5 years of about 3% in a follow-up study of breast-cancer patients. A study published in this issue show a high complete resection rate and less excised tissue volume as compared to other localisation techniques or excision by palpation only. There are two provisions: the tumour and its gross delineation must be visible by ultrasound, and the breast surgeon needs to learn the technique and apply it sensibly. Generally speaking, ultrasound-guided breast-conserving resection of invasive breast cancer may well lead to more initially complete resections and better cosmetic results.

  13. Older breast cancer survivors' views and preferences for physical activity.

    PubMed

    Whitehead, Sarah; Lavelle, Katrina

    2009-07-01

    Evidence suggests that physical activity improves quality of life and physical functioning among breast cancer patients and survivors. However, previous studies have tended to focus on younger patients, despite higher incidence and lower survival among older breast cancer survivors. In this study we explored physical activity preferences of older breast cancer survivors to inform the development of future targeted interventions. Twenty-nine female breast cancer survivors (1 to 5 years postdiagnosis) aged 59 to 86 (mean 66.54, SD 6.50) took part in either a semistructured interview or a focus group exploring physical activity patterns, motivators, facilitators, barriers, and preferences. The main factors influencing physical activity were body image, weight issues, vitality, mood, and the desire to carry on as normal. Preference was expressed for activities that were gentle, tailored to age and cancer-related abilities, holistic, involving other older breast cancer survivors, and with an instructor who was knowledgeable about both breast cancer and aging.

  14. Amplification and over-expression of MAP3K3 gene in human breast cancer promotes formation and survival of breast cancer cells

    PubMed Central

    Fan, Yihui; Ge, Ningling; Wang, Xiaosong; Sun, Wenjing; Mao, Renfang; Bu, Wen; Creighton, Chad J; Zheng, Pingju; Vasudevan, Sanjeev; An, Lei; Yang, Jinshu; Zhao, Yi-Jue; Zhang, Huiyuan; Li, Xiao-Nan; Rao, Pulivarthi H; Leung, Eastwood; Lu, Yong-Jie; Gray, Joe W; Schiff, Rachel; Hilsenbeck, Susan G; Osborne, C Kent; Yang, Jianhua; Zhang, Hong

    2014-01-01

    Gene amplifications in the 17q chromosomal region are observed frequently in breast cancers. An integrative bioinformatics analysis of this region nominated the MAP3K 3 gene as a potential therapeutic target in breast cancer. This gene encodes mitogen-activated protein kinase kinase kinase 3 (MAP3K3/MEKK3), which has not yet been reported to be associated with cancer-causing genetic aberrations. We found that MAP3K3 was amplified in approximately 8–20% of breast cancers. Knockdown of MAP3K3 expression significantly inhibited cell proliferation and colony formation in MAP3K3-amplified breast cancer cell lines MCF-7 and MDA-MB-361 but not in MAP3K3 non-amplified breast cancer cells. Knockdown of MAP3K3 expression in MAP3K3-amplified breast cancer cells sensitized breast cancer cells to apoptotic induction by TNFα and TRAIL, as well as doxorubicin, VP-16 and fluorouracil, three commonly used chemotherapeutic drugs for treating breast cancer. In addition, ectopic expression of MAP3K3, in collaboration with Ras, induced colony formation in both primary mouse embryonic fibroblasts and immortalized human breast epithelial cells (MCF-10A). Combined, these results suggest that MAP3K3 contributes to breast carcinogenesis and may endow resistance of breast cancer cells to cytotoxic chemotherapy. Therefore, MAP3K3 may be a valuable therapeutic target in patients with MAP3K3-amplified breast cancers, and blocking MAP3K3 kinase activity with a small molecule inhibitor may sensitize MAP3K3-amplified breast cancer cells to chemotherapy. PMID:24122835

  15. Variations in cancer survival and patterns of care across Europe: roles of wealth and health-care organization.

    PubMed

    Gatta, Gemma; Trama, Annalisa; Capocaccia, Riccardo

    2013-01-01

    Cancer survival varies markedly across Europe. We analyzed variations in all-cancer 5-year relative survival in relation to macroeconomic and health-care indicators, and 5-year relative survival for three major cancers (colorectal, prostate, breast) in relation to application of standard treatments, to serve as baseline for monitoring the efficacy of new European initiatives to improve cancer survival. Five-year relative survival data were from the European cancer registry-based study of cancer patients' survival and care (EUROCARE-4). Macroeconomic and health system data were from the Organisation for Economic Co-operation and Development, and European Observatory on Health Care Systems. Information on treatments given was from EUROCARE studies. Total national health spending varied widely across Europe and correlated linearly with survival (R = 0.8). Countries with high spending had high numbers of diagnostic and radiotherapy units, and 5-year relative survival was good (>50%). The treatments given for major cancers also varied; advanced stage at diagnosis was associated with poor 5-year relative survival and low odds of receiving standard treatment for breast and colorectal cancer.

  16. Primary breast diffuse large B-cell lymphoma in the era of rituximab

    PubMed Central

    Zhang, Na; Cao, Caineng; Zhu, Yuan; Liu, Peng; Liu, Luying; Lu, Ke; Luo, Jialin; Zhou, Ning

    2016-01-01

    Background and objective The aim of this study was to summarize the clinical characteristics and evaluate the management approaches of primary breast diffuse large B-cell lymphoma (DLBCL) in the era of rituximab. Patients and methods A total of 24 female patients with newly diagnosed primary breast DLBCL treated between April 2006 and May 2013 were analyzed retrospectively. Ten patients (41.7%) received rituximab. Results For the whole group, the median age was 50 years (range 24–69 years). All patients had the disease detected with a palpable mass. The estimated 5-year overall survival and progression-free survival (PFS) rates of all the patients were 78.9% and 79.2%, respectively. A nonstatistically significant increase in PFS and overall survival was observed when rituximab was administered (5-year PFS: 90% vs 71.4%, P=0.285; 5-year overall survival: 90% vs 71.4%, P=0.239). Conclusion Primary breast DLBCL appears to be a rare disease. Adding rituximab might improve survival in patients with primary breast DLBCL. Further prospective studies are needed to evaluate the role of rituximab for primary breast DLBCL. PMID:27785056

  17. Breast cancer: a 21 year experience with conservative surgery and radiation

    SciTech Connect

    Clack, R.M.; Wilkinson, R.H.; Mahoney, L.J.; Reid, J.G.; MacDonald, W.D.

    1982-06-01

    Evidence is presented from a study of 680 patients followed over a period of 21 years that conservative treatment of breast cancer by local excision of the primary tumor followed by breast irradiation yields results equivalent to the traditional radical approach, with the added benefit of an excellent cosmetic result and improved quality of life. The relative survivals were 83% at 5 years and 71% at 10 years. There was no difference in survival when radiation was given. Breast irradiation significantly reduced relapse in the breast, but axillary irradiation did not influence relapse at this site. Relapse in the breast alone was not detrimental to survival if treated appropriately. Axillary relapse indicated a much poorer prognosis as might be expected.

  18. Gene modules associated with breast cancer distant metastasis-free survival in the PAM50 molecular subtypes

    PubMed Central

    Liu, Rong; Zhang, Wei; Liu, Zhao-Qian; Zhou, Hong-Hao

    2016-01-01

    To identify PAM50 subtype–specific associations between distant metastasis-free survival (DMFS) in breast cancer (BC) patients and gene modules describing potentially targetable oncogenic pathways, a comprehensive analysis evaluating the prognostic efficacy of published gene signatures in 2027 BC patients from 13 studies was conducted. We calculated 21 gene modules and computed hazard ratios (HRs) for DMFS for one-unit increases in module score, with and without adjustment for clinical characteristics. By comparing gene expression to survival outcomes, we derived four subtype-specific prognostic signatures for BC. Univariate and multivariate analyses showed that in the luminal A subgroup, E2F3, PTEN and GGI gene module scores were associated with clinical outcome. In the luminal B tumors, RAS was associated with DMFS and in the basal-like tumors, ER was associated with DMFS. Our defined gene modules predicted high-risk patients in multivariate analyses for the basal-like (HR: 2.19, p=2.5×10−4), luminal A (HR: 3.03, p=7.2×10−5), luminal B (HR: 3.00, p=2.4×10−10) and HER2+ (HR: 5.49, p=9.7×10−10) subgroups. We found that different modules are associated with DMFS in different BC subtypes. The results of this study could help to identify new therapeutic strategies for specific molecular subgroups of BC, and could enhance efforts to improve patient-specific therapy options. PMID:26934123

  19. Angiogenesis-associated sequence variants relative to breast cancer recurrence and survival

    PubMed Central

    Brock, Guy N.; VanCleave, Tiva T.; Benford, Marnita L.; Lavender, Nicole A.; Kruer, Traci L.; Wittliff, James L.

    2016-01-01

    Introduction Breast cancer (BrCA) risk stratification using clinico-pathological biomarkers helps improve disease prognosis prediction. However, disease recurrence rates remain unfavorable and individualized clinical management strategies are needed. Consequently, we evaluated the influence of 14 sequence variants detected in IL-10, TGF-β1, VEGF, and their associated receptors as effective predictors of BrCA clinical outcomes. Methods Tumor DNA samples collected from 441 BrCA patients were genotyped using TaqMan-PCR. Most selected targets alter cytokine serum/plasma levels or signaling pathways. Relationships between genetic profiles and recurrence as well as disease-related mortality were evaluated using cumulative incidence curves and competing risk regression models. Results The VEGF−2578 C allele was associated with a 1.3-to 1.6-fold increase in BrCA recurrence (HRtrend = 1.28; 95% CI = 0.96–1.72) and disease-related mortality (HRtrend = 1.56; 95% CI = 0.93–2.56). Although this marker was marginally significant relative to BrCA outcomes, there were substantial gains in the 5- and 8-year predictive accuracy compared to standard prognostic indicators. Among ER+/PR+ status patients, there was a significant impact of the VEGF−2578 CC genotype on disease recurrence and predictive accuracy. Conclusions Our findings suggest inheritance of the VEGF−2578 C allele could serve as an independent prognostic indicator of BrCA prognosis. The VEGF−2578 marker may have clinical implications among a subset of ER+/ PR+ patients with an aggressive phenotype. Because the VEGF−2578 C allele is linked to high VEGF expression, this cytokine is a potential prognostic and targeted clinical management tool. PMID:20571871

  20. Can pathologic complete response (pCR) be used as a surrogate marker of survival after neoadjuvant therapy for breast cancer?

    PubMed

    Wang-Lopez, Qian; Chalabi, Nassera; Abrial, Catherine; Radosevic-Robin, Nina; Durando, Xavier; Mouret-Reynier, Marie-Ange; Benmammar, Kheir-Eddine; Kullab, Sharif; Bahadoor, Mohun; Chollet, Philippe; Penault-Llorca, Frédérique; Nabholtz, Jean-Marc

    2015-07-01

    Breast cancer is heterogeneous in clinical, morphological, immunohistochemical and biological features, as reflected by several different prognostic subgroups. Neoadjuvant approaches are currently used for the "in vivo" efficacy assessment of treatments. Pathological complete response (pCR) has been reported as a reliable predictive factor of survival in that setting. However, pCR remains a subject of controversy in terms of definition and its evaluation methods. In addition, its predictive value for patient outcome in various breast cancer biological subtypes has been under debate. In this review, we will present the existing definitions of pCR, the impact of its evaluation methods on its rate and the assessment of its predictive value for patient outcome in the molecular subtypes of breast cancer (luminal A and B, Triple Negative and HER2-positive).

  1. New spatially continuous indices of redlining and racial bias in mortgage lending: links to survival after breast cancer diagnosis and implications for health disparities research.

    PubMed

    Beyer, Kirsten M M; Zhou, Yuhong; Matthews, Kevin; Bemanian, Amin; Laud, Purushottam W; Nattinger, Ann B

    2016-07-01

    Racial health disparities continue to be a serious problem in the United States and have been linked to contextual factors, including racial segregation. In some cases, including breast cancer survival, racial disparities appear to be worsening. Using the Home Mortgage Disclosure Act (HMDA) database, we extend current spatial analysis methodology to derive new, spatially continuous indices of (1) racial bias in mortgage lending and (2) redlining. We then examine spatial patterns of these indices and the association between these new measures and breast cancer survival among Black/African American women in the Milwaukee, Wisconsin metropolitan area. These new measures can be used to examine relationships between mortgage discrimination and patterns of disease throughout the United States.

  2. New spatially continuous indices of redlining and racial bias in mortgage lending: links to survival after breast cancer diagnosis and implications for health disparities research.

    PubMed

    Beyer, Kirsten M M; Zhou, Yuhong; Matthews, Kevin; Bemanian, Amin; Laud, Purushottam W; Nattinger, Ann B

    2016-07-01

    Racial health disparities continue to be a serious problem in the United States and have been linked to contextual factors, including racial segregation. In some cases, including breast cancer survival, racial disparities appear to be worsening. Using the Home Mortgage Disclosure Act (HMDA) database, we extend current spatial analysis methodology to derive new, spatially continuous indices of (1) racial bias in mortgage lending and (2) redlining. We then examine spatial patterns of these indices and the association between these new measures and breast cancer survival among Black/African American women in the Milwaukee, Wisconsin metropolitan area. These new measures can be used to examine relationships between mortgage discrimination and patterns of disease throughout the United States. PMID:27173381

  3. Genetic and epigenetic factors affect RET gene expression in breast cancer cell lines and influence survival in patients

    PubMed Central

    Griseri, Paola; Garrone, Ornella; Lo Sardo, Alessandra; Monteverde, Martino; Rusmini, Marta; Tonissi, Federica; Merlano, Marco; Bruzzi, Paolo

    2016-01-01

    Germline and somatic mutations play a crucial role in breast cancer (BC), driving the initiation, progression, response to therapy and outcome of the disease. Hormonal therapy is limited to patients with tumors expressing steroid hormone receptors, such as estrogen receptor (ER), nevertheless resistance often limits its success. The RET gene is known to be involved in neurocristopathies such as Hirschsprung disease and Multiple Endocrine Neoplasia type 2, in the presence of loss-of-function and gain-of-function mutations, respectively. More recently, RET over-expression has emerged as a new player in ER-positive (ER+) BC, and as a potential target to enhance sensitivity and avoid resistance to tamoxifen therapy. Therefore, targeting the RET pathway may lead to new therapies in ER+ BC. To this end, we have investigated the molecular mechanisms which underlie RET overexpression and its possible modulation in two BC cell lines, MCF7 and T47D, showing different RET expression levels. Moreover, we have carried out a pilot association study in 93 ER+ BC patients. Consistent with the adverse role of RET over-expression in BC, increased overall survival was observed in carriers of the variant allele of SNP rs2435357, a RET polymorphism already known to be associated with reduced RET expression. PMID:27034161

  4. Combination of cyclopamine and tamoxifen promotes survival and migration of mcf-7 breast cancer cells--interaction of hedgehog-gli and estrogen receptor signaling pathways.

    PubMed

    Sabol, Maja; Trnski, Diana; Uzarevic, Zvonimir; Ozretic, Petar; Musani, Vesna; Rafaj, Maja; Cindric, Mario; Levanat, Sonja

    2014-01-01

    Hedgehog-Gli (Hh-Gli) signaling pathway is one of the new molecular targets found upregulated in breast tumors. Estrogen receptor alpha (ERα) signaling has a key role in the development of hormone-dependent breast cancer. We aimed to investigate the effects of inhibiting both pathways simultaneously on breast cancer cell survival and the potential interactions between these two signaling pathways. ER-positive MCF-7 cells show decreased viability after treatment with cyclopamine, a Hh-Gli pathway inhibitor, as well as after tamoxifen (an ERα inhibitor) treatment. Simultaneous treatment with cyclopamine and tamoxifen on the other hand, causes short-term survival of cells, and increased migration. We found upregulated Hh-Gli signaling under these conditions and protein profiling revealed increased expression of proteins involved in cell proliferation and migration. Therefore, even though Hh-Gli signaling seems to be a good potential target for breast cancer therapy, caution must be advised, especially when combining therapies. In addition, we also show a potential direct interaction between the Shh protein and ERα in MCF-7 cells. Our data suggest that the Shh protein is able to activate ERα independently of the canonical Hh-Gli signaling pathway. Therefore, this may present an additional boost for ER-positive cells that express Shh, even in the absence of estrogen.

  5. Combination of Cyclopamine and Tamoxifen Promotes Survival and Migration of MCF-7 Breast Cancer Cells – Interaction of Hedgehog-Gli and Estrogen Receptor Signaling Pathways

    PubMed Central

    Uzarevic, Zvonimir; Ozretic, Petar; Musani, Vesna; Rafaj, Maja; Cindric, Mario; Levanat, Sonja

    2014-01-01

    Hedgehog-Gli (Hh-Gli) signaling pathway is one of the new molecular targets found upregulated in breast tumors. Estrogen receptor alpha (ERα) signaling has a key role in the development of hormone-dependent breast cancer. We aimed to investigate the effects of inhibiting both pathways simultaneously on breast cancer cell survival and the potential interactions between these two signaling pathways. ER-positive MCF-7 cells show decreased viability after treatment with cyclopamine, a Hh-Gli pathway inhibitor, as well as after tamoxifen (an ERα inhibitor) treatment. Simultaneous treatment with cyclopamine and tamoxifen on the other hand, causes short-term survival of cells, and increased migration. We found upregulated Hh-Gli signaling under these conditions and protein profiling revealed increased expression of proteins involved in cell proliferation and migration. Therefore, even though Hh-Gli signaling seems to be a good potential target for breast cancer therapy, caution must be advised, especially when combining therapies. In addition, we also show a potential direct interaction between the Shh protein and ERα in MCF-7 cells. Our data suggest that the Shh protein is able to activate ERα independently of the canonical Hh-Gli signaling pathway. Therefore, this may present an additional boost for ER-positive cells that express Shh, even in the absence of estrogen. PMID:25503972

  6. Neural Stem Cells Secreting Anti-HER2 Antibody Improve Survival in a Preclinical Model of HER2 Overexpressing Breast Cancer Brain Metastases.

    PubMed

    Kanojia, Deepak; Balyasnikova, Irina V; Morshed, Ramin A; Frank, Richard T; Yu, Dou; Zhang, Lingjiao; Spencer, Drew A; Kim, Julius W; Han, Yu; Yu, Dihua; Ahmed, Atique U; Aboody, Karen S; Lesniak, Maciej S

    2015-10-01

    The treatment of human epidermal growth factor receptor 2 (HER2)-overexpressing breast cancer has been revolutionized by trastuzumab. However, longer survival of these patients now predisposes them to forming HER2 positive brain metastases, as the therapeutic antibodies cannot cross the blood brain barrier. The current oncologic repertoire does not offer a rational, nontoxic targeted therapy for brain metastases. In this study, we used an established human neural stem cell line, HB1.F3 NSCs and generated a stable pool of cells secreting a high amount of functional full-length anti-HER2 antibody, equivalent to trastuzumab. Anti-HER2Ab secreted by the NSCs (HER2Ab-NSCs) specifically binds to HER2 overexpressing human breast cancer cells and inhibits PI3K-Akt signaling. This translates to HER2Ab-NSC inhibition of breast cancer cell growth in vitro. Preclinical in vivo experiments using HER2Ab overexpressing NSCs in a breast cancer brain metastases (BCBM) mouse model demonstrate that intracranial injection of HER2Ab-NSCs significantly improves survival. In effect, these NSCs provide tumor localized production of HER2Ab, minimizing any potential off-target side effects. Our results establish HER2Ab-NSCs as a novel, nontoxic, and rational therapeutic approach for the successful treatment of HER2 overexpressing BCBM, which now warrants further preclinical and clinical investigation.

  7. Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival

    PubMed Central

    Tobin, N. P.; Harrell, J. C.; Lövrot, J.; Egyhazi Brage, S.; Frostvik Stolt, M.; Carlsson, L.; Einbeigi, Z.; Linderholm, B.; Loman, N.; Malmberg, M.; Walz, T.; Fernö, M.; Perou, C. M.; Bergh, J.; Hatschek, T.; Lindström, L. S.; Hatschek, Thomas; Fernö, Mårten; Lindström, Linda Sofie; Hedenfalk, Ingrid; Brandberg, Yvonne; Carstensen, John; Egyhazy, Suzanne; Stolt, Marianne Frostvik; Skoog, Lambert; Hellström, Mats; Maliniemi, Maarit; Svensson, Helene; Åström, Gunnar; Bergh, Jonas; Bjöhle, Judith; Lidbrink, Elisabet; Rotstein, Sam; Wallberg, Birgitta; Einbeigi, Zakaria; Carlsson, Per; Linderholm, Barbro; Walz, Thomas; Loman, Niklas; Malmström, Per; Söderberg, Martin; Malmberg, Martin; Carlsson, Lena; Umeå; Lindh, Birgitta; Sundqvist, Marie; Malmberg, Lena

    2015-01-01

    Background We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients. Patients and methods The translational aspect of the Swedish multicenter randomized trial called TEX included 111 patients with at least one biopsy from a morphologically confirmed locoregional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up, and metastasis gene expression information (Affymetrix array GPL10379). We assessed the previously published gene expression modules describing biological processes [proliferation, apoptosis, human epidermal receptor 2 (HER2) and estrogen (ER) signaling, tumor invasion, immune response, and angiogenesis] and pathways (Ras, MAPK, PTEN, AKT-MTOR, PI3KCA, IGF1, Src, Myc, E2F3, and β-catenin) and the intrinsic subtypes (PAM50). Furthermore, by contrasting genes expressed in the metastases in relation to survival, we derived a poor metastasis survival signature. Results A significant reduction in post-relapse breast cancer-specific survival was associated with low-ER receptor signaling and apoptosis gene module scores, and high AKT-MTOR, Ras, and β-catenin module scores. Similarly, intrinsic subtyping of the metastases provided statistically significant post-relapse survival information with the worst survival outcome in the basal-like [hazard ratio (HR) 3.7; 95% confidence interval (CI) 1.3–10.9] and HER2-enriched (HR 4.4; 95% CI 1.5–12.8) subtypes compared with the luminal A subtype. Overall, 25% of the metastases were basal-like, 32% HER2-enriched, 10% luminal A, 28% luminal B

  8. CD117 expression in breast phyllodes tumors correlates with adverse pathologic parameters and reduced survival.

    PubMed

    Tan, Wai Jin; Thike, Aye Aye; Tan, Sie Yong; Tse, Gary M-K; Tan, Min-Han; Bay, Boon Huat; Tan, Puay Hoon

    2015-03-01

    CD117 (c-kit) is a type III receptor tyrosine kinase encoded by the KIT gene. Deregulation of expression and mutations in the gene are implicated in various tumors. Reports of CD117 expression in phyllodes tumors have been controversial. We aim to investigate the protein expression of CD117 and mutations in the KIT gene in phyllodes tumors, and correlate the findings with pathological parameters and clinical outcome. A total of 272 cases were included in this study. CD117 expression was investigated by immunohistochemistry on tissue microarray sections. Toluidine blue staining was performed to indicate mast cells. Overall, 28 (10%) cases were CD117 positive. CD117 expression was significantly associated with tumor grade (P<0.001), increased stromal hypercellularity (P=0.003), stromal atypia (P=0.01), and stromal mitotic activity (P<0.001), permeative microscopic margins (P=0.002), and presence of hemorrhage (P=0.001). Expression was also associated with poorer overall survival (P=0.003). Nineteen cases were further selected for mutation screening through the Affymetrix OncoScan platform. No mutation of the KIT gene was found. Despite a lack of mutations in the KIT gene, CD117 protein expression is associated with unfavorable pathological parameters and poorer prognosis, suggesting an underlying role in the biology of phyllodes tumors.

  9. Insights on the antitumor effects of kahweol on human breast cancer: Decreased survival and increased production of reactive oxygen species and cytotoxicity

    SciTech Connect

    Cárdenas, Casimiro; Quesada, Ana R.; Medina, Miguel Ángel

    2014-05-09

    Highlights: • Kahweol inhibits growth and attachment-independent proliferation of tumor cells. • Kahweol induces apoptosis in MDA-MB231 human breast cancer cells. • Kahweol-induced apoptosis involves caspase activation and cytochrome c release. • Kahweol does not protect against hydrogen peroxide cytotoxicity. • Kahweol increases hydrogen peroxide production by human breast cancer cells. - Abstract: The present study aims to identify the modulatory effects of kahweol, an antioxidant diterpene present in coffee beans, on a panel of human tumor cell lines. Kahweol inhibits tumor cell proliferation and clonogenicity and induces apoptosis in several kinds of human tumor cells. In the estrogen receptor-negative MDA-MB231 human breast cancer, the mentioned effects are accompanied by caspases 3/7 and 9 activation and cytochrome c release. On the other hand, kahweol increases the production of reactive oxygen species and their cytotoxicity in human breast cancer cells but not in normal cells. Taken together, our data suggest that kahweol is an antitumor compound with inhibitory effects on tumor cell growth and survival, especially against MDA-MB231 breast cancer cells.

  10. Does vascular endothelial growth factor (VEGF) predict local relapse and survival in radiotherapy-treated node-negative breast cancer?

    PubMed Central

    Linderholm, B; Tavelin, B; Grankvist, K; Henriksson, R

    1999-01-01

    The aim of this study was to determine the association of vascular endothelial growth factor (VEGF) content in 302 consecutive node-negative breast cancer (NNBC) patients treated with only locoregional radiotherapy to relapse free- (RFS) and overall survival (OS). VEGF content in tumour cytosols was measured by an enzymatic immunoassay for the major isoform VEGF165. The median age was 56 years, the median follow-up time 56 months. A wide range (0.01–144.79 pg μg−1 DNA) of VEGF content was found (median 1.92). Significant associations were found between VEGF and oestrogen receptor (ER) content, progesterone receptor (PR) and tumour size (P = 0.005). Univariate analysis displayed significant reduced RFS and OS for patients with higher VEGF content (P = 0.0113 and P = 0.0075 respectively). A total of 43 recurrences have been found (ten local relapses within the breast, five in the axillary or supraclavicular lymph nodes and 28 distant metastasis). There was no significant correlation between the localization of the relapse and the VEGF content. Multivariate analysis suggested VEGF as the only predictor of OS (relative risk (RR) = 3.6, 95% confidence interval (CI) = 0.97–13.37), and in patients with T1 tumours (n = 236) the multivariate analysis clearly displayed VEGF as the only independent predictor of both RFS and OS (RR = 5.1, CI = 1.07–24.59). In the sub-group with ER-positive tumours (n = 229), multivariate analysis showed VEGF as the only significant predictor of RFS and OS (RR = 10.44, CI = 1.26–86.38). The results suggest VEGF165 as a predictor of RFS and OS in NNBC patients treated with locoregional radiotherapy, comprising especially patients with favourable prognosis of T1 tumours, or ER-positive tumours. The high VEGF expression might define a radioresistant phenotype, or indicate an early distant spread which might require adjuvant systemic treatment. © 1999 Cancer Research Campaign PMID:10574263

  11. Capecitabine in Combination with Standard (Neo)Adjuvant Regimens in Early Breast Cancer: Survival Outcome from a Meta-Analysis of Randomized Controlled Trials

    PubMed Central

    Li, Xu-Yuan

    2016-01-01

    Capecitabine has been investigated in early breast cancer in several studies, but it was undefined that whether it could improve survival. To investigate whether the addition of capecitabine affected survival in patients with early breast cancer, a meta-analysis was conducted and overall survival (OS), disease-free survival (DFS), and toxicity were assessed. The PubMed, Embase databases and the Cochrane Central Register of Controlled Trials were searched for studies between January 2006 and April 2016. Hazard ratios (HRs) with their 95% confidence intervals (CIs), or data for calculating HRs with 95% CI were derived. Seven trials with 9097 patients, consisted of 4 adjuvant and 3 neoadjuvant studies, were included in this meta-analysis. Adding capecitabine showed no improvement in DFS (HR = 0.93; 95% CI, 0.85–1.02; P = 0.12), whereas a significant improvement in OS was observed (HR = 0.85; 95% CI, 0.75–0.96; P = 0.008). A sub-analysis of DFS showed that benefit of capecitabine derived from patients with triple negative subtype and with extensive axillary involvement. Safety profiles were consistent with the known side-effects of capecitabine, but more patients discontinued scheduled treatment in the capecitabine group. Combining capecitabine with standard (neo)adjuvant regimens in early breast cancer demonstrated a significantly superior OS, and indicated DFS improvement in some subtypes with high risk of recurrence. Selection of subtypes was a key to identify patients who might gain survival benefit from capecitabine. PMID:27741288

  12. The Effect of Early Detection of Occult Brain Metastases in HER2-Positive Breast Cancer Patients on Survival and Cause of Death

    SciTech Connect

    Niwinska, Anna; Tacikowska, Malgorzata; Murawska, Magdalena

    2010-07-15

    Purpose: The aim of the study is to evaluate disease-free survival, survival from the detection of brain metastases, overall survival, and cause of death in patients with occult brain metastases (Group I) vs. patients with symptomatic brain metastases (Group II). Methods and Materials: In 80 HER2-positive breast cancer patients, treated with trastuzumab and cytostatic agents for metastatic disease, magnetic resonance imaging screening of the brain was performed, and in 29 patients (36%) occult brain metastasis was detected (Group I). Whole-brain radiotherapy was delivered to Group I. This first group was compared with 52 patients who had symptomatic brain metastases (Group II) and was treated the same way, at the same clinic, during the same time period. Results: Median disease-free survival was 17 months in Group I and 19.9 months in Group II (p = 0.58). The median time interval between the dissemination of the disease and the detection of occult or symptomatic brain metastases was 9 and 15 months, respectively (p = 0.11). When the brain metastases were detected, the median survival was 9 and 8.78 months, respectively (p = 0.80). The median overall survival was 53 and 51 months, respectively (p = 0.94). In the group with occult brain metastases (Group I) 16% of patients died because of progression within the brain. In the group with symptomatic brain metastases (Group II) the rate of cerebral death was 48% (p = 0.009). Conclusions: Whole-brain radiotherapy of occult brain metastases in HER2-positive breast cancer patients with visceral dissemination produces a three-fold decrease in cerebral deaths but does not prolong survival.

  13. Cancer survival disparities by health insurance status.

    PubMed

    Niu, Xiaoling; Roche, Lisa M; Pawlish, Karen S; Henry, Kevin A

    2013-06-01

    Previous studies found that uninsured and Medicaid insured cancer patients have poorer outcomes than cancer patients with private insurance. We examined the association between health insurance status and survival of New Jersey patients 18-64 diagnosed with seven common cancers during 1999-2004. Hazard ratios (HRs) with 95% confidence intervals for 5-year cause-specific survival were calculated from Cox proportional hazards regression models; health insurance status was the primary predictor with adjustment for other significant factors in univariate chi-square or Kaplan-Meier survival log-rank tests. Two diagnosis periods by health insurance status were compared using Kaplan-Meier survival log-rank tests. For breast, colorectal, lung, non-Hodgkin lymphoma (NHL), and prostate cancer, uninsured and Medicaid insured patients had significantly higher risks of death than privately insured patients. For bladder cancer, uninsured patients had a significantly higher risk of death than privately insured patients. Survival improved between the two diagnosis periods for privately insured patients with breast, colorectal, or lung cancer and NHL, for Medicaid insured patients with NHL, and not at all for uninsured patients. Survival from cancer appears to be related to a complex set of demographic and clinical factors of which insurance status is a part. While ensuring that everyone has adequate health insurance is an important step, additional measures must be taken to address cancer survival disparities.

  14. Altered S-nitrosothiol homeostasis provides a survival advantage to breast cancer cells in HER2 tumors and reduces their sensitivity to trastuzumab.

    PubMed

    Cañas, Amanda; López-Sánchez, Laura M; Peñarando, Jon; Valverde, Araceli; Conde, Francisco; Hernández, Vanessa; Fuentes, Elena; López-Pedrera, Chary; de la Haba-Rodríguez, Juan R; Aranda, Enrique; Rodríguez-Ariza, Antonio

    2016-04-01

    The monoclonal antibody trastuzumab against HER2/neu, which is overexpressed in 15-20% of breast cancers, has clinical efficacy but many patients do not respond to initial treatment or develop resistance during treatment. Nitric oxide (NO) regulates cell signaling by targeting specific cysteine residues in proteins, forming S-nitrosothiols (SNO) in a process known as S-nitrosylation. We previously reported that molecular characteristics in breast cancer may dictate the tumor response to impaired SNO homeostasis. In the present study, we explored the role of SNO homeostasis in HER2 breast tumors. The antiproliferative action of trastuzumab in HER2-overexpressing BT-474 and SKBR-3 cells was suppressed when S-nitrosoglutathione reductase (GSNOR/ADH5) activity, which plays a key role in SNO homeostasis, was specifically inhibited with the pyrrole derivative compound N6022. Moreover, GSNOR inhibition restored the activation of survival signaling pathways involved in the resistance to anti-HER2 therapies (AKT, Src and c-Abl kinases and TrkA/NRTK1, TrkB/NRTK2, EphA1 and EphA3 receptors) and reduced the apoptotic effect of trastuzumab. Accordingly, GSNOR inhibition augmented the S-nitrosylation of apoptosis-related proteins, including Apaf-1, pSer73/63 c-Jun, calcineurin subunit α and HSF1. In agreement with in vitro data, immunohistochemical analyses of 51 breast tumors showed that HER2 expression was associated with lower expression of GSNOR protein. Moreover, gene expression analysis confirmed that high ADH5/GSNOR gene expression was associated with high patient survival rates in HER2 tumors. In conclusion, our data provide evidence of molecular mechanisms contributing to the progression of HER2+ breast cancers and could facilitate the development of therapeutic options to counteract resistance to anti-HER2 therapies. PMID:26854735

  15. Altered S-nitrosothiol homeostasis provides a survival advantage to breast cancer cells in HER2 tumors and reduces their sensitivity to trastuzumab.

    PubMed

    Cañas, Amanda; López-Sánchez, Laura M; Peñarando, Jon; Valverde, Araceli; Conde, Francisco; Hernández, Vanessa; Fuentes, Elena; López-Pedrera, Chary; de la Haba-Rodríguez, Juan R; Aranda, Enrique; Rodríguez-Ariza, Antonio

    2016-04-01

    The monoclonal antibody trastuzumab against HER2/neu, which is overexpressed in 15-20% of breast cancers, has clinical efficacy but many patients do not respond to initial treatment or develop resistance during treatment. Nitric oxide (NO) regulates cell signaling by targeting specific cysteine residues in proteins, forming S-nitrosothiols (SNO) in a process known as S-nitrosylation. We previously reported that molecular characteristics in breast cancer may dictate the tumor response to impaired SNO homeostasis. In the present study, we explored the role of SNO homeostasis in HER2 breast tumors. The antiproliferative action of trastuzumab in HER2-overexpressing BT-474 and SKBR-3 cells was suppressed when S-nitrosoglutathione reductase (GSNOR/ADH5) activity, which plays a key role in SNO homeostasis, was specifically inhibited with the pyrrole derivative compound N6022. Moreover, GSNOR inhibition restored the activation of survival signaling pathways involved in the resistance to anti-HER2 therapies (AKT, Src and c-Abl kinases and TrkA/NRTK1, TrkB/NRTK2, EphA1 and EphA3 receptors) and reduced the apoptotic effect of trastuzumab. Accordingly, GSNOR inhibition augmented the S-nitrosylation of apoptosis-related proteins, including Apaf-1, pSer73/63 c-Jun, calcineurin subunit α and HSF1. In agreement with in vitro data, immunohistochemical analyses of 51 breast tumors showed that HER2 expression was associated with lower expression of GSNOR protein. Moreover, gene expression analysis confirmed that high ADH5/GSNOR gene expression was associated with high patient survival rates in HER2 tumors. In conclusion, our data provide evidence of molecular mechanisms contributing to the progression of HER2+ breast cancers and could facilitate the development of therapeutic options to counteract resistance to anti-HER2 therapies.

  16. Genetic variants in interleukin genes are associated with breast cancer risk and survival in a genetically admixed population: the Breast Cancer Health Disparities Study.

    PubMed

    Slattery, Martha L; Herrick, Jennifer S; Torres-Mejia, Gabriella; John, Esther M; Giuliano, Anna R; Hines, Lisa M; Stern, Mariana C; Baumgartner, Kathy B; Presson, Angela P; Wolff, Roger K

    2014-08-01

    Interleukins (ILs) are key regulators of immune response. Genetic variation in IL genes may influence breast cancer risk and mortality given their role in cell growth, angiogenesis and regulation of inflammatory process. We examined 16 IL genes with breast cancer risk and mortality in an admixed population of Hispanic/Native American (NA) (2111 cases and 2597 controls) and non-Hispanic white (NHW) (1481 cases and 1585 controls) women. Adaptive Rank Truncated Product (ARTP) analysis was conducted to determine gene significance and lasso (least absolute shrinkage and selection operator) was used to identify potential gene by gene and gene by lifestyle interactions. The pathway was statistically significant for breast cancer risk overall (P ARTP = 0.0006), for women with low NA ancestry (P(ARTP) = 0.01), for premenopausal women (P(ARTP) = 0.02), for estrogen receptor (ER)+/progesterone receptor (PR)+ tumors (P(ARTP) = 0.03) and ER-/PR- tumors (P(ARTP) = 0.02). Eight of the 16 genes evaluated were associated with breast cancer risk (IL1A, IL1B, IL1RN, IL2, IL2RA, IL4, IL6 and IL10); four genes were associated with breast cancer risk among women with low NA ancestry (IL1B, IL6, IL6R and IL10), two were associated with breast cancer risk among women with high NA ancestry (IL2 and IL2RA) and four genes were associated with premenopausal breast cancer risk (IL1A, IL1B, IL2 and IL3). IL4, IL6R, IL8 and IL17A were associated with breast cancer-specific mortality. We confirmed associations with several functional polymorphisms previously associated with breast cancer risk and provide support that their combined effect influences the carcinogenic process. PMID:24670917

  17. The role of lymphatic and blood vessel invasion in predicting survival and methods of detection in patients with primary operable breast cancer.

    PubMed

    Gujam, Fadia J A; Going, James J; Edwards, Joanne; Mohammed, Zahra M A; McMillan, Donald C

    2014-02-01

    Lymphovascular invasion (LBVI) has long been recognized as an essential step of metastases in patients with cancer. However, the process of invasion into lymphatic and blood vessels is still not well defined in breast cancer. To examine the evidence for LBVI, lymphatic vessel invasion (LVI) and blood vessel invasion (BVI) in predicting survival in patients with primary operable breast cancer, and to evaluate the detection methods of vessel invasion. A systematic review of data published from 1964 to 2012 was undertaken according to a pre-defined protocol. There is robust evidence that general LBVI and LVI are independent prognostic factors of poorer survival. The prognostic role of BVI remains unclear. Most studies detected LBVI using H&E stained sections. The overall weighted average of the LBVI rate using immunostaining was higher (35%) than H&E (24%). The LBVI rate using H&E was variable (9-50%) and less variable using immunostaining (32-41%). The overall weighted average of the LVI rate was similar using H&E and immunostaining (33% vs. 25%). The LVI rate using H&E was variable (10-49%) and less variable using immunostaining (21-42%). The overall weighted average of the BVI rate was similar using H&E and/or classical staining and immunostaining (16% vs. 10%). The BVI rates using H&E and/or classical staining approach (4-46%) and immunostaining (1-29%) were both variable. The LBVI and LVI are powerful prognostic factors in primary operable breast cancer. However, BVI was rarely specifically examined and its role in predicting survival is not clear. Further work is required using reliable specific staining to establish the routine use of LVI and BVI in the prediction of outcome in patients with primary operable breast cancer.

  18. Glucocorticoid receptor-induced MAPK phosphatase-1 (MPK-1) expression inhibits paclitaxel-associated MAPK activation and contributes to breast cancer cell survival.

    PubMed

    Wu, Wei; Pew, Travis; Zou, Min; Pang, Diana; Conzen, Suzanne D

    2005-02-11

    Glucocorticoid receptor (GR) activation has recently been shown to inhibit apoptosis in breast epithelial cells. We have previously described a group of genes that is rapidly up-regulated in these cells following dexamethasone (Dex) treatment. In an effort to dissect the mechanisms of GR-mediated breast epithelial cell survival, we now examine the molecular events downstream of GR activation. Here we show that GR activation leads to both the rapid induction of MAPK phosphatase-1 (MKP-1) mRNA and its sustained expression. Induction of the MKP-1 protein in the MCF10A-Myc and MDA-MB-231 breast epithelial cell lines was also seen. Paclitaxel treatment resulted in MAPK activation and apoptosis of MDA-MB-231 breast cancer cells, and both processes were inhibited by Dex pretreatment. Furthermore, induction of MKP-1 correlated with the inhibition of extracellular signal-regulated kinase (ERK1/2) and c-Jun N-terminal kinase (JNK) activity, whereas p38 activity was minimally affected. Blocking Dex-induced MKP-1 induction using small interfering RNA increased ERK1/2 and JNK phosphorylation and decreased cell survival. ERK1/2 and JNK inactivation was associated with Ets-like transcription factor-1 (ELK-1) dephosphorylation. To explore the gene expression changes that occur downstream of ELK-1 dephosphorylation, we used a combination of temporal gene expression data and promoter element analyses. This approach revealed a previously unrecognized transcriptional target of ELK-1, the human tissue plasminogen activator (tPA). We verified the predicted ELK-1--> tPA transcriptional regulatory relationship using a luciferase reporter assay. We conclude that GR-mediated MAPK inactivation contributes to cell survival and that the potential transcriptional targets of this inhibition can be identified from large scale gene array analysis.

  19. Bimodality of intratumor Ki67 expression is an independent prognostic factor of overall survival in patients with invasive breast carcinoma.

    PubMed

    Laurinavicius, Arvydas; Plancoulaine, Benoit; Rasmusson, Allan; Besusparis, Justinas; Augulis, Renaldas; Meskauskas, Raimundas; Herlin, Paulette; Laurinaviciene, Aida; Abdelhadi Muftah, Abir A; Miligy, Islam; Aleskandarany, Mohammed; Rakha, Emad A; Green, Andrew R; Ellis, Ian O

    2016-04-01

    Proliferative activity, assessed by Ki67 immunohistochemistry (IHC), is an established prognostic and predictive biomarker of breast cancer (BC). However, it remains under-utilized due to lack of standardized robust measurement methodologies and significant intratumor heterogeneity of expression. A recently proposed methodology for IHC biomarker assessment in whole slide images (WSI), based on systematic subsampling of tissue information extracted by digital image analysis (DIA) into hexagonal tiling arrays, enables computation of a comprehensive set of Ki67 indicators, including intratumor variability. In this study, the tiling methodology was applied to assess Ki67 expression in WSI of 152 surgically removed Ki67-stained (on full-face sections) BC specimens and to test which, if any, Ki67 indicators can predict overall survival (OS). Visual Ki67 IHC estimates and conventional clinico-pathologic parameters were also included in the study. Analysis revealed linearly independent intrinsic factors of the Ki67 IHC variance: proliferation (level of expression), disordered texture (entropy), tumor size and Nottingham Prognostic Index, bimodality, and correlation. All visual and DIA-generated indicators of the level of Ki67 expression provided significant cutoff values as single predictors of OS. However, only bimodality indicators (Ashman's D, in particular) were independent predictors of OS in the context of hormone receptor and HER2 status. From this, we conclude that spatial heterogeneity of proliferative tumor activity, measured by DIA of Ki67 IHC expression and analyzed by the hexagonal tiling approach, can serve as an independent prognostic indicator of OS in BC patients that outperforms the prognostic power of the level of proliferative activity. PMID:26818835

  20. Distinguishing Low-Risk Luminal A Breast Cancer Subtypes with Ki-67 and p53 Is More Predictive of Long-Term Survival.

    PubMed

    Lee, Se Kyung; Bae, Soo Youn; Lee, Jun Ho; Lee, Hyun-Chul; Yi, Hawoo; Kil, Won Ho; Lee, Jeong Eon; Kim, Seok Won; Nam, Seok Jin

    2015-01-01

    Overexpression of p53 is the most frequent genetic alteration in breast cancer. Recently, many studies have shown that the expression of mutant p53 differs for each subtype of breast cancer and is associated with different prognoses. In this study, we aimed to determine the suitable cut-off value to predict the clinical outcome of p53 overexpression and its usefulness as a prognostic factor in each subtype of breast cancer, especially in luminal A breast cancer. Approval was granted by the Institutional Review Board of Samsung Medical Center. We analyzed a total of 7,739 patients who were surgically treated for invasive breast cancer at Samsung Medical Center between Dec 1995 and Apr 2013. Luminal A subtype was defined as ER&PR + and HER2- and was further subclassified according to Ki-67 and p53 expression as follows: luminal A (Ki-67-,p53-), luminal A (Ki-67+, p53-), luminal A (Ki-67 -, p53+) and luminal A (Ki-67+, p53+). Low-risk luminal A subtype was defined as negative for both Ki-67 and p53 (luminal A [ki-67-, p53-]), and others subtypes were considered to be high-risk luminal A breast cancer. A cut-off value of 10% for p53 was a good predictor of clinical outcome in all patients and luminal A breast cancer patients. The prognostic role of p53 overexpression for OS and DFS was only significant in luminal A subtype. The combination of p53 and Ki-67 has been shown to have the best predictive power as calculated by the area under curve (AUC), especially for long-term overall survival. In this study, we have shown that overexpression of p53 and Ki-67 could be used to discriminate low-risk luminal A subtype in breast cancer. Therefore, using the combination of p53 and Ki-67 expression in discriminating low-risk luminal A breast cancer may improve the prognostic power and provide the greatest clinical utility.

  1. Impact of local surgical treatment on survival in young women with T1 breast cancer: long-term results of a population-based cohort.

    PubMed

    Jeon, Ye Won; Choi, Jung Eun; Park, Heung Kyu; Kim, Ku Sang; Lee, Jee Yeon; Suh, Young Jin

    2013-04-01

    The aim of this study was to analyze the effect of the type of local surgical treatment on survival in young women aged less than 40 years with T1 breast cancer. We analyzed data from 3,512 patients aged ≤40 years old who were diagnosed with T1 breast cancer from the Korean Breast Cancer Registry database between January 1988 and December 2006 and underwent either breast-conserving therapy (BCT) or mastectomy. The overall survival (OS) and breast-cancer-specific survival (BCSS) were compared between BCT and mastectomy. Of the 3,512 patients analyzed, 1,951 (55.6 %) underwent BCT, and 1,561 (44.4 %) underwent mastectomy. The median follow-up period was 111.0 (79.0-131.5) months. Overall, the 10-year OS rates for BCT and mastectomy were 95 and 92.1 %, respectively (p = 00004), and the 10-year BCSS rates for BCT and mastectomy patients were 96.9 and 94.9 %, respectively (p = 0.12). In node-negative patients, no significant difference was observed in either the OS (adjusted hazard ratio [HR] 1.072; 95 % CI, 0.750-1.5332, p = 0.704) or BCSS (adjusted HR 0.988; 95 % CI, 0.620-1.574, p = 0.960) rate between the BCT and mastectomy groups. In node-positive patients, no significant difference was observed in the OS (adjusted HR 1.634; 95 % CI, 0.982-2.272, p = 0.59) and BCSS (adjusted HR 1.410; 95 % CI, 0.755-2.633, p = 0.281) rates between the BCT and mastectomy groups. In this large, population-based analysis of young women with T1 breast cancer, the OS and BCSS were not different between BCT and mastectomy. PMID:23456232

  2. Does self-regulation and autonomic regulation have an influence on survival in breast and colon carcinoma patients? results of a prospective outcome study

    PubMed Central

    2011-01-01

    Background Cancer Related Fatigue (CRF) and circadian rhythm have a great impact on the quality of life (HRQL) of patients with breast (BC) and colon cancer (CRC). Other patient related outcomes in oncology are measured by new instruments focusing on adaptive characteristics such as sense of coherence or self-regulation, which could be more appropriate as a prognostic tool than classical HRQL. The aim of this study was to assess the association of autonomic regulation (aR) and self-regulation (SR) with survival. Methods 146 cancer patients and 120 healthy controls took part in an initial evaluation in 2000/2001. At a median follow up of 5.9 years later, 62 of 95 BC, 17 of 51 CRC patients, and 85 of 117 healthy controls took part in the follow-up study. 41 participants had died. For the follow-up evaluation, participants were requested to complete the standardized aR and SR questionnaires. Results On average, cancer patients had survived for 10.1 years with the disease. Using a Cox proportional hazard regression with stepwise variables such as age, diagnosis group, Charlson co-morbidity index, body mass index (BMI)) aR and SR. SR were identified as independent parameters with potential prognostic relevance on survival While aR did not significantly influence survival, SR showed a positive and independent impact on survival (OR = 0.589; 95%-CI: 0.354 - 0.979). This positive effect persisted significantly in the sensitivity analysis of the subgroup of tumour patients and in the subscale 'Achieve satisfaction and well-being' and by tendency in the UICC stages nested for the different diagnoses groups. Conclusions Self-regulation might be an independent prognostic factor for the survival of breast and colon carcinoma patients and merits further prospective studies. PMID:21961625

  3. Selective small molecule Stat3 inhibitor reduces breast cancer tumor-initiating cells and improves recurrence free survival in a human-xenograft model.

    PubMed

    Dave, Bhuvanesh; Landis, Melissa D; Tweardy, David J; Chang, Jenny C; Dobrolecki, Lacey E; Wu, Meng-Fen; Zhang, Xiaomei; Westbrook, Thomas F; Hilsenbeck, Susan G; Liu, Dan; Lewis, Michael T

    2012-01-01

    Metastasis and disease relapse are hypothesized to result from tumor initiating cells (TICs). Previously, we have defined a CD44+/CD24-/low mammosphere-forming tumorigenic 493-gene signature in breast cancer. Stat3 was identified as a critical node in self-renewal based on an ongoing lentiviral shRNA screen being conducted in two breast cancer cell lines SUM159 and BT549. In corroborating work, targeting the SH2 domain of Stat3 with a novel small molecule decreased the percentage of cells expressing TIC markers (CD44+/CD24-/low and ALDH+) and mammosphere formation in p-Stat3 overexpressing human breast cancer xenografts in SCID-beige mice. Importantly, we observed a four-fold improvement in the 30-day recurrence-free survival relative to docetaxel alone with the addition of the Stat3 inhibitor in the chemoresistant tumor model. Thus, these findings provide a strong impetus for the development of selective Stat3 inhibitors in order to improve survival in patients with p-Stat3 overexpressing tumors. PMID:22879872

  4. An RNAi screen identifies metabolic regulators NR1D1 and PBP as novel survival factors for breast cancer cells with the ERBB2 signature

    PubMed Central

    Kourtidis, Antonis; Jain, Ritu; Carkner, Richard D.; Eifert, Cheryl; Brosnan, M. Julia; Conklin, Douglas S.

    2010-01-01

    Overexpression of the adverse prognostic marker ERBB2 occurs in 30% of breast cancers, however, therapies targeting this gene have not proven to be as effective as was initially hoped. Transcriptional profiling meta-analyses have shown that there are approximately 150 genes co-overexpressed with ERBB2, suggesting that these genes may represent alternative factors influencing ERBB2-positive tumors. Here we describe an RNA interference-based analysis of these genes that identifies transcriptional regulators of fat synthesis and storage as being critical for the survival of these cells. These transcription factors, NR1D1 and PBP, both reside on ERBB2-containing 17q12-21 amplicons and are part of the ERBB2 expression signature. We show that NR1D1 and PBP act through a common pathway in upregulating several genes in the de novo fatty acid synthesis network that is highly active in ERBB2-positive breast cancer cells. MDH1 and ME1, enzymes that link glycolysis and fatty acid synthesis, are also regulated by NR1D1. The resulting high-level fat production from increased expression of these genes likely contributes to an abnormal cellular energy metabolism based on aerobic glycolysis. Together, these results demonstrate that the cells of this aggressive form of breast cancer are genetically preprogrammed to depend on NR1D1 and PBP for the energy production necessary for survival. PMID:20160030

  5. The impact of complementary and alternative medicines on cancer symptoms, treatment side effects, quality of life, and survival in women with breast cancer--a systematic review.

    PubMed

    Leggett, S; Koczwara, B; Miller, M

    2015-01-01

    Breast cancer is the most common form of cancer amongst women. Women with breast cancer frequently consult dietitians for advice, and increasingly advice on complementary alternative medicines (CAM). The aim of this systematic review was to evaluate evidence of CAM administered orally on cancer-related outcomes. Databases were searched for studies recruiting women with a history of breast cancer reporting on the use of CAM administered orally as tablets, capsules, powders, and liquids for any 1 or more of the following: alleviation of cancer-related symptoms and treatment side effects, improvement to quality of life, physical and emotional wellbeing, survival, and mortality. Twenty-two studies were identified as meeting the inclusion criteria. Ten CAM categories were established with no more than 4 articles published in each category. Although the evidence is of varying quality there is some data to support that guarana and Ganoderma lucidum may improve fatigue, whereas glutamine may also be effective in improving oral mucositis symptoms. Overall, the current available evidence is inconclusive to make definitive recommendations regarding the effectiveness for individuals' use of CAM in women with breast cancer. Further high-quality randomized controlled trials exploring safety, toxicity, and other potential adverse effects of CAM are required. PMID:25811312

  6. Care and survival of Mexican American women with node negative breast cancer: historical cohort evidence of health insurance and barrio advantages.

    PubMed

    Richter, Nancy L; Gorey, Kevin M; Haji-Jama, Sundus; Luginaah, Isaac N

    2015-06-01

    We hypothesized 3-way ethnicity by barrio by health insurance interactions such that the advantages of having adequate health insurance were greatest among Mexican American (MA) women who lived in barrios. Barrios were neighborhoods with relatively high concentrations of MAs (60% or more). Data were analyzed for 194 MA and 2,846 non-Hispanic white women diagnosed with, very treatable, node negative breast cancer in California between 1996 and 2000 and followed until 2011. Significant interactions were observed such that the protective effects of Medicare or private health insurance on radiation therapy access and long term survival were largest for MA women who resided in MA barrios, neighborhoods that also tended to be extremely poor. These paradoxical findings are consistent with the theory that more facilitative social and economic capital available to MA women in barrios enables them to better absorb the indirect and direct, but uncovered, costs of breast cancer care.

  7. Depression in older breast cancer survivors

    PubMed Central

    2012-01-01

    Background Breast cancer is the most commonly diagnosed cancer among U.S. women .The 5-year survival rate for this tumour is nowadays 85%, and the 61% of these women are still alive at 15 years. When depression symptoms are present as a consequence of breast cancer treatments, they may interfere negatively with patients’ quality of life. The aim of this study was to examine the effects of breast cancer treatment on the quality of life and the impact of depression on the health-related life. Methods We enrolled 173 women aged 65-75 years with early stage breast cancer diagnosed over the last 10 years, initially recruited to participate in a study examining heath-related quality of life in the first 5 years after breast cancer diagnosis. Participants were divided into four groups: 1) 46 breast cancer survivors (aged 65-70); 2) 62 women diagnosed with breast cancer (aged 65-69); 3) 32 women with recurrent breast cancer after 10 years (aged 66-75); 4) 30 women in good health status (aged 60-70). The Geriatric Depression Scale was used as a routine part of a comprehensive geriatric assessment. Collection of data for the application of instruments, such as sociodemographic variables (age, educational level, social state) and clinical date (stage and time of the disease and treatment), was carried out by trained researcher assistants. Results Our results demonstrated the correlation between depression and previous cancer experiences. In fact, in patients with cancer experience, the grade of depression was significantly higher compared to healthy subjects. Furthermore, we demonstrated that the patients with recurrent breast cancer were severely depressed compared to other groups. Conclusions A high percentage of participants were identified as having emotional and/or well being problems. Further investigations on the cause of depression problems cancer-related are needed. PMID:23173836

  8. Avoiding a Systematic Error in Assessing Fat Graft Survival in the Breast with Repeated Magnetic Resonance Imaging

    PubMed Central

    Herly, Mikkel; Müller, Felix C.; Elberg, Jens J.; Kølle, Stig-Frederik T.; Fischer-Nielsen, Anne; Thomsen, Carsten; Drzewiecki, Krzysztof T.

    2016-01-01

    Summary: Several techniques for measuring breast volume (BV) are based on examining the breast on magnetic resonance imaging. However, when techniques designed to measure total BV are used to quantify BV changes, for example, after fat grafting, a systematic error is introduced because BV changes lead to contour alterations of the breast. The volume of the altered breast includes not only the injected volume but also tissue previously surrounding the breast. Therefore, the quantitative difference in BV before and after augmentation will differ from the injected volume. Here, we present a new technique to measure BV changes that compensates for this systematic error by defining the boundaries of the breast to immovable osseous pointers. This approach avoids the misinterpretation of tissue included within the expanded boundaries as graft tissue. This new method of analysis may be a reliable tool for assessing BV changes to determine fat graft retention and may be useful for evaluating and comparing available surgical techniques for breast augmentation and reconstruction using fat grafting. PMID:27757341

  9. Relationship between cathepsin-D content and disease-free survival in node-negative breast cancer patients: a meta-analysis.

    PubMed Central

    Ferrandina, G.; Scambia, G.; Bardelli, F.; Benedetti Panici, P.; Mancuso, S.; Messori, A.

    1997-01-01

    Several reports have evaluated the correlation between cathepsin-D and overall survival or disease-free survival in node-negative breast cancer patients. Because conflicting data have so far been reported, a meta-analysis was conducted to clarify this problem. Eleven studies were included in our meta-analysis (total of 2690 patients). A specific meta-analytical methodology for censored data was used, and disease-free survival was the primary end point. Patients with low cathepsin-D levels had a significantly better disease-free survival than patients with high cathepsin-D values (meta-analytical odds ratio from 0.59 to 0.60 over the interval from 1 to 7 years). A secondary meta-analysis conducted exclusively on the data from eight studies based on cytosol assay gave substantially similar results. One limitation of our study is that the cut-off values to define high and low cathepsin-D concentrations were not identical in the various studies included in our meta-analysis (range from 20 to 78 pmol mg(-1) protein), thus introducing a possible bias in the statistical analysis of the data. However, a simulation based on the well-accepted method of the so-called publication bias showed that more than 100 null studies would be required to lead our results to a statistical level of non-significance. Considering the results of our meta-analysis, we conclude that the data presently available confirm a statistically significant association between high cathepsin-D values and poor disease-free survival in node-negative breast cancer patients. PMID:9303368

  10. Diagnostic Intervals and Its Association with Breast, Prostate, Lung and Colorectal Cancer Survival in England: Historical Cohort Study Using the Clinical Practice Research Datalink

    PubMed Central

    Redaniel, Maria Theresa; Martin, Richard M.; Ridd, Matthew J.; Wade, Julia; Jeffreys, Mona

    2015-01-01

    Rapid diagnostic pathways for cancer have been implemented, but evidence whether shorter diagnostic intervals (time from primary care presentation to diagnosis) improves survival is lacking. Using the Clinical Practice Research Datalink, we identified patients diagnosed with female breast (8,639), colorectal (5,912), lung (5,737) and prostate (1,763) cancers between 1998 and 2009, and aged >15 years. Presenting symptoms were classified as alert or non-alert, according to National Institute for Health and Care Excellence guidance. We used relative survival and excess risk modeling to determine associations between diagnostic intervals and five-year survival. The survival of patients with colorectal, lung and prostate cancer was greater in those with alert, compared with non-alert, symptoms, but findings were opposite for breast cancer. Longer diagnostic intervals were associated with lower mortality for colorectal and lung cancer patients with non-alert symptoms, (colorectal cancer: Excess Hazards Ratio, EHR >6 months vs <1 month: 0.85; 95% CI: 0.72-1.00; Lung cancer: EHR 3-6 months vs <1 month: 0.87; 95% CI: 0.80-0.95; EHR >6 months vs <1 month: 0.81; 95% CI: 0.74-0.89). Prostate cancer mortality was lower in patients with longer diagnostic intervals, regardless of type of presenting symptom. The association between diagnostic intervals and cancer survival is complex, and should take into account cancer site, tumour biology and clinical practice. Nevertheless, unnecessary delay causes patient anxiety and general practitioners should continue to refer patients with alert symptoms via the cancer pathways, and actively follow-up patients with non-alert symptoms in the community. PMID:25933397

  11. Effect of a low fat versus a low carbohydrate weight loss dietary intervention on biomarkers of long term survival in breast cancer patients ('CHOICE'): study protocol

    PubMed Central

    2011-01-01

    Background Weight loss in overweight or obese breast cancer patients is associated with an improved prognosis for long term survival. However, it is not clear whether the macronutrient composition of the chosen weight loss dietary plan imparts further prognostic benefit. A study protocol is presented for a dietary intervention to investigate the effects of weight loss dietary patterns that vary markedly in fat and carbohydrate contents on biomarkers of exposure to metabolic processes that may promote tumorigenesis and that are predictive of long term survival. The study will also determine how much weight must be lost for biomarkers to change in a favorable direction. Methods/Design Approximately 370 overweight or obese postmenopausal breast cancer survivors (body mass index: 25.0 to 34.9 kg/m2) will be accrued and assigned to one of two weight loss intervention programs or a non-intervention control group. The dietary intervention is implemented in a free living population to test the two extremes of popular weight loss dietary patterns: a high carbohydrate, low fat diet versus a low carbohydrate, high fat diet. The effects of these dietary patterns on biomarkers for glucose homeostasis, chronic inflammation, cellular oxidation, and steroid sex hormone metabolism will be measured. Participants will attend 3 screening and dietary education visits, and 7 monthly one-on-one dietary counseling and clinical data measurement visits in addition to 5 group visits in the intervention arms. Participants in the control arm will attend two clinical data measurement visits at baseline and 6 months. The primary outcome is high sensitivity C-reactive protein. Secondary outcomes include interleukin-6, tumor necrosis factor-α, insulin-like growth factor-1 (IGF), IGF binding protein-3, 8-isoprostane-F2-alpha, estrone, estradiol, progesterone, sex hormone binding globulin, adiponectin, and leptin. Discussion While clinical data indicate that excess weight for height is associated

  12. Hypofractionation with no boost after breast conservation in early-stage breast cancer patients.

    PubMed

    Arcadipane, Francesca; Franco, Pierfrancesco; De Colle, Chiara; Rondi, Nadia; Di Muzio, Jacopo; Pelle, Emanuela; Martini, Stefania; Ala, Ada; Airoldi, Mario; Donadio, Michela; De Sanctis, Corrado; Castellano, Isabella; Ragona, Riccardo; Ricardi, Umberto

    2016-10-01

    The aim of this study was to evaluate local control, survival and toxicity profile of a consecutive cohort of early-stage breast cancer (EBC) patients treated with adjuvant hypofractionated radiotherapy (HF) with no boost delivered to the lumpectomy cavity, after breast-conserving surgery (BCS). Between 2005 and 2015, a total of 493 women affected with EBC were treated with HF (46 Gy/20 fractions or 40.05 Gy/15 fractions) to the whole breast without boost to tumor bed, because of age and/or favorable tumor characteristics. The primary endpoint was 5-year actuarial local control (LC); secondary endpoints included survival, toxicity profile and cosmesis. Median follow-up was 57 months (range 6-124). Actuarial 5-year overall, cancer-specific, disease-free survival and LC were 96.3, 98.9, 97.8 and 98.6 %, respectively. On multivariate analysis, tumor stage (T1 vs. T2) and hormonal status (positive vs. negative estrogen receptors) were significantly correlated with LC. Only 2 % of patients experienced ≥G3 acute skin toxicity. Late toxicity was mild with only 1 case of G3 fibrosis. Most of the patients (95 %) had good-excellent cosmetic results. HF to the whole breast with no boost delivered to the tumor bed is a safe and effective option for a population of low-risk breast cancer patients after BCS, with excellent 5-year LC, mild toxicity profile and promising cosmetic outcome. A subgroup of patients with larger tumors and/or with no estrogen receptor expression may potentially benefit from treatment intensification with a boost dose to the lumpectomy cavity. PMID:27573380

  13. Increased regucalcin gene expression extends survival in breast cancer patients: Overexpression of regucalcin suppresses the proliferation and metastatic bone activity in MDA-MB-231 human breast cancer cells in vitro.

    PubMed

    Yamaguchi, Masayoshi; Osuka, Satoru; Weitzmann, M Neale; Shoji, Mamoru; Murata, Tomiyasu

    2016-08-01

    Human breast cancer is highly metastatic to bone and drives bone turnover. Breast cancer metastases cause osteolytic lesions and skeletal damage that leads to bone fractures. Regucalcin, which plays a pivotal role as an inhibitor of signal transduction and transcription activity, has been suggested to act as a suppressor of human cancer. In the present study, we compared the clinical outcome between 44 breast cancer patients with higher regucalcin expression and 43 patients with lower regucalcin expression. Prolonged relapse-free survival was identified in the patients with increased regucalcin gene expression. We further demonstrated that overexpression of full length, but not alternatively spliced variants of regucalcin, induces G1 and G2/M phase cell cycle arrest, suppressing the proliferation of MDA-MB-231 cells, a commonly used in vitro model of human breast cancer that metastasize to bone causing osteolytic lesions. Overexpression of regucalcin was found to suppress multiple signaling pathways including Akt, MAP kinase and SAPK/JNK, and NF-κB p65 and β-catenin along with increased p53, a tumor suppressor, and decreased K-ras, c-fos and c-jun. Moreover, we found that co-culture of regucalcin-overexpressing MDA-MB-231 cells with mouse bone marrow cells prevented enhanced osteoclastogenesis and suppressed mineralization in mouse bone marrow cells in vitro. Taken together, the present study suggests that regucalcin may have important anticancer properties in human breast cancer patients. Mechanistically, these effects are likely mediated through suppression of multiple signaling pathways, upregulation of p53 and downregulation of oncogenes leading to anti-proliferative effects and reduced metastases to bone, a phenotype associated with poor clinical outcome. PMID:27221776

  14. The cancer survival gap between elderly and middle-aged patients in Europe is widening.

    PubMed

    Quaglia, Alberto; Tavilla, Andrea; Shack, Lorraine; Brenner, Hermann; Janssen-Heijnen, Maryska; Allemani, Claudia; Colonna, Marc; Grande, Enrico; Grosclaude, Pascale; Vercelli, Marina

    2009-04-01

    The present study is aimed to compare survival and prognostic changes over time between elderly (70-84 years) and middle-aged cancer patients (55-69 years). We considered seven cancer sites (stomach, colon, breast, cervix and corpus uteri, ovary and prostate) and all cancers combined (but excluding prostate and non-melanoma skin cancers). Five-year relative survival was estimated for cohorts of patients diagnosed in 1988-1999 in a pool of 51 European populations covered by cancer registries. Furthermore, we applied the period-analysis method to more recent incidence data from 32 cancer registries to provide 1- and 5-year relative survival estimates for the period of follow-up 2000-2002. A significant survival improvement was observed from 1988 to 1999 for all cancers combined and for every cancer site, except cervical cancer. However, survival increased at a slower rate in the elderly, so that the gap between younger and older patients widened, particularly for prostate cancer in men and for all considered cancers except cervical cancer in women. For breast and prostate cancers, the increasing gap was likely attributable to a larger use of, respectively, mammographic screening and PSA test in middle-aged with respect to the elderly. In the period analysis of the most recent data, relative survival was much higher in middle-aged patients than in the elderly. The differences were higher for breast and gynaecological cancers, and for prostate cancer. Most of this age gap was due to a very large difference in survival after the 1st year following the diagnosis. Differences were much smaller for conditional 5-year relative survival among patients who had already survived the first year. The increase of survival in elderly men is encouraging but the lesser improvement in women and, in particular, the widening gap for breast cancer suggest that many barriers still delay access to care and that enhanced prevention and clinical management remain major issues.

  15. Lapatinib Plus Capecitabine in Women with HER-2–Positive Advanced Breast Cancer: Final Survival Analysis of a Phase III Randomized Trial

    PubMed Central

    Casey, Michelle; Oliva, Cristina; Newstat, Beth; Imwalle, Bradley; Geyer, Charles E.

    2010-01-01

    Objectives. A planned interim analysis of study EGF100151 prompted early termination of enrollment based on a longer time to progression with lapatinib and capecitabine than with capecitabine alone in patients with human epidermal growth factor receptor (HER)-2+ previously treated advanced breast cancer or metastatic breast cancer (MBC). Here, we report final analyses of overall survival. Patients and Methods. Women with HER-2+ MBC who progressed after regimens that included, but were not limited to, anthracyclines, taxanes, and trastuzumab, were randomized to lapatinib (1,250 mg/day) plus capecitabine (2,000 mg/m2) or capecitabine monotherapy (2,500 mg/m2) on days 1–14 of a 21-day cycle. Results. At enrollment termination, 399 patients were randomized, and nine were being screened and were offered combination treatment. In total, 207 and 201 patients were enrolled to combination therapy and monotherapy, respectively. Thirty-six patients receiving monotherapy crossed over to combination therapy following enrollment termination. The median overall survival times were 75.0 weeks for the combination arm and 64.7 weeks for the monotherapy arm (hazard ratio [HR], 0.87; 95% confidence interval [CI], 0.71–1.08; p = .210). A Cox regression analysis considering crossover as a time-dependent covariate suggested a 20% lower risk for death for patients treated with combination therapy (HR, 0.80; 95% CI, 0.64–0.99; p = .043). The low incidence of serious adverse events was consistent with previously reported rates. Conclusions. Although premature enrollment termination and subsequent crossover resulted in insufficient power to detect differences in overall survival, exploratory analyses demonstrate a trend toward a survival advantage with lapatinib plus capecitabine. These data continue to support the efficacy of lapatinib in patients with HER-2+ MBC. PMID:20736298

  16. Improved Survival of HER2+ Breast Cancer Patients Treated with Trastuzumab and Chemotherapy Is Associated with Host Antibody Immunity against the HER2 Intracellular Domain.

    PubMed

    Knutson, Keith L; Clynes, Raphael; Shreeder, Barath; Yeramian, Patrick; Kemp, Kathleen P; Ballman, Karla; Tenner, Kathleen S; Erskine, Courtney L; Norton, Nadine; Northfelt, Donald; Tan, Winston; Calfa, Carmen; Pegram, Mark; Mittendorf, Elizabeth A; Perez, Edith A

    2016-07-01

    The addition of trastuzumab to chemotherapy extends survival among patients with HER2(+) breast cancer. Prior work showed that trastuzumab and chemotherapy augments HER2 extracellular domain (ECD)-specific antibodies. The current study investigated whether combination therapy induced immune responses beyond HER2-ECD and, importantly, whether those immune responses were associated with survival. Pretreatment and posttreatment sera were obtained from 48 women with metastatic HER2(+) breast cancer on NCCTG (now Alliance for Clinical Trials in Oncology) studies, N0337 and N983252. IgG to HER2 intracellular domain (ICD), HER2-ECD, p53, IGFBP2, CEA, and tetanus toxoid were examined. Sera from 25 age-matched controls and 26 surgically resected HER2(+) patients were also examined. Prior to therapy, some patients with metastatic disease had elevated antibodies to IGFBP2, p53, HER2-ICD, HER2-ECD, and CEA, but not to tetanus toxin, relative to controls and surgically resected patients. Treatment augmented antibody responses to HER2-ICD in 69% of metastatic patients, which was highly associated with improved progression-free survival (PFS; HR = 0.5, P = 0.0042) and overall survival (OS; HR = 0.7, P = 0.038). Augmented antibody responses to HER2-ICD also correlated (P = 0.03) with increased antibody responses to CEA, IGFBP2, and p53, indicating that treatment induces epitope spreading. Paradoxically, patients who already had high preexisting immunity to HER2-ICD did not respond to therapy with increased antibodies to HER2-ICD and demonstrated poorer PFS (HR = 1.6, P < 0.0001) and OS (HR = 1.4, P = 0.0006). Overall, the findings further demonstrate the importance of the adaptive immune system in the efficacy of trastuzumab-containing regimens. Cancer Res; 76(13); 3702-10. ©2016 AACR. PMID:27197192

  17. Pretreatment TG/HDL-C Ratio Is Superior to Triacylglycerol Level as an Independent Prognostic Factor for the Survival of Triple Negative Breast Cancer Patients

    PubMed Central

    Dai, Danian; Chen, Bo; Wang, Bin; Tang, Hailin; Li, Xing; Zhao, Zhiping; Li, Xuan; Xie, Xiaoming; Wei, Weidong

    2016-01-01

    Purpose: Previous studies have reported that the triacylglycerol (TG) level and high-density lipoprotein cholesterol (HDL-C) are connected with breast cancer. However, the prognostic utility of the TG level and the TG/HDL-C ratio (THR) as conventional biomarkers in patients with triple negative breast cancer (TNBC) has not been elucidated. In this research, we investigate and compare the predictive value of the pretreatment serum TG level and THR in TNBC patients. Methods: We evaluated 221 patients with TNBC who had pretreatment conventional blood biochemical examinations and calculated the THR. Univariate and multivariate logistic regression analyses were used to assess the effect of the TG level and the THR on overall survival (OS) and disease-free survival (DFS). Results: The optimal cutoff values of the TG level and the THR were determined to be 0.935 mmol/L and 0.600, respectively. As shown in a Kaplan-Meier analysis, TNBC patients with a high TG level and THR had shorter OS and DFS than patients in the low-level groups (p < 0.05). The multivariate analysis suggested that the pretreatment THR level is an independent prognostic factor of OS (HR: 1.935; 95%CI: 1.032-3.629; p = 0.040) in TNBC patients. Conclusions: In conclusion, our data indicate that a high THR is an independent predictor and is superior to the TG level for predicting poor clinical outcomes in TNBC patients.

  18. Cancer survival in Barshi, India, 1993-2000.

    PubMed

    Jayant, K; Nene, B M; Dinshaw, K A; Badwe, R A; Panse, N S; Thorat, R V

    2011-01-01

    The rural cancer registry of Barshi, Paranda and Bhum, was the first of its kind in India and was established in 1987. Registration of cases is carried out entirely by active methods. Data on survival from 15 cancer sites or types registered during 1993-2000 are reported in this study. Follow-up has been carried out predominantly by active methods, with median follow-up time ranging between 2-49 months for different cancers. The proportion of histologically verified diagnosis for various cancers ranged between 73-98%; death certificates only (DCOs) comprised 0-2%; 98-100% of total registered cases were included for survival analysis. Complete follow-up at five years ranged between 96-100% for different cancers. The 5-year age-standardized relative survival rates for selected cancers were non-melanoma skin (86%), penis (63%), breast (61%), cervix (32%), mouth (23%), hypopharynx (11%) and oesophagus (4%). The 5-year relative survival by age group did not display any particular pattern. Five-year relative survival trend between 1988-1992 and 1993-2000 showed a marked decrease for cancers of the tongue, hypopharynx, stomach, rectum, larynx, lung and penis; but a notable increase for breast and non-Hodgkin lymphoma. PMID:21675411

  19. T-bet expression in intratumoral lymphoid structures after neoadjuvant trastuzumab plus docetaxel for HER2-overexpressing breast carcinoma predicts survival

    PubMed Central

    Ladoire, S; Arnould, L; Mignot, G; Apetoh, L; Rébé, C; Martin, F; Fumoleau, P; Coudert, B; Ghiringhelli, F

    2011-01-01

    Background: In HER2-overexpressing breast cancer, accumulating preclinical evidences suggest that some chemotherapies, like trastuzumab, but also taxanes, are able to trigger a T helper 1 (Th1) anticancer immune response that contribute to treatment success. T helper 1 immune response is characterised by the expression of the transcription factor T-bet in CD4 T lymphocytes. We hypothesised that the presence of such T cells in the tumour immune infiltrates following neoadjuvant chemotherapy would predict patient survival. Methods: In a series of 102 consecutive HER2-overexpressing breast cancer patients treated by neoadjuvant chemotherapy incorporating antracyclines or taxane and trastuzumab, we studied by immunohistochemistry the peritumoral lymphoid infiltration by T-bet+ lymphocytes before and after chemotherapy in both treatment groups. Kaplan–Meier analysis and Cox modelling were used to assess relapse-free survival (RFS). Results: Fifty-eight patients have been treated with trastuzumab–taxane and 44 patients with anthracyclines-based neoadjuvant chemotherapy. The presence of T-bet+ lymphocytes in peritumoral lymphoid structures after chemotherapy was significantly more frequent in patients treated with trastuzumab–taxane (P=0.0008). After a median follow-up of 40 months, the presence of T-bet+ lymphocytes after neoadjuvant chemotherapy confers significantly better RFS (log-rank test P=0.011) only in patients treated with trastuzumab–taxane. In this population, multivariate Cox regression model showed that only the presence of T-bet+ lymphocytes in peritumoral lymphoid structures after neoadjuvant chemotherapy was independently associated with improved RFS (P=0.04). Conclusion: These findings indicate that the tumour infiltration by T-bet+ Th1 lymphocytes following neoadjuvant trastuzumab–taxane may represent a new independent prognostic factor of improved outcome in HER2-overexpressing breast carcinoma. PMID:21750556

  20. Survival Outcome of Combined GnRH Agonist and Tamoxifen Is Comparable to That of Sequential Adriamycin and Cyclophosphamide Chemotherapy Plus Tamoxifen in Premenopausal Patients with Lymph-Node–Negative, Hormone-Responsive, HER2-Negative, T1-T2 Breast Cancer

    PubMed Central

    Sohn, Guiyun; Ahn, Sei Hyun; Kim, Hee Jeong; Son, Byung-Ho; Lee, Jong Won; Ko, Beom Seok; Lee, Yura; Lee, Sae Byul; Baek, Seunghee

    2016-01-01

    Purpose The purpose of this study was to compare treatment outcomes between combined gonadotropin-releasing hormone agonist and tamoxifen (GnRHa+T) and sequential adriamycin and cyclophosphamide chemotherapy and tamoxifen (AC->T) in premenopausal patients with hormone-responsive, lymph-node–negative breast cancer. Materials and Methods In total, 994 premenopausal women with T1-T2, lymph-node–negative, hormone-receptor-positive, HER2-negative breast cancer between January 2003 and December 2008 were included in this retrospective cohort study. GnRHa+T and AC->T were administered to 608 patients (61.2%) and 386 patients (38.8%), respectively. Propensity score matching and inverse probability weighting were applied to the original cohort, and 260 patients for each treatment arm were included in the final analysis. Recurrence-free, cancer-specific, and overall survival was compared between the two treatment groups. Results A total of 994 patients were followed up for a median of 7.4 years (range, 0.5 to 11.4 years). The 5-year follow-up rate was 98.7%, and 13 patients were lost to follow-up. In propensity-matched cohorts (n=520), there was no difference in recurrence-free, cancer-specific, and overall survival rates between the two treatment groups (p=0.306, p=0.212, and p=0.102, respectively), and this was maintained after applying inverse probability weighting. Conclusion GnRHa+T is a reasonable alternative to AC->T in patients with premenopausal, hormone-responsive, HER2-negative, lymph-node–negative, T1-T2 breast cancer. PMID:27063654

  1. The Amphibian Research and Monitoring Initiative (ARMI): 5-year report

    USGS Publications Warehouse

    Muths, Erin; Gallant, Alisa L.; Campbell Grant, Evan H.; Battaglin, William A.; Green, David E.; Staiger, Jennifer S.; Walls, Susan C.; Gunzburger, Margaret S.; Kearney, Rick F.

    2006-01-01

    This report is a 5-year retrospective of the structure, methodology, progress, and contributions to the broader scientific community that have resulted from this national USGS program. We evaluate ARMI’s success to date, with regard to the challenges faced by the program and the strengths that have emerged. We chart objectives for the next 5 years that build on current accomplishments, highlight areas meriting further research, and direct efforts to overcome existing weaknesses.

  2. Who should not undergo breast conservation?

    PubMed

    Nijenhuis, Matthijs V; Rutgers, Emiel J Th

    2013-08-01

    Optimal local control is one of the three main aims of breast cancer treatment (next to optimal regional control and reducing the risk of distant relapses by adequate systemic treatments). To this end, many women desire breast conservation provided local control is comparable to that of ablative procedures, the cosmetic outcome is good and side effects of treatment are limited. To achieve this delicate balance the following should be part of the information to the patient with an operable breast cancer: Patients should have an open discussion with there care providers to enable a shared decision: this will lead to less anxiety and stress with the best satisfaction and recovery. The possibility of breast conservation should always be explored. Even with equal local control and survival outlook, quite a minority (about 20%) of patients opt for ablative procedures (with or without breast reconstruction). Higher risk of local relapse (i.e. persistent cancer growth in the breast) is associated with higher risk of distant disease and subsequent risk of dying of breast cancer. Rough estimates indicate that for every four local relapses one patient may die from breast cancer due to persistent disease. This estimate may vary substantially with the type of cancers (see dr. Morrow), age at diagnosis, application and duration of systemic treatments. To limit the negative effect on overall survival through local relapses, it is generally accepted that for early breast cancer local relapse rates should be within the limit of 1% per year, or within 10% at 10 years. Current population based overviews and hospital based studies show that the risk of local relapse after breast conservations are very well below this limit, being around 2-3% at 5 years. There is no absolute risk threshold of local relapse incidence above which breast conservation is absolutely contra indicated: this will remain an individual decision. Oncoplastic procedures should widely be available to adjust to the

  3. Outcomes After Breast Conservation Treatment With Radiation in Women With Prior Nonbreast Malignancy and Subsequent Invasive Breast Carcinoma

    SciTech Connect

    Nemani, Deepika; Vapiwala, Neha Hwang, W.-T.; Solin, Lawrence J.

    2009-03-15

    Purpose: Little information has been reported regarding outcomes after treatment for patients with early-stage invasive breast cancer and a prior nonbreast malignancy. This report analyzes the outcomes in patients with Stage I and II breast cancer after breast conservation treatment (BCT) with a prior nonbreast malignancy. Methods and Materials: The study cohort comprised 66 women with invasive breast cancer and a prior nonbreast malignancy. All patients were treated with breast conservation surgery followed by definitive breast irradiation between 1978 and 2003. Median ages at diagnosis of invasive breast cancer and prior malignancy were 57 and 50 years, respectively. The median interval between the prior malignancy and breast cancer was 7.0 years. Median and mean follow-up times after BCT were 5.3 and 7.0 years. Results: The 5-year and 10-year overall survival rates were 94% (95% confidence interval [CI], 82-98%) and 78% (95% CI, 59-89%), respectively. There were 4 patients (6%) with local failure and 10 patients (15%) with distant metastases. The 10-year rate of local failure rate was 5% (95% CI, 2-16%) and freedom from distant metastases was 78% (95% CI, 61-88%). No obvious differences in survival or local control were noted compared with the reported results in the literature for patients with invasive breast cancer alone. Conclusions: Both overall survival and local control at 5 and 10 years were comparable to rates observed in early-stage breast cancer patients without a prior malignancy. Prior nonbreast malignancy is not a contraindication to BCT, if the primary cancer is effectively controlled.

  4. Clinical Outcome of Breast Conservation Therapy for Breast Cancer in Hong Kong: Prognostic Impact of Ipsilateral Breast Tumor Recurrence and 2005 St. Gallen Risk Categories

    SciTech Connect

    Yau, T.-K. . E-mail: tkokyau@gmail.com; Soong, Inda S.; Chan, K.; Chan, M.; Cheung, P.; Lau, H.W.; Chang, Amy T.Y.; Lee, Anne W.M.

    2007-07-01

    Purpose: The aim of this study was to evaluate the clinical outcome of breast conservation therapy (BCT) for invasive breast cancers in our predominantly Chinese population. Methods and Materials: Clinical outcomes of 412 T1-2 invasive breast cancers treated by wide local excision and external radiotherapy from 1994 to 2003 were retrospectively analyzed. Only 7% lesions were first detected by mammograms. Adjuvant tamoxifen and chemotherapy were added in 74% and 45% patients, respectively. Results: The median follow-up was 5.4 years. The 5-year actuarial ipsilateral breast tumor recurrence (IBTR) rate, distant failure-free survival, cause-specific survival, and overall survival were 4%, 92%, 96%, and 98%, respectively. The 5-year distant failure-free survival for the low-risk, intermediate-risk, and high-risk categories (2005 St. Gallen) were 98%, 91%, and 80%, respectively (p 0.0003). Cosmetic results were good to excellent in more than 90% of the assessable patients. Grade 3 histology (hazard ratio [HR], 4.461; 95% CI, 1.216-16.360; p = 0.024), age (HR, 0.915; 95% CI, 0.846-0.990; p = 0.027), and close/positive final margins (HR, 3.499; 95% CI, 1.141-10.729; p = 0.028) were significant independent risk factors for IBTR. Both St. Gallen risk categories (p = 0.003) and IBTR (HR, 5.885; 95% CI, 2.494-13.889; p < 0.0005) were independent prognostic factors for distant failure-free survival. Conclusions: Despite the low percentage of mammographically detected lesions, the overall clinical outcome of BCT for invasive breast cancers in the Chinese population is comparable to the Western series. The 2005 St. Gallen risk category is a promising clinical tool, but further validation by large studies is warranted.

  5. Hydroxychloroquine, chloroquine, and all-trans retinoic acid regulate growth, survival, and histone acetylation in breast cancer cells.

    PubMed

    Rahim, Rayhana; Strobl, Jeannine S

    2009-09-01

    The antimalarial drugs chloroquine (CQ) and hydroxychloroquine (HCQ) have potential applications in cancer treatment. The growth of MCF-7 and MDA-MB-231 human breast cancer cells in vitro was inhibited by CQ and HCQ and these cells were more sensitive than nontumorigenic MCF-10A breast epithelial cells. Furthermore, all-trans retinoic acid (ATRA) augmented the anticancer effects of CQ and HCQ as evidenced by significant reductions in Ki67-positive cancer cells and clonogenicity compared with cells treated with CQ or HCQ in the absence of ATRA. As an earlier study suggested that CQ, HCQ, and ATRA are breast cancer cell differentiation agents, these agents were screened in cell-free histone deacetylase (HDAC) and histone acetyltransferase (HAT) assays. ATRA, but not CQ or HCQ, inhibited HDAC activity in HeLa nuclear extracts. Growth inhibitory concentrations of HCQ and ATRA stimulated purified p300/CBP-associated factor, where CBP is the cAMP-response element binding protein, HAT activity. To investigate whether growth inhibitory concentrations of these agents influenced protein acetylation in cells, gel-purified histone H3 and histone H4 were analyzed using mass spectrometry. HCQ alone and HCQ+ATRA treatments altered the acetylation status in the N-terminal lysines of histones H3 and H4 compared with dimethyl sulfoxide (DMSO) controls. The results indicated that HCQ and ATRA regulate protein acetylation events in MCF-7 breast cancer cells, and identify a potential mechanism for their effects on breast cancer cell growth and differentiation. PMID:19584707

  6. Development of predictive models for the survival of Campylobacter jejuni (ATCC 43051) on cooked chicken breast patties and in broth as a function of temperature.

    PubMed

    Yoon, K S; Burnette, C N; Oscar, T P

    2004-01-01

    The objective of this study was to model the kinetics of the survival of Campylobacter jejuni on cooked chicken breast patties and in broth as a function of temperature. Both patties and broth were inoculated with 10(6) stationary-phase cells of a single strain of C. jejuni (ATCC 43051) and incubated at constant temperatures from 4 to 30 degrees C in 2 degrees C increments under aerobic conditions. In most cases, a three-phase linear model fit the primary survival curves well (r2 = 0.97 to 0.99) at all incubation temperatures regardless of model medium, indicating the presence of a resistant subpopulation of C. jejuni that would not be eliminated without thermal processing. Secondary models predicting lag time (LT) and specific death rate (SDR) as functions of temperature were also developed. The Davey and Boltzmann models were identified as appropriate secondary models for LT and SDR, respectively, on the basis of goodness of fit (Boltzmann model, r2 = 0.96; Davey model, r2 = 0.93) and prediction bias and accuracy factor tests. The results obtained indicate that C. jejuni can survive well at both refrigeration and ambient temperatures regardless of model medium. Reduced survival of C. jejuni, characterized by shorter lag times and faster death rates, was observed both on patties and in broth at ambient temperatures. In addition, the average maximum reduction of C. jejuni at 4 to 30 degrees C was 1.5 log units regardless of storage temperature or model medium. These findings suggest that C. jejuni found on contaminated poultry products has the potential to survive under conditions that are not permissive for growth and thus could cause foodborne illness if the poultry is not sufficiently cooked. PMID:14717353

  7. c-erbB-2 oncoprotein detected by automated quantitative immunocytochemistry in breast carcinomas correlates with patients' overall and disease-free survival.

    PubMed Central

    Charpin, C.; Garcia, S.; Bouvier, C.; Martini, F.; Lavaut, M. N.; Allasia, C.; Bonnier, P.; Andrac, L.

    1997-01-01

    The prognostic significance of c-erbB-2 oncoprotein overexpression detected in tumours by immunocytochemical assays (ICAs) was investigated in 148 breast carcinomas. ICAs were performed under optimal technical conditions with frozen tissue sections and included automated immunoperoxidase technique and computer-assisted analysis (densitometry) of digitized coloured microscopic images. Results of quantitative ICAs (expressed in percentages of c-erbB-2-positive surfaces and mean optical densities) were correlated with the patients' follow-up in axillary lymph node-positive (N+) and node-negative (N-) subgroups of patients. Patients' follow-up ranged from 9 months (for the first death) to 101 months (for the 121 alive patients) with a 62.5 months mean overall follow-up. It was shown that marked c-erbB-2 immunocytochemical expression in tumours (cut-off point 35%) significantly correlated with the patients' poor overall survival in N+ and in N- patients (Kaplan-Meier, log-rank test, P = 0.045 and P = 0.015). Also, marked c-erbB-2 immunohistochemical expression correlates with short disease-free (P = 0.005), recurrence-free (P = 0.048) and metastasis-free survival (P = 0.05) (Kaplan-Meier, log-rank test) in N+, but not in N- subgroups. It is concluded that in optimal conditions (automated and quantitative ICAs on frozen sections) c-erbB immunohistochemical expression is a significant prognostic indicator in terms of overall and disease-free survival. The c-erbB-2 protein prognostic significance is independent of node status in terms of overall survival, but not of disease-free survival. Images Figure 1 PMID:9184184

  8. The danger of applying uniform clinical policies across populations: the case of breast cancer in American Indians.

    PubMed Central

    Nutting, P A; Calonge, B N; Iverson, D C; Green, L A

    1994-01-01

    OBJECTIVES. This study examined the implications of annual screening mammography for cost and mortality in American Indian populations with differing baseline breast cancer rates. METHODS. A decision tree compared annual screening mammography and screening clinical breast examination with referral for diagnostic mammography when appropriate. The decision tree was constructed to examine the effect of different base-line cancer rates, stage at diagnosis, and stage-specific survival. Outcomes included 5-year relative survival, deaths prevented at 5 years, cost per death prevented, and total costs. RESULTS. The findings suggest that the total cost of breast cancer is 3.6 times higher with the screening mammography program but results in a 27.9% reduction in breast cancer deaths over the first 5 years of the program. Both costs and deaths prevented are sensitive to the incidence of breast cancer in the population and are less favorable in the range of incidence seen in American Indians. CONCLUSIONS. The cost and impact of a given strategy for cancer screening vary among communities with different disease incidence, stage at diagnosis, and stage-specific survival, as seen in American Indian populations. PMID:7943483

  9. An expression signature for p53 status in human breast cancer predicts mutation status, transcriptional effects, and patient survival.

    PubMed

    Miller, Lance D; Smeds, Johanna; George, Joshy; Vega, Vinsensius B; Vergara, Liza; Ploner, Alexander; Pawitan, Yudi; Hall, Per; Klaar, Sigrid; Liu, Edison T; Bergh, Jonas

    2005-09-20

    Perturbations of the p53 pathway are associated with more aggressive and therapeutically refractory tumors. However, molecular assessment of p53 status, by using sequence analysis and immunohistochemistry, are incomplete assessors of p53 functional effects. We posited that the transcriptional fingerprint is a more definitive downstream indicator of p53 function. Herein, we analyzed transcript profiles of 251 p53-sequenced primary breast tumors and identified a clinically embedded 32-gene expression signature that distinguishes p53-mutant and wild-type tumors of different histologies and outperforms sequence-based assessments of p53 in predicting prognosis and therapeutic response. Moreover, the p53 signature identified a subset of aggressive tumors absent of sequence mutations in p53 yet exhibiting expression characteristics consistent with p53 deficiency because of attenuated p53 transcript levels. Our results show the primary importance of p53 functional status in predicting clinical breast cancer behavior. PMID:16141321

  10. Survival trends in European cancer patients diagnosed from 1988 to 1999.

    PubMed

    Verdecchia, Arduino; Guzzinati, Stefano; Francisci, Silvia; De Angelis, Roberta; Bray, Freddie; Allemani, Claudia; Tavilla, Andrea; Santaquilani, Mariano; Sant, Milena

    2009-04-01

    We analysed data from 49 cancer registries in 18 European countries over the period 1988-1999 to delineate time trends in cancer survival. Survival increased in Europe over the study period for all cancer sites that were considered. There were major survival increases in 5 year age-adjusted relative survival for prostate (from 58% to 79%), colon and rectum (from 48% to 54% men and women), and breast (from 74% to 83%). Improvements were also significant for stomach (from 22% to 24%), male larynx (from 62% to 64%), skin melanoma (from 78% to 83%), Hodgkin disease (from 77% to 83%), non-Hodgkin lymphoma (from 49% to 56%), leukaemias (from 37% to 42%), and for all cancers combined (from 34% to 39% in men, and from 52% to 59% in women). Survival did not change significantly for female larynx, lung, cervix or ovary. The largest increases in survival typically occurred in countries with the lowest survival, and contributed to the overall reduction of survival disparities across Europe over the study period. Differences in the extent of PSA testing and mammographic screening, and increasing use of colonoscopy and faecal blood testing together with improving cancer care are probably the major underlying reasons for the improvements in survival for cancers of prostate, breast, colon and rectum. The marked survival improvements in countries with poor survival may indicate that these countries have made efforts to adopt the new diagnostic procedures and the standardised therapeutic protocols in use in more affluent countries.

  11. Local Control, Toxicity, and Cosmesis in Women >70 Years Enrolled in the American Society of Breast Surgeons Accelerated Partial Breast Irradiation Registry Trial

    SciTech Connect

    Khan, Atif J.; Vicini, Frank A.; Beitsch, Peter; Goyal, Sharad; Kuerer, Henry M.; Keisch, Martin; Quiet, Coral; Zannis, Victor; Keleher, Angela; Snyder, Howard; Gittleman, Mark; Whitworth, Pat; Fine, Richard; Lyden, Maureen; Haffty, Bruce G.

    2012-10-01

    Purpose: The American Society of Breast Surgeons enrolled women in a registry trial to prospectively study patients treated with the MammoSite Radiation Therapy System breast brachytherapy device. The present report examined the outcomes in women aged >70 years enrolled in the trial. Methods and Materials: A total of 1,449 primary early stage breast cancers were treated in 1,440 women. Of these, 537 occurred in women >70 years old. Fisher's exact test was performed to correlate age ({<=}70 vs. >70 years) with toxicity and with cosmesis. The association of age with local recurrence (LR) failure times was investigated by fitting a parametric model. Results: Older women were less likely to develop telangiectasias than younger women (7.9% vs. 12.4%, p = 0.0083). The incidence of other toxicities was similar. Cosmesis was good or excellent in 92% of the women >70 years old. No significant difference was found in LR as a function of age. The 5-year actuarial LR rate with invasive disease for the older vs. younger population was 2.79% and 2.92%, respectively (p = 0.5780). In women >70 years with hormone-sensitive tumors {<=}2 cm who received hormonal therapy (n = 195), the 5-year actuarial rate of LR, overall survival, disease-free survival, and cause-specific survival was 2.06%, 89.3%, 87%, and 97.5%, respectively. These outcomes were similar in women who did not receive hormonal therapy. Women with small, estrogen receptor-negative disease had worse LR, overall survival, and disease-free survival compared with receptor-positive patients. Conclusions: Accelerated partial breast irradiation with the MammoSite radiation therapy system resulted in low toxicity and produced similar cosmesis and local control at 5 years in women >70 years compared with younger women. This treatment should be considered as an alternative to omitting adjuvant radiotherapy for older women with small-volume, early-stage breast cancer.

  12. Primary non-Hodgkin's lymphomas of the female breast.

    PubMed

    Giardini, R; Piccolo, C; Rilke, F

    1992-02-01

    The charts of 35 women with primary malignant non-Hodgkin's lymphomas (NHL) of the breast were retrieved from the files of the Istituto Nazionale Tumori, Milan, over a 30-year period (1957 to 1986). These cases represented 0.1% of the more than 25,000 primary malignant tumors of the breast treated during the same period. The median age of these patients was 57 years (range, 28 to 81 years). In most cases, the clinical diagnosis was carcinoma. The tumors were either Stage IE(48%) or IIE(52%) at presentation, and only two patients had B symptoms. The right breast was involved in 17 patients, the left breast in 14, and both breasts in two. According to the updated Kiel classification and the Working Formulation (WF) for Clinical Usage, three cases were lymphoplasmacytoid (immunocytoma) NHL (WF, A); three, centroblastic-centrocytic, follicular NHL (WF, B); four, centroblastic-centrocytic, diffuse NHL (WF, F); 17 centroblastic NHL (WF, G); three immunoblastic NHL (WF, H); two B-lymphoblastic NHL (WF, I); and one, a Burkitt-like NHL (WF, J). Treatment consisted either of a combination of surgery, radiation therapy, and chemotherapy or radiation therapy and chemotherapy. The follow-up period for 32 patients ranged from 6 to 161 months (mean, 45 months); 17 patients died of their disease. The prognosis appeared to be related to the histologic type and stage of the disease. Median survival periods were 63, 52, 42, and 47 months for centroblastic-centrocytic follicular, centroblastic-centrocytic diffuse, centroblastic, and immunoblastic NHL, respectively. The overall 5-year survival rate was 43%; the 5-year survival rate and the probability of freedom from progression at 5 years were, respectively, 61% and 50% for Stage I and 27% and 26% for Stage II disease.

  13. Increasing Disadvantages in Cancer Survival in New Zealand Compared to Australia, between 2000-05 and 2006-10.

    PubMed

    Elwood, J Mark; Aye, Phyu Sin; Tin Tin, Sandar

    2016-01-01

    New Zealand has lower cancer survival compared to its neighbour Australia. If this were due to long established differences between the two patient populations, it might be expected to be either constant in time, or decreasing, as improving health services deals with inequities. In this study we compared trends in relative cancer survival ratios in New Zealand and Australia between 2000-05 and 2006-10, using data from the New Zealand Cancer Registry and the Australian Institute for Health and Welfare. Over this period, Australia showed significant improvements (6.0% in men, 3.0% in women) in overall 5-year cancer survival, with substantial increases in survival from major cancer sites such as lung, bowel, prostate, and breast cancers. New Zealand had only a 1.8% increase in cancer survival in men and 1.3% in women, with non-significant changes in survival from lung and bowel cancers, although there were increases in survival from prostate and breast cancers. For all cancers combined, and for lung and bowel cancer, the improvements in survival and the greater improvements in Australia were mainly in 1-year survival, suggesting factors related to diagnosis and presentation. For breast cancer, the improvements were similar in each country and seen in survival after the first year. The findings underscore the need to accelerate the efforts to improve early diagnosis and optimum treatment for New Zealand cancer patients to catch up with the progress in Australia.

  14. Increasing Disadvantages in Cancer Survival in New Zealand Compared to Australia, between 2000-05 and 2006-10

    PubMed Central

    Elwood, J. Mark; Aye, Phyu Sin; Tin Tin, Sandar

    2016-01-01

    New Zealand has lower cancer survival compared to its neighbour Australia. If this were due to long established differences between the two patient populations, it might be expected to be either constant in time, or decreasing, as improving health services deals with inequities. In this study we compared trends in relative cancer survival ratios in New Zealand and Australia between 2000–05 and 2006–10, using data from the New Zealand Cancer Registry and the Australian Institute for Health and Welfare. Over this period, Australia showed significant improvements (6.0% in men, 3.0% in women) in overall 5-year cancer survival, with substantial increases in survival from major cancer sites such as lung, bowel, prostate, and breast cancers. New Zealand had only a 1.8% increase in cancer survival in men and 1.3% in women, with non-significant changes in survival from lung and bowel cancers, although there were increases in survival from prostate and breast cancers. For all cancers combined, and for lung and bowel cancer, the improvements in survival and the greater improvements in Australia were mainly in 1-year survival, suggesting factors related to diagnosis and presentation. For breast cancer, the improvements were similar in each country and seen in survival after the first year. The findings underscore the need to accelerate the efforts to improve early diagnosis and optimum treatment for New Zealand cancer patients to catch up with the progress in Australia. PMID:26938056

  15. Increasing Disadvantages in Cancer Survival in New Zealand Compared to Australia, between 2000-05 and 2006-10.

    PubMed

    Elwood, J Mark; Aye, Phyu Sin; Tin Tin, Sandar

    2016-01-01

    New Zealand has lower cancer survival compared to its neighbour Australia. If this were due to long established differences between the two patient populations, it might be expected to be either constant in time, or decreasing, as improving health services deals with inequities. In this study we compared trends in relative cancer survival ratios in New Zealand and Australia between 2000-05 and 2006-10, using data from the New Zealand Cancer Registry and the Australian Institute for Health and Welfare. Over this period, Australia showed significant improvements (6.0% in men, 3.0% in women) in overall 5-year cancer survival, with substantial increases in survival from major cancer sites such as lung, bowel, prostate, and breast cancers. New Zealand had only a 1.8% increase in cancer survival in men and 1.3% in women, with non-significant changes in survival from lung and bowel cancers, although there were increases in survival from prostate and breast cancers. For all cancers combined, and for lung and bowel cancer, the improvements in survival and the greater improvements in Australia were mainly in 1-year survival, suggesting factors related to diagnosis and presentation. For breast cancer, the improvements were similar in each country and seen in survival after the first year. The findings underscore the need to accelerate the efforts to improve early diagnosis and optimum treatment for New Zealand cancer patients to catch up with the progress in Australia. PMID:26938056

  16. RSK-mediated down-regulation of PDCD4 is required for proliferation, survival, and migration in a model of triple-negative breast cancer.

    PubMed

    Cuesta, Rafael; Holz, Marina K

    2016-05-10

    The p90 ribosomal S6 kinase (RSK) is a family of MAPK-activated serine/threonine kinases (RSK1-4) whose expression and/or activity are deregulated in several cancers, including breast cancer. Up-regulation of RSKs promotes cellular processes that drive tumorigenesis in Triple Negative Breast Cancer (TNBC) cells. Although RSKs regulate protein synthesis in certain cell types, the role of RSK-mediated translational control in oncogenic progression has yet to be evaluated. We demonstrate that proliferation and migration of TNBC MDA-MB-231 cells, unlike ER/PR-positive MCF7 cells, rely on RSK activity. We show that RSKs regulate the activities of the translation initiation factor eIF4B and the translational repressor PDCD4 in TNBC cells with up-regulated MAPK pathway, but not in breast cancer cells with hyperactivated PI3K/Akt/mTORC1 pathway. These results identify PDCD4 as a novel RSK substrate. We demonstrate that RSK-mediated phosphorylation of PDCD4 at S76 promotes PDCD4 degradation. Low PDCD4 levels reduce PDCD4 inhibitory effect on the translation initiation factor eIF4A, which increases translation of "eIF4A sensitive" mRNAs encoding factors involved in cell cycle progression, survival, and migration. Consequently, low levels of PDCD4 favor proliferation and migration of MDA-MB-231 cells. These results support the therapeutic use of RSK inhibitors for treatment of TNBC with deregulated MAPK/RSK pathway. PMID:27028868

  17. Increased Proportion of Variance Explained and Prediction Accuracy of Survival of Breast Cancer Patients with Use of Whole-Genome Multiomic Profiles

    PubMed Central

    Vazquez, Ana I.; Veturi, Yogasudha; Behring, Michael; Shrestha, Sadeep; Kirst, Matias; Resende, Marcio F. R.; de los Campos, Gustavo

    2016-01-01

    Whole-genome multiomic profiles hold valuable information for the analysis and prediction of disease risk and progression. However, integrating high-dimensional multilayer omic data into risk-assessment models is statistically and computationally challenging. We describe a statistical framework, the Bayesian generalized additive model ((BGAM), and present software for integrating multilayer high-dimensional inputs into risk-assessment models. We used BGAM and data from The Cancer Genome Atlas for the analysis and prediction of survival after diagnosis of breast cancer. We developed a sequence of studies to (1) compare predictions based on single omics with those based on clinical covariates commonly used for the assessment of breast cancer patients (COV), (2) evaluate the benefits of combining COV and omics, (3) compare models based on (a) COV and gene expression profiles from oncogenes with (b) COV and whole-genome gene expression (WGGE) profiles, and (4) evaluate the impacts of combining multiple omics and their interactions. We report that (1) WGGE profiles and whole-genome methylation (METH) profiles offer more predictive power than any of the COV commonly used in clinical practice (e.g., subtype and stage), (2) adding WGGE or METH profiles to COV increases prediction accuracy, (3) the predictive power of WGGE profiles is considerably higher than that based on expression from large-effect oncogenes, and (4) the gain in prediction accuracy when combining multiple omics is consistent. Our results show the feasibility of omic integration and highlight the importance of WGGE and METH profiles in breast cancer, achieving gains of up to 7 points area under the curve (AUC) over the COV in some cases. PMID:27129736

  18. Increased Proportion of Variance Explained and Prediction Accuracy of Survival of Breast Cancer Patients with Use of Whole-Genome Multiomic Profiles.

    PubMed

    Vazquez, Ana I; Veturi, Yogasudha; Behring, Michael; Shrestha, Sadeep; Kirst, Matias; Resende, Marcio F R; de Los Campos, Gustavo

    2016-07-01

    Whole-genome multiomic profiles hold valuable information for the analysis and prediction of disease risk and progression. However, integrating high-dimensional multilayer omic data into risk-assessment models is statistically and computationally challenging. We describe a statistical framework, the Bayesian generalized additive model ((BGAM), and present software for integrating multilayer high-dimensional inputs into risk-assessment models. We used BGAM and data from The Cancer Genome Atlas for the analysis and prediction of survival after diagnosis of breast cancer. We developed a sequence of studies to (1) compare predictions based on single omics with those based on clinical covariates commonly used for the assessment of breast cancer patients (COV), (2) evaluate the benefits of combining COV and omics, (3) compare models based on (a) COV and gene expression profiles from oncogenes with (b) COV and whole-genome gene expression (WGGE) profiles, and (4) evaluate the impacts of combining multiple omics and their interactions. We report that (1) WGGE profiles and whole-genome methylation (METH) profiles offer more predictive power than any of the COV commonly used in clinical practice (e.g., subtype and stage), (2) adding WGGE or METH profiles to COV increases prediction accuracy, (3) the predictive power of WGGE profiles is considerably higher than that based on expression from large-effect oncogenes, and (4) the gain in prediction accuracy when combining multiple omics is consistent. Our results show the feasibility of omic integration and highlight the importance of WGGE and METH profiles in breast cancer, achieving gains of up to 7 points area under the curve (AUC) over the COV in some cases. PMID:27129736

  19. RSK-mediated down-regulation of PDCD4 is required for proliferation, survival, and migration in a model of triple-negative breast cancer

    PubMed Central

    Cuesta, Rafael; Holz, Marina K.

    2016-01-01

    The p90 ribosomal S6 kinase (RSK) is a family of MAPK-activated serine/threonine kinases (RSK1-4) whose expression and/or activity are deregulated in several cancers, including breast cancer. Up-regulation of RSKs promotes cellular processes that drive tumorigenesis in Triple Negative Breast Cancer (TNBC) cells. Although RSKs regulate protein synthesis in certain cell types, the role of RSK-mediated translational control in oncogenic progression has yet to be evaluated. We demonstrate that proliferation and migration of TNBC MDA-MB-231 cells, unlike ER/PR-positive MCF7 cells, rely on RSK activity. We show that RSKs regulate the activities of the translation initiation factor eIF4B and the translational repressor PDCD4 in TNBC cells with up-regulated MAPK pathway, but not in breast cancer cells with hyperactivated PI3K/Akt/mTORC1 pathway. These results identify PDCD4 as a novel RSK substrate. We demonstrate that RSK-mediated phosphorylation of PDCD4 at S76 promotes PDCD4 degradation. Low PDCD4 levels reduce PDCD4 inhibitory effect on the translation initiation factor eIF4A, which increases translation of “eIF4A sensitive” mRNAs encoding factors involved in cell cycle progression, survival, and migration. Consequently, low levels of PDCD4 favor proliferation and migration of MDA-MB-231 cells. These results support the therapeutic use of RSK inhibitors for treatment of TNBC with deregulated MAPK/RSK pathway. PMID:27028868

  20. Immunological metagene signatures derived from immunogenic cancer cell death associate with improved survival of patients with lung, breast or ovarian malignancies: A large-scale meta-analysis

    PubMed Central

    Garg, Abhishek D.; De Ruysscher, Dirk; Agostinis, Patrizia

    2016-01-01

    ABSTRACT The emerging role of the cancer cell-immune cell interface in shaping tumorigenesis/anticancer immunotherapy has increased the need to identify prognostic biomarkers. Henceforth, our primary aim was to identify the immunogenic cell death (ICD)-derived metagene signatures in breast, lung and ovarian cancer that associate with improved patient survival. To this end, we analyzed the prognostic impact of differential gene-expression of 33 pre-clinically-validated ICD-parameters through a large-scale meta-analysis involving 3,983 patients (‘discovery’ dataset) across lung (1,432), breast (1,115) and ovarian (1,436) malignancies. The main results were also substantiated in ‘validation’ datasets consisting of 818 patients of same cancer-types (i.e. 285 breast/274 lung/259 ovarian). The ICD-associated parameters exhibited a highly-clustered and largely cancer type-specific prognostic impact. Interestingly, we delineated ICD-derived consensus-metagene signatures that exhibited a positive prognostic impact that was either cancer type-independent or specific. Importantly, most of these ICD-derived consensus-metagenes (acted as attractor-metagenes and thereby) ‘attracted’ highly co-expressing sets of genes or convergent-metagenes. These convergent-metagenes also exhibited positive prognostic impact in respective cancer types. Remarkably, we found that the cancer type-independent consensus-metagene acted as an ‘attractor’ for cancer-specific convergent-metagenes. This reaffirms that the immunological prognostic landscape of cancer tends to segregate between cancer-independent and cancer-type specific gene signatures. Moreover, this prognostic landscape was largely dominated by the classical T cell activity/infiltration/function-related biomarkers. Interestingly, each cancer type tended to associate with biomarkers representing a specific T cell activity or function rather than pan-T cell biomarkers. Thus, our analysis confirms that ICD can serve as a

  1. A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival: the Women's Healthy Eating and Living (WHEL) Study.

    PubMed

    Pierce, John P; Faerber, Susan; Wright, Fred A; Rock, Cheryl L; Newman, Vicky; Flatt, Shirley W; Kealey, Sheila; Jones, Vicky E; Caan, Bette J; Gold, Ellen B; Haan, Mary; Hollenbach, Kathryn A; Jones, Lovell; Marshall, James R; Ritenbaugh, Cheryl; Stefanick, Marcia L; Thomson, Cynthia; Wasserman, Linda; Natarajan, Loki; Thomas, Ronald G; Gilpin, Elizabeth A

    2002-12-01

    The Women's Healthy Eating and Living (WHEL) Study is a multisite randomized controlled trial of the effectiveness of a high-vegetable, low-fat diet, aimed at markedly raising circulating carotenoid concentrations from food sources, in reducing additional breast cancer events and early death in women with early-stage invasive breast cancer (within 4 years of diagnosis). The study randomly assigned 3088 such women to an intensive diet intervention or to a comparison group between 1995 and 2000 and is expected to follow them through 2006. Two thirds of these women were under 55 years of age at randomization. This research study has a coordinating center and seven clinical sites. Randomization was stratified by age, stage of tumor and clinical site. A comprehensive intervention program that includes intensive telephone counseling, cooking classes and print materials helps shift the dietary pattern of women in the intervention. Through an innovative telephone counseling program, dietary counselors encourage women in the intervention group to meet the following daily behavioral targets: five vegetable servings, 16 ounces of vegetable juice, three fruit servings, 30 g of fiber and 15-20% energy from fat. Adherence assessments occur at baseline, 6, 12, 24 or 36, 48 and 72 months. These assessments can include dietary intake (repeated 24-hour dietary recalls and food frequency questionnaire), circulating carotenoid concentrations, physical measures and questionnaires about health symptoms, quality of life, personal habits and lifestyle patterns. Outcome assessments are completed by telephone interview every 6 months with medical record verification. We will assess evidence of effectiveness by the length of the breast cancer event-free interval, as well as by overall survival separately in all the women in the study as well as specifically in women under and over the age of 55 years.

  2. Cost of treatment for breast cancer in central Vietnam

    PubMed Central

    Hoang Lan, Nguyen; Laohasiriwong, Wongsa; Stewart, John Frederick; Tung, Nguyen Dinh; Coyte, Peter C.

    2013-01-01

    Background In recent years, cases of breast cancer have been on the rise in Vietnam. To date, there has been no study on the financial burden of the disease. This study estimates the direct medical cost of a 5-year treatment course for women with primary breast cancer in central Vietnam. Methods Retrospective patient-level data from medical records at the Hue Central Hospital between 2001 and 2006 were analyzed. Cost analysis was conducted from the health care payers’ perspective. Various direct medical cost categories were computed for a 5-year treatment course for patients with breast cancer. Costs, in US dollars, discounted at a 3% rate, were converted to 2010 after adjusting for inflation. For each cost category, the mean, standard deviation, median, and cost range were estimated. Median regression was used to investigate the relationship between costs and the stage, age at diagnosis, and the health insurance coverage of the patients. Results The total direct medical cost for a 5-year treatment course for breast cancer in central Vietnam was estimated at $975 per patient (range: $11.7–$3,955). The initial treatment cost, particularly the cost of chemotherapy, was found to account for the greatest proportion of total costs (64.9%). Among the patient characteristics studied, stage at diagnosis was significantly associated with total treatment costs. Patients at later stages of breast cancer did not differ significantly in their total costs from those at earlier stages however, but their survival time was much shorter. The absence of health insurance was the main factor limiting service uptake. Conclusion From the health care payers’ perspective, the Government subsidization of public hospital charges lowered the direct medical costs of a 5-year treatment course for primary breast cancer in central Vietnam. However, the long treatment course was significantly influenced by out-of-pocket payments for patients without health insurance. PMID:23394855

  3. Cdk5 promotes DNA replication stress checkpoint activation through RPA-32 phosphorylation, and impacts on metastasis free survival in breast cancer patients.

    PubMed

    Chiker, Sara; Pennaneach, Vincent; Loew, Damarys; Dingli, Florent; Biard, Denis; Cordelières, Fabrice P; Gemble, Simon; Vacher, Sophie; Bieche, Ivan; Hall, Janet; Fernet, Marie

    2015-01-01

    Cyclin dependent kinase 5 (Cdk5) is a determinant of PARP inhibitor and ionizing radiation (IR) sensitivity. Here we show that Cdk5-depleted (Cdk5-shRNA) HeLa cells show higher sensitivity to S-phase irradiation, chronic hydroxyurea exposure, and 5-fluorouracil and 6-thioguanine treatment, with hydroxyurea and IR sensitivity also seen in Cdk5-depleted U2OS cells. As Cdk5 is not directly implicated in DNA strand break repair we investigated in detail its proposed role in the intra-S checkpoint activation. While Cdk5-shRNA HeLa cells showed altered basal S-phase dynamics with slower replication velocity and fewer active origins per DNA megabase, checkpoint activation was impaired after a hydroxyurea block. Cdk5 depletion was associated with reduced priming phosphorylations of RPA32 serines 29 and 33 and SMC1-Serine 966 phosphorylation, lower levels of RPA serine 4 and 8 phosphorylation and DNA damage measured using the alkaline Comet assay, gamma-H2AX signal intensity, RPA and Rad51 foci, and sister chromatid exchanges resulting in impaired intra-S checkpoint activation and subsequently higher numbers of chromatin bridges. In vitro kinase assays coupled with mass spectrometry demonstrated that Cdk5 can carry out the RPA32 priming phosphorylations on serines 23, 29, and 33 necessary for this checkpoint activation. In addition we found an association between lower Cdk5 levels and longer metastasis free survival in breast cancer patients and survival in Cdk5-depleted breast tumor cells after treatment with IR and a PARP inhibitor. Taken together, these results show that Cdk5 is necessary for basal replication and replication stress checkpoint activation and highlight clinical opportunities to enhance tumor cell killing. PMID:26237679

  4. Pathological complete response and survival according to the level of HER-2 amplification after trastuzumab-based neoadjuvant therapy for breast cancer

    PubMed Central

    Guiu, S; Gauthier, M; Coudert, B; Bonnetain, F; Favier, L; Ladoire, S; Tixier, H; Guiu, B; Penault-Llorca, F; Ettore, F; Fumoleau, P; Arnould, L

    2010-01-01

    Background: We analysed whether the level of human epidermal growth factor receptor-2 (HER-2) amplification significantly influenced either pathological complete response (pCR) or recurrence-free survival (RFS) and overall survival (OS) after trastuzumab-based neoadjuvant therapy. Methods: In all, 99 patients with an HER-2-amplified breast tumour treated with trastuzumab-based neoadjuvant therapy were included. Tumours were classified as low amplified (LA; 6–10 signals per nuclei) or highly amplified (HA; >10 signals). Pathological response was assessed according to Chevallier's classification (pCR was defined as grade 1 or 2). Median follow-up lasted 46 months (6–83). Cox uni- and multivariate analyses were performed. Results: In all, 33 tumour samples were LA and 66 were HA. The pCR in HA tumours was significantly higher than in LA tumours (55% vs 24%, P=0.005), whereas no association was found between the pCR rate and tumour stage, grade or hormone receptor status. In multivariate analysis, the pathological nodal status (P=0.005) and adjuvant trastuzumab (P=0.037) were independently associated with RFS, whereas the level of HER-2 amplification nearly reached statistical significance (P=0.057). There was no significant difference between LA and HA tumours for OS (P=0.22, log-rank). Conclusion: The level of HER-2 gene amplification significantly influenced pCR but not RFS or OS in non-metastatic breast cancer treated with trastuzumab-based neoadjuvant therapy. However, RFS in patients with HA tumours tended to be shorter. PMID:20978512

  5. Gene polymorphisms in cyclophosphamide metabolism pathway, treatment-related toxicity and disease-free survival in SWOG 8897 clinical trial for breast cancer

    PubMed Central

    Yao, Song; Barlow, William E.; Albain, Kathy S.; Choi, Ji-Yeob; Zhao, Hua; Livingston, Robert B.; Davis, Warren; Rae, James M.; Yeh, I-Tien; Hutchins, Laura F.; Ravdin, Peter M.; Martino, Silvana; Lyss, Alan P.; Osborne, C. Kent; Abeloff, Martin; Hortobagyi, Gabriel N.; Hayes, Daniel F.; Ambrosone, Christine B.

    2010-01-01

    Purpose There are no established genetic markers for prediction of outcomes after cyclophosphamide (CP)-containing adjuvant therapy for breast cancer. In an ancillary study to a Southwest Oncology Group trial (S8897), we investigated functional polymorphisms in 4 genes in CP pharmacokinetic pathways in relation to hematological toxicity and disease-free survival (DFS). Experimental Design Germline DNA was available from 458 women who were at high risk of relapse and randomized to CAF vs CMF ± tamoxifen and from 874 women who had a presumed favorable prognosis and did not receive adjuvant therapy. Odds ratios for grade 3 and 4 hematological toxicity in the treated group and hazard ratios for DFS associated with selected functional polymorphisms in CYP2B6, CYP3A4, GSTA1, and GSTP1 were estimated by logistic regression and Cox proportional hazard regression. Results Compared to women with AA genotypes, those with at least one GSTP1 variant G allele had reduced risk of grade 3 and 4 neutropenia (OR=0.63, 95% CI=0.41–0.97) and leucopenia (OR=0.59, 95% CI=0.39–0.89). No other associations between SNPs and toxicity or survival were found in the treated or untreated group. Conclusion Known genetic variants in genes involved in CP pharmacokinetics may not have major effects on DFS in breast cancer patients. The lower risk of developing high grade hematological toxicity among women with variant GSTP1 alleles suggests that genetic markers in combination with clinical factors may be useful in defining a subgroup of women who are less susceptible to adverse hematological toxicities with CP-containing therapies. PMID:21169260

  6. MicroRNA networks regulated by all-trans retinoic acid and Lapatinib control the growth, survival and motility of breast cancer cells

    PubMed Central

    Kurosaki, Mami; Paroni, Gabriela; Zanetti, Adriana; Gianni, Maurizio; Bolis, Marco; Lupi, Monica; Tsykin, Anna; Goodall, Gregory J.; Garattini, Enrico

    2015-01-01

    SKBR3-cells, characterized by ERBB2/RARA co-amplification, represent a subgroup of HER2+ breast-cancers sensitive to all-trans retinoic acid (ATRA) and Lapatinib. In this model, the two agents alone or in combination modulate the expression of 174 microRNAs (miRs). These miRs and predicted target-transcripts are organized in four interconnected modules (Module-1 to -4). Module-1 and Module-3 consist of ATRA/Lapatinib up-regulated and potentially anti-oncogenic miRs, while Module-2 contains ATRA/Lapatinib down-regulated and potentially pro-oncogenic miRs. Consistent with this, the expression levels of Module-1/-3 and Module-2 miRs are higher and lower, respectively, in normal mammary tissues relative to ductal-carcinoma-in-situ, invasive-ductal-carcinoma and metastases. This indicates associations between tumor-progression and the expression profiles of Module-1 to -3 miRs. Similar associations are observed with tumor proliferation-scores, staging, size and overall-survival using TCGA (The Cancer Genome Atlas) data. Forced expression of Module-1 miRs, (miR-29a-3p; miR-874-3p) inhibit SKBR3-cell growth and Module-3 miRs (miR-575; miR-1225-5p) reduce growth and motility. Module-2 miRs (miR-125a; miR-193; miR-210) increase SKBR3 cell growth, survival and motility. Some of these effects are of general significance, being replicated in other breast cancer cell lines representing the heterogeneity of this disease. Finally, our study demonstrates that HIPK2-kinase and the PLCXD1-phospholipase-C are novel targets of miR-193a-5p/miR-210-3p and miR-575/miR-1225-5p, respectively. PMID:25961594

  7. Cdk5 promotes DNA replication stress checkpoint activation through RPA-32 phosphorylation, and impacts on metastasis free survival in breast cancer patients

    PubMed Central

    Chiker, Sara; Pennaneach, Vincent; Loew, Damarys; Dingli, Florent; Biard, Denis; Cordelières, Fabrice P; Gemble, Simon; Vacher, Sophie; Bieche, Ivan; Hall, Janet; Fernet, Marie

    2015-01-01

    Cyclin dependent kinase 5 (Cdk5) is a determinant of PARP inhibitor and ionizing radiation (IR) sensitivity. Here we show that Cdk5-depleted (Cdk5-shRNA) HeLa cells show higher sensitivity to S-phase irradiation, chronic hydroxyurea exposure, and 5-fluorouracil and 6-thioguanine treatment, with hydroxyurea and IR sensitivity also seen in Cdk5-depleted U2OS cells. As Cdk5 is not directly implicated in DNA strand break repair we investigated in detail its proposed role in the intra-S checkpoint activation. While Cdk5-shRNA HeLa cells showed altered basal S-phase dynamics with slower replication velocity and fewer active origins per DNA megabase, checkpoint activation was impaired after a hydroxyurea block. Cdk5 depletion was associated with reduced priming phosphorylations of RPA32 serines 29 and 33 and SMC1-Serine 966 phosphorylation, lower levels of RPA serine 4 and 8 phosphorylation and DNA damage measured using the alkaline Comet assay, gamma-H2AX signal intensity, RPA and Rad51 foci, and sister chromatid exchanges resulting in impaired intra-S checkpoint activation and subsequently higher numbers of chromatin bridges. In vitro kinase assays coupled with mass spectrometry demonstrated that Cdk5 can carry out the RPA32 priming phosphorylations on serines 23, 29, and 33 necessary for this checkpoint activation. In addition we found an association between lower Cdk5 levels and longer metastasis free survival in breast cancer patients and survival in Cdk5-depleted breast tumor cells after treatment with IR and a PARP inhibitor. Taken together, these results show that Cdk5 is necessary for basal replication and replication stress checkpoint activation and highlight clinical opportunities to enhance tumor cell killing. PMID:26237679

  8. True or False: Do 5-Year-Olds Understand Belief?

    ERIC Educational Resources Information Center

    Fabricius, William V.; Boyer, Ty W.; Weimer, Amy A.; Carroll, Kathleen

    2010-01-01

    In 3 studies (N = 188) we tested the hypothesis that children use a perceptual access approach to reason about mental states before they understand beliefs. The perceptual access hypothesis predicts a U-shaped developmental pattern of performance in true belief tasks, in which 3-year-olds who reason about reality should succeed, 4- to 5-year-olds…

  9. 2001 IFT Education Standards: A 5-Year Perspective

    ERIC Educational Resources Information Center

    Hartel, Richard W.

    2006-01-01

    The current IFT Education Standards used to evaluate Food Science programs for IFT approval have been in place now for 5 years. Most Food Science programs in the United States (as well as some in Mexico and Canada) have been reviewed according to these standards. The transition to instruction based on assessment of student learning outcomes, in…

  10. WCTC 5-Year Graduation Rates. Retention for Learning Presentation.

    ERIC Educational Resources Information Center

    Brenner, Viktor; Sanford, Doug

    This study addresses Waukesha County Technical College's (WCTC) 5-year retention and graduate rates. Some of the key findings of the report are as follow: (1) overall, 35.4% of cohort students graduated; (2) a 4-year combined graduation rate for ethnic minorities was 26%, well below the overall average; (3) the percent of cohort that graduated…

  11. Stimulant Treatment over 5 Years: Effects on Growth

    ERIC Educational Resources Information Center

    Charach, Alice; Figueroa, Max; Chen, Shirley; Ickowicz, Abel; Schachar, Russell

    2006-01-01

    Objective: Long-term effects of psychostimulants on growth in height and in weight are investigated in children with attention-deficit/hyperactivity disorder. Method: Participants were 79 children, 6 to 12 years of age, with attention-deficit/hyperactivity disorder, who were followed annually for up to 5 years, between the years 1993 and 1994 and…

  12. The effects of erythropoiesis-stimulating agents on the short-term and long-term survivals in metastatic breast cancer patients receiving chemotherapy: a SEER population-based study.

    PubMed

    Lai, Yinzhi; Ye, Zhong; Civan, Jesse M; Wang, Chun; Cristofanilli, Massimo; Mu, Zhaomei; Austin, Laura; Palazzo, Juan P; Myers, Ronald E; Yang, Hushan

    2015-09-01

    Current clinical guidelines state that the use of erythropoiesis-stimulating agents (ESAs) may be considered to treat chemotherapy-induced anemia in the non-curative setting to alleviate anemia-related symptoms. However, no convincing survival benefit has been demonstrated to support the use of ESAs in these patients. Using the comprehensive data collected in the National Cancer Institute (NCI)-surveillance epidemiology and end results (SEER) and Medicare-linked database, we analyzed the effect of ESA use on the short-term (18-month) and long-term (60-month) survival rates of chemotherapy-treated metastatic breast cancer patients. Confounding variables were adjusted using a propensity score approach. We also analyzed the effects of ESA on the survival of patients receiving trastuzumab, a commonly prescribed targeted therapy agent in treating HER2-positive tumors. Metastatic breast cancer patients who received ESA treatment exhibited similar 60-month survival rate to those without ESA treatment (22.8 vs. 24.9%, p = 0.8). ESA-treated patients had a trend toward better 18-month survival [crude hazard ratio (HR) 0.86, 95% confidence intervals (CI) 0.68-1.09, p = 0.21]. This protective effect during the first 18 months of chemotherapy became marginally significant after adjusting for the propensity of receiving ESAs (HR 0.80, 95% CI 0.63-1.01, p = 0.070). An interaction effect between ESA and trastuzumab on patient survival was noticeable but not statistically significant. ESAs did not negatively affect the long-term survival of metastatic breast cancer patients. Moreover, ESAs improved patients' survival during the first 18 months of chemotherapy treatment. These findings endorse the current clinical guideline. Given the short survival of these patients, the potential short-term beneficial effects of ESAs are clinically meaningful.

  13. Important Role of FTO in the Survival of Rare Panresistant Triple-Negative Inflammatory Breast Cancer Cells Facing a Severe Metabolic Challenge

    PubMed Central

    Singh, Balraj; Kinne, Hannah E.; Milligan, Ryan D.; Washburn, Laura J.; Olsen, Mark; Lucci, Anthony

    2016-01-01

    We have previously shown that only 0.01% cells survive a metabolic challenge involving lack of glutamine in culture medium of SUM149 triple-negative Inflammatory Breast Cancer cell line. These cells, designated as SUM149-MA for metabolic adaptability, are resistant to chemotherapeutic drugs, and they efficiently metastasize to multiple organs in nude mice. We hypothesized that obesity-related molecular networks, which normally help in cellular and organismal survival under metabolic challenges, may help in the survival of MA cells. The fat mass and obesity-associated protein FTO is overexpressed in MA cells. Obesity-associated cis-acting elements in non-coding region of FTO regulate the expression of IRX3 gene, thus activating obesity networks. Here we found that IRX3 protein is significantly overexpressed in MA cells (5 to 6-fold) as compared to the parental SUM149 cell line, supporting our hypothesis. We also obtained evidence that additional key regulators of energy balance such as ARID5B, IRX5, and CUX1 P200 repressor could potentially help progenitor-like TNBC cells survive in glutamine-free medium. MO-I-500, a pharmacological inhibitor of FTO, significantly (>90%) inhibited survival and/or colony formation of SUM149-MA cells as compared to untreated cells or those treated with a control compound MO-I-100. Curiously, MO-I-500 treatment also led to decreased levels of FTO and IRX3 proteins in the SUM149 cells initially surviving in glutamine-free medium as compared to MO-I-100 treatment. Interestingly, MO-I-500 treatment had a relatively little effect on cell growth of either the SUM149 or SUM149-MA cell line when added to a complete medium containing glutamine that does not pose a metabolic challenge. Importantly, once selected and cultured in glutamine-free medium, SUM149-MA cells were no longer affected by MO-I-500 even in Gln-free medium. We conclude that panresistant MA cells contain interconnected molecular networks that govern developmental status and

  14. Important Role of FTO in the Survival of Rare Panresistant Triple-Negative Inflammatory Breast Cancer Cells Facing a Severe Metabolic Challenge.

    PubMed

    Singh, Balraj; Kinne, Hannah E; Milligan, Ryan D; Washburn, Laura J; Olsen, Mark; Lucci, Anthony

    2016-01-01

    We have previously shown that only 0.01% cells survive a metabolic challenge involving lack of glutamine in culture medium of SUM149 triple-negative Inflammatory Breast Cancer cell line. These cells, designated as SUM149-MA for metabolic adaptability, are resistant to chemotherapeutic drugs, and they efficiently metastasize to multiple organs in nude mice. We hypothesized that obesity-related molecular networks, which normally help in cellular and organismal survival under metabolic challenges, may help in the survival of MA cells. The fat mass and obesity-associated protein FTO is overexpressed in MA cells. Obesity-associated cis-acting elements in non-coding region of FTO regulate the expression of IRX3 gene, thus activating obesity networks. Here we found that IRX3 protein is significantly overexpressed in MA cells (5 to 6-fold) as compared to the parental SUM149 cell line, supporting our hypothesis. We also obtained evidence that additional key regulators of energy balance such as ARID5B, IRX5, and CUX1 P200 repressor could potentially help progenitor-like TNBC cells survive in glutamine-free medium. MO-I-500, a pharmacological inhibitor of FTO, significantly (>90%) inhibited survival and/or colony formation of SUM149-MA cells as compared to untreated cells or those treated with a control compound MO-I-100. Curiously, MO-I-500 treatment also led to decreased levels of FTO and IRX3 proteins in the SUM149 cells initially surviving in glutamine-free medium as compared to MO-I-100 treatment. Interestingly, MO-I-500 treatment had a relatively little effect on cell growth of either the SUM149 or SUM149-MA cell line when added to a complete medium containing glutamine that does not pose a metabolic challenge. Importantly, once selected and cultured in glutamine-free medium, SUM149-MA cells were no longer affected by MO-I-500 even in Gln-free medium. We conclude that panresistant MA cells contain interconnected molecular networks that govern developmental status and

  15. Clinical and Organizational Issues in the Management of Surviving Breast and Colorectal Cancer Patients: Attitudes and Feelings of Medical Oncologists

    PubMed Central

    Numico, Gianmauro; Pinto, Carmine; Gori, Stefania; Ucci, Giovanni; Di Maio, Massimo; Cancian, Maurizio; De Lorenzo, Francesco; Silvestris, Nicola

    2014-01-01

    Background The fast growing demand and the shortage of resources are pushing toward more efficient models of survivorship care delivery. The Associazione Italiana di Oncologia Medica (AIOM) established an interdisciplinary working group with the purpose of promoting organizational improvements at the national level. A survey aimed at assessing attitudes and feelings of oncologists was considered preliminary to further initiatives. Methods A 25-item questionnaire, sent to the mailing list of the Society, explored the following issues on the practice of breast and colorectal cancer patients' follow up: 1) organization; 2) clinical features; 3) feelings about the different meanings of follow-up. Results Ninety-one oncologists of 160 institutions (57%) answered to the questionnaire. Although follow up is considered a distinct oncological activity in 68%, a fully shared organization between specialists is not common and communications with Primary Care Physicians are not structured in the majority of the cases. Fifty-five and 30% of the oncologists follow breast and colorectal cancer patients indefinitely. In case of discharge a survivorship care plan is delivered in only 9%. The majority of respondents do not hold a role of follow up in mortality reduction. Conclusions Although survivorship care represents a significant part of the oncologists' workload, an “oncology-centered” model is largely adopted and established care pathways are still incomplete. Survivorship care needs to be put at the center of an educational policy and of a widespread organizational effort, directed at improving appropriateness and quality. PMID:24983237

  16. General paediatric surgery for patients aged under 5 years: a 5-year experience at a district general hospital.

    PubMed

    Kwok, C-S; Gordon, A C

    2016-09-01

    Introduction The gradual shift of general paediatric surgery (GPS) provision from district general hospitals (DGH) to specialised units is well recognised in the UK. The consequences of centralisation include a reduction in exposure to GPS for current surgical trainees. The GPS practice of a DGH is examined here. Methods All operations performed on children aged under 5 years over a 5-year period were identified using the local electronic operation database. Electronic hospital records and clinic letters were accessed to collect data on demographics, operations performed and outcome measures. Results 472 GPS operations were performed on children between the age of 22 days and 5 years between 2009 and 2014, of which 43 were on an emergency basis and 105 were performed on patients aged less than 1 year. Three patients were admitted following day case surgery. Six patients were readmitted within 30 days. Complication rates for all procedures and the four most common procedures were similar to those found in published literature. Conclusions GPS for patients aged less than 5 years is comparatively safe in the DGH setting. The training opportunities available at DGHs are invaluable to surgical trainees and vital for sustaining the future provision of GPS by such hospitals. PMID:27269243

  17. Prone Accelerated Partial Breast Irradiation After Breast-Conserving Surgery: Five-year Results of 100 Patients

    SciTech Connect

    Formenti, Silvia C.; Hsu, Howard; Fenton-Kerimian, Maria; Roses, Daniel; Guth, Amber; Jozsef, Gabor; Goldberg, Judith D.; DeWyngaert, J. Keith

    2012-11-01

    Purpose: To report the 5-year results of a prospective trial of three-dimensional conformal external beam radiotherapy (3D-CRT) to deliver accelerated partial breast irradiation in the prone position. Methods and Materials: Postmenopausal patients with Stage I breast cancer with nonpalpable tumors <2 cm, negative margins and negative nodes, positive hormone receptors, and no extensive intraductal component were eligible. The trial was offered only after eligible patients had refused to undergo standard whole-breast radiotherapy. Patients were simulated and treated on a dedicated table for prone setup. 3D-CRT was delivered at a dose of 30 Gy in five 6-Gy/day fractions over 10 days with port film verification at each treatment. Rates of ipsilateral breast failure, ipsilateral nodal failure, contralateral breast failure, and distant failure were estimated using the cumulative incidence method. Rates of disease-free, overall, and cancer-specific survival were recorded. Results: One hundred patients were enrolled in this institutional review board-approved prospective trial, one with bilateral breast cancer. One patient withdrew consent after simulation, and another patient elected to interrupt radiotherapy after receiving two treatments. Ninety-eight patients were evaluable for toxicity, and, in 1 case, both breasts were treated with partial breast irradiation. Median patient age was 68 years (range, 53-88 years); in 55% of patients the tumor size was <1 cm. All patients had hormone receptor-positive cancers: 87% of patients underwent adjuvant antihormone therapy. At a median follow-up of 64 months (range, 2-125 months), there was one local recurrence (1% ipsilateral breast failure) and one contralateral breast cancer (1% contralateral breast failure). There were no deaths due to breast cancer by 5 years. Grade 3 late toxicities occurred in 2 patients (one breast edema, one transient breast pain). Cosmesis was rated good/excellent in 89% of patients with at least 36

  18. A prospective cohort study on the survival experience of under five children in rural western India.

    PubMed

    Hirve, S; Ganatra, B

    1997-11-01

    Findings are presented from a prospective study conducted in 45 villages in Shirur Development Block in Pune District, Maharashtra, to gain insight into the role of birth weight, nutrition, immunization, and other medical and social factors in determining child survival. 4129 children were followed from birth until age 5 years, with child weight and length/height measured at birth and at 3 monthly home visits. Information was also obtained on common childhood morbidities, immunization status, and other biomedical factors, and the cause of death was ascertained through verbal autopsy. The neonatal, infant, and under-five mortality rates were estimated to be 37, 60, and 79 per 1000 live births, respectively. Diarrhea and acute respiratory infections (ARI) contributed to the major mortality burden. The Kaplan Meier Survival curve showed a sharp fall in the neonatal period, a less rapid decline during the post-neonatal period, followed by a marginal fall in the post-infancy period until age 5 years. Girls had a better survival during the early neonatal period, but the trend reversed during the late neonatal period. Normal birth weight children had better survival curves compared to low birth weight children. Survival improved with increasing birth order. Multivariate analysis found that birth weight, immunization status, and mother's and child's nutritional status influenced infant and under-five mortality. Since birth weight continues to influence survival and mortality even up to age 5 years, strategies to improve child survival should include immunization and breast-feeding. PMID:9567529

  19. Breast Cancer Screening at the Breast Examination Center of Harlem

    PubMed Central

    Manning, Aidan T.; Eaton, Anne; Azu, Michelle; Sampson, Michelle; Patil, Sujata; Godfrey, Diana; Beesen, Ayshe A.; Liberman, Laura; Gemignani, Mary L.

    2015-01-01

    Synopsis Here we describe patient, disease, and treatment characteristics of women diagnosed with breast cancer at the Breast Examination Center of Harlem to determine if these characteristics have changed in comparison to an earlier study period. The BECH continues to serve a population of ethnic minorities. The majority of breast cancer cases diagnosed in this population are now of early stage with good prognosis; however, compliance with follow-up and patient outcomes remain poor. Background To describe patient, disease, and treatment characteristics of women diagnosed with breast cancer at the Breast Examination Center of Harlem (BECH), and determine if these characteristics have changed over time. Methods Retrospective chart review of women diagnosed with breast cancer at BECH from 2000-2008 was performed. Comparisons were made to data from an earlier study period (1995-2000). Results From 2000-2008, 339 women were diagnosed with breast cancer following attendance at BECH—55% were Black, 39% Hispanic, 5% of other race/ethnicity. 52% had no health insurance. Hispanic patients were significantly more likely to have no health insurance compared with Black patients (p=.0091). 29% of patients had pre-invasive disease; 36.5% had stage I disease. Almost 40% of the entire group was followed for <1 year. 5-year overall survival for the entire group was 83% (95% CI, 75-89%) and 79% for 188 Black women (95% CI, 68-87%). Compared to the earlier study period (1995-2000), fewer patients presented with palpable masses (45.4% versus 67%) and more had either stage 0 or stage I disease (65.6% versus 46%). Conclusions Women diagnosed with breast cancer at BECH are predominantly Black and Hispanic, and most of these patients do not have health insurance. An increasing proportion of women diagnosed with breast cancer are presenting with non-palpable, early-stage disease. Despite improved access to breast cancer screening, early stage at diagnosis, and access to appropriate

  20. Male breast cancer - a single center experience

    PubMed Central

    Bystricky, Branislav; Kohutek, Filip; Rosik, Andrej

    2016-01-01

    Due to its rarity, male breast cancer remains a poorly characterized disease. The present study obtained retrospective clinicopathological data, treatment patterns and outcomes for all male patients diagnosed with breast cancer in the Oncology Department, Faculty Hospital Trenčín (Trenčín, Slovakia) over the last 20 years from January 1995 to December 2015. A total of 21 patients with male breast cancer were analyzed, with a median patient age of 65.6 years. Two patients were diagnosed with lobular invasive cancer; all others were diagnosed with cancer of a ductal origin. One patient presented with metastatic disease in the pleural cavity. The primary tumors in 8 patients were staged as pT1, whilst 6 patients were staged as pT2 and 7 as pT4. Axillary lymph node involvement was present in 11 patients (52%) and 15 patients were hormone receptor-positive (83%). All but 1 patient underwent mastectomy and surgical staging of the axilla. Adjuvant chemotherapy, radiotherapy and hormone treatment was administered in the same manner as breast cancer treatment in female patients. The median follow-up time was 4.5 years. The 5- and 10-year overall survival rates were 87 and 74%, respectively, and the estimated median disease-free survival for the same population was 9.5 years (95% confidence interval, 6.2–14.6). The survival rates reported in the present retrospective study are comparable with previously published studies. In addition, the current study reported predominant hormone-positive characteristics and rare expression of human epidermal growth factor receptor 2. However, further multi-institutional trials are required to allow for informed treatment decisions in this uncommon disease. PMID:27446481

  1. Family history in breast cancer is not a prognostic factor?

    PubMed

    Jobsen, J J; Meerwaldt, J H; van der Palen, J

    2000-04-01

    The aim of this study is to determine if breast conservative treatment is justified for patients with a positive family history of breast cancer and to investigate whether they have a worse prognosis. We performed a prospective cohort study of breast cancer patients, treated with breast conservative treatment with radiotherapy at the Radiotherapy Department of the Medisch Spectrum Twente. Between 1984 and 1996, 1204 patients with T1 and T2 < or =3 cm were treated. Family history (FH) was recorded according to first degree relative (FDR). Treatment consisted of lumpectomy with axillary dissection followed by radiotherapy to the whole breast with a boost to the primary area. Adjuvant systemic therapy was given to patients with positive nodes. A positive FH was noted in 243 (20.5%) patients, of whom 208 (17.6%) had one FDR, and 35 (3.0%) > or =2 FDRs. The local recurrence rate was 4.1%, with similar rates for all groups. In young patients, < or =40 years, a significant relation between local recurrence and FH was found. The distant metastasis rate was 15.5%, with the lowest rate (5.7%) among patients with > or =2 FDRs. Patients with a positive FH had significantly more contralateral tumours. The 5-year corrected survival was 91.3%. Among patients with a positive FH, a 5-year corrected survival of 91% was observed and the survival 100% among patients with one and > or =2 FDR. Family history is not a contraindication for breast conservative treatment and is not associated with a worse prognosis. Family history is not a prognostic factor for local recurrence rate in patients older than 40 years. PMID:14731704

  2. Family history in breast cancer is not a prognostic factor?

    PubMed

    Jobsen, J J; Meerwaldt, J H; van der Palen, J

    2000-04-01

    The aim of this study is to determine if breast conservative treatment is justified for patients with a positive family history of breast cancer and to investigate whether they have a worse prognosis. We performed a prospective cohort study of breast cancer patients, treated with breast conservative treatment with radiotherapy at the Radiotherapy Department of the Medisch Spectrum Twente. Between 1984 and 1996, 1204 patients with T1 and T2 < or =3 cm were treated. Family history (FH) was recorded according to first degree relative (FDR). Treatment consisted of lumpectomy with axillary dissection followed by radiotherapy to the whole breast with a boost to the primary area. Adjuvant systemic therapy was given to patients with positive nodes. A positive FH was noted in 243 (20.5%) patients, of whom 208 (17.6%) had one FDR, and 35 (3.0%) > or =2 FDRs. The local recurrence rate was 4.1%, with similar rates for all groups. In young patients, < or =40 years, a significant relation between local recurrence and FH was found. The distant metastasis rate was 15.5%, with the lowest rate (5.7%) among patients with > or =2 FDRs. Patients with a positive FH had significantly more contralateral tumours. The 5-year corrected survival was 91.3%. Among patients with a positive FH, a 5-year corrected survival of 91% was observed and the survival 100% among patients with one and > or =2 FDR. Family history is not a contraindication for breast conservative treatment and is not associated with a worse prognosis. Family history is not a prognostic factor for local recurrence rate in patients older than 40 years.

  3. Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis

    PubMed Central

    2013-01-01

    Introduction Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification. Methods We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003–02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype. Results Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype. Conclusions Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes. PMID:24192331

  4. Tracheobronchopathia osteochondroplastica in a 5 year-old girl.

    PubMed

    Sant'Anna, Clemax Couto; Pires-de-Mello, Paulo; Morgado, Maria de Fátima; March, Maria de Fátima Pombo

    2012-12-01

    Tracheobronchopathia osteochondroplastica (TO) is considered an orphan disease with exceptional occurrence in children. We report a 5 year old female child who was referred to us with chronic cough and recurrent pneumonia. After several investigations, bronchoscopy showed multiple nodules in the tracheobronchial lumen, whose distribution was consistent with TO. The patient was followed for four years, with no change in the pattern of the disease.

  5. [5-year experience with BCG immunoprophylaxis in superficial bladder cancer].

    PubMed

    Romics, I; Bach, D; Rüssel, C

    1992-09-01

    Our 5-year experience with BCG in the tumor stage pTis, pTa and pT1, G I-II shows a lasting remission of 88.5% (73%) in 78 (26) patients treated with BCG preparation Pasteur (Connaught) after transurethral resection. A complete remission in patients with carcinoma in situ (12 patients) could be found in 92%. The local and systemic side-effects, which are of limited duration, are tolerable, well treatable and fully reversible.

  6. The Amphibian Research and Monitoring Initiative (ARMI): 5-year report

    USGS Publications Warehouse

    Muths, Erin; Gallant, Alisa L.; Campbell Grant, Evan H.; Battaglin, William A.; Green, David E.; Staiger, Jennifer S.; Walls, Susan C.; Gunzburger, Margaret S.; Kearney, Rick F.

    2006-01-01

    Over the last 5 years, ARMI has partnered with an extensive list of government, academic, and private entities. These partnerships have been fruitful and have assisted ARMI in developing new field protocols and analytic tools, in using and refining emerging technologies to improve accuracy and efficiency of data handling, in conducting amphibian disease, malformation, and environmental effects research, and in implementing a network of mon

  7. Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients1

    PubMed Central

    Park, See-Hyoung; Noh, Sang Jae; Kim, Kyoung Min; Bae, Jun Sang; Kwon, Keun Sang; Jung, Sung Hoo; Kim, Jung Ryul; Lee, Ho; Chung, Myoung Ja; Moon, Woo Sung; Kang, Myoung Jae; Jang, Kyu Yun

    2015-01-01

    BACKGROUND: Poly(ADP-ribose) polymerase 1 (PARP1), γH2AX, BRCA1, and BRCA2 are conventional molecular indicators of DNA damage in cells and are often overexpressed in various cancers. In this study, we aimed, using immunohistochemical detection, whether the co-expression of PARP1, γH2AX, BRCA1, and BRCA2 in breast carcinoma (BCA) tissue can provide more reliable prediction of survival of BCA patients. MATERIALS AND METHODS: We investigated immunohistochemical expression and prognostic significance of the expression of PARP1, γH2AX, BRCA1, and BRCA2 in 192 cases of BCAs. RESULTS: The expression of these four molecules predicted earlier distant metastatic relapse, shorter overall survival (OS), and relapse-free survival (RFS) by univariate analysis. Multivariate analysis revealed the expression of PARP1, γH2AX, and BRCA2 as independent poor prognostic indicators of OS and RFS. In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph) was an additional independent prognostic predictor for OS (P < .001) and RFS (P < .001). The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1) subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4) subgroup. CONCLUSION: This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents. PMID:26310369

  8. Individualized survival and treatment response predictions for breast cancers using phospho-EGFR, phospho-ER, phospho-HER2/neu, phospho-IGF-IR/In, phospho-MAPK, and phospho-p70S6K proteins.

    PubMed

    Guo, L; Abraham, J; Flynn, D C; Castranova, V; Shi, X; Qian, Y

    2007-01-01

    The development and progression of breast cancer involves the activation of numerous protein kinases, and the change in phosphorylation is a hallmark of protein kinase activation. In this study, we identified a comprehensive profile to predict individual breast cancer patients' survival and treatment responses using the Random Committee algorithm. The profile incorporated a subset of phosphorylated signal protein expressions and several selected clinical factors of breast cancer. The parameters of our profile were identified by supervised feature selection algorithms, Gain Ratio Attribute Evaluation and Relief. The results showed that the overall accuracy of survival prediction reached 92.3% for individual breast cancer patients with the use of the expression profiles of phospho-EGFR, phospho-ER, phospho-HER2/neu, phospho-IGFIR/In, phospho-MAPK, and phospho-p70S6K plus the selected clinical factors. The results also indicated that the overall accuracy of treatment response prediction was 92.6% with the use of the level of phospho-EGFR, phospho-ER, phospho-HER2/neu, phospho-MAPK, and phospho-p70S6K plus the selected clinical information. The prediction system combines multiple signal protein activation profiles and relevant clinical information, and provides a unique guideline to aid individualized decision-making in the clinical management of breast cancer.

  9. Giant parietal lobe infantile gliosarcoma in a 5-year-old child

    PubMed Central

    Savant, Hemant V.; Balasubramaniam, Srikant; Mahajan, Vijay

    2015-01-01

    The relative frequency of pediatric gliosarcoma (GSM) is 1.9% among glioblastomas and 0.5% among pediatric central nervous system tumors. A 5-year-old female child came to us with history of fever and loss of appetite since 2 weeks and right sided weakness since 4 days. Magnetic resonance imaging showed a large heterogeneously enhancing space occupying lesion in the left parieto-occipital region. A parieto-occipital craniotomy with radical excision of tumor was performed. The patient was given adjuvant therapy following surgery and survived until 9 months following surgery. The etiopathogenesis, treatment modalities and prognosis of GSM is discussed. PMID:26167224

  10. Giant parietal lobe infantile gliosarcoma in a 5-year-old child.

    PubMed

    Savant, Hemant V; Balasubramaniam, Srikant; Mahajan, Vijay

    2015-01-01

    The relative frequency of pediatric gliosarcoma (GSM) is 1.9% among glioblastomas and 0.5% among pediatric central nervous system tumors. A 5-year-old female child came to us with history of fever and loss of appetite since 2 weeks and right sided weakness since 4 days. Magnetic resonance imaging showed a large heterogeneously enhancing space occupying lesion in the left parieto-occipital region. A parieto-occipital craniotomy with radical excision of tumor was performed. The patient was given adjuvant therapy following surgery and survived until 9 months following surgery. The etiopathogenesis, treatment modalities and prognosis of GSM is discussed.

  11. Metaplastic carcinoma of the breast: A retrospective review

    SciTech Connect

    Dave, Giatri . E-mail: giatridave@yahoo.com; Cosmatos, Harry; Do, Tri; Lodin, Kenneth; Varshney, Dolly

    2006-03-01

    Purpose: Metaplastic carcinoma of the breast represents a rare and heterogeneous group of malignancies that accounts for less than 1% of all breast cancers. The purpose of this study is to better characterize the clinical management of this disease including the role of radiation therapy after surgery. We compared patients that have been treated with either modified radical mastectomy (MRM) or breast-conserving surgery (BCS). Methods and Materials: We performed a retrospective review of 43 patients with metaplastic breast cancer who were evaluated in our regional radiation oncology department between 1987 and 2002. Twenty-one patients were treated with an MRM and 22 with BCS. Five patients from the MRM group received adjuvant radiation, as did 19 patients from the BCS group. Univariate and multivariate analysis of pathologic and treatment-related factors was performed. Local control, disease-free, and overall survival rates were calculated by the Kaplan-Meier method and compared for the two groups. Results: Mean follow-up for all patients was 44.2 months. Mean tumor size was 3.4 cm. Four patients (9%) had positive estrogen receptors and 20 (25%) had positive nodes. The overall 5-year projected local recurrence-free (88% vs. 85%, p = 0.86), disease-free (55% vs. 84%, p = 0.13), and overall survivals (80% vs. 89%, p = 0.58) were not significantly different for both groups. The only tumor parameter significantly associated with overall survival was nodal status. Conclusion: Our study suggests that breast conservation appears to be a reasonable treatment option for women with metaplastic breast cancer, achieving equal survival to mastectomy. The use of adjuvant radiation seems essential for achieving high local control rates after conservation therapy. Further studies will be needed to determine the impact of chemotherapy on survival outcomes.

  12. Adjuvant Effect of Biogenic Selenium Nanoparticles Improves the Immune Responses and Survival of Mice Receiving 4T1 Cell Antigens as Vaccine in Breast Cancer Murine Model.

    PubMed

    Yazdi, Mohammad Hossein; Varastehmoradi, Bardia; Faghfuri, Elnaz; Mavandadnejad, Faranak; Mahdavi, Mehdi; Shahverdi, Ahmad Reza

    2015-12-01

    The modification of tumor-associated antigen-based vaccine to elicit a more robust immune response has been addressed in several ways. In the present work, we aimed to investigate the immunomodulatory effect of selenium nanoparticles as an immunoadjuvant in formulation of a tumor-associated antigen-based vaccine in a preventive form. Fortyfive female inbred BALB/c mice five-to-seven weeks old were used and divided into three groups of test and control, each containing fifteen mice. Group one injected by PBS and used as a control. Group two injected by breast tumor cell lysate alone as vaccine. Group three injected by SeNPs with tumor cell lysate as vaccine. All injections were carried out on day fourteen, twentyone and twentyeight of the study. Tumor induction was done at day thirty. Twenty days after tumor induction serum samples were gathered to measure the cytokine assay. Tumor growth and weight of mice as well as delayed type hyper sensitivity (DTH) response were monitored during the study. Results of the present work showed a significant increase in the level of serum IFN-γ, IL-2, IL-12 and decreased TGF-β in SeNPs/vaccine injected mice as well as lower tumor volume, more potent DTH responses and longer survival rate in comparison to control and tumor lysate vaccine. Taken together, it can be deduced from this work that SeNPs can be considered as an adjuvant in vaccine in triggering robust immune response against breast cancer. But further evaluations are still needed to find the best formula for this agent in antitumor vaccines. PMID:26682463

  13. Nitric oxide synthase (NOS3) variants and disease-free survival among treated and untreated breast cancer patients in a SWOG Clinical Trial (S8897)

    PubMed Central

    Choi, Ji-Yeob; Barlow, William E.; Albain, Kathy S.; Hong, Chi-Chen; Blanco, Javier G.; Livingston, Robert B.; Davis, Warren; Rae, James M.; Yeh, I-Tien; Hutchins, Laura F.; Ravdin, Peter M.; Martino, Silvana; Lyss, Alan P.; Osborne, C. Kent; Abeloff, Martin D.; Hayes, Daniel F.; Ambrosone, Christine B.

    2009-01-01

    Purpose Numerous chemotherapeutic agents are cytotoxic through generation of reactive species, and variability in genes related to oxidative stress may influence disease free survival (DFS). We examined relationships between DFS and variants in NOS3, as well as NQO1, NQO2 and CBR3 among treated and untreated breast cancer patients in a Southwest Oncology Group clinical trial (S8897). Experimental Design In the parent trial, women were assigned according to prognostic features; the high risk group was randomized to CMF or CAF ± tamoxifen, and the low risk group did not receive adjuvant therapy. We extracted DNA from normal lymph node tissue and examined functional polymorphisms in NOS3, NQO1, NQO2 and CBR3, in relation to DFS, using Cox proportional hazard model. Results There were significant interactions between DFS, adjuvant therapy, and NOS3 Glu298Asp and -786 polymorphisms, alone and in combination (p for interaction=0.008). When NOS3 genotypes were combined, women with genotypes encoding for lower NO who received chemotherapy had more than a two fold increase in hazard of progression (HR=2.32, 95% CI=1.26-4.25), while there was reduced risk for those who did not receive adjuvant therapy (HR=0.42, 95% CI=0.19-0.95). There were no associations between the other genotypes and DFS in either group. Conclusion Variants encoding lower activity of NOS3 may affect outcomes in breast cancer patients, with the direction of risk differing depending upon chemotherapy status. These results may mirror the known dual functions of NO and NOS, depending upon oxidative environment. PMID:19671875

  14. The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients.

    PubMed

    Fagerholm, Rainer; Schmidt, Marjanka K; Khan, Sofia; Rafiq, Sajjad; Tapper, William; Aittomäki, Kristiina; Greco, Dario; Heikkinen, Tuomas; Muranen, Taru A; Fasching, Peter A; Janni, Wolfgang; Weinshilboum, Richard; Loehberg, Christian R; Hopper, John L; Southey, Melissa C; Keeman, Renske; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Chenevix-Trench, Georgia; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Seibold, Petra; Couch, Fergus J; Olson, Janet E; Andrulis, Irene L; Knight, Julia A; García-Closas, Montserrat; Figueroa, Jonine; Hooning, Maartje J; Jager, Agnes; Shah, Mitul; Perkins, Barbara J; Luben, Robert; Hamann, Ute; Kabisch, Maria; Czene, Kamila; Hall, Per; Easton, Douglas F; Pharoah, Paul D P; Liu, Jianjun; Eccles, Diana; Blomqvist, Carl; Nevanlinna, Heli

    2015-04-10

    We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1 -mediated regulatory pathway.

  15. The SNP rs6500843 in 16p13.3 is associated with survival specifically among chemotherapy-treated breast cancer patients

    PubMed Central

    Fagerholm, Rainer; Schmidt, Marjanka K.; Khan, Sofia; Rafiq, Sajjad; Tapper, William; Aittomäki, Kristiina; Greco, Dario; Heikkinen, Tuomas; Muranen, Taru A.; Fasching, Peter A.; Janni, Wolfgang; Weinshilboum, Richard; Loehberg, Christian R.; Hopper, John L.; Southey, Melissa C.; Keeman, Renske; Lindblom, Annika; Margolin, Sara; Mannermaa, Arto; Kataja, Vesa; Chenevix-Trench, Georgia; Investigators, kConFab; Lambrechts, Diether; Wildiers, Hans; Chang-Claude, Jenny; Seibold, Petra; Couch, Fergus J.; Olson, Janet E.; Andrulis, Irene L.; Knight, Julia A.; García-Closas, Montserrat; Figueroa, Jonine; Hooning, Maartje J.; Jager, Agnes; Shah, Mitul; Perkins, Barbara J.; Luben, Robert; Hamann, Ute; Kabisch, Maria; Czene, Kamila; Hall, Per; Easton, Douglas F.; Pharoah, Paul D.P.; Liu, Jianjun; Eccles, Diana; Blomqvist, Carl; Nevanlinna, Heli

    2015-01-01

    We have utilized a two-stage study design to search for SNPs associated with the survival of breast cancer patients treated with adjuvant chemotherapy. Our initial GWS data set consisted of 805 Finnish breast cancer cases (360 treated with adjuvant chemotherapy). The top 39 SNPs from this stage were analyzed in three independent data sets: iCOGS (n=6720 chemotherapy-treated cases), SUCCESS-A (n=3596), and POSH (n=518). Two SNPs were successfully validated: rs6500843 (any chemotherapy; per-allele HR 1.16, 95% C.I. 1.08-1.26, p=0.0001, p(adjusted)=0.0091), and rs11155012 (anthracycline therapy; per-allele HR 1.21, 95% C.I. 1.08-1.35, p=0.0010, p(adjusted)=0.0270). The SNP rs6500843 was found to specifically interact with adjuvant chemotherapy, independently of standard prognostic markers (p(interaction)=0.0009), with the rs6500843-GG genotype corresponding to the highest hazard among chemotherapy-treated cases (HR 1.47, 95% C.I. 1.20-1.80). Upon trans-eQTL analysis of public microarray data, the rs6500843 locus was found to associate with the expression of a group of genes involved in cell cycle control, notably AURKA, the expression of which also exhibited differential prognostic value between chemotherapy-treated and untreated cases in our analysis of microarray data. Based on previously published information, we propose that the eQTL genes may be connected to the rs6500843 locus via a RBFOX1-FOXM1-mediated regulatory pathway. PMID:25823661

  16. Olfactory dysfunction predicts 5-year mortality in older adults.

    PubMed

    Pinto, Jayant M; Wroblewski, Kristen E; Kern, David W; Schumm, L Philip; McClintock, Martha K

    2014-01-01

    Prediction of mortality has focused on disease and frailty, although antecedent biomarkers may herald broad physiological decline. Olfaction, an ancestral chemical system, is a strong candidate biomarker because it is linked to diverse physiological processes. We sought to determine if olfactory dysfunction is a harbinger of 5-year mortality in the National Social Life, Health and Aging Project [NSHAP], a nationally representative sample of older U.S. adults. 3,005 community-dwelling adults aged 57-85 were studied in 2005-6 (Wave 1) and their mortality determined in 2010-11 (Wave 2). Olfactory dysfunction, determined objectively at Wave 1, was used to estimate the odds of 5-year, all cause mortality via logistic regression, controlling for demographics and health factors. Mortality for anosmic older adults was four times that of normosmic individuals while hyposmic individuals had intermediate mortality (p<0.001), a "dose-dependent" effect present across the age range. In a comprehensive model that included potential confounding factors, anosmic older adults had over three times the odds of death compared to normosmic individuals (OR, 3.37 [95%CI 2.04, 5.57]), higher than and independent of known leading causes of death, and did not result from the following mechanisms: nutrition, cognitive function, mental health, smoking and alcohol abuse or frailty. Olfactory function is thus one of the strongest predictors of 5-year mortality and may serve as a bellwether for slowed cellular regeneration or as a marker of cumulative toxic environmental exposures. This finding provides clues for pinpointing an underlying mechanism related to a fundamental component of the aging process.

  17. Trisomy 13 in a female over 5 years of age.

    PubMed Central

    Mankinen, C B; Sears, J W

    1976-01-01

    A case of simple trisomy 13, confirmed by G-banded chromosome analysis, is reported in a Caucasian female over 5 years of age. There is no cytogenetic evidence available for mosaicism in the propositus or her parents. The patient's salient clinical features are: profound mental and motor retardation; microcephaly with trigonocephaly; ear malformations; small, sunken eyes; unusual eyebrows; cleft lip and palate; bulbar nose; coloboma iris; polydactyly; unusual dermatoglyphic patterns; large adductor thumbs; enlarged great toes; multiple capillary haemangiomas; club feet; inguinal and umbilical hernias; hyperconvexed fingernails; and seizure disorder. Images PMID:933114

  18. [The results of 5-year-long research of sclerotherapy of liver metastases by ultrasonography].

    PubMed

    Borsukov, A V

    2001-01-01

    64 patients with liver metastases have been studied (mammary gland--6 cases, stomach--15, colon--32, other locations--11) and US metastasis semiotics and the fine aspiration biopsy have been identified. 12 cases had underwent intraoperative 96% ethanol infusion, 52 had got transdermal infusions under US control. The survival rate of colon cases with dissemination was: 1 year S.--100%, 3 year S.--53.1%, 5 year S.--3.1%. In cases with noncolon dissemination the percentage of survival was: 1 year S.--68.8%, 2 year S.--9.4%, 3 year S.--3.0%. 96% ethanol sclerotherapy proved to be more effective in single metachronic metastases of the colon malignancies.

  19. Fulvestrant 500 mg Versus Anastrozole 1 mg for the First-Line Treatment of Advanced Breast Cancer: Overall Survival Analysis From the Phase II FIRST Study

    PubMed Central

    Ellis, Matthew J.; Llombart-Cussac, Antonio; Feltl, David; Dewar, John A.; Jasiówka, Marek; Hewson, Nicola; Rukazenkov, Yuri; Robertson, John F.R.

    2015-01-01

    Purpose To compare overall survival (OS) for fulvestrant 500 mg versus anastrozole as first-line endocrine therapy for advanced breast cancer. Patients and Methods The Fulvestrant First-Line Study Comparing Endocrine Treatments (FIRST) was a phase II, randomized, open-label, multicenter trial. Postmenopausal women with estrogen receptor–positive, locally advanced/metastatic breast cancer who had no previous therapy for advanced disease received either fulvestrant 500 mg (days 0, 14, 28, and every 28 days thereafter) or anastrozole 1 mg (daily). The primary end point (clinical benefit rate [72.5% and 67.0%]) and a follow-up analysis (median time to progression [23.4 months and 13.1 months]) have been reported previously for fulvestrant 500 mg and anastrozole, respectively. Subsequently, the protocol was amended to assess OS by unadjusted log-rank test after approximately 65% of patients had died. Treatment effect on OS across several subgroups was examined. Tolerability was evaluated by adverse event monitoring. Results In total, 205 patients were randomly assigned (fulvestrant 500 mg, n = 102; anastrozole, n = 103). At data cutoff, 61.8% (fulvestrant 500 mg, n = 63) and 71.8% (anastrozole, n = 74) had died. The hazard ratio (95% CI) for OS with fulvestrant 500 mg versus anastrozole was 0.70 (0.50 to 0.98; P = .04; median OS, 54.1 months v 48.4 months). Treatment effects seemed generally consistent across the subgroups analyzed. No new safety issues were observed. Conclusion There are several limitations of this OS analysis, including that it was not planned in the original protocol but instead was added after time-to-progression results were analyzed, and that not all patients participated in additional OS follow-up. However, the present results suggest fulvestrant 500 mg extends OS versus anastrozole. This finding now awaits prospective confirmation in the larger phase III FALCON (Fulvestrant and Anastrozole Compared in Hormonal Therapy Naïve Advanced Breast

  20. Global surveillance of cancer survival 1995–2009: analysis of individual data for 25 676 887 patients from 279 population-based registries in 67 countries (CONCORD-2)

    PubMed Central

    Allemani, Claudia; Weir, Hannah K; Carreira, Helena; Harewood, Rhea; Spika, Devon; Wang, Xiao-Si; Bannon, Finian; Ahn, Jane V; Johnson, Christopher J; Bonaventure, Audrey; Marcos-Gragera, Rafael; Stiller, Charles; Silva, Gulnar Azevedo e; Chen, Wan-Qing; Ogunbiyi, Olufemi J; Rachet, Bernard; Soeberg, Matthew J; You, Hui; Matsuda, Tomohiro; Bielska-Lasota, Magdalena; Storm, Hans; Tucker, Thomas C; Coleman, Michel P

    2015-01-01

    Summary Background Worldwide data for cancer survival are scarce. We aimed to initiate worldwide surveillance of cancer survival by central analysis of population-based registry data, as a metric of the effectiveness of health systems, and to inform global policy on cancer control. Methods Individual tumour records were submitted by 279 population-based cancer registries in 67 countries for 25·7 million adults (age 15–99 years) and 75 000 children (age 0–14 years) diagnosed with cancer during 1995–2009 and followed up to Dec 31, 2009, or later. We looked at cancers of the stomach, colon, rectum, liver, lung, breast (women), cervix, ovary, and prostate in adults, and adult and childhood leukaemia. Standardised quality control procedures were applied; errors were corrected by the registry concerned. We estimated 5-year net survival, adjusted for background mortality in every country or region by age (single year), sex, and calendar year, and by race or ethnic origin in some countries. Estimates were age-standardised with the International Cancer Survival Standard weights. Findings 5-year survival from colon, rectal, and breast cancers has increased steadily in most developed countries. For patients diagnosed during 2005–09, survival for colon and rectal cancer reached 60% or more in 22 countries around the world; for breast cancer, 5-year survival rose to 85% or higher in 17 countries worldwide. Liver and lung cancer remain lethal in all nations: for both cancers, 5-year survival is below 20% everywhere in Europe, in the range 15–19% in North America, and as low as 7–9% in Mongolia and Thailand. Striking rises in 5-year survival from prostate cancer have occurred in many countries: survival rose by 10–20% between 1995–99 and 2005–09 in 22 countries in South America, Asia, and Europe, but survival still varies widely around the world, from less than 60% in Bulgaria and Thailand to 95% or more in Brazil, Puerto Rico, and the USA. For cervical cancer

  1. Natural history of alcoholic myopathy: a 5-year study.

    PubMed

    Estruch, R; Sacanella, E; Fernández-Solá, J; Nicolás, J M; Rubin, E; Urbano-Márquez, A

    1998-12-01

    Chronic myopathy is a common complication of alcoholism, but its natural history has not been well described. We, therefore, studied muscle structure and function in a 5-year study of 30 chronic alcoholics who became abstinent and 20 who relapsed, and 40 control subjects. The mean strength of the abstaining alcoholics increased from 18.6 to 23.2 kg; but, after 5 years, they were still substantially weaker than controls. In a subset who showed histological myopathy, the strength of half of the patients remained two standard deviations below that of controls. Alcoholics who relapsed tended to become progressively weaker (21.7 kg vs. 18.2 kg) and develop histological evidence of myopathy. Thus, continued alcohol abuse was generally reflected in deterioration of muscle strength and the appearance of histological injury to muscle. Importantly, almost half of the sober patients did not recover to normal levels, indicating that alcoholic myopathy is only partially reversible. We also unexpectedly found that, in some alcoholics, a substantial reduction in the amount of alcohol consumed may be as effective as complete abstinence in improving muscle strength or preventing its deterioration.

  2. The acquired cardiac disease domain: the next 5 years.

    PubMed

    Pepper, John R

    2013-01-01

    At a recent in-house meeting at the European Association for Cardiothoracic Surgery (EACTS) headquarters in Windsor, the Chairs of the four domains were asked by the President to present their perception of the next 5 years in their respective domains. This review represents a distillation of our discussions on adult cardiac surgery. Advances in technology and imaging are having a radical effect on the working lives of surgeons. In clinical practice, the growth of heart teams and the breaking down of artificial barriers between specialities are altering the way we practice for the better. We see the development of hybrid approaches to many areas such as coronary artery surgery and operations on the thoracic aorta. These changes require careful analysis to ensure that they produce better outcomes that are also cost-effective. All health-care systems are at breaking point, and it is our responsibility to harness new technology to benefit our patients. This is all part of placing the patient at the centre of our activities. Hence, we see the involvement of patients in the design and analysis of clinical trials, which also require great mutual trust and cooperation between surgeons in different countries. Because of the dramatic changes in the pattern of working, we have had to alter our patterns of training and education, and we will continue to make significant innovations in the future. These are exciting challenges that will keep us all busy for the next 5 years at least.

  3. Predictive 5-Year Survivorship Model of Cystic Fibrosis

    PubMed Central

    Liou, Theodore G.; Adler, Frederick R.; FitzSimmons, Stacey C.; Cahill, Barbara C.; Hibbs, Jonathan R.; Marshall, Bruce C.

    2007-01-01

    The objective of this study was to create a 5-year survivorship model to identify key clinical features of cystic fibrosis. Such a model could help researchers and clinicians to evaluate therapies, improve the design of prospective studies, monitor practice patterns, counsel individual patients, and determine the best candidates for lung transplantation. The authors used information from the Cystic Fibrosis Foundation Patient Registry (CFFPR), which has collected longitudinal data on approximately 90% of cystic fibrosis patients diagnosed in the United States since 1986. They developed multivariate logistic regression models by using data on 5,820 patients randomly selected from 11,630 in the CFFPR in 1993. Models were tested for goodness of fit and were validated for the remaining 5,810 patients for 1993. The validated 5-year survivorship model included age, forced expiratory volume in 1 second as a percentage of predicted normal, gender, weight-for-age z score, pancreatic sufficiency, diabetes mellitus, Staphylococcus aureus infection, Burkerholderia cepacia infection, and annual number of acute pulmonary exacerbations. The model provides insights into the complex nature of cystic fibrosis and supplies a rigorous tool for clinical practice and research. PMID:11207152

  4. Loss of stromal caveolin-1 expression predicts poor clinical outcome in triple negative and basal-like breast cancers.

    PubMed

    Witkiewicz, Agnieszka K; Dasgupta, Abhijit; Sammons, Sara; Er, Ozlem; Potoczek, Magdalena B; Guiles, Fran; Sotgia, Federica; Brody, Jonathan R; Mitchell, Edith P; Lisanti, Michael P

    2010-07-15

    Here, we investigated the possible predictive value of stromal caveolin-1 (Cav-1) as a candidate biomarker for clinical outcome in triple negative (TN) breast cancer patients. A cohort of 85 TN breast cancer patients was available, with the necessary annotation and nearly 12 years of follow-up data. Our primary outcome of interest in this study was overall survival. Interestingly, TN patients with high-levels of stromal Cav-1 had a good clinical outcome, with >50% of the patients remaining alive during the follow-up period. In contrast, the median survival for TN patients with moderate stromal Cav-1 staining was 33.5 months. Similarly, the median survival for TN patients with absent stromal Cav-1 staining was 25.7 months. A comparison of 5-year survival rates yields a similar pattern. TN patients with high stromal Cav-1 had a good 5-year survival rate, with 75.5% of the patients remaining alive. In contrast, TN patients with moderate or absent stromal Cav-1 levels had progressively worse 5-year survival rates, with 40 and 9.4% of the patients remaining alive. In contrast, in a parallel analysis, the levels of tumor epithelial Cav-1 had no prognostic significance. As such, the prognostic value of Cav-1 immunostaining in TN breast cancer patients is compartment-specific, and selective for an absence of Cav-1 staining in the stromal fibroblast compartment. A recursive-partitioning algorithm was used to assess which factors are most predictive of overall survival in TN breast cancer patients. In this analysis, we included tumor size, histologic grade, whether the patient received surgery, radiotherapy or chemotherapy, CK5/6, EGFR, p53 and Ki67 status, as well as the stromal Cav-1 score. This analysis indicated that stromal loss of Cav-1 expression was the most important prognostic factor for overall survival in TN breast cancer. Virtually identical results were obtained with CK5/6 (+) and/or EGFR (+) TN breast cancer cases, demonstrating that a loss of stromal Cav-1 is

  5. Patterns of Utilization of Adjuvant Radiotherapy and Outcomes in Black Women After Breast Conservation at a Large Multidisciplinary Cancer Center;Black women; Breast cancer; Radiotherapy; RT; Breast conservation

    SciTech Connect

    Edwards-Bennett, Sophia M.; Jacks, Lindsay M.; McCormick, Beryl; Zhang, Zhigang; Azu, Michelle; Ho, Alice; Powell, Simon; Brown, Carol

    2011-07-15

    Purpose: Population-based studies have reported that as many of 35% of black women do not undergo radiotherapy (RT) after breast conservation surgery (BCS). The objective of the present study was to determine whether this trend persisted at a large multidisciplinary cancer center, and to identify the factors that predict for noncompliance with RT and determine the outcomes for this subset of patients. Methods and Materials: Between January 2002 and December 2007, 83 black women underwent BCS at Memorial Sloan-Kettering Cancer Center and were therefore eligible for the present study. Of the 83 women, 38 (46%) had Stage I, 38 (46%) Stage II, and 7 (8%) Stage III disease. Of the study cohort, 31 (37%) had triple hormone receptor-negative tumors. RT was recommended for 81 (98%) of the 83 patients (median dose, 60 Gy). Results: Of the 81 women, 12 (15%) did not receive the recommended adjuvant breast RT. Nonreceipt of chemotherapy (p = .003) and older age (p = .009) were associated with nonreceipt of RT. With a median follow-up of 70 months, the 3-year local control, locoregional control, recurrence-free survival, disease-free survival, and overall survival rate was 99% (actuarial 5-year rate, 97%), 96% (actuarial 5-year rate, 93%), 95% (actuarial 5-year rate, 92%), 92% (actuarial 5-year rate, 89%), and 95% (actuarial 5-year rate, 91%), respectively. Conclusion: We found a greater rate of utilization adjuvant breast RT (85%) among black women after BCS than has been reported in recent studies, indicating that excellent outcomes are attainable for black women after BCS when care is administered in a multidisciplinary cancer center.

  6. Pathway-Centric Integrative Analysis Identifies RRM2 as a Prognostic Marker in Breast Cancer Associated with Poor Survival and Tamoxifen Resistance123

    PubMed Central

    Putluri, Nagireddy; Maity, Suman; Kommangani, Ramakrishna; Creighton, Chad J.; Putluri, Vasanta; Chen, Fengju; Nanda, Sarmishta; Bhowmik, Salil Kumar; Terunuma, Atsushi; Dorsey, Tiffany; Nardone, Agostina; Fu, Xiaoyong; Shaw, Chad; Sarkar, Tapasree Roy; Schiff, Rachel; Lydon, John P.; O’Malley, Bert W.; Ambs, Stefan; Das, Gokul M.; Michailidis, George; Sreekumar, Arun

    2014-01-01

    Breast cancer (BCa) molecular subtypes include luminal A, luminal B, normal-like, HER-2–enriched, and basal-like tumors, among which luminal B and basal-like cancers are highly aggressive. Biochemical pathways associated with patient survival or treatment response in these more aggressive subtypes are not well understood. With the limited availability of pathologically verified clinical specimens, cell line models are routinely used for pathway-centric studies. We measured the metabolome of luminal and basal-like BCa cell lines using mass spectrometry, linked metabolites to biochemical pathways using Gene Set Analysis, and developed a novel rank-based method to select pathways on the basis of their enrichment in patient-derived omics data sets and prognostic relevance. Key mediators of the pathway were then characterized for their role in disease progression. Pyrimidine metabolism was altered in luminal versus basal BCa, whereas the combined expression of its associated genes or expression of one key gene, ribonucleotide reductase subunit M2 (RRM2) alone, associated significantly with decreased survival across all BCa subtypes, as well as in luminal patients resistant to tamoxifen. Increased RRM2 expression in tamoxifen-resistant patients was verified using tissue microarrays, whereas the metabolic products of RRM2 were higher in tamoxifen-resistant cells and in xenograft tumors. Both genetic and pharmacological inhibition of this key enzyme in tamoxifen-resistant cells significantly decreased proliferation, reduced expression of cell cycle genes, and sensitized the cells to tamoxifen treatment. Our study suggests for evaluating RRM2-associated metabolites as noninvasive markers for tamoxifen resistance and its pharmacological inhibition as a novel approach to overcome tamoxifen resistance in BCa. PMID:25016594

  7. Pathway-centric integrative analysis identifies RRM2 as a prognostic marker in breast cancer associated with poor survival and tamoxifen resistance.

    PubMed

    Putluri, Nagireddy; Maity, Suman; Kommagani, Ramakrishna; Kommangani, Ramakrishna; Creighton, Chad J; Putluri, Vasanta; Chen, Fengju; Nanda, Sarmishta; Bhowmik, Salil Kumar; Terunuma, Atsushi; Dorsey, Tiffany; Nardone, Agostina; Fu, Xiaoyong; Shaw, Chad; Sarkar, Tapasree Roy; Schiff, Rachel; Lydon, John P; O'Malley, Bert W; Ambs, Stefan; Das, Gokul M; Michailidis, George; Sreekumar, Arun

    2014-05-01

    Breast cancer (BCa) molecular subtypes include luminal A, luminal B, normal-like, HER-2-enriched, and basal-like tumors, among which luminal B and basal-like cancers are highly aggressive. Biochemical pathways associated with patient survival or treatment response in these more aggressive subtypes are not well understood. With the limited availability of pathologically verified clinical specimens, cell line models are routinely used for pathway-centric studies. We measured the metabolome of luminal and basal-like BCa cell lines using mass spectrometry, linked metabolites to biochemical pathways using Gene Set Analysis, and developed a novel rank-based method to select pathways on the basis of their enrichment in patient-derived omics data sets and prognostic relevance. Key mediators of the pathway were then characterized for their role in disease progression. Pyrimidine metabolism was altered in luminal versus basal BCa, whereas the combined expression of its associated genes or expression of one key gene, ribonucleotide reductase subunit M2 (RRM2) alone, associated significantly with decreased survival across all BCa subtypes, as well as in luminal patients resistant to tamoxifen. Increased RRM2 expression in tamoxifen-resistant patients was verified using tissue microarrays, whereas the metabolic products of RRM2 were higher in tamoxifen-resistant cells and in xenograft tumors. Both genetic and pharmacological inhibition of this key enzyme in tamoxifen-resistant cells significantly decreased proliferation, reduced expression of cell cycle genes, and sensitized the cells to tamoxifen treatment. Our study suggests for evaluating RRM2-associated metabolites as noninvasive markers for tamoxifen resistance and its pharmacological inhibition as a novel approach to overcome tamoxifen resistance in BCa. PMID:25016594

  8. PG545, a heparan sulfate mimetic, reduces heparanase expression in vivo, blocks spontaneous metastases and enhances overall survival in the 4T1 breast carcinoma model.

    PubMed

    Hammond, Edward; Brandt, Ralf; Dredge, Keith

    2012-01-01

    PG545 is a clinically relevant heparan sulfate (HS) mimetic which, in addition to possessing anti-angiogenic pr