Science.gov

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.

  4. 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

  5. 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

  6. The impact factors on 5-year survival rate in patients operated with oral cancer

    PubMed Central

    Geum, Dong-Ho; Roh, Young-Chea; Yoon, Sang-Yong; Kim, Hyo-Geon; Lee, Jung-Han; Song, Jae-Min; Lee, Jae-Yeol; Hwang, Dae-Seok; Kim, Yong-Deok; Shin, Sang-Hun; Chung, In-Kyo

    2013-01-01

    Objectives The purpose of this study is to analyze clinical impact factors on the survival rate, and to acquire basic clinical data for the diagnosis of oral cancer, for a determination of the treatment plan with long-term survival in oral cancer patients. Materials and Methods Through a retrospective review of the medical records, the factors for long-term survival rate were analyzed. Thirty-seven patients, among patient database with oral cancer treated in the Department of Oral and Maxillofacial Surgery at Pusan National University Hospital within a period from March 1998 to March 2008, were selected within the study criteria and were followed-up for more than 5 years. The analyzed factors were gender, age, drinking, smoking, primary tumor site, type of cancer, TNM stage, recurrence of affected region, and metastasis of cervical lymph node. The 5-year survival rate on the impact factors was calculated statistically using the Kaplan-Meier method. Results By classification of clinical TNM at the 1st visit, there were 11 (29.7%) cases for stage I, 11 (29.7%) cases for stage II, 3 (8.1%) cases for stage III, and 12 (32.5%) cases for stage IV. The 5-year survival rate of total oral cancer patients after the operation were 75.7%, pathological TNM stage related 5-year survival rate were as follows: stage I 90.0%, stage II 81.8%, stage III 100% and stage IV 45.5%; in which the survival rate difference by each stage was significantly observed. The recurrence of cervical lymph node was the significant impact factor for the survival rate, because only 30.0% the survival rate in recurrent cases existed. During the follow-up, there were 15 (40.5%) patients with confirmed recurrence, and the 5-year survival rate of these patients was decreased as 46.7%. Conclusion The classification of clinical and pathological TNM stage, local recurrence after surgery, and metastasis of cervical lymph node after surgery were analyzed as the 3 most significant factors. PMID:24471047

  7. 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.

  8. Long-term survival with diaphanospondylodysostosis (DSD): survival to 5 years and further phenotypic characteristics.

    PubMed

    Scottoline, Brian; Rosenthal, Scott; Keisari, Rami; Kirpekar, Rashmi; Angell, Cathy; Wallerstein, Robert

    2012-06-01

    We report on the natural history of diaphanospondylodysostosis (DSD) in the longest known survivor. DSD is a rare form of autosomal recessive vertebral dysotosis recently identified to be caused by a mutation in the BMPER gene. This condition is characterized by absent or severely delayed ossification of vertebral bodies, short broad thorax, short neck, protuberant abdomen, marked respiratory insufficiency, and normal appendicular skeleton. It is one of a number of spinal dysostoses, which are a heterogeneous group of axial skeletal malformations occurring during blastogenesis with continued evolution after birth. Significant medical intervention and at-home support contributed to the long-term survival of our patient. The patient had tracheomalacia, which resulted in respiratory insufficiency with thoracic insufficiency syndrome (TIS). Tracheostomy and vertical expandable prosthetic titanium rib (VEPTR) insertion operations ameliorated his symptoms. In addition, comprehensive physical and occupational therapy was performed due to chronic hypotonia. A consistent feature of all described DSD cases thus far are renal findings of dysplasia, nephrogenic rests or nephroblastomatosis, and/or cysts. The patient's renal cysts were monitored with serial ultrasounds at approximately 6-month intervals. The patient was diagnosed with bilateral renal cysts by ultrasound as a neonate, with eventual diagnosis at approximately 20 months of age with nephroblastoma suggesting this maybe an intrinsic part of DSD. The lack of other cases with nephroblastoma is likely related to the previously reported short period of survival.

  9. 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.

  10. Diabetic foot reconstruction using free flaps increases 5-year-survival rate.

    PubMed

    Oh, Tae Suk; Lee, Ho Seung; Hong, Joon Pio

    2013-02-01

    The purpose of this study was to evaluate the outcome of the diabetic foot reconstructed with free flaps and analyse the preoperative risk factors. This study reviews 121 cases of reconstructed diabetic foot in 113 patients over 9 years (average follow-up of 53.2 months). Patients' age ranged from 26 to 78 years (average, 54.6 years). Free flaps used were anterolateral thigh (ALT, 90), superficial circumflex iliac artery perforator (SCIP, 20), anteromedial thigh (AMT, 5), upper medial thigh (UMT, 3), and other perforator free flaps (3). Correlation between the surgical outcome and preoperative risk factors were analysed using logistic regression model. Total loss was seen in 10 cases and 111 free-tissue transfers were successful (flap survival rate of 91.7%). During follow-up, limb was eventually lost in 17 patients and overall limb salvage rate was 84.9% and the 5-year survival was 86.8%. Correlation between flap loss and 14 preoperative risk factors (computed tomography (CT) angiogram showing intact numbers of major vessels, history of previous angioplasty, peripheral arterial disease (PAD), heart problem, chronic renal failure (CRF), American Society of Anaesthesiologists (ASA) physical status classification system, smoking, body mass index (BMI), HBA1c, lymphocyte count, ankle-brachial index (ABI), osteomyelitis, C-reactive protein (CRP) level and whether taking immunosuppressive agents) were analysed. Significant odds ratio were seen in patients who underwent lower extremity angioplasties (odds ratio: 17.590, p<0.001), with PAD (odds ratio: 10.212, p=0.032) and taking immunosuppressive agents after kidney transplantation (odds ratio: 4.857, p<0.041). Diabetic foot reconstruction using free flaps has a high chance for success and significantly increases the 5-year survival rate. Risk factors such as PAD, history of angioplasties in the extremity and using immunosuppressive agents after transplant may increase the chance for flap loss.

  11. Loneliness May Sabotage Breast Cancer Survival: Study

    MedlinePlus

    ... gov/news/fullstory_162498.html Loneliness May Sabotage Breast Cancer Survival: Study Weak social ties linked to higher ... 2016 (HealthDay News) -- Loneliness may impede long-term breast cancer survival, a new study suggests. In the years ...

  12. 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.

  13. 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

  14. Status after 5 Years of Survival Compliance Testing in the Federal Columbia River Power System (FCRPS)

    SciTech Connect

    Skalski, John R.; Weiland, Mark A.; Ham, Kenneth D.; Ploskey, Gene R.; McMichael, Geoffrey A.; Colotelo, Alison H.; Carlson, Thomas J.; Woodley, Christa M.; Eppard, M. Brad; Hockersmith, Eric E.

    2016-06-27

    Survival studies of juvenile salmonids implanted with acoustic tags have been conducted at hydroelectric dams within the Federal Columbia River Power System (FCRPS) in the Columbia and Snake rivers between 2010 and 2014 to assess compliance with dam passage survival standards stipulated in the 2008 Biological Opinion (BiOp). For juvenile salmonids migrating downstream in the spring, dam passage survival defined as survival from the upstream dam face to the tailrace mixing zone must be ≥96% and for summer migrants, ≥93%, and estimated with a standard error ≤1.5% (i.e., 95% confidence interval of ±3%). A total of 29 compliance tests have been conducted at 6 of 8 FCRPS main-stem dams, using over 109,000 acoustic-tagged salmonid smolts. Of these 29 compliance studies, 23 met the survival standards and 26 met the precision requirements. Of the 6 dams evaluated to date, individual survival estimates range from 0.9597 to 0.9868 for yearling Chinook Salmon, 0.9534 to 0.9952 for steelhead, and 0.9076 to 0.9789 for subyearling Chinook Salmon. These investigations suggest the large capital investment over the last 20 years to improve juvenile salmon passage through the FCRPS dams has been beneficial.

  15. 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

  16. 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.

  17. Erythrocyte survival following intraoperative autotransfusion in spinal surgery: an in vivo comparative study and 5-year update

    SciTech Connect

    Ray, J.M.; Flynn, J.C.; Bierman, A.H.

    1986-11-01

    A 5-year prospective study of intraoperative blood transfusion in 239 patients, most of whom had major spinal surgery, has been completed. Autotransfusion is safe, practical, and it reduces donor blood requirements and total blood loss by 50%. It eliminates host versus graft reactions and disease transmission. In 33 patients having major spinal surgery, the in vivo survival of autologous, homologous, and processed red blood cells (RBC) using the Cell Saver System were compared. The RBC survival studies were performed using chromium-51 isotope labeling technique. The long-term survival of processed RBCs was normal over a 30-day period. There was no significant difference in the survival rate of the three groups studied.

  18. 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.

  19. Accelerated partial breast irradiation in the elderly: 5-year results of high-dose rate multi-catheter brachytherapy

    PubMed Central

    2014-01-01

    Objective To evaluate clinical outcome after accelerated partial breast irradiation (APBI) in the elderly after high-dose-rate interstitial multi-catheter brachytherapy (HIBT). Methods and materials Between 2005 and 2013, 70 patients underwent APBI using HIBT. Catheter implant was performed intra or post-operatively (referred patients) after lumpectomy and axillary sentinel lymph node dissection. Once the pathological results confirmed the indication of APBI, planification CT-scan was performed to deliver 34 Gy/10f/5d or 32 Gy/8f/4d. Dose-volume adaptation was manually achieved (graphical optimization). Dosimetric results and clinical outcome were retrospectively analyzed. Physician cosmetic evaluation was reported. Results With a median follow-up of 60.9 months [4.6 – 90.1], median age was 80.7 years [62 – 93.1]. Regarding APBI ASTRO criteria, 61.4%, 18.6% and 20% were classified as suitable, cautionary and non-suitable respectively. Axillary sentinel lymph node dissection was performed in 94.3%; 8 pts (11.5%) presented an axillary involvement. A median dose of 34 Gy [32 – 35] in 8 to 10 fractions was delivered. Median CTV was 75.2 cc [16.9 – 210], median D90 EQD2 was 43.3 Gy [35 – 72.6] and median DHI was 0.54 [0.19 – 0.74]. One patient experienced ipsilateral recurrence (5-year local free recurrence rate: 97.6%. Five-year specific and overall survival rates were 97.9% and 93.2% respectively. Thirty-four patients (48%) presented 47 late complications classified grade 1 (80.8%) and grade 2 (19.2%) with no grade ≥ 3. Cosmetic results were considered excellent/good for 67 pts (95.7%). Conclusion APBI using HIBT and respecting strict rules of implantation and planification, represents a smart alternative between no post-operative irradiation and whole breast irradiation delivered over 6 consecutive weeks. PMID:24886680

  20. Breast self examination and survival from breast cancer.

    PubMed Central

    Le Geyte, M.; Mant, D.; Vessey, M. P.; Jones, L.; Yudkin, P.

    1992-01-01

    The survival of 616 women aged 15-59 with breast cancer, 226 of whom had been taught and practised breast self examination (BSE) prior to diagnosis and 390 of whom had not, is reported. Six year survival rates were 73.1% in the BSE taught group and 66.1% in other women (P = 0.07). PMID:1419636

  1. Breast cancer survivorship--intersecting gendered discourses in a 5-year follow-up study.

    PubMed

    Norberg, Monika; Magnusson, Eva; Egberg Thyme, Karin; Åström, Sture; Lindh, Jack; Öster, Inger

    2015-01-01

    In this article the authors present a follow-up study of women's interview narratives about life 5 to 7 years after a breast cancer operation. The women had taken part in a study during the 6-month postoperation period. Art therapy contributed to well-being, including strengthening personal boundaries. In the new study, interview analysis informed by critical discursive psychology indicated three problematic discourses that the women still struggled with several years after the operation: the female survivor, the "good woman," and individual responsibility. We concluded that many women with a history of breast cancer need support several years after their medical treatment is finished.

  2. 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.

  3. Virtual HDR CyberKnife SBRT for Localized Prostatic Carcinoma: 5-Year Disease-Free Survival and Toxicity Observations

    PubMed Central

    Fuller, Donald Blake; Naitoh, John; Mardirossian, George

    2014-01-01

    Purpose: Prostate stereotactic body radiotherapy (SBRT) may substantially recapitulate the dose distribution of high-dose-rate (HDR) brachytherapy, representing an externally delivered “Virtual HDR” treatment method. Herein, we present 5-year outcomes from a cohort of consecutively treated virtual HDR SBRT prostate cancer patients. Methods: Seventy-nine patients were treated from 2006 to 2009, 40 low-risk, and 39 intermediate-risk, under IRB-approved clinical trial, to 38 Gy in four fractions. The planning target volume (PTV) included prostate plus a 2-mm volume expansion in all directions, with selective use of a 5-mm prostate-to-PTV expansion and proximal seminal vesicle coverage in intermediate-risk patients, to better cover potential extraprostatic disease; rectal PTV margin reduced to zero in all cases. The prescription dose covered >95% of the PTV (V100 ≥95%), with a minimum 150% PTV dose escalation to create “HDR-like” PTV dose distribution. Results: Median pre-SBRT PSA level of 5.6 ng/mL decreased to 0.05 ng/mL 5 years out and 0.02 ng/mL 6 years out. At least one PSA bounce was seen in 55 patients (70%) but only 3 of them subsequently relapsed, biochemical-relapse-free survival was 100 and 92% for low-risk and intermediate-risk patients, respectively, by ASTRO definition (98 and 92% by Phoenix definition). Local relapse did not occur, distant metastasis-free survival was 100 and 95% by risk-group, and disease-specific survival was 100%. Acute and late grade 2 GU toxicity incidence was 10 and 9%, respectively; with 6% late grade 3 GU toxicity. Acute urinary retention did not occur. Acute and late grade 2 GI toxicity was 0 and 1%, respectively, with no grade 3 or higher toxicity. Of patient’s potent pre-SBRT, 65% remained so at 5 years. Conclusion: Virtual HDR prostate SBRT creates a very low PSA nadir, a high rate of 5-year disease-free survival and an acceptable toxicity incidence, with results closely resembling those reported

  4. 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.

  5. 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

  6. Endomedullary radiofrequency ablation of metastatic lesion of the right femur 5 years after primary breast carcinoma: a case report.

    PubMed

    Majerović, Mate; Augustin, Goran; Jelincić, Zeljko; Buković, Damir; Burcar, Ivan; Smud, Dubravko; Kekez, Tihomir; Kinda, Emil; Matosević, Petar; Turcić, Josip

    2008-12-01

    Metastatic tumors of the long bones usually present with severe pain refractory to analgesic therapy. Pathologic fractures of the bone may lead to the significant decrease of patient's quality of life and necessitate further surgical therapy. We present 66 year old female with metastatic left breast carcinoma (T2N0M0) diagnosed 5 years before presentation of the metastatic lesion of the right femur causing severe pain in the middle of the right upper leg. Pain persisted after palliative irradiation therapy. We performed radiofrequency ablation of the metastatic lesion of the right femur using R.I.TA. Medical System Generator. This resulted in total necrosis of the tumor mass that caused osteolysis of the internal part of the femoral cortex. First three months after RFA procedure, the pain and tenderness were absent and normal daily activities were performed without restrictions.

  7. Pathologic complete response and disease-free survival are not surrogate endpoints for 5-year survival in rectal cancer: an analysis of 22 randomized trials

    PubMed Central

    Borgonovo, Karen; Cabiddu, Mary; Ghilardi, Mara; Lonati, Veronica; Barni, Sandro

    2017-01-01

    Background We performed a literature-based analysis of randomized clinical trials to assess the pathologic complete response (pCR) (ypT0N0 after neoadjuvant therapy) and 3-year disease-free survival (DFS) as potential surrogate endpoints for 5-year overall survival (OS) in rectal cancer treated with neoadjuvant (chemo)radiotherapy (CT)RT. Methods A systematic literature search of PubMed, EMBASE, the Web of Science, SCOPUS, CINAHL, and the Cochrane Library was performed. Treatment effects on 3-year DFS and 5-year OS were expressed as rates of patients alive (%), and those on pCR as differences in pCR rates (∆pCR%). A weighted regression analysis was performed at individual- and trial-level to test the association between treatment effects on surrogate (∆pCR% and ∆3yDFS) and the main clinical outcome (∆5yOS). Results Twenty-two trials involving 10,050 patients, were included in the analysis. The individual level surrogacy showed that the pCR% and 3-year DFS were poorly correlated with 5-year OS (R=0.52; 95% CI, 0.31–0.91; P=0.002; and R=0.60; 95% CI, 0.36–1; P=0.002). The trial-level surrogacy analysis confirmed that the two treatment effects on surrogates (∆pCR% and ∆3yDFS) are not strong surrogates for treatment effects on 5-year OS % (R=0.2; 95% CI, −0.29–0.78; P=0.5 and R=0.64; 95% CI, 0.29–1; P=0.06). These findings were confirmed in neoadjuvant CTRT studies but not in phase III trials were 3-year DFS could still represent a valid surrogate. Conclusions This analysis does not support the use of pCR and 3-year DFS% as appropriate surrogate endpoints for 5-year OS% in patients with rectal cancer treated with neoadjuvant therapy. PMID:28280607

  8. [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.

  9. Juvenile Breast Hypertrophy: A Successful Breast Reduction of 14.9% Body Weight without Recurrence in a 5-Year Follow-Up

    PubMed Central

    Abd Latib, Marzida; Basiron, Normala

    2017-01-01

    Juvenile hypertrophy of the breast (JHB) is a rare and relentless disease affecting women in the peripubertal period. We present a 13-year-old girl with massive bilateral JHB, successfully treated with a breast reduction and free nipple graft technique. A total of 7300 grams of breast tissue had been removed, accounting for 14.9% of the patient's total body weight. Prophylactic hormonal therapy was not commenced. During the 5-year follow-up period, there was no recurrence and the patient remains satisfied with the aesthetic outcome. A recent meta-analysis study indicates that subcutaneous mastectomy is associated with reduced risk of recurrence, but it is more deforming and the aesthetic result is inferior to a reduction mammaplasty. In patients treated with the latter technique, some evidence exists suggesting that the use of a free nipple graft is associated with a less frequent risk of recurrence than a pedicle technique. This present case is unique as it demonstrates the clinical course of this patient at a considerably longer follow-up period than most reported studies. We adhered to the limited available evidence and highlight the long-term reliability of breast reduction with free nipple grafting as the first line surgical option in JHB, eliminating the need for repeated surgeries. PMID:28255494

  10. Polychlorinated biphenyls and their association with survival following breast cancer

    PubMed Central

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

    2015-01-01

    Background Polychlorinated biphenyls (PCBs) are hypothesized to influence breast carcinogenesis due to their persistence and potential to induce estrogenic and anti-estrogenic effects. Whether PCBs influence survival following breast cancer is unknown. Methods A population-based cohort of women diagnosed with first primary invasive or in situ breast cancer in 1996–1997 and with blood-measured PCBs (n=627) collected shortly after diagnosis was followed for vital status through 2011. After 5 and 15 years we identified 54 and 187 deaths, respectively, of which 36 and 74 were breast cancer-related. Using Cox regression, we estimated hazard ratios (HR) and 95% confidence intervals (CI) for mortality for baseline PCB concentrations, individually and as estrogenic (ΣGroup 1B: PCB101, PCB174, PCB177, PCB187, PCB199), anti-estrogenic (ΣGroup 2A: PCB66, PCB74, PCB105, PCB118; Σ2B: PCB138, PCB170), and cytochrome P450 enzyme-inducing (ΣGroup 3: PCB99, PCB153, PCB180, PCB183, PCB203) groups. Results The highest PCB174 tertile was associated with an increase in all-cause (HR=2.22, 95%CI: 1.14–4.30) and breast cancer-specific (HR=3.15, 95%CI: 1.23–8.09) mortality within 5 years of diagnosis and remained associated with breast cancer-specific mortality (HR=1.88, 95%CI: 1.05–3.36) at 15 years. At 5 years, the highest tertile of PCB177 was positively associated with all-cause mortality (HR=2.12, 95%CI: 1.05–4.30). At 15 years, the highest tertiles of ΣGroup 2A congeners and PCB118 were inversely associated with all-cause mortality (HR=0.60, 95%CI: 0.39–0.83; HR=0.63, 95%CI: 0.43–0.92, respectively). Conclusions In this first US study of PCBs and breast cancer survival, PCBs were associated with mortality in biologically plausible directions. The investigation of other, structurally similar, chemicals may be warranted. PMID:26798968

  11. Association of Breast Cancer Risk loci with Breast Cancer Survival

    PubMed Central

    Barrdahl, Myrto; Canzian, Federico; Lindström, Sara; Shui, Irene; Black, Amanda; Hoover, Robert N.; Ziegler, Regina G.; Buring, Julie E.; Chanock, Stephen J.; Diver, W. Ryan; Gapstur, Susan M.; Gaudet, Mia M.; Giles, Graham G.; Haiman, Christopher; Henderson, Brian E.; Hankinson, Susan; Hunter, David J.; Joshi, Amit D.; Kraft, Peter; Lee, I-Min; Le Marchand, Loic; Milne, Roger L.; Southey, Melissa C.; Willett, Walter; Gunter, Marc; Panico, Salvatore; Sund, Malin; Weiderpass, Elisabete; Sánchez, María-José; Overvad, Kim; Dossus, Laure; Peeters, Petra H; Khaw, Kay-Tee; Trichopoulos, Dimitrios; Kaaks, Rudolf; Campa, Daniele

    2015-01-01

    The survival of breast cancer patients is largely influenced by tumor characteristics, such as TNM stage, tumor grade and hormone receptor status. However, there is growing evidence that inherited genetic variation might affect the disease prognosis and response to treatment. Several lines of evidence suggest that alleles influencing breast cancer risk might also be associated with breast cancer survival. We examined the associations between 35 breast cancer susceptibility loci and the disease over-all survival (OS) in 10,255 breast cancer patients from the National Cancer Institute Breast and Prostate Cancer Cohort Consortium (BPC3) of which 1,379 died, including 754 of breast cancer. We also conducted a meta-analysis of almost 35,000 patients and 5,000 deaths, combining results from BPC3 and the Breast Cancer Association Consortium (BCAC) and performed in silico analyses of SNPs with significant associations. In BPC3, the C allele of LSP1-rs3817198 was significantly associated with improved OS (HRper-allele=0.70; 95% CI: 0.58–0.85; Ptrend=2.84×10−4; HRheterozygotes=0.71; 95% CI: 0.55–0.92; HRhomozygotes=0.48; 95% CI: 0.31–0.76; P2DF=1.45×10−3). In silico, the C allele of LSP1-rs3817198 was predicted to increase expression of the tumor suppressor cyclin-dependent kinase inhibitor 1C (CDKN1C). In the meta-analysis, TNRC9-rs3803662 was significantly associated with increased death hazard (HRMETA =1.09; 95% CI: 1.04–1.15; Ptrend=6.6×10−4; HRheterozygotes=0.96 95% CI: 0.90–1.03; HRhomozygotes= 1.21; 95% CI: 1.09–1.35; P2DF=1.25×10−4). In conclusion, we show that there is little overlap between the breast cancer risk single nucleotide polymorphisms (SNPs) identified so far and the SNPs associated with breast cancer prognosis, with the possible exceptions of LSP1-rs3817198 and TNRC9-rs3803662. PMID:25611573

  12. The 5-year survival following the marginal resection of a primary leiomyosarcoma of the distal femur and a stump fracture.

    PubMed

    Plath, J; Gurk, S; Strophal, G; Johnson, M; Jansson, V

    2001-09-01

    In this case, we present a 5-year follow-up of a 3-fault-affected primary leiomyosarcoma of the distal femur (spontaneous fracture treated by osteosynthesis; marginal resection; stump fracture after adequate trauma) with an extended local recurrence but without metastasis.

  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. Alternative endpoints to the 5-year overall survival and locoregional control for nasopharyngeal carcinoma: A retrospective analysis of 2,450 patients.

    PubMed

    Chen, Chen; Yi, Wei; Gao, Jin; Li, Xiao-Hui; Shen, Lu-Jun; Li, Bo-Fei; Tu, Zi-Wei; Tao, Ya-Lan; Jiang, Chang-Bin; Xia, Yun-Fei

    2014-05-01

    The purpose of the present study was to investigate alternative endpoints to the 5-year overall survival (OS) and locoregional control (LRC) for nasopharyngeal carcinoma (NPC). A total of 2,450 NPC patients were enrolled in this study, including 1,842 patients treated with two-dimensional (2D) radiotherapy (RT), 451 treated with 3D conformal RT (CRT) and 157 treated with intensity-modulated RT (IMRT). We sequentially calculated the 1-, 2-, 3- and 4-year survival rates using a life table and compared these with the 5-year survival rate using the McNemar method, with the survival rate of the last indifferent comparison being considered as the alternative endpoint. For 2D RT, stage I patients exhibited similar survival rates at 1 and 5 years (98.9 vs. 94.4%, respectively; P=0.125 for both OS and LRC); stage N3 patients exhibited similar 4-year OS (55.2 vs. 53.5%; P=1.000) and 2-year LRC (78.3 vs. 71.2%; P=0.125) to the 5-year OS and LRC. For IMRT, the 1-, 2-, 3-, 4- and 5-year OS and LRC rates in stage I/II NPC patients were 100, 98, 96, 94 and 94% for OS and 100, 98, 96, 96 and 96% for LRC, respectively. No significant differences were observed for all the comparisons. For stage III/IV NPC patients treated with IMRT, the 1-, 2-, 3-, 4- and 5-year rates were 99.1, 96.3, 92.5, 88.8 and 85.0% for OS and 98.1, 97.2, 95.3, 90.7 and 89.7% for LRC, respectively. Only the 4-year OS and LRC rates were indifferent from those at 5 years (P=0.125 for OS and P=1.00 for LRC). In conclusion, the 1-year OS and LRC for stage I NPC patients treated with 2D RT or stage I/II NPC patients treated with IMRT, the 4-year OS and 2-year LRC for stage N3 NPC patients treated with 2D RT and the 4-year OS and LRC for stage III/IV NPC patients treated with IMRT were determined as the alternative endpoints to the 5-year OS and LRC for NPC patients.

  15. Could Grilled, Smoked Meats Lower Survival After Breast Cancer?

    MedlinePlus

    ... html Could Grilled, Smoked Meats Lower Survival After Breast Cancer? Study can't prove cause and effect, but ... and smoked meats could increase the risk of breast cancer. Now, a new study finds these cooking methods ...

  16. Conditional disease-free survival among patients with breast cancer.

    PubMed

    Paik, Hyun-June; Lee, Se Kyung; Ryu, Jai Min; Park, Sungmin; Kim, Isaac; Bae, Soo Youn; Yu, Jonghan; Lee, Jeong Eon; Kim, Seok Won; Nam, Seok Jin

    2017-01-01

    Conditional disease-free survival (CDFS) reflects changes over time. Because traditional disease-free survival (DFS) is estimated from the date of diagnosis, it is limited in the ability to predict risk of recurrence in patients who have been disease free. In this study, we determined CDFS of breast cancer patients and estimated the prognostic factors for DFS.We retrospectively reviewed clinical data of 7587 consecutive patients who underwent curative surgery for breast cancer between January 2004 and December 2013 at Samsung Medical Center. Univariate and multivariate analyses were performed to identify risk factors for DFS, which was computed using the Kaplan-Meier method. CDFS rates were based on cumulative DFS estimates.Median follow-up duration was 20.59 months. Three-year DFS was 93.46% at baseline. Three-year CDFS survival estimates for patients who had been disease free for 1, 2, 3, 4, and 5 years after treatment were calculated as 92.84%, 92.37%, 93.03%, 89.41%, and 79.64%, respectively. Three-year CDFS increased continuously each year after 1 year of DFS in hormone receptor (HR)-negative patients but decreased each year in HR-positive patients.In HR-positive patients who are disease free after 3 years, continuous care including surveillance and metastases workup should be considered, although this is not recommended in the current guidelines. On the other hand, the social costs may be reduced in HR-negative patients by extending the surveillance interval. Further studies are needed to identify indicators of DFS prognosis in breast cancer patients.

  17. 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.

  18. 5-Year Survival in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia in a Randomized, Phase III Trial of Fludarabine Plus Cyclophosphamide With or Without Oblimersen

    PubMed Central

    O'Brien, Susan; Moore, Joseph O.; Boyd, Thomas E.; Larratt, Loree M.; Skotnicki, Aleksander B.; Koziner, Benjamin; Chanan-Khan, Asher A.; Seymour, John F.; Gribben, John; Itri, Loretta M.; Rai, Kanti R.

    2009-01-01

    Purpose A randomized trial of oblimersen plus fludarabine/cyclophosphamide (OBL-FC; n = 120) versus FC (n = 121) was conducted in patients with relapsed/refractory chronic lymphocytic leukemia (CLL). The primary end point was met: the complete response (CR) rate, defined as complete or nodular partial response, was significantly greater with OBL-FC than with FC (17% v 7%; P = .025). Among patients with CR, response duration was significantly longer with OBL-FC than with FC (median not reached; > 36 months v 22 months; P = .03). Maximum benefit with OBL-FC, including a four-fold increase in CR rate and a survival benefit with 3 years of follow-up (hazard ratio, 0.53; P = .05), was observed in patients with fludarabine-sensitive disease. We evaluated long-term survival and poststudy CLL therapy among all randomly assigned patients. Methods Poststudy CLL treatment information was collected. Patients were observed for survival for up to 5 years from the date of random assignment. Results Poststudy CLL treatment was balanced between arms. Intent-to-treat analysis of 5-year survival showed no significant between-treatment difference (hazard ratio, 0.87; P = .34). Among the greater than 40% of patients with complete or partial remission, a significant 5-year survival benefit was observed with OBL-FC (hazard ratio, 0.60; P = .038). Among patients with fludarabine-sensitive disease who had previously demonstrated maximum benefit with OBL-FC, the previously observed survival benefit improved: a 50% reduction in the risk of death was observed (P = .004). Conclusion In relapsed/refractory CLL, OBL combined with FC offers patients who achieve complete or partial remission, as well as those who have fludarabine-sensitive disease, a significant survival benefit. PMID:19738118

  19. 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.

  20. Factors influencing survival in hemodialysis patients aged older than 75 years: 2.5-year outcome study.

    PubMed

    Chauveau, P; Combe, C; Laville, M; Fouque, D; Azar, R; Cano, N; Canaud, B; Roth, H; Leverve, X; Aparicio, M

    2001-05-01

    The incidence of malnutrition is widely held to be greater in the elderly, but this specific factor has not been extensively studied in elderly dialysis patients. In a 30-month follow-up prospective study, we evaluated the role of nutrition on the outcome of 290 stable hemodialysis (HD) outpatients aged older than 75 years followed up in 20 French HD centers (167 men, 123 women; age, 79.8 +/- 4.2 years; previous time on dialysis, 41 +/- 38 months). On the same day in January 1996, predialysis and postdialysis blood samples were collected according to recommended procedures for dialysis quantification. Normalized protein catabolic rate, dialysis adequacy parameters, and estimation of lean body mass (LBM; expressed as observed/expected LBM values [obs/exp LBM]) were computed from predialysis and postdialysis urea and creatinine levels. Overall survival rates were 80% and 65% after 1 and 2 years of follow-up, respectively, and were significantly less in patients with the lower quartile of obs/exp LBM. In univariate analysis using the Cox proportional hazards model, survival was significantly influenced by age, albumin level, prealbumin level, body mass index, and diabetes, but not by sex, Kt/V, duration of dialysis, cholesterol level, hemoglobin level, or obs/exp LBM. In multivariate analysis, no variable remained significant. Cardiovascular mortality accounted for 52.1% of the patient deaths. We conclude that in elderly HD patients, malnutrition influences overall survival despite adequate dialysis treatment.

  1. Efficacy of continuous positive airway pressure treatment on 5-year survival in patients with ischaemic stroke and obstructive sleep apnea: a randomized controlled trial.

    PubMed

    Parra, Olga; Sánchez-Armengol, Ángeles; Capote, Francisco; Bonnin, Marc; Arboix, Adrià; Campos-Rodríguez, Francisco; Pérez-Ronchel, José; Durán-Cantolla, Joaquín; Martínez-Null, Cristina; de la Peña, Mónica; Jiménez, Maria Carmen; Masa, Fernando; Casadon, Ignacio; Alonso, Maria Luz; Macarrón, José L

    2015-02-01

    The main purpose of the present analysis is to assess the influence of introducing early nasal continuous positive airway pressure (nCPAP) treatment on cardiovascular recurrences and mortality in patients with a first-ever ischaemic stroke and moderate-severe obstructive sleep apnea (OSA) with an apnea-hypopnea index (AHI) ≥20 events h(-1) during a 5-year follow-up. Patients received conventional treatment for stroke and were assigned randomly to the nCPAP group (n = 71) or the control group (n = 69). Cardiovascular events and mortality were registered for all patients. Survival and cardiovascular event-free survival analysis were performed after 5-year follow-up using the Kaplan-Meier test. Patients in the nCPAP group had significantly higher cardiovascular survival than the control group (100 versus 89.9%, log-rank test 5.887; P = 0.015) However, and also despite a positive tendency, there were no significant differences in the cardiovascular event-free survival at 68 months between the nCPAP and control groups (89.5 versus 75.4%, log-rank test 3.565; P = 0.059). Early nCPAP therapy has a positive effect on long-term survival in ischaemic stroke patients and moderate-severe OSA.

  2. Short duration of breast-feeding as a risk-factor for beta-cell autoantibodies in 5-year-old children from the general population.

    PubMed

    Holmberg, Hanna; Wahlberg, Jeanette; Vaarala, Outi; Ludvigsson, Johnny

    2007-01-01

    Breast-feeding has been suggested to have a protective effect against the development of type 1 diabetes. In the present study, we investigated the relation between duration of breast-feeding and beta-cell autoantibodies in 5-year-old non-diabetic children who participated in a prospective population-based follow-up study (the All Babies in Southeast Sweden study). Autoantibodies to insulin (IAA), glutamic acid decarboxylase (GADA) and the protein tryosine phosphatase-like IA-2 (IA-2A) were measured by radiobinding assays. A short duration of total breast-feeding was associated with an increased risk of GADA and/or IAA above the ninety-fifth percentile at 5 years of age (OR 2.09, 95% CI 1.45, 3.02; P<0.000) as well as with an increased risk of IAA above the ninety-fifth percentile at this age (OR 2.89, 95% CI 1.81, 4.62, P<0.000). A short duration of exclusive breast-feeding was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 2.01, 95% CI 1.08, 3.73; P=0.028) as well as with an increased risk of IA-2A above the ninety-ninth percentile (OR 3.50, 95% CI 1.38, 8.92, P=0.009) at 5 years of age. An early introduction of formula was associated with an increased risk of GADA, IAA and/or IA-2A above the ninety-ninth percentile (OR 1.84, 95% CI 1.01, 3.37; P=0.047) at 5 years of age. The positive association between a short duration of both total and exclusive breast-feeding, as well as an early introduction of formula, and positivity for beta-cell autoantibodies in children from the general population suggest that breast-feeding modifies the risk of beta-cell autoimmunity, even years after finishing breast-feeding.

  3. Operable Breast Cancer of the Inner Hemisphere Is Associated with Poor Survival

    PubMed Central

    Xue, Cong; Peng, Rou Jun; Wang, Shu Sen; Shi, Yan Xia; An, Xin; Xu, Fei

    2015-01-01

    Purpose This study investigated the clinicopathological features of operable breast cancer lesions located in different hemispheres of the breast and determined related survival outcomes. Methods Data from 5,330 patients with invasive ductal carcinoma were retrospectively analyzed based on tumor location. Results The median follow-up time was 68 months (range, 18-176 months). Patients with breast cancer located in the outer hemisphere of the breast had lesions with more advanced nodal stages and more frequently received adjuvant chemotherapy than patients with breast cancer in the inner hemisphere. The 5-year disease-free survival (DFS) rates of patients with tumors located in outer versus inner hemispheres were 81.5% and 77.0%, respectively (p=0.004); the overall survival (OS) rates were 90.7% and 88.8%, respectively (p<0.001). The association between tumor location and the 5-year DFS rate was most apparent in node-positive patients (73.1% vs. 65.8% for outer vs. inner hemisphere lesions, p<0.001) and in patients with primary tumors greater than 2 cm in diameter (78.2% vs. 72.3%, p=0.002). Multivariate analysis showed that tumor location was an independent predictor of DFS (hazard ratio [HR], 1.23; p=0.002) and OS (HR, 1.28; p=0.006). There were no significant differences in 5-year DFS or OS rates between patients with outer versus inner hemisphere tumors when internal mammary node irradiation was performed. Conclusion This study demonstrated that tumor location was an independent prognostic factor for operable breast cancer. Internal mammary node irradiation is recommended for patients with breast cancer of the inner hemisphere and positive axillary lymph nodes or large primary tumors. PMID:25834609

  4. Evaluation of the Correlation between CD44, Tumor Prognosis and the 5-Year Survival Rate in Patients with Oral Tongue SCC

    PubMed Central

    Kaboodkhani, Reza; Karimi, Ebrahim; Khorsandi Ashtiani, Mohammad Taghi; Kowkabi, Safoura; Firouzifar, Mohammad Reza; Yazdani, Farzad; Yazdani, Nasrin

    2016-01-01

    Introduction: 90% of the tumors in the head and neck are squamous-cell carcinomas (HNSCC), which have overall 5- year survival rate between 50% -60%. CD44 has been shown to be associated with the prognosis. Materials and Methods: Biopsy specimens of 51 patients with oral tongue SCC were evaluated by Immunohistochemistry (IHC) for the CD44 antibody. Results: There was no significant correlation between CD44 and survival (P=0.77), age (P=0.4), CD44 and lymph node metastasis (P=0.87), sex (P=0.947), smoking (P=0.287) and tumor size (P=0.813). However, there was significant correlation between smoking and survival. Conclusion: There are widespread discrepancies among the findings in the literature regarding the prognosis of CD44 expression in OCSCC. Our study shows that the expression of CD44 is not a marker of aggressive behavior in oral tongue SCC. Consequently, CD44 cannot be considered as handy tool to establish the tumor behavior, prognosis and 5- year survival rate of these tumors. PMID:28008391

  5. Inbreeding and homozygosity in breast cancer survival.

    PubMed

    Thomsen, Hauke; Filho, Miguel Inacio da Silva; Woltmann, Andrea; Johansson, Robert; Eyfjörd, Jorunn E; Hamann, Ute; Manjer, Jonas; Enquist-Olsson, Kerstin; Henriksson, Roger; Herms, Stefan; Hoffmann, Per; Chen, Bowang; Huhn, Stefanie; Hemminki, Kari; Lenner, Per; Försti, Asta

    2015-11-12

    Genome-wide association studies (GWASs) help to understand the effects of single nucleotide polymorphisms (SNPs) on breast cancer (BC) progression and survival. We performed multiple analyses on data from a previously conducted GWAS for the influence of individual SNPs, runs of homozygosity (ROHs) and inbreeding on BC survival. (I.) The association of individual SNPs indicated no differences in the proportions of homozygous individuals among short-time survivors (STSs) and long-time survivors (LTSs). (II.) The analysis revealed differences among the populations for the number of ROHs per person and the total and average length of ROHs per person and among LTSs and STSs for the number of ROHs per person. (III.) Common ROHs at particular genomic positions were nominally more frequent among LTSs than in STSs. Common ROHs showed significant evidence for natural selection (iHS, Tajima's D, Fay-Wu's H). Most regions could be linked to genes related to BC progression or treatment. (IV.) Results were supported by a higher level of inbreeding among LTSs. Our results showed that an increased level of homozygosity may result in a preference of individuals during BC treatment. Although common ROHs were short, variants within ROHs might favor survival of BC and may function in a recessive manner.

  6. 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

  7. Basic Facts of Breast Cancer in Korea in 2014: The 10-Year Overall Survival Progress

    PubMed Central

    Park, Eun Hwa; Min, Sun Young; Kim, Zisun; Yoon, Chan Seok; Jung, Kyu-Won; Nam, Seok Jin; Oh, Se Jeong; Lee, Seeyoun; Park, Byeong-Woo; Lim, Woosung

    2017-01-01

    We, the Korean Breast Cancer Society (KBCS), present the facts and the trends of breast cancer in Korea in 2014. Data on the total number of newly diagnosed patients was obtained from the Korea Central Cancer Registry database, other data were collected from the KBCS online registry database, and the overall survival data of patients were updated from Statistics Korea. A total of 21,484 female patients were newly diagnosed with breast cancer in 2014. The crude incidence rate and the age-standardized incidence rate (ASR) of breast cancer in female patients, including carcinoma in situ, were 83.4 cases and 63.9 cases per 100,000 women, respectively. The ASR showed an annual increase of 6.1% from 1999 to 2014; however, although the increase of the ASR had slowed since 2008, the incidence rate itself continuously increased. The proportion of early breast cancer increased consistently, and the pathological features changed accordingly. While breast-conserving surgery was mainly performed, the proportion of total mastectomy was slightly increased. The total number of breast reconstruction surgeries increased rapidly. The 5-year and 10-year overall survival rates for all stages of breast cancer patients were 91.2% and 84.8%, respectively. The overall survival rate of Korean patients with breast cancer was extremely high, compared with other developed countries. Thus, we consider that the clinical characteristics of breast cancer have changed over the past decade. A nationwide registry data will contribute to a better understanding of the characteristics of breast cancer in Korea. PMID:28382089

  8. Pathobiology of breast cancer: hypothesis of biological predetermination and long-term survival.

    PubMed

    Vorherr, H

    1981-08-03

    Th pathobiology of breast cancer is complex: clinically "early" breast cancer may be tumor biologically "late" progressing rapidly toward death. Accordingly, it has been suggested that two different breast cancer populations (slow tumor growth and long survival-fast tumor growth and short survival) exist, which cannot be identified by pathohistological criteria. However, these "populations" are most likely either patients with localized disease and occult metastases (long survival) or with diagnosable regional and occult or overt systemic spread (short survival). Since even small tumors (0.1 to 0.3 cm in diameter) can spread systemically, in most patients breast cancer upon clinical diagnosis may be considered an inevitably lethal disease. Present treatment modalities can only improve the quality of life and delay death, even though the overall long-term survival rates of breast cancer are better or at least equal to those of other cancers. However, with other cancers (Table 2) it is decided within the first 5 years which patients are cured because the survival rates for 5, 10, 15, and 20 years are similar. In contrast, survival rates of patients with breast cancer steadily decline and there is no point in time when patients can feel really safe; this is indicative of a peculiar tumor pathobiology of this disease, the nature of which remains to be investigated. Progress in the fight against breast cancer is only possible by application of sensitive physical, reliable immunological, and specific biochemical methods for early diagnosis and development of efficient therapeutic modalities for inhibition of growth or complete eradication of metastasized cancer cells.

  9. 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.

  10. Loco-regional treatment in metastatic breast cancer patients: is there a survival benefit?

    PubMed

    Ly, Bevan H; Nguyen, Nam P; Vinh-Hung, Vincent; Rapiti, Elisabetta; Vlastos, Georges

    2010-02-01

    A number of studies have recently demonstrated a survival benefit in stage IV breast cancer patients following surgical resection of the primary tumor. Here, we investigate the relationship between loco-regional treatment and survival in patients with metastatic breast cancer and evaluate the impact of different loco-regional treatments. We conducted a systematic review of the literature using PubMed to analyze studies with the following criteria: Type of loco-regional treatment (surgery alone or combined with radiation, radiotherapy), overall survival, progression-free survival, selection factors for local treatment, and complication rates. Thirteen studies evaluated the effect of loco-regional treatment on overall survival with overall median survival increasing from a range of 12.6-28.3 months among patients without surgery to a range of 25-42 months among patients with surgery. In addition, six studies reported a 3-year survival benefit of 28-95% and 17-79% in women with and without locoregional therapy respectively. Two studies did not find any improvement in overall survival. One study found an improvement in 5-year breast cancer-specific survival of 27% with negative surgical margins versus 12% with no surgery. Three studies reported an advantage in progression-free survival in the treatment group compared with the non-treatment group. Loco-regional treatment for breast cancer patients with distant metastases at diagnosis is an important issue because of possible improvement of survival or disease-free survival. The possibility of surgery and/or radiotherapy following induction chemotherapy should be weighed and left to individual practice. Participation in randomized controlled trials should be encouraged.

  11. Breast-feeding, day-care attendance and the frequency of antibiotic treatments from 1.5 to 5 years: a population-based longitudinal study in Canada.

    PubMed

    Dubois, Lise; Girard, Manon

    2005-05-01

    This paper aims to study, at the population level, the protective role of breast-feeding on child health and its relation to day-care attendance during the first 5 years of life. The analysis, done on a national sample of children, uses antibiotic treatments as a general measure of health. It takes into account mother's education level, family poverty level, mother's smoking status during pregnancy and after birth, mother's age, sex, gestation duration, and birth rank. The analyses were performed using data from the Longitudinal Study of Child Development in Quebec (LSCDQ), conducted by Santé Québec, a division of the Institut de la Statistique du Québec (ISQ). The study was based on face-to-face interviews and included a set of questionnaires addressed to the children's mothers and fathers. A total of 1841 were included in the sample analyzed. Detailed information on breast-feeding and complementary feeding was collected at 5 and 17 months through face-to-face interviews with the most knowledgeable person, generally the mother. From this information, it has been possible to estimate breast-feeding duration and exclusivity. Our results indicate that the positive effects of breast-feeding on health persist up to the second year of life, even in the presence of day-care attendance. The analyses indicate that breast-feeding reduced the number of antibiotic treatments given to children entering day care before 2.5 years of age. The study also indicates that the more-at-risk children could be protected by breast-feeding and by being taken care of in a familial setting, especially before 2.5 years of age. Mother's education, family poverty level, and other social inequality indicators did not play a role in the frequency of antibiotic treatments. Over the long term, it will be important to continue to monitor the health of children and to implement public health interventions aimed at reducing health problems among children of preschool age.

  12. 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

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

    PubMed Central

    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.

    2015-01-01

    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, 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; 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

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. Survival of women with breast cancer in Kaunas Region, Lithuania.

    PubMed

    Ivanauskienė, Rugilė; Gedminaitė, Jurgita; Juozaitytė, Elona; Vanagas, Giedrius; Simoliūnienė, Renata; Padaiga, Zilvinas

    2012-01-01

    OBJECTIVE. The assessment of breast cancer survival rates and comparison with those of other countries may help to deepen knowledge among decision makers in the health care system and to improve the inequalities in accessibility to early detection and effective treatment. The aim of this study was to evaluate breast cancer survival rates in Kaunas region, Lithuania, and to compare them with those in the selected European countries. MATERIAL AND METHODS. A retrospective study was carried out using medical records and data gathered from the Lithuanian Cancer Registry. A group of 240 patients with primary breast cancer diagnosed in 2008 in Kaunas region was analyzed. All causes of death were included in the analysis. The closing date of follow-up was September 30, 2010. Survival was determined using the life-table method and the Kaplan-Meier method. Cox proportional hazard models were used to estimate the effects of prognostic risk factors on survival. RESULTS. The median age of the patients was 63 years (range, 28-95). The 1-year and 2-year cumulative survival for breast cancer patients in Kaunas region, Lithuania, was 94.2% and 90.1%, respectively. As expected, the survival of patients with diagnosed advanced disease (stage III and IV) was significantly worse than that of patients with stage I (P<0.001) and II (P=0.003) disease. The screening group (aged 50-69 years) showed better survival in comparison with the group older than 69 years. Age, T4 tumor, and distant metastasis were the prognostic factors significantly associated with an increased relative mortality risk of breast cancer. CONCLUSIONS. Compared to the European survival rates, the 1-year and 2-year survival of patients with breast cancer in Lithuania was found to be similar to most European countries.

  20. A retrospective analysis of survival and prognostic factors of male breast cancer from a single center

    PubMed Central

    2014-01-01

    Background Less than 1% of all breast cancer cases are found in men, who reportedly have inferior outcomes compared with matched women patients. Ethnic differences may also affect their prognosis. Here, we investigated overall survival (OS) and major prognostic factors for male breast cancer (MBC) in a cohort of Egyptian patients. Methods We retrospectively analyzed OS in a cohort of 69 male patients with MBC who were surgically treated at the Mansoura Cancer Center, Egypt between 2000 and 2007. We registered demographic data, age, height, weight and body mass index, tumor size, histology, number of infiltrated axillary lymph nodes, hormone receptor (HR) status and metastatic presence, and TNM staging. Patients’ OS was the primary endpoint. Patients received treatment to the medical standards at the time of their diagnosis. Results In the 69 patients who met the inclusion criteria and had complete stored patient data, tumors ranged from T1c to T3. We could gather cancer-related survival data from only 56 patients. The collective 5-year survival in this cohort was 46.4%. Only five patients had distant metastasis at diagnosis, but they showed a null percent 5-year survival, whereas those with no lymph node infiltration showed a 100% 5-year survival. Lymph node status and tumor grading were the only prognostic factors that significantly affected OS. Conclusions Lymph node status and tumor grade are the most important prognostic factors for overall survival of MBC in Egyptian male patients; whereas even remarkably low HR expression in MBC did not significantly affect OS. Further research is needed to understand the factors that affect this disease. PMID:24673740

  1. 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.

  2. Survival rates of breast cancer: a hospital-based study from northeast of Thailand.

    PubMed

    Poum, Amornsak; Kamsa-ard, Supot; Promthet, Supannee

    2012-01-01

    A retrospective cohort study was carried out with 340 female breast cancer at a teaching university in northeast of Thailand recruited and followed-up until the end of 2006. Survival probabilities were estimated using the Kaplan-Meier method. 161 cases were alive after five years and 58 patients were lost to follow-up. The overall observed survival rates at 1, 3 and 5 years were 83.3%, 59.9% and 42.9%, respectively. When analysis was conducted for stage combined into 2 groups, early (stage I, II and unknown) and late (stage III and IV), the 5-year survival rate for early stage (60%; 95%CI: 0.51-0.67), was higher than for late stage (27%; 95%CI: 0.19-0.34) with high statistical significance (p<0.001). The hazard ratio of patients with stage IV was 11.6 times greater than for stage I (p=0.03). The findings indicate that the different stages of breast cancer markedly effect the overall survival rate.

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

    PubMed

    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; Safaei Diba, Chakameh; 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

    2013-03-01

    Breast cancer survival is reportedly higher in the US than in Europe. The first worldwide study (CONCORD) found wide international differences in age-standardized 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-standardized net survival and the excess hazard of death up to 5 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 tumors were more frequent in the US (39%) than in Europe (32%), while locally advanced tumors were twice as frequent in Europe (8%), and metastatic tumors of similar frequency (5-6%). Net survival in Northern, Western and Southern Europe (81-84%) was similar to that in the US (84%), but lower in Eastern Europe (69%). 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 tumors. 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.

  4. Survival status and predictors of mortality among severely acute malnourished children <5 years of age admitted to stabilization centers in Gedeo Zone: a retrospective cohort study.

    PubMed

    Girum, Tadele; Kote, Mesfin; Tariku, Befikadu; Bekele, Henok

    2017-01-01

    Despite the existence of standard protocol, many stabilization centers (SCs) continue to experience high mortality of children receiving treatment for severe acute malnutrition. Assessing treatment outcomes and identifying predictors may help to overcome this problem. Therefore, a 30-month retrospective cohort study was conducted among 545 randomly selected medical records of children <5 years of age admitted to SCs in Gedeo Zone. Data was entered by Epi Info version 7 and analyzed by STATA version 11. Cox proportional hazards model was built by forward stepwise procedure and compared by the likelihood ratio test and Harrell's concordance, and fitness was checked by Cox-Snell residual plot. During follow-up, 51 (9.3%) children had died, and 414 (76%) and 26 (4.8%) children had recovered and defaulted (missed follow-up for 2 consecutive days), respectively. The survival rates at the end of the first, second and third weeks were 95.3%, 90% and 85%, respectively, and the overall mean survival time was 79.6 days. Age <24 months (adjusted hazard ratio [AHR] =2.841, 95% confidence interval [CI] =1.101-7.329), altered pulse rate (AHR =3.926, 95% CI =1.579-9.763), altered temperature (AHR =7.173, 95% CI =3.05-16.867), shock (AHR =3.805, 95% CI =1.829-7.919), anemia (AHR =2.618, 95% CI =1.148-5.97), nasogastric tube feeding (AHR =3.181, 95% CI =1.18-8.575), hypoglycemia (AHR =2.74, 95% CI =1.279-5.87) and treatment at hospital stabilization center (AHR =4.772, 95% CI =1.638-13.9) were independent predictors of mortality. The treatment outcomes and incidence of death were in the acceptable ranges of national and international standards. Intervention to further reduce deaths has to focus on young children with comorbidities and altered general conditions.

  5. A study of donepezil in female breast cancer survivors with self-reported cognitive dysfunction 1 to 5 years following adjuvant chemotherapy

    PubMed Central

    Griffin, L.; Balcueva, E. P.; Groteluschen, D. L.; Samuel, T. A.; Lesser, G. J.; Naughton, M. J.; Case, L. D.; Shaw, E. G.; Rapp, S. R.

    2016-01-01

    Purpose Some breast cancer survivors report cognitive difficulties greater than 1 year after chemotherapy. Acetylcholinesterase inhibitors (AChEI) may improve cognitive impairment. We conducted a randomized, placebo-controlled, pilot study to assess the feasibility of using the AChEI, donepezil, to improve subjective and objective measures of cognitive function in breast cancer survivors. Methods Women who received adjuvant chemotherapy 1–5 years prior with current cognitive dysfunction symptoms were randomized to 5 mg of donepezil/day vs placebo for 6 weeks and if tolerated 10 mg/day for 18 weeks for a total of 24 weeks. A battery of validated measures of attention, memory, language, visuomotor skills, processing speed, executive function, and motor dexterity and speed was administered at baseline and at 24 and 36 weeks. Subjective cognitive function, fatigue, sleep, mood, and health-related quality of life were evaluated at baseline and at 12, 24, and 36 weeks. Results Sixty-two patients were enrolled, 76 % completed the study, self-reported compliance was 98 %, and toxicities were minimal. At the end of treatment, the donepezil group performed significantly better than the control group on two parameters of memory—the Hopkins Verbal Learning Test -Revised (HVLT-R) Total Recall (p=0.033) and HVLT-R Discrimination (p=0.036). There were no significant differences on other cognitive variables or in subjective cognitive function or quality of life. Conclusion Accrual to this feasibility trial was robust, retention was good, compliance was excellent, and toxicities were minimal. Implications for Cancer Survivors Randomized clinical trials in breast cancer survivors to improve cognitive dysfunction are feasible. A phase III trial testing the efficacy of donepezil is warranted given these pilot results. PMID:26130292

  6. Survival in Norwegian BRCA1 mutation carriers with breast cancer.

    PubMed

    Hagen, Anne Irene; Tretli, Steinar; Maehle, Lovise; Apold, Jaran; Vedå, Nina; Møller, Pål

    2009-04-14

    Several studies of survival in women with BRCA1 mutations have shown either reduced survival or no difference compared to controls. Programmes for early detection and treatment of inherited breast cancer, have failed to demonstrate a significant improvement in survival in BRCA1 mutation carriers.One hundred and sixty-seven women with disease-associated germline BRCA1 mutations and breast cancer from 1980 to 2001 were identified. Tumour characteristics, treatment given and survival were recorded. A control group comprising three hundred and four women matched for age, time of diagnosis and stage were used to compare survival.BRCA1 mutation carriers were found to have a poorer prognosis, which could be explained by neither the mode of surgical treatment nor the use of adjuvant chemotherapy. BRCA1 mutation carriers with node negative breast cancer had worse overall survival than controls.Our findings confirm the serious prognosis of BRCA1-associated breast cancer even when diagnosed at an early stage, and that type of treatment does not influence prognosis.

  7. 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

  8. The joint contribution of tumor phenotype and education to breast cancer survival disparity between Hispanic and non-Hispanic white women.

    PubMed

    Boone, S D; Baumgartner, K B; Joste, N E; Pinkston, C M; Yang, D; Baumgartner, R N

    2014-03-01

    Some studies suggest that Hispanic women are more likely to have ER- and triple-negative (ER-/PR-/HER2-) tumors and subsequently poorer prognosis than non-Hispanic white (NHW) women. In addition, only a handful of studies have examined period-specific effects of tumor phenotype and ethnicity on breast cancer survival, leaving the time-varying effects of hormonal status and ethnicity on breast cancer survival poorly defined. This study describes short and long-term breast cancer survival by ethnicity at 0-5 years and 5+ years post-diagnosis using data from the New Mexico Health, Eating, Activity, and Lifestyle cohort of Hispanic and NHW women ages 29-88 years newly diagnosed with stages I-IIIA breast cancer. The survival rate for Hispanics at 0-5 years was 82.2 % versus 94.3 % for NHW. Hispanics were more likely to have larger tumors, more advanced stage, and ER- phenotypes compared to NHW women. There was a significantly higher risk of breast cancer mortality in Hispanics over 5 years of follow-up compared to NHW (HR = 2.78, 95 % CI 1.39-5.56), adjusting for age, tumor phenotype, stage, and tumor size. This ethnic difference in survival, however, was attenuated and no longer statistically significant when additional adjustment was made for education, although a >1.5-fold increase in mortality was observed. In contrast, there was no difference between ethnic groups for survival after 5 years (HR = 1.08, 95 % CI 0.36-3.24). Our results indicate that the difference in survival between Hispanic and NHW women with breast cancer occurs in the first few years following diagnosis and is jointly associated with tumor phenotype and socio-demographic factors related to education.

  9. Soyfood intake and breast cancer survival: a followup of the Shanghai Breast Cancer Study.

    PubMed

    Boyapati, Sonia M; Shu, Xiao-ou; Ruan, Zhi Xian; Dai, Qi; Cai, Qiuyin; Gao, Yu-tang; Zheng, Wei

    2005-07-01

    Soy and its constituents have been shown in many in vivo and in vitro studies and in some epidemiological studies to have anti-cancer effects. Some soy constituents, however, also stimulate cell proliferation, which has raised concerns in promoting soy intake among breast cancer survivors. To investigate whether soy intake may be associated with breast cancer survival, we evaluated data from a cohort of 1459 breast cancer patients who participated in the Shanghai Breast Cancer Study between 1996 and 1998. Usual soy food intake was assessed using a validated food frequency questionnaire at baseline. The median follow-up time for this cohort of women was 5.2 years. We found that soy intake prior to cancer diagnosis was unrelated to disease-free breast cancer survival (adjusted hazard ratio [HR]=0.99, 95% confidence interval [CI], 0.73-1.33 for the highest tertile compared to the lowest tertile). The association between soy protein intake and breast cancer survival did not differ according to ER/PR status, tumor stage, age at diagnosis, body mass index (BMI), waist to hip ratio (WHR), or menopausal status. Additionally, the soy-survival association did not appear to vary according to XbaI or PvuII polymorphisms in ER-alpha, or C(14206)T, G(25652)A, or A(50766)G polymorphisms in ER-beta. These data suggest that soyfoods do not have an adverse effect on breast cancer survival.

  10. Survival status and predictors of mortality among severely acute malnourished children <5 years of age admitted to stabilization centers in Gedeo Zone: a retrospective cohort study

    PubMed Central

    Girum, Tadele; Kote, Mesfin; Tariku, Befikadu; Bekele, Henok

    2017-01-01

    Despite the existence of standard protocol, many stabilization centers (SCs) continue to experience high mortality of children receiving treatment for severe acute malnutrition. Assessing treatment outcomes and identifying predictors may help to overcome this problem. Therefore, a 30-month retrospective cohort study was conducted among 545 randomly selected medical records of children <5 years of age admitted to SCs in Gedeo Zone. Data was entered by Epi Info version 7 and analyzed by STATA version 11. Cox proportional hazards model was built by forward stepwise procedure and compared by the likelihood ratio test and Harrell’s concordance, and fitness was checked by Cox–Snell residual plot. During follow-up, 51 (9.3%) children had died, and 414 (76%) and 26 (4.8%) children had recovered and defaulted (missed follow-up for 2 consecutive days), respectively. The survival rates at the end of the first, second and third weeks were 95.3%, 90% and 85%, respectively, and the overall mean survival time was 79.6 days. Age <24 months (adjusted hazard ratio [AHR] =2.841, 95% confidence interval [CI] =1.101–7.329), altered pulse rate (AHR =3.926, 95% CI =1.579–9.763), altered temperature (AHR =7.173, 95% CI =3.05–16.867), shock (AHR =3.805, 95% CI =1.829–7.919), anemia (AHR =2.618, 95% CI =1.148–5.97), nasogastric tube feeding (AHR =3.181, 95% CI =1.18–8.575), hypoglycemia (AHR =2.74, 95% CI =1.279–5.87) and treatment at hospital stabilization center (AHR =4.772, 95% CI =1.638–13.9) were independent predictors of mortality. The treatment outcomes and incidence of death were in the acceptable ranges of national and international standards. Intervention to further reduce deaths has to focus on young children with comorbidities and altered general conditions. PMID:28176953

  11. Survival among women with triple receptor-negative breast cancer and brain metastases

    PubMed Central

    Dawood, S.; Broglio, K.; Esteva, F. J.; Yang, W.; Kau, S.-W.; Islam, R.; Albarracin, C.; Yu, T. K.; Green, M.; Hortobagyi, G. N.; Gonzalez-Angulo, A. M.

    2009-01-01

    Background: The purpose of this study was to determine the incidence of and survival following brain metastases among women with triple receptor-negative breast cancer. Patients and methods: In all, 679 patients with nonmetastatic triple receptor-negative breast cancer diagnosed from 1980 to 2006 were identified. Cumulative incidence of brain metastases was computed. Cox proportional hazards models were fitted to explore factors that predict for development of brain metastases. Survival was computed using the Kaplan–Meier product limit method. Results: Median follow-up was 26.9 months. In all, 42 (6.2%) patients developed brain metastases with a cumulative incidence at 2 and 5 years of 5.6% [95% confidence interval (CI) 3.8% to 7.9%] and 9.6% (95% CI 6.8% to 13%), respectively. A total of 24 (3.5%) patients developed brain metastases as the first site of recurrence with cumulative incidence at 2 and 5 years of 2.0% (95% CI 2.6% to 6.0%) and 4.9% (95% CI 3.2% to 7.0%), respectively. In the multivariable model, no specific factor was observed to be significantly associated with time to brain metastases. Median survival for all patients who developed brain metastases and those who developed brain metastases as the first site of recurrence was 2.9 months (95% CI 2.0–7.6 months) and 5.8 months (95% CI 1.7–11.0 months), respectively. Conclusion: In this single-institutional study, patients with nonmetastatic triple receptor-negative breast tumors have a high early incidence of brain metastases associated with poor survival and maybe an ideal cohort to target brain metastases preventive strategies. PMID:19150943

  12. Time trends in breast cancer survival: experience in a single centre, 1975-89.

    PubMed Central

    Bradburn, M. J.; Altman, D. G.; Smith, P.; Fentiman, I. S.; Rubens, R. D.

    1998-01-01

    The aim of this retrospective cohort study was to investigate whether survival of patients with breast cancer has changed over the period 1975-89. A total of 2604 women diagnosed as having invasive breast cancer at a clinical oncology unit in London were followed up for between 5 and 20 years. Patients were divided into four groups according to menstrual status (pre or post) and the staging of cancer (operable or inoperable). For each group, survival from diagnosis was compared between three consecutive 5-year cohorts, both with and without adjustments made for relevant prognostic factors. No temporal patterns were found in patients with inoperable cancer, in whom the survival rate was consistently low. Of women with operable cancers, differences were seen only among post-menopausal women, for whom the best survival patterns were seen in patients diagnosed between 1985-89. This is probably due to tamoxifen being commonly prescribed as adjuvant treatment for this cohort of patients. We cannot explain an apparently worse survival in the group of patients presenting in the early 1980s compared with that observed in the late 1970s. PMID:9667672

  13. Genetic variation in SIPA1 in relation to breast cancer risk and survival after breast cancer diagnosis.

    PubMed

    Gaudet, Mia M; Hunter, Kent; Pharoah, Paul; Dunning, Alison M; Driver, Kristy; Lissowska, Jolanta; Sherman, Mark; Peplonska, Beata; Brinton, Louise A; Chanock, Stephen; Garcia-Closas, Montserrat

    2009-04-01

    Genetic variation in SIPA1, signal-induced proliferation-associated gene 1, has been proposed to be associated with aggressive breast tumor characteristics related to metastasis and worse prognosis in humans and rodents. To test this hypothesis, we genotyped 3 single nucleotide polymorphisms (SNP) located at -3092 (AT, rs3741378), and exon 14 + 14 (C>T, rs746429), and examined them in relation to breast cancer risk and overall survival, stratified by tumor characteristics in 2 independent case-control studies conducted in Poland (1,995 cases, 2,296 controls) and in Britain (2,142 cases, 2,257 controls). Vital status (n = 396 deaths) was available for 911 Polish and 1,919 British breast cancer cases with an average follow-up time of 5.5 years. Overall, we found no significant associations between genetic variants of SIPA1 SNPs and breast cancer risk (per allele odds ratios, 95% confidence intervals (CI): rs931127-0.99, 0.93-1.06; rs3741378-1.03, 0.94-1.13; and, rs74642-0.98, 0.92-1.04). In both studies, SIPA1 polymorphisms were not related to overall mortality (per allele hazard ratios, 95% CI: 1.02, 0.88-1.17; 0.90, 0.72-1.11; 1.04, 0.90-1.21, respectively). Our results do not support a relationship between SIPA1 polymorphisms and breast cancer risk or subsequent survival.

  14. Clinical Predictors of Long-term Survival in HER2-positive Metastatic Breast Cancer

    PubMed Central

    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

    2016-01-01

    Purpose 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. Methods 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. Results 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. Conclusions 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 associated with molecular determinants of prolonged survival with may provide insights for individualizing treatment selection. PMID:26875184

  15. Microchimerism and survival after breast and colon cancer diagnosis.

    PubMed

    Kamper-Jørgensen, Mads

    2012-01-01

    Recently, we reported microchimerism to be oppositely associated with maternal breast and colon cancer. In women with a blood test positive for male microchimerism the risk of breast cancer development was reduced to one third, whereas the risk of colon cancer was elevated 4-fold. In this article addendum, I report the survival of cases in the original study after being diagnosed with cancer. Despite small numbers, the analysis suggests that microchimerism may be positively associated with survival after breast and maybe colon cancer diagnosis. Despite the findings on colon cancer in our original report, I speculate whether microchimerism could have a general beneficial role in cancer, which in some sites may not be evident because an allogeneic maternal immune reaction hastens cancer development.

  16. 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

  17. Oral contraceptives and survival in breast cancer patients aged 20 to 54 years.

    PubMed

    Trivers, Katrina F; Gammon, Marilie D; Abrahamson, Page E; Lund, Mary Jo; Flagg, Elaine W; Moorman, Patricia G; Kaufman, Jay S; Cai, Jianwen; Porter, Peggy L; Brinton, Louise A; Eley, J William; Coates, Ralph J

    2007-09-01

    Recent oral contraceptive (OC) use is associated with modestly higher breast cancer incidence among younger women, but its impact on survival is unclear. This study examined the relationship between OC use before breast cancer diagnosis and survival. A population-based sample of 1,264 women aged 20 to 54 years with a first primary invasive breast cancer during 1990 to 1992 were followed up for 8 to 10 years. OC and covariate data were obtained by interviews conducted shortly after diagnosis and from medial records. All-cause mortality was ascertained through the National Death Index (n = 292 deaths). Age- and income-adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated by Cox regression methods. All-cause mortality was not associated with ever use of OCs or duration of use. Compared with nonusers, mortality estimates were elevated among women who were using OCs at diagnosis or stopped use in the previous year (HR, 1.57; 95% CI, 0.95-2.61). The HR for use of high-dose estrogen pills within 5 years before diagnosis was double that of nonusers (HR, 2.39; 95% CI, 1.29-4.41) or, if the most recent pill included the progestin levonorgestrel, compared with nonusers (HR, 2.01; 95% CI, 1.03-3.91). Because subgroup estimates were based on small numbers of OC users, these results should be cautiously interpreted. Overall, most aspects of OC use did not seem to influence survival, although there is limited evidence that OC use just before diagnosis, particularly use of some pill types, may negatively impact survival in breast cancer patients aged 20 to 54 years.

  18. Polyphosphate Affects on Breast Cancer Cell Survival

    DTIC Science & Technology

    2007-04-01

    vortexing), heating , and pellet resuspensions. Figure 12 depicts the steps of the procedure. E . coli cultures were pelleted in a 1.5-mL tube and...biosynthetic enzyme, polyphosphate kinase (PPK) has been purified from Escherichia coli ( E . coli ) (Akiyama et al., 1992), as have an exopolyphosphatase (PPX...respond to and survive environmental challenges, such as nutrient deprivation, heat shock , phosphate deficiency, oxidative stress, and osmotic

  19. 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

  20. [Postoperative adjuvant chemotherapy using NCS (neocarzinostatin) and 5-FU in the treatment of gastric cancer. First report--A comparison with the 5-year survival rate of patients undergoing combined therapy with MMC and 5-FU].

    PubMed

    Yokomori, T; Taniguchi, T; Iesato, H; Sakata, Y; Watanabe, T; Kawabe, K

    1987-11-01

    As a postoperative adjuvant chemotherapy for gastric cancer, we have administered a combination of NCS (Neocarzinostatin) and 5-FU (NF treatment method) and in this paper we have compiled the results obtained in patients who were treated for 5 years in an attempt to compare the 5-year survival rate with that of patients administered a combination of MMC and 5-FU (MF treatment group) and a control group administered no anticancer agents. As the selection of either NF or MF treatment was conducted on an annual basis, this study can be considered an historical controlled study. The results obtained are summarized as follows. On comparing the survival rate of the NF treatment group and the control group, the 5-year survival rate for all patients who underwent curative resection and all patients with histological stage III cancers and the curative resection PS (+) group, as well as the survival period of the non-resected patients, showed a statistically significant difference, indicating that the survival rate was higher in the NF group. On comparing the NF group and the MF group, although no statistically significant difference was observed between then based on a stratified analysis of all resected cases, histological stage differences and n.ps factors, etc., certain values tended to indicate a higher survival rate for the NF group. Moreover, the survival rate of the non-resected patients was more favorable in the NF group. These results confirm that NCS is useful for the treatment of stomach cancer and compares favorably with MMC. The appearance of side-effects was significantly lower in the NF group in comparison with the MF group and the number of patients who had to discontinue therapy was extremely low.

  1. Hormone receptor status and survival of medullary breast cancer patients

    PubMed Central

    Aksoy, Asude; Odabas, Hatice; Kaya, Serap; Bozkurt, Oktay; Degirmenci, Mustafa; Topcu, Turkan O.; Aytekin, Aydın; Arpaci, Erkan; Avci, Nilufer; Pilanci, Kezban N.; Cinkir, Havva Y.; Bozkaya, Yakup; Cirak, Yalcin; Gumus, Mahmut

    2017-01-01

    Objectives: To analyze the relationship between clinical features, hormonal receptor status, and survival in patients who were diagnosed with medullary breast cancer (MBC). Methods: Demographic characteristics, histopathological features, and survival statuses of 201 patients diagnosed with MBC between 1995 and 2015 were retrospectively recorded. Survival analyses were conducted with uni- and multivariate cox regression analysis. Results: Median follow-up time was 54 (4-272) months. Median patient age at the time of diagnosis was 47 years old (26-90). Of the patients, 91.5% were triple negative. Five-year recurrence free survival time (RFS) rate was 87.4% and overalll survival (OS) rate 95.7%. For RFS, progesterone receptor (PR) negativity, atypical histopathological evaluation, absence of lymphovascular invasion, smaller tumor, lower nodal involvement were found to be favourable prognostic factors by univariate analysis (p<0.05). The PR negativity and smaller tumor were found to be favourable factors by univariate analysis (p<0.05). However, none of these factors were determined as significant independent prognostic factors for OS (p>0.05). Conclusion: Turkish MBC patients exhibited good prognosis, which was comparable with survival outcomes achieved in the literature. The PR negativity was related to a better RFS and OS rates. PMID:28133688

  2. Junctional epidermolysis bullosa incidence and survival: 5-year experience of the Dystrophic Epidermolysis Bullosa Research Association of America (DebRA) nurse educator, 2007 to 2011.

    PubMed

    Kelly-Mancuso, Geraldine; Kopelan, Brett; Azizkhan, Richard G; Lucky, Anne W

    2014-01-01

    Junctional epidermolysis bullosa (JEB) is a particularly devastating type of epidermolysis bullosa, especially in the newborn period. Data about the number of new cases of JEB in the United States were collected from the records of the Dystrophic Epidermolysis Bullosa Research Association of America (DebRA) nurse educator. Seventy-one children with JEB were reported to have been born in the 5 years between 2007 and 2011, reflecting an incidence of at least 3.59 per million per year, significantly higher than previously estimated (2.04 per million). There was a high prevalence of morbidity and infant mortality of at least 73%, as 52 of the 71 cases proved fatal by June 2012. These data emphasize the need for future research to develop treatment and ultimately a cure for this disorder.

  3. Prolonged Survival (>48 months) in a Squamous Cell Carcinoma of the Cervix After Late Skin Metastasis (>5 year) to Incision Site: A Case Report.

    PubMed

    Ozmen, Batuhan; Sükür, Yavuz Emre; Atabekoğlu, Cem; Güngör, Mete

    2009-01-01

    Metastasis to the incision site of squamous cervical cancer (SCC) is an extremely rare entity which is strictly related with extremely poor prognosis. The vast majority of the reported cases died in a year due to distant recurrences, whereby skin metastases were predominantly observed close to the primary tumor site. A SCC with skin metastasis which was diagnosed 5 years after the radical surgery and postoperative radiotherapy which involved the midline incision site was reported. Large surgical excision of the metastasis with remaining surgical free margins (>2 cm) and combined chemo-radiotherapy with single agent (cisplatinum) was performed. The patient did not show any recurrences for 4 years follow-up. Apparently, palliative combined chemo-radiotherapy along with large excision seems favorable for controlling symptoms and progression of skin metastasis of squamous cervical cancer.

  4. Inferential statistics from Black Hispanic breast cancer survival data.

    PubMed

    Khan, Hafiz M R; Saxena, Anshul; Ross, Elizabeth; Ramamoorthy, Venkataraghavan; Sheehan, Diana

    2014-01-01

    In this paper we test the statistical probability models for breast cancer survival data for race and ethnicity. Data was collected from breast cancer patients diagnosed in United States during the years 1973-2009. We selected a stratified random sample of Black Hispanic female patients from the Surveillance Epidemiology and End Results (SEER) database to derive the statistical probability models. We used three common model building criteria which include Akaike Information Criteria (AIC), Bayesian Information Criteria (BIC), and Deviance Information Criteria (DIC) to measure the goodness of fit tests and it was found that Black Hispanic female patients survival data better fit the exponentiated exponential probability model. A novel Bayesian method was used to derive the posterior density function for the model parameters as well as to derive the predictive inference for future response. We specifically focused on Black Hispanic race. Markov Chain Monte Carlo (MCMC) method was used for obtaining the summary results of posterior parameters. Additionally, we reported predictive intervals for future survival times. These findings would be of great significance in treatment planning and healthcare resource allocation.

  5. Do Breast Cancer Risk Factors Affect the Survival of Breast Cancer Patients in Southern Sri Lanka?

    PubMed

    Peiris, H H; Mudduwa, L K B; Thalagala, N I; Jayatilaka, K A P W

    2017-01-01

    Background: Breast cancer continues to be a major cause of morbidity among women in Sri Lanka. Possible effects of etiological risk factors on breast cancer specific survival (BCSS) of the disease is not clear.This study was designed to explore the impact of breast cancer risk factors on the BCSS of patients in Southern Sri Lanka. Method: This retro-prospective study included all breast cancer patients who had sought immunohistochemistry services at our unit from May 2006 to December 2012. A pre-tested, interviewer-administered questionnaire was used to gather information on risk factors. BCSS was estimated using the Kaplan-Meier model. Univariate Cox-regression analysis was performed with 95% confidence intervals using the SPSS statistical package. Results: A total of 944 breast cancer patients were included. Five year BCSS was 78.8%. There was a statistically significant difference between the patients who had a family history of breast cancer and no family history of any cancer in terms of the presence/absence of lymph node metastasis (p=0.011) and pathological stage (p=0.042). The majority of the premenopausal patients had associated DCIS (p<0.001) and large tumours (p=0.015) with positive lymph nodes (p=0.016). There was no statistically significant association between hormone receptor subtypes and hormone related risk factors. Univariate analysis revealed that breast cancer risk factors had no significant effect on the BCSS. Conclusion: Even though family history of breast cancer and premenopausal status are associated with poor prognostic features, they, in line with the other breast cancer risk factors, appear to have no significant effect on the BCSS of patients in Southern Sri Lanka.

  6. Worse survival in breast cancer among women with recent childbirth: results from a Swedish population-based register study.

    PubMed

    Bladström, Anna; Anderson, Harald; Olsson, Håkan

    2003-10-01

    This study was designed to investigate how time since childbirth affects breast cancer survival using unselected population-based data linking data from the Swedish Cancer Registry, fertility register, and population census registers. A total of 14,693 parous women < or =45 years of age with breast cancer were identified. Information on deaths was collected, and 5- and 10-year survival rates were calculated according to time since most recent childbirth. Mortality during the first 10 years of follow-up was further investigated in a Cox analysis, with adjustments for age at diagnosis, time period during which the diagnosis was made, number of children, and age at the time of the first child's birth. Women with diagnosis during pregnancy had a 5-year survival rate of 52.1% (95% CI, 41.2%-61.9%) and a 10-year survival rate of 43.9% (95% CI, 33.1%-54.2%), compared with survival rates of 80.0% (95% CI, 79.6%-81.4%) and 68.6% (95% CI, 67.5%-69.7%), respectively, in women diagnosed >10 years since childbirth. In the multivariate model, we found that time since childbirth was associated with inferior survival rates in cases of diagnosis <8 years after childbirth, in which the lowest survival rates were seen in women with diagnosis during pregnancy in the first 5 years of follow-up (adjusted relative risk compared with women with >10 years since last childbirth, 2.6; 95% CI, 1.8-3.4). The adjusted hazard ratios could be described by a decreasing function of a logarithmic transformation of years since childbirth. We found that the time of follow-up was of importance, in that women with a recent pregnancy had particularly lower survival rates during the first 5 years after diagnosis. The mechanisms behind the poor survival in breast cancer for women with recent childbirth are not known, but we suggest that one explanation might be a lower proportion of hormone receptor-positive tumors.

  7. Trends in net survival from breast cancer in six European Latin countries: results from the SUDCAN population-based study.

    PubMed

    Crocetti, Emanuele; Roche, Laurent; Buzzoni, Carlotta; di Costanzo, Francesco; Molinié, Florence; Caldarella, Adele

    2017-01-01

    Survival from breast cancer (BC) is influenced by the timeliness of diagnosis and appropriateness of treatment, and may constitute a measure of the global effectiveness of a healthcare system. As the healthcare systems of several European Latin countries have some similarities, the search for differences in cancer survival may provide interesting information on the efficacy of these systems. The SUDCAN study is a collaboration between the Group for Epidemiology and Cancer Registration in Latin language countries (GRELL) and EUROCARE. BC data from six countries (Belgium, France, Italy, Portugal, Spain, and Switzerland) were extracted from the EUROCARE-5 database. First, we focus on 1- and 5-year age-standardized net survival (NS) from BC by country over the 2000-2004 period. Then, trends in NS over the 1989-2004 period and changes in the pattern of cancer excess mortality rate (EMR) up to 5 years after diagnosis were examined using a multivariate EMR model. There were little differences in age-standardized NS from BC. Over the 2000-2004 period, the 5-year survival ranged between 82 (Spain, Belgium, and Portugal) and 86% (France). There was an increase in age-standardized survival between 1989 and 2004 at 1 year as well as at 5 years. This increase was observed at all ages and in all countries. There was a decrease in the cancer EMR both immediately after diagnosis and by the second and third year of follow-up. There were only minor differences in survival from BC between European Latin countries. The general improvement in NS is presumably because of advances in early cancer diagnosis and improvements in treatment.

  8. 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

  9. 5-Year Budget Forecasting.

    ERIC Educational Resources Information Center

    Conyers, John G.; Lingel, George; Piekarski, Robert

    2000-01-01

    Financial planning is the key to providing a high-quality instructional plan. A 5-year financial plan is typically updated by looking at district financial history, future instructional plans, staffing requirements, and revenue projections. Planning assumptions must be clearly understood by the financial team and the community. (MLH)

  10. Breast Cancer Survival among African-Americans Living in the Midwest: Disparities and Recommendations to Decrease Mortality.

    PubMed

    Hill, Jackie; Watanabe-Galloway, Shinobu; Shostrom, Valerie; Nsiah-Kumi, Phyllis

    2015-07-01

    Socioeconomic status is highly correlated with breast cancer risk and outcomes. Omaha, Nebraska has the third highest African-American poverty rate of the 100 largest U.S. metropolitan areas. Access to healthcare is a major issue in this community. This study analyzed the state cancer registry data to establish a baseline for breast cancer survivorship among African-American women in Nebraska. Specifically, the study examined the 5-year survivorship difference between African-American women and White women and the factors associated with poor survival. It was found that the 5-year survival rate for African-American women was 43% compared to 75% for White women and that this disparity persisted after taking into consideration the staging differences. The multivariable analysis results indicated that in addition to being African-American, increasing age, late-stage diagnosis, and lower socioeconomic status were factors independently associated with reduced survival in this sample. Because of the younger age at diagnosis among African-American women, we recommend that health promotion and educational programs be directed toward younger women. A significantly larger proportion of African-Americans being diagnosed at a late stage also underscores the importance of education of women of all ages. Future research should examine quality and timing of treatment as well as comorbidity issues affecting African-American women.

  11. 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

  12. 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

  13. Developmental milestones record - 5 years

    MedlinePlus

    ... Childhood growth milestones - 5 years; Growth milestones for children - 5 years; Well child - 5 years ... skill milestones for a typical 5-year-old child include: Gains about 4 to 5 pounds (1. ...

  14. Soy Food Intake, Tamoxifen Use, Estrogen Receptor Polymorphism, and Breast Cancer Survival

    DTIC Science & Technology

    2005-07-01

    Results from the soy food intake and breast cancer survival manuscript indicate that there is no association between soy protein intake and breast cancer...tertile). The association between soy protein intake and breast cancer survival did not differ according to ER/PR status, tumor stage, age at diagnosis...reported a decrease. standard protocol. Soy protein content of each food item was estimated Patients were followed up through January 2003 with based on the

  15. Landmark risk prediction of residual life for breast cancer survival.

    PubMed

    Parast, Layla; Cai, Tianxi

    2013-09-10

    The importance of developing personalized risk prediction estimates has become increasingly evident in recent years. In general, patient populations may be heterogenous and represent a mixture of different unknown subtypes of disease. When the source of this heterogeneity and resulting subtypes of disease are unknown, accurate prediction of survival may be difficult. However, in certain disease settings, the onset time of an observable short-term event may be highly associated with these unknown subtypes of disease and thus may be useful in predicting long-term survival. One approach to incorporate short-term event information along with baseline markers for the prediction of long-term survival is through a landmark Cox model, which assumes a proportional hazards model for the residual life at a given landmark point. In this paper, we use this modeling framework to develop procedures to assess how a patient's long-term survival trajectory may change over time given good short-term outcome indications along with prognosis on the basis of baseline markers. We first propose time-varying accuracy measures to quantify the predictive performance of landmark prediction rules for residual life and provide resampling-based procedures to make inference about such accuracy measures. Simulation studies show that the proposed procedures perform well in finite samples. Throughout, we illustrate our proposed procedures by using a breast cancer dataset with information on time to metastasis and time to death. In addition to baseline clinical markers available for each patient, a chromosome instability genetic score, denoted by CIN25, is also available for each patient and has been shown to be predictive of survival for various types of cancer. We provide procedures to evaluate the incremental value of CIN25 for the prediction of residual life and examine how the residual life profile changes over time. This allows us to identify an informative landmark point, t(0) , such that

  16. 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

  17. Tumor RNA disruption predicts survival benefit from breast cancer chemotherapy.

    PubMed

    Parissenti, Amadeo M; Guo, Baoqing; Pritzker, Laura B; Pritzker, Kenneth P H; Wang, Xiaohui; Zhu, Mu; Shepherd, Lois E; Trudeau, Maureen E

    2015-08-01

    In a prior substudy of the CAN-NCIC-MA.22 clinical trial (ClinicalTrials.gov identifier NCT00066443), we observed that neoadjuvant chemotherapy reduced tumor RNA integrity in breast cancer patients, a phenomenon we term "RNA disruption." The purpose of the current study was to assess in the full patient cohort the relationship between mid-treatment tumor RNA disruption and both pCR post-treatment and, subsequently, disease-free survival (DFS) up to 108 months post-treatment. To meet these objectives, we developed the RNA disruption assay (RDA) to quantify RNA disruption and stratify it into 3 response zones of clinical importance. Zone 1 is a level of RNA disruption inadequate for pathologic complete response (pCR); Zone 2 is an intermediate level, while Zone 3 has high RNA disruption. The same RNA disruption cut points developed for pCR response were then utilized for DFS. Tumor RDA identified >fourfold more chemotherapy non-responders than did clinical response by calipers. pCR responders were clustered in RDA Zone 3, irrespective of tumor subtype. DFS was about 2-fold greater for patients with tumors in Zone 3 compared to Zone 1 patients. Kaplan-Meier survival curves corroborated these findings that high tumor RNA disruption was associated with increased DFS. DFS values for patients in zone 3 that did not achieve a pCR were similar to that of pCR recipients across tumor subtypes, including patients with hormone receptor positive tumors that seldom achieve a pCR. RDA appears superior to pCR as a chemotherapy response biomarker, supporting the prospect of its use in response-guided chemotherapy.

  18. Clinical outcomes and prognostic factors in patients with breast diffuse large B cell lymphoma; Consortium for Improving Survival of Lymphoma (CISL) study

    PubMed Central

    2010-01-01

    Background The breast is a rare extranodal site of non-Hodgkin lymphoma, and primary breast lymphoma (PBL) has been arbitrarily defined as disease localized to one or both breasts with or without regional lymph nodes involvement. The aim of this study was to evaluate the clinical outcomes in patients with diffuse large B cell lymphoma (DLBCL) and breast involvement, and to find the criteria of PBL reflecting the outcome and prognosis. Methods We retrospectively analyzed data from 68 patients, newly diagnosed with DLBCL and breast involvement at 16 Korean institutions between January 1994 and June 2009. Results Median age at diagnosis was 48 years (range, 20-83 years). Forty-three (63.2%) patients were PBL according to previous arbitrary criteria, sixteen (23.5%) patients were high-intermediate to high risk of international prognostic index. The patients with one extranodal disease in the breast (OED) with or without nodal disease were 49 (72.1%), and those with multiple extranodal disease (MED) were 19 (27.9%). During median follow-up of 41.5 months (range, 2.4-186.0 months), estimated 5-year progression-free survival (PFS) was 53.7 ± 7.6%, and overall survival (OS) was 60.3 ± 7.2%. The 5-year PFS and OS was significantly higher for patients with the OED group than those with the MED group (5-year PFS, 64.9 ± 8.9% vs. 27.5 ± 11.4%, p = 0.001; 5-year OS, 74.3 ± 7.6% vs. 24.5 ± 13.0%, p < 0.001). In multivariate analysis, MED (hazard ratio [HR], 3.61; 95% confidence interval [CI], 1.07-12.2) and fewer than four cycles of systemic chemotherapy with or without local treatments (HR, 4.47; 95% CI, 1.54-12.96) were independent prognostic factors for worse OS. Twenty-five (36.8%) patients experienced progression, and the cumulative incidence of progression in multiple extranodal sites or other than breasts and central nervous system was significantly different between the OED group and the MED group (5-year cumulative incidence, 9.7 ± 5.4% vs. 49.0 ± 15.1%, p = 0

  19. 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

  20. Induction Chemotherapy Improved Long-term Outcomes of Patients with Locoregionally Advanced Nasopharyngeal Carcinoma: A Propensity Matched Analysis of 5-year Survival Outcomes in the Era of Intensity-modulated Radiotherapy

    PubMed Central

    Peng, Hao; Chen, Lei; Zhang, Jian; Li, Wen-Fei; Mao, Yan-Ping; Zhang, Yuan; Liu, Li-Zhi; Tian, Li; Lin, Ai-Hua; Sun, Ying; Ma, Jun

    2017-01-01

    Background: The aim of this study is to evaluate the long-term therapeutic gain of induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (NPC) in the era of intensity-modulated radiotherapy (IMRT). Methods: Data on 957 patients with stage T1-2N2-3 or T3-4N1-3 NPC treated with IMRT were retrospectively reviewed. Propensity score matching (PSM) method was adopted to balance influence of various covariates. Patient survival between IC and non-IC groups were compared. Results: For the 318 pairs selected from the original 957 patients by PSM, the median follow-up duration was 57.13 months (range, 1.27-78.1 months). The 5-year overall survival (OS), distant metastasis-free survival (DMFS), disease-free survival (DFS) and locoregional relapse-free survival (LRRFS) rates for IC group vs. non-IC group were 87.2% vs. 80.8% (P = 0.023), 88.1% vs. 83.2% (P = 0.071), 80.7% vs. 71.4% (P = 0.011) and 92.1% vs. 86.7% (P = 0.081), respectively. Multivariate analysis identify IC as an independent prognostic factor for OS (HR, 0.595; 95% CI, 0.397-0.891; P = 0.012) and DFS (HR, 0.627; 95% CI, 0.451-0.872; P = 0.006). After excluding the patients not receiving concurrent chemotherapy, IC was found to be an independent prognostic factor for OS (HR, 0.566; 95% CI, 0.368-0.872; P = 0.01), DMFS (HR, 0.580; 95% CI, 0.367-0.916; P = 0.02) and DFS (HR, 0.633; 95% CI, 0.444-0.903; P = 0.012). Conclusions: IC is an effective treatment modality for patients with stage T1-2N2-3 and T3-4N1-3 NPC, and the incorporation of IC with standard CCRT could achieve the best therapeutic gain. PMID:28261337

  1. Prediagnostic serum inflammatory markers in relation to breast cancer risk, severity at diagnosis and survival in breast cancer patients.

    PubMed

    Wulaningsih, Wahyu; Holmberg, Lars; Garmo, Hans; Malmstrom, Håkan; Lambe, Mats; Hammar, Niklas; Walldius, Göran; Jungner, Ingmar; Van Hemelrijck, Mieke

    2015-10-01

    Inflammation has been linked to cancer but its role in breast cancer is unclear. We investigated common serum markers of inflammation: C-reactive protein (CRP), albumin, haptoglobin and white blood cells (WBC) in relation to breast cancer incidence, severity and survival. A total of 155179 women aged 20 and older without any history of cancer were selected from a large Swedish cohort. Hazard ratios (HRs) for breast cancer were estimated with Cox regression, adjusting for potential confounders. Ordered and binomial logistic regression models were used to assess the associations of serum inflammatory markers with breast cancer severity and oestrogen receptor (ER) positivity at diagnosis, on the other. Cumulative incidence functions by levels of inflammatory markers were assessed for early death from breast cancer and all causes. During a mean follow-up of 18.3 years, 6606 women were diagnosed with breast cancer, of whom 1474 died. A positive association with incident breast cancer was seen for haptoglobin ≥ 1.4g/l [HR 1.09; 95% confidence interval (CI): 1.00-1.18] compared to lower levels. No association was observed between inflammatory markers and breast cancer severity or ER positivity. Higher haptoglobin was linked to risk of early death from breast cancer (HR: 1.27, 95% CI: 1.02-1.59), whereas higher risk of early death from all causes was additionally found with CRP ≥ 10mg/l (HR: 1.19, 95% CI: 1.04-1.36) and WBC ≥ 10×10(9)/l (HR: 1.57, 1.14-2.16). Our findings indicate that prediagnostic serum inflammatory markers were weakly linked to incident breast cancer but corresponded to worse survival after diagnosis.

  2. Can lifestyle modification increase survival in women diagnosed with breast cancer?

    PubMed

    Rock, Cheryl L; Demark-Wahnefried, Wendy

    2002-11-01

    Epidemiologic studies have linked diets high in vegetables and fruit with an increased likelihood of survival after the diagnosis of breast cancer, and clinical and epidemiologic studies have identified obesity as an important negative prognostic factor. Of the 26 studies published since 1990 that examined the relationship with obesity and survival, 17 reported a significant inverse relationship. Five of the eight cohort studies of breast cancer survivors that examined intakes of vegetables, fruit and related micronutrients published since 1985 reported a positive relationship between these factors and survival. The hypothesis that lifestyle factors such as diet and physical activity may improve the prognosis in women who have been diagnosed with breast cancer is currently under study. The Women's Healthy Eating and Living Study is a randomized controlled study that tests the effects of a diet high in vegetables, fruit and fiber and low in fat on disease-free survival after treatment for early stage breast cancer (n = 3109). In the Healthy Weight Management for Breast Cancer Survivors Study, a multifaceted approach to promoting weight loss and long-term weight maintenance is being tested in 85 women at risk for breast cancer recurrence. The intervention emphasizes increased physical activity, strategies to improve body image and self-acceptance, and cognitive-behavioral therapy to promote healthy eating attitudes and behaviors. The results of these studies will contribute to understanding the roles of diet and physical activity in the progression of breast cancer.

  3. 5-year Follow-up of a Randomized Controlled Trial of Immediate versus Delayed Zoledronic Acid for Prevention of Bone Loss in Postmenopausal Women with Breast Cancer Starting Letrozole after Tamoxifen: N03CC (Alliance)

    PubMed Central

    Wagner-Johnston, Nina D.; Sloan, Jeff A.; Liu, Heshan; Kearns, Ann E.; Hines, Stephanie L.; Puttabasavaiah, Suneetha; Dakhil, Shaker R.; Lafky, Jacqueline M.; Perez, Edith A.; Loprinzi, Charles L.

    2015-01-01

    Background Postmenopausal women with breast cancer (BC) receiving aromatase inhibitors are at increased risk for bone loss. The current study was undertaken to determine whether upfront versus delayed treatment with zoledronic acid (ZA) impacted bone loss. This report describes the 5-year follow-up results. Methods 551 postmenopausal women with BC completing tamoxifen and undergoing daily letrozole treatment were randomized to upfront (274) or delayed (277) ZA 4 mg IV every 6 months. In the delayed arm, ZA was initiated for post-baseline bone mineral density (BMD) T-score < -2.0 or fracture. Results The incidence of a 5% decrease in total lumbar spine BMD at 5 years was 10.2% in the upfront arm versus 41.2% in the delayed arm, p < 0.0001. 41 patients in the delayed arm were eventually started on ZA. With the exception of increased grade 1/2 elevated creatinine and fever in the upfront arm and cerebrovascular ischemia in the delayed arm, there were no significant differences between arms with respect to the most common adverse events of arthralgia and back pain. Osteoporosis occurred less frequently in the upfront arm (2 versus 8 cumulative cases) though this difference was not statistically significant. Bone fractures occurred in 24 patients in the upfront arm versus 25 patients in the delayed arm. Conclusions Immediate treatment with ZA prevented bone loss compared with delayed treatment in postmenopausal women on letrozole and these differences were maintained at 5 years. The incidence of osteoporosis or fractures was not different between arms. PMID:25930719

  4. Selective Estrogen Receptor Modulator-Associated Nonalcoholic Fatty Liver Disease Improved Survival in Patients With Breast Cancer

    PubMed Central

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

    2015-01-01

    Abstract 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

  5. 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

  6. Topoisomerase II{alpha} expression correlates with diminished disease-free survival in invasive breast cancer

    SciTech Connect

    O'Connor, John K. . E-mail: joconno@yahoo.com; Hazard, Lisa J.; Lee, R. Jeffrey; Fischbach, Jennifer; Gaffney, David K.

    2006-08-01

    Purpose: Topoisomerase II{alpha} (Topo II{alpha}) plays a role in DNA replication and is the molecular target for anthracyline-based chemotherapy. The purpose of this study was to evaluate the relationship between Topo II{alpha} expression and survival in patients with invasive breast cancer. Methods and Materials: Formalin-fixed, paraffin-embedded tumor specimens from 24 women with invasive breast cancer were stained for Topo II{alpha} expression. All women underwent mastectomy. Radiotherapy was given at University of Utah Department of Radiation Oncology. Of the patients, 23 (96%) received chemotherapy. The level of Topo II{alpha} expression within tumor cells was compared with clinical factors and overall survival. Results: The median percentage of tumor cells expressing Topo II{alpha} was 70%. Increased Topo II{alpha} tumor expression significantly correlated with diminished disease-free survival. Five-year disease-free survival was 100% for patients with <70% of breast cancer cells expressing Topo II{alpha} compared with 42% for patients with {>=}70% Topo II{alpha} expression (p 0.008). The level of Topo II{alpha} expression within tumor cells correlated with T stage (p = 0.008) but not with other pathologic factors. Conclusions: Increased Topo II{alpha} expression significantly correlated with diminished disease-free survival in patients with invasive breast cancer. These findings may indicate a role for Topo II{alpha} expression as a prognostic factor in breast cancer.

  7. Breast preservation versus mastectomy--recurrence and survival rates of primary breast cancer patients treated at the UFK Bonn.

    PubMed

    Schmolling, J; Maus, B; Rezek, D; Fimmers, R; Höller, T; Schüller, H; Krebs, D

    1997-01-01

    The aim of this retrospective long-term analysis was to evaluate the approach of breast conservation in the light of the results obtained, on the basis of mastectomy, in patients with early breast carcinoma. Additionally, the effect of internal mammary and supraclavicular radiotherapy was analyzed. Therefore, local-regional recurrence (LRR) and survival rates were examined in 411 patients with T1 and T2 stages who had undergone either breast-preserving surgery with radiation or mastectomy. Individual risk factors such as nodal status, lymphangiosis carcinomatosa and age of the patients were evaluated, too. The rate of local-regional recurrence in patients who were treated by mastectomy and conservative surgery was 9.2% and 11.0%, respectively, with relapse happening earlier in the latter group (median of 16 vs. 24 months). Survival rates, however, were not different in the two groups. Tumour stage and nodal status had no influence on the local-regional recurrence rate in either group. In connection with lymphangiosis carcinomatosa, however, the rate increased to 14.5% (mastectomy) and 19.0% (breast-preserving surgery), respectively. Patients < or = 40 years had an even higher risk of LRR, with 20.6% when they underwent mastectomy and 30.8% following breast conservation. Internal mammary and supraclavicular radiotherapy had no positive effect on the survival rates, neither in the mastectomy nor in the breast conservation group. As a conclusion, in more than 60% of all T1 stages. and more than 50% of all T2 stages, the therapeutic concept of breast preservation seems to be justified.

  8. HER2 somatic mutations are associated with poor survival in HER2-negative breast cancers.

    PubMed

    Wang, Tonghui; Xu, Ye; Sheng, Shuyan; Yuan, Hua; Ouyang, Tao; Li, Jinfeng; Wang, Tianfeng; Fan, Zhaoqing; Fan, Tie; Lin, Benyao; Xie, Yuntao

    2017-02-06

    It is well documented that HER2 overexpression/amplification is associated with the poor survival in breast cancer patients. However, it is largely unknown whether HER2 somatic mutations are associated with the survival in HER2-negative breast cancer patients. Here, we identified HER2 somatic mutations in tumors from 1,348 unselected breast cancer patients by sequencing the entire HER2 coding region. All these mutations were tested for in corresponding blood samples to determine whether they were somatic or germline mutations. We further investigated the associations between the HER2 somatic mutations and recurrence-free survival (RFS) and distant recurrence-free survival (DRFS) in this cohort of patients. We found that 27 of 1,348 (2.0%) of these patients carried a HER2 somatic mutation. In vitro experiments demonstrated that some of novel mutations and those with unknown functions increased HER2 activity. HER2 status was available for 1,306 patients, and the HER2 somatic mutation rates in HER2-positive (n=353) and HER2-negative breast cancers (n=953) were 1.4% and 2.3%, respectively. Among the HER2-negative patients, those with a HER2 somatic mutation had a significantly worse recurrence-free survival (unadjusted hazard ratio [HR] =2.67; 95% confidence interval [CI]: 1.25-5.72, P=0.002) and distant recurrence-free survival (unadjusted HR=2.50; 95% CI: 1.10-5.68, P=0.004) than those with wild-type HER2. Taken together, our findings suggested that HER2 somatic mutations occur at a higher frequency in HER2-negative breast cancer, and HER2-negative breast cancer patients with these mutations have poor survival. Therefore, HER2-negative patients with a HER2 somatic mutation are potentially good candidates for HER2-targeted therapy. This article is protected by copyright. All rights reserved.

  9. 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.

  10. Neighborhood influences on recreational physical activity and survival after breast cancer

    PubMed Central

    Shariff-Marco, Salma; Sangaramoorthy, Meera; Koo, Jocelyn; Hertz, Andrew; Schupp, Clayton W.; Yang, Juan; John, Esther M.; Gomez, Scarlett L.

    2014-01-01

    Purpose Higher levels of physical activity have been associated with improved survival after breast cancer diagnosis. However, no previous studies have considered the influence of the social and built environment on physical activity and survival among breast cancer patients. Methods Our study included 4,345 women diagnosed with breast cancer (1995–2008) from two population-based studies conducted in the San Francisco Bay Area. We examined questionnaire-based moderate/strenuous recreational physical activity during the 3 years before diagnosis. Neighborhood characteristics were based on data from the 2000 US Census, business listings, parks, farmers’ markets, and Department of Transportation. Survival was evaluated using multivariable Cox proportional hazards models, with follow-up through 2009. Results Women residing in neighborhoods with no fast-food restaurants (vs. fewer fast-food restaurants) to other restaurants, high traffic density, and a high percentage of foreign-born residents were less likely to meet physical activity recommendations set by the American Cancer Society. Women who were not recreationally physically active had a 22 % higher risk of death from any cause than women that were the most active. Poorer overall survival was associated with lower neighborhood socioeconomic status (SES) (p trend = 0.02), whereas better breast cancer-specific survival was associated with a lack of parks, especially among women in high-SES neighborhoods. Conclusion Certain aspects of the neighborhood have independent associations with recreational physical activity among breast cancer patients and their survival. Considering neighborhood factors may aide in the design of more effective, tailored physical activity programs for breast cancer survivors. PMID:25088804

  11. Elevated nuclear S100P expression is associated with poor survival in early breast cancer patients.

    PubMed

    Maciejczyk, Adam; Łacko, Aleksandra; Ekiert, Marcin; Jagoda, Ewa; Wysocka, Teresa; Matkowski, Rafał; Hałoń, Agnieszka; Györffy, Balázs; Lage, Hermann; Surowiak, Paweł

    2013-04-01

    S100P - low molecular weight acidic protein has been shown to be involved in processes of proliferation, survival, angiogenesis, multidrug resistance and metastasis in various human malignancies. In breast cancer, S100P expression is associated with immortalization of neoplastic cells and aggressive tumour behaviour, indicating that this protein may have adverse prognostic value. We analyzed nuclear and cytoplasmic expression of S100P in 85 stage II breast cancer patients with a median follow up of 17 years. Immunohistochemical reactions were performed on paraffin sections of primary tumours, using monoclonal antibodies against S100P. We also studied prognostic value of S100P mRNA expression using the KM plotter which assessed the effect of 22,277 genes on survival in 2422 breast cancer patients. Moreover, the relationship was examined between expression of S100P in cells of four breast cancer cell lines and their sensitivity to the 11 most frequently applied cytotoxic drugs. Univariate and multivariate analyses showed that higher expression of nuclear S100P (S100Pn) was typical for cases of a shorter overall survival and disease-free time. KM plotter analysis showed that elevated S100P expression was specific for cases of a relapse-free survival and distant metastases-free survival. No relationship could be documented between expression of S100P and sensitivity of breast cancer cells to cytostatic drugs. We demonstrated that a high S100Pn expression level was associated with poor survival in early stage breast cancer patients. Since preliminary data indicated that expression of S100P was up-regulated by activation of glucocorticoid receptor and several agents manifested potential to activate or inhibit S100P promoter activity, this protein might become a therapy target and warrants further studies with respect to its prognostic, predictive and potentially therapeutic value.

  12. Are diet quality scores after breast cancer diagnosis associated with improved breast cancer survival?

    PubMed Central

    Izano, Monika A.; Fung, Teresa T.; Chiuve, Stephanie S; Hu, Frank B.; Holmes, Michelle D.

    2013-01-01

    Background Previous studies have found that diets rich in fruits and vegetables are associated with reduced breast cancer mortality. However, these eating patterns do not necessarily reflect overall diet quality. The association of breast cancer mortality with a priori defined dietary scores, which are based on recommended dietary guidelines and reflect diet quality, has not been evaluated. We hypothesized that diet quality indices based on recommended guidelines are associated with decreased risk of breast cancer and non-breast cancer mortality in breast cancer survivors. Methods We examined the association between the Dietary Approaches to Stop Hypertension (DASH) score, and the Alternative Healthy Eating Index (AHEI)-2010, and the risk of breast cancer mortality and total mortality among women from the Nurses’ Health Study diagnosed with breast cancer. Results Adherence to DASH-style and AHEI-2010 diets were associated with reduced risk of non-breast cancer mortality (comparing the fifth quintile with the first quintile RR = 0.72, 95% CI: 0.53–0.99, p-trend = 0.03 for DASH, and RR = 0.57, 95% CI: 0.42–0.77, p-trend <0.0001 for AHEI-2010). Diet scores were not significantly associated with breast cancer mortality. Conclusions Our findings suggest that adherence to a higher quality diet after breast cancer diagnosis does not considerably change the risk of breast cancer death and recurrence. However, healthy dietary choices after breast cancer were associated with reduced risk of non-breast cancer mortality in women with breast cancer. PMID:23909725

  13. Delay in Breast Cancer: Implications for Stage at Diagnosis and Survival

    PubMed Central

    Caplan, Lee

    2014-01-01

    Breast cancer continues to be a disease with tremendous public health significance. Primary prevention of breast cancer is still not available, so efforts to promote early detection continue to be the major focus in fighting breast cancer. Since early detection is associated with decreased mortality, one would think that it is important to minimize delays in detection and diagnosis. There are two major types of delay. Patient delay is delay in seeking medical attention after self-discovering a potential breast cancer symptom. System delay is delay within the health care system in getting appointments, scheduling diagnostic tests, receiving a definitive diagnosis, and initiating therapy. Earlier studies of the consequences of delay on prognosis tended to show that increased delay is associated with more advanced stage cancers at diagnosis, thus resulting in poorer chances for survival. More recent studies have had mixed results, with some studies showing increased survival with longer delays. One hypothesis is that diagnostic difficulties could perhaps account for this survival paradox. A rapidly growing lump may suggest cancer to both doctors and patients, while a slow growing lump or other symptoms could be less obvious to them. If this is the case, then the shorter delays would be seen with the more aggressive tumors for which the prognosis is worse leading to reduced survival. It seems logical that a tumor that is more advanced at diagnosis would lead to shorter survival but the several counter-intuitive studies in this review show that it is dangerous to make assumptions. PMID:25121080

  14. Prediagnostic body size and breast cancer survival in the E3N cohort study.

    PubMed

    His, Mathilde; Fagherazzi, Guy; Mesrine, Sylvie; Boutron-Ruault, Marie-Christine; Clavel-Chapelon, Françoise; Dossus, Laure

    2016-09-01

    Obesity has been associated with poor breast cancer prognosis, however most studies have focused on body mass index (BMI) and few have considered the distribution of adipose tissue. We investigated associations between prediagnostic adiposity and breast cancer survival, considering BMI, waist and hip circumferences (WC and HC), and waist-to-hip ratio (WHR). Analyses included 3,006 women from the French E3N prospective cohort study diagnosed with primary invasive breast cancer between 1995 and 2008. We investigated overall, breast cancer-specific, and disease-free survival, overall and according to stage, menopausal and hormonal status and year of diagnosis, using Cox proportional hazard models adjusted for tumor characteristics and lifestyle risk factors. Women with a prediagnostic HC > 100 cm were at increased risk of death from all causes (hazard ratio (HR)>100 vs < 95 cm  = 1.38, 95% Confidence Interval (CI) = 1.02-1.86, Ptrend  = 0.02) and from breast cancer (HR>100 vs < 95 cm  = 1.50, CI = 1.03-2.17, Ptrend  = 0.03), and of second invasive cancer event (HR>100 vs < 95 cm  = 1.36, CI = 1.11-1.67, Ptrend  = 0.002), compared to those with HC <95 cm. Associations were stronger after adjustment for BMI. BMI, WC and WHR were not associated with survival after breast cancer. Our study underlines the importance of going beyond BMI when studying the association between adiposity and breast cancer survival. Further studies should be conducted to confirm our results on hip circumference.

  15. 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

  16. Human mitochondrial pyrroline-5-carboxylate reductase 1 promotes invasiveness and impacts survival in breast cancers.

    PubMed

    Ding, Jiefeng; Kuo, Mei-Ling; Su, Leila; Xue, Lijun; Luh, Frank; Zhang, Hang; Wang, Jianghai; Lin, Tiffany G; Zhang, Keqiang; Chu, Peiguo; Zheng, Shu; Liu, Xiyong; Yen, Yun

    2017-04-03

    Human mitochondrial pyrroline-5-carboxylate reductase (PYCR) is a house-keeping enzyme that catalyzes the reduction of Δ1-pyrroline-5-carboxylate to proline. This enzymatic cycle plays pivotal roles in amino acid metabolism, intracellular redox potential and mitochondrial integrity. Here, we hypothesize that PYCR1 might be a novel prognostic biomarker and therapeutic target for breast cancer. In this study, breast cancer tissue samples were obtained from Zhejiang University (ZJU set). Immunohistochemistry analysis was performed to detect the protein level of PYCR1, and Kaplan-Meier and Cox proportional analyses were employed in this outcome study. The prognostic significance and performance of PYCR1 mRNA were validated on 13 worldwide independent microarray data sets, composed of 2500 assessable breast cancer cases. Our findings revealed that both PYCR1 mRNA and protein expression were significantly associated with tumor size, grade and invasive molecular subtypes of breast cancers. Independent and pooled analyses verified that higher PYCR1 mRNA levels were significantly associated with poor survival of breast cancer patients, regardless of estrogen receptor (ER) status. For in vitro studies, inhibition of PYCR1 by small-hairpin RNA significantly reduced the growth and invasion capabilities of the cells, while enhancing the cytotoxicity of doxorubicin in breast cancer cell lines MCF-7 (ER positive) and MDA-MB-231 (ER negative). Further population study also validated that chemotherapy significantly improved survival in early-stage breast cancer patients with low PYCR1 expression levels. Therefore, PYCR1 might serve as a prognostic biomaker for either ER-positive or ER-negative breast cancer subtypes and can also be a potential target for breast cancer therapy.

  17. 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)

  18. Regulation of Survival by IKKe in Inflammatory Breast Cancer Involves EpCAM

    DTIC Science & Technology

    2016-02-01

    based chemo therapy or cisplatin , tumors frequently relapse, resulting in decreased disease-free and overall survival compared with other breast...Supplemental Figure 2A). Response to neoadjuvant cisplatin therapy failed to correlate with IKBKE expression status in another cohort of patients with

  19. Polycyclic aromatic hydrocarbon-DNA adducts and survival among women with breast cancer

    SciTech Connect

    Sagiv, Sharon K. Gaudet, Mia M.; Eng, Sybil M.; Abrahamson, Page E.; Shantakumar, Sumitra; Teitelbaum, Susan L.; Bell, Paula; Thomas, Joyce A.; Neugut, Alfred I.; Santella, Regina M.; Gammon, Marilie D.

    2009-04-15

    Polycyclic aromatic hydrocarbons (PAH) are mammary carcinogens in animal studies, and a few epidemiologic studies have suggested a link between elevated levels of PAH-DNA adducts and breast cancer incidence. An association between PAH-DNA adducts and survival among breast cancer cases has not been previously reported. We conducted a survival analysis among women with newly diagnosed invasive breast cancer between 1996 and 1997, enrolled in the Long Island Breast Cancer Study Project. DNA was isolated from blood samples that were obtained from cases shortly after diagnosis and assayed for PAH-DNA adducts using ELISA. Among the 722 cases with PAH-DNA adduct measurements, 97 deaths (13.4%) from all causes and 54 deaths (7.5%) due to breast cancer were reported to National Death Index (NDI) by December 31, 2002. Using Cox proportional hazards models and controlling for age at diagnosis, we did not find evidence that all-cause mortality (hazard ratio (HR)=0.88; 95% confidence interval (CI): 0.57-1.37), or breast cancer mortality (HR=1.20; 95% CI: 0.63-2.28) was strongly associated with detectable PAH-DNA adduct levels compared with non-detectable adducts; additionally, no dose-response association was observed. Among a subgroup with treatment data (n=520), adducts were associated with over a two-fold higher mortality among those receiving radiation, but mortality for adducts was reduced among hormone therapy users. Results from this large population-based study do not provide strong support for an association between detectable PAH-DNA adducts and survival among women with breast cancer, except perhaps among those receiving radiation treatment.

  20. Correlating transcriptional networks to breast cancer survival: a large-scale coexpression analysis.

    PubMed

    Clarke, Colin; Madden, Stephen F; Doolan, Padraig; Aherne, Sinead T; Joyce, Helena; O'Driscoll, Lorraine; Gallagher, William M; Hennessy, Bryan T; Moriarty, Michael; Crown, John; Kennedy, Susan; Clynes, Martin

    2013-10-01

    Weighted gene coexpression network analysis (WGCNA) is a powerful 'guilt-by-association'-based method to extract coexpressed groups of genes from large heterogeneous messenger RNA expression data sets. We have utilized WGCNA to identify 11 coregulated gene clusters across 2342 breast cancer samples from 13 microarray-based gene expression studies. A number of these transcriptional modules were found to be correlated to clinicopathological variables (e.g. tumor grade), survival endpoints for breast cancer as a whole (disease-free survival, distant disease-free survival and overall survival) and also its molecular subtypes (luminal A, luminal B, HER2+ and basal-like). Examples of findings arising from this work include the identification of a cluster of proliferation-related genes that when upregulated correlated to increased tumor grade and were associated with poor survival in general. The prognostic potential of novel genes, for example, ubiquitin-conjugating enzyme E2S (UBE2S) within this group was confirmed in an independent data set. In addition, gene clusters were also associated with survival for breast cancer molecular subtypes including a cluster of genes that was found to correlate with prognosis exclusively for basal-like breast cancer. The upregulation of several single genes within this coexpression cluster, for example, the potassium channel, subfamily K, member 5 (KCNK5) was associated with poor outcome for the basal-like molecular subtype. We have developed an online database to allow user-friendly access to the coexpression patterns and the survival analysis outputs uncovered in this study (available at http://glados.ucd.ie/Coexpression/).

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

    PubMed

    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

    2015-09-01

    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. >70×10(3)/mm(3) (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.

  2. 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

  3. 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.

  4. 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

  5. FANCM c.5101C>T mutation associates with breast cancer survival and treatment outcome

    PubMed Central

    Kiiski, Johanna I.; Fagerholm, Rainer; Tervasmäki, Anna; Pelttari, Liisa M.; Khan, Sofia; Jamshidi, Maral; Mantere, Tuomo; Pylkäs, Katri; Bartek, Jiri; Bartkova, Jirina; Mannermaa, Arto; Tengström, Maria; Kosma, Veli‐Matti; Winqvist, Robert; Kallioniemi, Anne; Aittomäki, Kristiina; Blomqvist, Carl

    2016-01-01

    Breast cancer (BC) is a heterogeneous disease, and different tumor characteristics and genetic variation may affect the clinical outcome. The FANCM c.5101C > T nonsense mutation in the Finnish population associates with increased risk of breast cancer, especially for triple‐negative breast cancer patients. To investigate the association of the mutation with disease prognosis, we studied tumor phenotype, treatment outcome, and patient survival in 3,933 invasive breast cancer patients, including 101 FANCM c.5101C > T mutation carriers and 3,832 non‐carriers. We also examined association of the mutation with nuclear immunohistochemical staining of DNA repair markers in 1,240 breast tumors. The FANCM c.5101C > T mutation associated with poor 10‐year breast cancer‐specific survival (hazard ratio (HR)=1.66, 95% confidence interval (CI) 1.09–2.52, p = 0.018), with a more pronounced survival effect among familial cases (HR = 2.93, 95% CI 1.5–5.76, p = 1.80 × 10−3). Poor disease outcome of the carriers was also found among the estrogen receptor (ER) positive subgroup of patients (HR = 1.8, 95% CI 1.09–2.98, p = 0.021). Reduced survival was seen especially among patients who had not received radiotherapy (HR = 3.43, 95% CI 1.6–7.34, p = 1.50 × 10−3) but not among radiotherapy treated patients (HR = 1.35, 95% CI 0.82–2.23, p = 0.237). Significant interaction was found between the mutation and radiotherapy (p = 0.040). Immunohistochemical analyses show that c.5101C > T carriers have reduced PAR‐activity. Our results suggest that FANCM c.5101C > T nonsense mutation carriers have a reduced breast cancer survival but postoperative radiotherapy may diminish this survival disadvantage. PMID:27542569

  6. 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

  7. 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.

  8. 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

  9. Allelic expression imbalance polymorphisms in susceptibility chromosome regions and the risk and survival of breast cancer.

    PubMed

    Lin, Wei; Lin, Hong-Da; Guo, Xing-Yi; Lin, Ying; Su, Feng-Xi; Jia, Wei-Hua; Tang, Lu-Ying; Zheng, Wei; Long, Ji-Rong; Ren, Ze-Fang

    2017-01-01

    Allelic expression imbalance (AEI) has been applied to indicate potential function of genetic variants. Combining earlier results from global differential allele-specific expression analysis and genome wide association studies (GWASs), we select the single nuclear polymorphisms (SNPs) exhibiting AEI phenomenon located in breast cancer susceptibility chromosome regions, and evaluate their associations with breast cancer risk and survival. We examined the genotypes of 10 AEI SNPs in 1551 incident breast cancer cases and 1605 age-frequency matched controls from Guangzhou, China. In total, 1168 cases were followed up. MUC16 rs2591592 (AT/AA vs. TT) was associated with an increased risk of premenopausal breast cancer (OR [95%CI]: 1.30 [1.07, 1.57]); SLAMF1 rs1061217 (CT/TT vs. CC) decreased the risk of breast cancer among overweight women (OR [95%CI]: 0.74 [0.57, 0.96]) but increased the risk among normal-weight women (OR [95%CI]: 1.15 [1.01, 1.39]); ZNF331 rs8109631 (AG/AA vs. GG) and CHRAC1 rs10216653 (GC/GG vs. CC) were associated with progression free survival among breast cancer patients with negative ER/PR status and higher clinical stage (HRs [95%CIs]: 2.39 [1.14, 5.00], 1.85 [1.03, 3.32], and 0.49 [0.30, 0.80], respectively). ZNF331 rs8109631 and CHRAC1 rs10216653 were further found to represent several functional SNPs through bioinformatic analysis. In conclusion, our findings demonstrated suggestive associations of AEI polymorphisms with breast cancer risk (MUC16 rs2591592 and SLAMF1 rs1061217) and prognosis (ZNF331 rs8109631 and CHRAC1 rs10216653). © 2016 Wiley Periodicals, Inc.

  10. Predicting Survival of De Novo Metastatic Breast Cancer in Asian Women: Systematic Review and Validation Study

    PubMed Central

    Miao, Hui; Hartman, Mikael; Bhoo-Pathy, Nirmala; Lee, Soo-Chin; Taib, Nur Aishah; Tan, Ern-Yu; Chan, Patrick; Moons, Karel G. M.; Wong, Hoong-Seam; Goh, Jeremy; Rahim, Siti Mastura; Yip, Cheng-Har; Verkooijen, Helena M.

    2014-01-01

    Background In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia. Materials and Methods We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic). Results We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s) and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48–0.53) to 0.63 (95% CI, 0.60–0.66). Conclusion The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making. PMID:24695692

  11. Kaiso depletion attenuates the growth and survival of triple negative breast cancer cells.

    PubMed

    Bassey-Archibong, Blessing I; Rayner, Lyndsay G A; Hercules, Shawn M; Aarts, Craig W; Dvorkin-Gheva, Anna; Bramson, Jonathan L; Hassell, John A; Daniel, Juliet M

    2017-03-23

    Triple negative breast cancers (TNBC) are highly aggressive and lack specific targeted therapies. Recent studies have reported high expression of the transcription factor Kaiso in triple negative tumors, and this correlates with their increased aggressiveness. However, little is known about the clinical relevance of Kaiso in the growth and survival of TNBCs. Herein, we report that Kaiso depletion attenuates TNBC cell proliferation, and delays tumor onset in mice xenografted with the aggressive MDA-231 breast tumor cells. We further demonstrate that Kaiso depletion attenuates the survival of TNBC cells and increases their propensity for apoptotic-mediated cell death. Notably, Kaiso depletion downregulates BRCA1 expression in TNBC cells expressing mutant-p53 and we found that high Kaiso and BRCA1 expression correlates with a poor overall survival in breast cancer patients. Collectively, our findings reveal a role for Kaiso in the proliferation and survival of TNBC cells, and suggest a relevant role for Kaiso in the prognosis and treatment of TNBCs.

  12. Breast Cancer With Brain Metastases: Clinicopathologic Features, Survival, and Paired Biomarker Analysis

    PubMed Central

    Shen, Qi; Hess, Kenneth R.; Suki, Dima; Aldape, Kenneth D.; Sawaya, Raymond; Ibrahim, Nuhad K.

    2015-01-01

    Background. The aim of this study was to describe clinicopathologic features of patients with breast cancer brain metastasis (BCBM); to evaluate survival after diagnosis of BCBM; and to compare estrogen receptor (ER), progesterone receptor (PR), and HER2 expression in the paired primary and brain tumors. Materials and Methods. We identified 140 consecutive patients who underwent craniotomy for BCBM (either for diagnostic purpose or with therapeutic intent) at the University of Texas MD Anderson Cancer Center between 2002 and 2009. Results. Most patients had invasive ductal histology (91%), grade 3 tumors (67%), and positive axillary lymph node (64%). Of the tumors, 56% were ER-negative, 62% were PR-negative, 44% were HER2-positive, and 28% were triple negative (TN). Brain metastasis (BM) was solitary in 51% of patients. Median interval from breast cancer diagnosis to BM was 46 months; median survival after BM was 14.1 months. In the univariate analysis, younger age, solitary brain metastasis, and ER or PR positivity in the breast tumors were associated with longer survival. There was a statistical trend toward increased survival in HER2-positive patients compared with HER2-negative patients (18 vs. 11 months). In the multivariate analysis, predictors for longer survival included younger age, solitary brain lesion, and HER2 positivity in the breast cancer. Biomarkers were evaluated in paired primary and brain tumors in 35 patients for ER status, 34 for PR status, and 36 for HER2 status. Discordant rates were 28% for ER, 20% for PR, and 3% for HER2. Conclusion. Compared with unselected breast cancer patients at the same institution, patients with breast cancer who had brain metastases had a higher proportion of hormone receptor-negative, HER2-positive, and TN tumors. Younger age, solitary brain lesion, and HER2 expression were independent predictors of better survival in patients with BCBM. HER2 status was highly concordant between the paired primary and brain tumors

  13. Influence of Androgen Receptor Expression on the Survival Outcomes in Breast Cancer: A Meta-Analysis

    PubMed Central

    Kim, Yoonseok; Jae, Eunae

    2015-01-01

    Purpose Despite the fact that the androgen receptor (AR) is known to be involved in the pathogenesis of breast cancer, its prognostic effect remains controversial. In this meta-analysis, we explored AR expression and its impact on survival outcomes in breast cancer. Methods We searched PubMed, EMBASE, Cochrane Library, ScienceDirect, SpringerLink, and Ovid databases and references of articles to identify studies reporting data until December 2013. Disease-free survival (DFS) and overall survival (OS) were analyzed by extracting the number of patients with recurrence and survival according to AR expression. Results There were 16 articles that met the criteria for inclusion in our meta-analysis. DFS and OS were significantly longer in patients with AR expression compared with patients without AR expression (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.40-0.90; OR, 0.53; 95% CI, 0.38-0.73, respectively). In addition, hormone receptor (HR) positive patients had a longer DFS when AR was also expressed (OR, 0.63; 95% CI, 0.41-0.98). For patients with triple negative breast cancer (TNBC), AR expression was also associated with longer DFS and OS (OR, 0.44, 95% CI, 0.26-0.75; OR, 0.26, 95% CI, 0.12-0.55, respectively). Furthermore, AR expression was associated with a longer DFS and OS in women (OR, 0.42, 95% CI, 0.27-0.64; OR, 0.47, 95% CI, 0.38-0.59, respectively). However, in men, AR expression was associated with a worse DFS (OR, 6.00; 95% CI, 1.46-24.73). Conclusion Expression of AR in breast cancer might be associated with better survival outcomes, especially in patients with HR-positive tumors and TNBC, and women. Based on this meta-analysis, we propose that AR expression might be related to prognostic features and contribute to clinical outcomes. PMID:26155289

  14. No effect of scalp cooling on survival among women with breast cancer.

    PubMed

    Lemieux, J; Provencher, L; Perron, L; Brisson, J; Amireault, C; Blanchette, C; Maunsell, E

    2015-01-01

    Scalp cooling can prevent chemotherapy-induced alopecia in some cancer patients. It is not used in all countries. No data are available regarding its impact, if any, on survival. The aim of this study was to compare overall survival according to whether or not scalp cooling was used during neoadjuvant or adjuvant chemotherapy for non-metastatic breast cancer. We conducted a retrospective cohort study of 1,370 women with non-metastatic invasive breast carcinoma who received chemotherapy in the neoadjuvant or adjuvant setting. A total of 553 women who used scalp cooling came from a tertiary breast cancer clinic in Quebec City (diagnosed between 1998 and 2002) and 817 were treated in other hospitals in the province of Quebec (between 1998 and 2003) where scalp cooling was not routinely available. Overall survival of women who used scalp cooling and those who did not was compared using Cox proportional hazards models. Median follow-up for the scalp-cooled and the non-scalp-cooled groups was 6.3 years and 8.0 years, respectively. Overall mortality was no different (adjusted hazard ratio 0.89, 95 % confidence interval: 0.68-1.17, p = 0.40) among scalp-cooled women, compared to those not getting scalp cooling. Among women getting neoadjuvant or adjuvant chemotherapy for non-metastatic breast cancer, scalp cooling used to prevent chemotherapy-induced alopecia had no negative effect on survival. To our knowledge, this is the first study to compare survival of women who used scalp cooling to that of women who did not.

  15. 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

  16. 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.

  17. 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.

  18. 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.

  19. Higher survival of refractory metastatizing breast cancer after thermotherapy and autologous specific antitumoral immunotherapy.

    PubMed

    Pontiggia, P; Rizzo, S; Cuppone-Curto, F; Sabato, A; Rotella, G; Silvotti, M G; Martano, F

    1996-01-01

    46 women (average 54.3 yrs) with refractory metastatizing breast cancer were treated with thermotherapy and autologous specific immunotherapy (rhIL-2 ex vivo activated cells). Metastases involved one organ in 69%; in particular, bone, lung, liver. The PS after treatment was satisfactory in 41%; the outcome was better in those cases with metastases to one site. The women remaining alive were 31/46; 67% of thermoimmunotherapy treated patients were alive after a maximum survival time of 85 months (median 24 months). The 36 months of control showed a 5-fold higher survival rate in our series when challenged with that of compared women undergoing only chemotherapy (p < .001).

  20. Early-Stage Young Breast Cancer Patients: Impact of Local Treatment on Survival

    SciTech Connect

    Bantema-Joppe, Enja J.; Munck, Linda de; Willemse, Pax H.B.; Langendijk, Johannes A.; Siesling, Sabine; Maduro, John H.

    2011-11-15

    Purpose: In young women, breast-conserving therapy (BCT), i.e., lumpectomy followed by radiotherapy, has been associated with an increased risk of local recurrence. Still, there is insufficient evidence that BCT impairs survival. The aim of our study was to compare the effect of BCT with mastectomy on overall survival (OS) in young women with early-stage breast cancer. Methods and Materials: From two Dutch regional population-based cancer registries (covering 6.2 million inhabitants) 1,453 women <40 years with pathologically T1N0-1M0 breast cancer were selected. Cox regression survival analysis was used to study the effect of local treatment (BCT vs. mastectomy) stratified for nodal stage on survival and corrected for tumor size, age, period of diagnosis, and use of adjuvant systemic therapy. Results: With a median follow-up of 9.6 years, 10-year OS was 83% after BCT and 78% after mastectomy, respectively (unadjusted hazard ratio [HR], 1.37; 95% confidence interval [CI], 1.09-1.72). In N0-patients, 10-year OS was 84% after BCT and 81% after mastectomy and local treatment was not associated with differences in OS (HR 1.19; 95% CI, 0.89-1.58; p = 0.25). Within the N1-patient group, OS was better after BCT compared with mastectomy, 79% vs. 71% at 10 years (HR 1.91; 95% CI, 1.28-2.84; p = 0.001) and in patients treated with adjuvant hormonal therapy (HR 0.34; 95% CI, 0.18-0.66; p = 0.001). Conclusions: In this large population-based cohort of early-stage young breast cancer patients, 10-year OS was not impaired after BCT compared with mastectomy. Patients with 1 to 3 positive lymph nodes had better prognosis after BCT than after mastectomy.

  1. Prognosis for Survival of Young Women with Breast Cancer by Quantitative p53 Immunohistochemistry

    PubMed Central

    Axelrod, David E.; Shah, Kinsuk; Yang, Qifeng; Haffty, Bruce G.

    2015-01-01

    p53 protein detected immunohistochemically has not been accepted as a biomarker for breast cancer patients because of disparate reports of the relationship between the amount of p53 protein detected and patient survival. The purpose of this study was to determine experimental conditions and methods of data analysis for which p53 stain intensity could be prognostic for survival of young breast cancer patients. A tissue microarray of specimens from 93 patients was stained with anti-p53 antibody, and stain intensity measured with a computer-aided image analysis system. A cut-point at one standard deviation below the mean of the distribution of p53 stain intensity separated patients into two groups with significantly different survival. These results were confirmed by Quantitative Nuclear Grade determined by DNA-specific Feulgen staining. P53 provided information beyond ER and PR status. Therefore, under the conditions reported here, p53 protein can be an effective prognostic factor for young breast cancer patients. PMID:26322145

  2. Fibroblast growth factor receptor 4 (FGFR4) and fibroblast growth factor 19 (FGF19) autocrine enhance breast cancer cells survival.

    PubMed

    Tiong, Kai Hung; Tan, Boon Shing; Choo, Heng Lungh; Chung, Felicia Fei-Lei; Hii, Ling-Wei; Tan, Si Hoey; Khor, Nelson Tze Woei; Wong, Shew Fung; See, Sze-Jia; Tan, Yuen-Fen; Rosli, Rozita; Cheong, Soon-Keng; Leong, Chee-Onn

    2016-09-06

    Basal-like breast cancer is an aggressive tumor subtype with poor prognosis. The discovery of underlying mechanisms mediating tumor cell survival, and the development of novel agents to target these pathways, is a priority for patients with basal-like breast cancer. From a functional screen to identify key drivers of basal-like breast cancer cell growth, we identified fibroblast growth factor receptor 4 (FGFR4) as a potential mediator of cell survival. We found that FGFR4 mediates cancer cell survival predominantly via activation of PI3K/AKT. Importantly, a subset of basal-like breast cancer cells also secrete fibroblast growth factor 19 (FGF19), a canonical ligand specific for FGFR4. siRNA-mediated silencing of FGF19 or neutralization of extracellular FGF19 by anti-FGF19 antibody (1A6) decreases AKT phosphorylation, suppresses cancer cell growth and enhances doxorubicin sensitivity only in the FGFR4+/FGF19+ breast cancer cells. Consistently, FGFR4/FGF19 co-expression was also observed in 82 out of 287 (28.6%) primary breast tumors, and their expression is strongly associated with AKT phosphorylation, Ki-67 staining, higher tumor stage and basal-like phenotype. In summary, our results demonstrated the presence of an FGFR4/FGF19 autocrine signaling that mediates the survival of a subset of basal-like breast cancer cells and suggest that inactivation of this autocrine loop may potentially serve as a novel therapeutic intervention for future treatment of breast cancers.

  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. Glycan-related gene expression signatures in breast cancer subtypes; relation to survival.

    PubMed

    Potapenko, Ivan O; Lüders, Torben; Russnes, Hege G; Helland, Åslaug; Sørlie, Therese; Kristensen, Vessela N; Nord, Silje; Lingjærde, Ole C; Børresen-Dale, Anne-Lise; Haakensen, Vilde D

    2015-04-01

    Alterations in glycan structures are early signs of malignancy and have recently been proposed to be in part a driving force behind malignant transformation. Here, we explore whether differences in expression of genes related to the process of glycosylation exist between breast carcinoma subtypes - and look for their association to clinical parameters. Five expression datasets of 454 invasive breast carcinomas, 31 ductal carcinomas in situ (DCIS), and 79 non-malignant breast tissue samples were analysed. Results were validated in 1960 breast carcinomas. 419 genes encoding glycosylation-related proteins were selected. The DCIS samples appeared expression-wise similar to carcinomas, showing altered gene expression related to glycosaminoglycans (GAGs) and N-glycans when compared to non-malignant samples. In-situ lesions with different aggressiveness potentials demonstrated changes in glycosaminoglycan sulfation and adhesion proteins. Subtype-specific expression patterns revealed down-regulation of genes encoding glycan-binding proteins in the luminal A and B subtypes. Clustering basal-like samples using a consensus list of genes differentially expressed across discovery datasets produced two clusters with significantly differing prognosis in the validation dataset. Finally, our analyses suggest that glycolipids may play an important role in carcinogenesis of breast tumors - as demonstrated by association of B3GNT5 and UGCG genes to patient survival. In conclusion, most glycan-specific changes occur early in the carcinogenic process. We have identified glycan-related alterations specific to breast cancer subtypes including a prognostic signature for two basal-like subgroups. Future research in this area may potentially lead to markers for better prognostication and treatment stratification of breast cancer patients.

  5. 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.

  6. 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

  7. 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

  8. Preoperative Magnetic Resonance Imaging and Survival Outcomes in T1–2 Breast Cancer Patients Who Receive Breast-Conserving Therapy

    PubMed Central

    Ryu, Jaegyu; Park, Hyung Seok; Kim, Sanghwa; Kim, Jee Ye; Park, Seho

    2016-01-01

    Purpose The purpose of the study was to evaluate the effect of preoperative magnetic resonance imaging (MRI) on survival outcomes for breast cancer. Methods A total of 954 patients who had T1–2 breast cancer and received breast-conserving therapy (BCT) between 2007 and 2010 were enrolled. We divided the patients according to whether they received preoperative MRI or not. Survival outcomes, including locoregional recurrence-free survival (LRRFS), recurrence-free survival (RFS), and overall survival (OS), were analyzed. Results Preoperative MRI was performed in 743 of 954 patients. Clinicopathological features were not significantly different between patients with and without preoperative MRI. In the univariate analyses, larger tumors were marginally associated with poor LRRFS compared to smaller tumors (hazard ratio [HR], 3.22; p=0.053). Tumor size, histologic grade, estrogen receptor (ER), progesterone receptor (PR), hormonal therapy, and adjuvant chemotherapy status were associated with RFS. Larger tumor size, higher histologic grade, lack of ER and PR expression, and no hormonal therapy were associated with decreased OS. Tumor size was associated with LRRFS in the multivariate analyses (HR, 4.19; p=0.048). However, preoperative MRI was not significantly associated with LRRFS, RFS, or OS in either univariate or multivariate analyses. Conclusion Preoperative MRI did not influence survival outcomes in T1–2 breast cancer patients who underwent BCT. Routine use of preoperative MRI in T1–2 breast cancer may not translate into longer RFS and OS. PMID:28053631

  9. Better survival in PMRT of female breast cancer patients with >5 negative lymph nodes

    PubMed Central

    Wang, Haiyong; Zhang, Chenyue; Kong, Li; Zhu, Hui; Yu, Jinming

    2017-01-01

    Abstract Many studies have confirmed the role of postmastectomy radiotherapy (PMRT) for breast cancer patients with at least 4 lymph nodes invasion in the postoperative therapy. Recently, the number of negative lymph nodes (NLNs) has been increasingly paid attention to and recognized as a prognostic indicator in different kinds of caners. Therefore, it is very necessary to study the association between the number of NLNs and the prognosis of PMRT in breast cancer patients. In our study, we used Surveillance, Epidemiology, and End Results (SEER) population-based data and identified 16,686 breast cancer patients to explore their correlation. The ROC curve and the log-rank χ2 test were applied to determine the appropriate cutoff point of the number of NLNs and 5 was selected as the cutoff point. Furthermore, the cutoff point 5 was validated as an independent prognostic factor affecting cancer-specific survival (CSS) and overall survival (OS) in breast cancer patients, as confirmed by both univariate and multivariate analysis (P < 0.001). In addition, subgroup analysis showed that the number of NLNs >5 can be a prognostic indicator in patients with PMRT according to different clinical variables (all, P < 0.001). Importantly, our results showed that PMRT obviously improved CSS and OS in patients regardless of the number of NLNs (P < 0.001). In conclusion, our study showed the number of NLNs is an independent prognostic factor for breast cancer patients with PMRT, and those who have higher number of NLNs have an increased CSS and OS. PMID:28121956

  10. Angiopoietin-2 expression in breast cancer correlates with lymph node invasion and short survival.

    PubMed

    Sfiligoi, Christian; de Luca, Annarita; Cascone, Ilaria; Sorbello, Valentina; Fuso, Luca; Ponzone, Riccardo; Biglia, Nicoletta; Audero, Enrica; Arisio, Riccardo; Bussolino, Federico; Sismondi, Piero; De Bortoli, Michele

    2003-02-10

    Angiogenic factors produced by tumor cells are essential for tumor growth and metastasis. In our study, the expression of Angiopoietin-1 (ANG1) and Angiopoietin-2 (ANG2) mRNA in archival human breast cancer tumor samples and in 6 breast cancer cell lines was investigated. Total RNA from biopsies of 38 breast cancer patients was extracted and ANG1 and ANG2 mRNA expression was measured by means of quantitative real-time RT-PCR (Taqman). Matching data with available clinicopathologic and biochemical data revealed a significant association between ANG2 expression and axillary lymph node invasion. Univariate and multivariate survival analysis, by means of Kaplan-Meier method and Cox's proportional hazards model, showed significant and independent association between ANG2 mRNA level and both disease-free (p < 0.0001) and overall survival (p < 0.0003). An important fact is that, notwithstanding the small number of cases examined, this association was confirmed also in the group of lymph node-negative patients (DFS, p < 0.003; OS, p < 0.020). Immunohistochemical analysis demonstrated that Ang2 is expressed by both tumor cells and endothelial elements. Expression in tumor cells was confirmed by studying a panel of human breast carcinoma cell lines in culture by RT-PCR. In ZR75.1 and T47D cells, expression of ANG2 mRNA was increased up to 10-fold by treatment with estrogen within 24 hr. Although preliminary, these data suggest a possible role of ANG2 as a prognostic factor for primary breast cancer.

  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. The impact of pregnancy on breast cancer survival in women who carry a BRCA1 or BRCA2 mutation.

    PubMed

    Valentini, Adriana; Lubinski, Jan; Byrski, Tomasz; Ghadirian, Parviz; Moller, Pal; Lynch, Henry T; Ainsworth, Peter; Neuhausen, Susan L; Weitzel, Jeffrey; Singer, Christian F; Olopade, Olufunmilayo I; Saal, Howard; Lyonnet, Dominique Stoppa; Foulkes, William D; Kim-Sing, Charmaine; Manoukian, Siranoush; Zakalik, Dana; Armel, Susan; Senter, Leigha; Eng, Charis; Grunfeld, Eva; Chiarelli, Anna M; Poll, Aletta; Sun, Ping; Narod, Steven A

    2013-11-01

    Physicians are often approached by young women with a BRCA mutation and a recent history of breast cancer who wish to have a baby. They wish to know if pregnancy impacts upon their future risks of cancer recurrence and survival. To date, there is little information on the survival experience of women who carry a mutation in one of the BRCA genes and who become pregnant. From an international multi-center cohort study of 12,084 women with a BRCA1 or BRCA2 mutation, we identified 128 case subjects who were diagnosed with breast cancer while pregnant or who became pregnant after a diagnosis of breast cancer. These women were age-matched to 269 mutation carriers with breast cancer who did not become pregnant (controls). Subjects were followed from the date of breast cancer diagnosis until the date of last follow-up or death from breast cancer. The Kaplan-Meier method was used to estimate 15-year survival rates. The hazard ratio for survival associated with pregnancy was calculated using a left-truncated Cox proportional hazard model, adjusting for other prognostic factors. Among women who were diagnosed with breast cancer when pregnant or who became pregnant thereafter, the 15-year survival rate was 91.5 %, compared to a survival of 88.6 % for women who did not become pregnant (adjusted hazard ratio = 0.76; 95 % CI 0.31-1.91; p = 0.56). Pregnancy concurrent with or after a diagnosis of breast cancer does not appear to adversely affect survival among BRCA1/2 mutation carriers.

  13. 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

  14. [Psychosocial impact of breast cancer in long-term survival: proposal of an integral follow-up care for survivors].

    PubMed

    Vivar, Cristina G

    2012-05-01

    The aim of the article is to show the psychosocial impact of breast cancer in the long-term survival and to promote the idea of implementing a follow-up plan for survivors. A narrative review of published articles on the experience of survival in breast cancer survivors was conducted. Data were organised according to the domains of measurement (physical, psychological and social) of the Quality of Life of Long-term Breast Cancer Survivors Scale (LTQOL-BC). Breast cancer survivors may feel emotionally affected by the physical sequels (mastectomy, lymphedema, early menopause, and infertility), psychological (fear of recurrence and emotional stress) and/or social (family relationships and employment changes). The data are the foundation of a proposal of specific follow-up care for breast cancer survivors.

  15. Malignant Precursor Cells Pre-Exist in Human Breast DCIS and Require Autophagy for Survival

    PubMed Central

    Espina, Virginia; Mariani, Brian D.; Gallagher, Rosa I.; Tran, Khoa; Banks, Stacey; Wiedemann, Joy; Huryk, Heather; Mueller, Claudius; Adamo, Luana; Deng, Jianghong; Petricoin, Emanuel F.; Pastore, Lucia; Zaman, Syed; Menezes, Geetha; Mize, James; Johal, Jasbir; Edmiston, Kirsten; Liotta, Lance A.

    2010-01-01

    Background While it is accepted that a majority of invasive breast cancer progresses from a ductal carcinoma in situ (DCIS) precursor stage, very little is known about the factors that promote survival of DCIS neoplastic cells within the hypoxic, nutrient deprived intraductal microenvironment. Methodology and Principal Findings We examined the hypothesis that fresh human DCIS lesions contain pre-existing carcinoma precursor cells. We characterized these cells by full genome molecular cytogenetics (Illumina HumanCytoSNP profile), and signal pathway profiling (Reverse Phase Protein Microarray, 59 endpoints), and demonstrated that autophagy is required for survival and anchorage independent growth of the cytogenetically abnormal tumorigenic DCIS cells. Ex vivo organoid culture of fresh human DCIS lesions, without enzymatic treatment or sorting, induced the emergence of neoplastic epithelial cells exhibiting the following characteristics: a) spontaneous generation of hundreds of spheroids and duct-like 3-D structures in culture within 2–4 weeks; b) tumorigenicity in NOD/SCID mice; c) cytogenetically abnormal (copy number loss or gain in chromosomes including 1, 5, 6, 8, 13, 17) compared to the normal karyotype of the non-neoplastic cells in the source patient's breast tissue; d) in vitro migration and invasion of autologous breast stroma; and e) up-regulation of signal pathways linked to, and components of, cellular autophagy. Multiple autophagy markers were present in the patient's original DCIS lesion and the mouse xenograft. We tested whether autophagy was necessary for survival of cytogenetically abnormal DCIS cells. The lysosomotropic inhibitor (chloroquine phosphate) of autophagy completely suppressed the generation of DCIS spheroids/3-D structures, suppressed ex vivo invasion of autologous stroma, induced apoptosis, suppressed autophagy associated proteins including Atg5, AKT/PI3 Kinase and mTOR, eliminated cytogenetically abnormal spheroid forming cells from

  16. Triple-negative breast cancer: the impact of guideline-adherent adjuvant treatment on survival--a retrospective multi-centre cohort study.

    PubMed

    Schwentner, L; Wolters, R; Koretz, K; Wischnewsky, M B; Kreienberg, R; Rottscholl, R; Wöckel, A

    2012-04-01

    Triple-negative breast cancer (TNBC) (ER-/PGR-/erb-2-) constitutes an aggressive subtype in breast cancer because it is accompanied by a significant decrease in overall survival (OAS) and recurrence-free survival (RFS) compared with hormone receptor positive breast cancers. This retrospective cohort study investigates the following issues: (1) Is there an impact of guideline-adherent treatment on RFS and OAS in TNBC? (2) Which adjuvant treatment has the most important impact on RFS and OAS in TNBC? This German retrospective multi-centre cohort study included 3,658 patients with primary breast cancer recruited from 2000 to 2005. The definition of guideline adherence was based on the German national S3 guideline for diagnosis and treatment of breast cancer (2004). A total of 371 patients (10.1%) had TNBC. Compared with HR+/erb-2- breast cancer (P = 0.001; HR = 1.75; 95% CI: 1.27-2.40), the recurrence rate of TNBC was significantly higher (P < 0.001; HR = 2.86; 95% CI: 2.17-3.76). Furthermore, the 5-year RFS and OAS was significantly lower in TNBC (RFS: 74.8% [95% CI: 68.8-80.8%] vs. 86.5% [95% CI: 84.6-88.4%] [log-rank P = 0.0001]) (OAS: 75.8% [95% CI: 69.9-81.8%] vs. 86.0% [95% CI: 84.1-87.9%] [log-rank P = 0.0001]). The most important parameters predicting RFS and OAS in TNBC after receiving guideline-conform chemotherapy are guideline-adherent surgery, radiotherapy, nodal status and grading. Overall, 66.8% TNBC were found with one or more (18%) guideline violations, which subsequently impaired OAS and RFS. The most important impact on OAS and RFS in TNBC patients was because of guideline violations (GV) concerning adjuvant radiotherapy and GV concerning adjuvant chemotherapy. Patients with TNBC primarily have a worse prognosis in terms of RFS and OAS than patients of a primarily non-TNBC phenotype. There is a strong association between guideline-adherent adjuvant treatment and improved survival outcome in TNBC. The outcome significantly decreases with the number

  17. Hyaluronan in Peritumoral Stroma and Malignant Cells Associates with Breast Cancer Spreading and Predicts Survival

    PubMed Central

    Auvinen, Päivi; Tammi, Raija; Parkkinen, Jyrki; Tammi, Markku; Ågren, Ulla; Johansson, Risto; Hirvikoski, Pasi; Eskelinen, Matti; Kosma, Veli-Matti

    2000-01-01

    Hyaluronan (HA) is an extracellular matrix polysaccharide that promotes cell migration through its cell surface receptors and by effecting changes in the physical environment. HA expression is frequently increased in malignant tumors, whereas its association with the invasive potential and patient outcome in breast cancer has not been reported. The localization and signal intensity of HA was analyzed in 143 paraffin-embedded tumor samples of human breast carcinoma using a biotinylated HA-specific probe. In the immediate peritumoral stroma, HA signal was moderately or strongly increased in 39% and 56% of the cases, respectively. Normal ductal epithelium showed no HA, whereas in 57% of the tumors at least some of the carcinoma cells were HA positive. The intensity of the stromal HA signal and the presence of cell-associated HA were both significantly related to poor differentiation of the tumors, axillary lymph node positivity, and short overall survival of the patients. In Cox’s multivariate analysis, both the intensity of stromal HA signal alone and that combined with the HA positivity in tumor cells were independent prognostic factors for overall survival. These results suggest that HA is directly involved in the spreading of breast cancer and may offer a potential target for new therapies. PMID:10666382

  18. 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.

  19. SPHK1 regulates proliferation and survival responses in triple-negative breast cancer.

    PubMed

    Datta, Arpita; Loo, Ser Yue; Huang, Baohua; Wong, Lingkai; Tan, Sheryl S L; Tan, Tuan Zea; Lee, Soo-Chin; Thiery, Jean Paul; Lim, Yaw Chyn; Yong, Wei Peng; Lam, Yulin; Kumar, Alan Prem; Yap, Celestial T

    2014-03-27

    Triple-negative breast cancer (TNBC) is characterized by unique aggressive behavior and lack of targeted therapies. Among the various molecular subtypes of breast cancer, it was observed that TNBCs express elevated levels of sphingosine kinase 1 (SPHK1) compared to other breast tumor subtypes. High levels of SPHK1 gene expression correlated with poor overall and progression- free survival, as well as poor response to Doxorubicin-based treatment. Inhibition of SPHK1 was found to attenuate ERK1/2 and AKT signaling and reduce growth of TNBC cells in vitro and in a xenograft SCID mouse model. Moreover, SPHK1 inhibition by siRNA knockdown or treatment with SKI-5C sensitizes TNBCs to chemotherapeutic drugs. Our findings suggest that SPHK1 inhibition, which effectively counteracts oncogenic signaling through ERK1/2 and AKT pathways, is a potentially important anti-tumor strategy in TNBC. A combination of SPHK1 inhibitors with chemotherapeutic agents may be effective against this aggressive subtype of breast cancer.

  20. SPHK1 regulates proliferation and survival responses in triple-negative breast cancer.

    PubMed

    Datta, Arpita; Loo, Ser Yue; Huang, Baohua; Wong, Lingkai; Tan, Sheryl S L; Tan, Tuan Zea; Lee, Soo-Chin; Thiery, Jean Paul; Lim, Yaw Chyn; Yong, Wei Peng; Lam, Yulin; Kumar, Alan Prem; Yap, Celestial T

    2014-08-15

    Triple-negative breast cancer (TNBC) is characterized by unique aggressive behavior and lack of targeted therapies. Among the various molecular subtypes of breast cancer, it was observed that TNBCs express elevated levels of sphingosine kinase 1 (SPHK1) compared to other breast tumor subtypes. High levels of SPHK1 gene expression correlated with poor overall and progression- free survival, as well as poor response to Doxorubicin-based treatment. Inhibition of SPHK1 was found to attenuate ERK1/2 and AKT signaling and reduce growth of TNBC cells in vitro and in a xenograft SCID mouse model. Moreover, SPHK1 inhibition by siRNA knockdown or treatment with SKI-5C sensitizes TNBCs to chemotherapeutic drugs. Our findings suggest that SPHK1 inhibition, which effectively counteracts oncogenic signaling through ERK1/2 and AKT pathways, is a potentially important anti-tumor strategy in TNBC. A combination of SPHK1 inhibitors with chemotherapeutic agents may be effective against this aggressive subtype of breast cancer.

  1. Improving Breast Cancer Survival Analysis through Competition-Based Multidimensional Modeling

    PubMed Central

    Bilal, Erhan; Dutkowski, Janusz; Guinney, Justin; Jang, In Sock; Logsdon, Benjamin A.; Pandey, Gaurav; Sauerwine, Benjamin A.; Shimoni, Yishai; Moen Vollan, Hans Kristian; Mecham, Brigham H.; Rueda, Oscar M.; Tost, Jorg; Curtis, Christina; Alvarez, Mariano J.; Kristensen, Vessela N.; Aparicio, Samuel; Børresen-Dale, Anne-Lise; Caldas, Carlos; Califano, Andrea; Friend, Stephen H.; Ideker, Trey; Schadt, Eric E.; Stolovitzky, Gustavo A.; Margolin, Adam A.

    2013-01-01

    Breast cancer is the most common malignancy in women and is responsible for hundreds of thousands of deaths annually. As with most cancers, it is a heterogeneous disease and different breast cancer subtypes are treated differently. Understanding the difference in prognosis for breast cancer based on its molecular and phenotypic features is one avenue for improving treatment by matching the proper treatment with molecular subtypes of the disease. In this work, we employed a competition-based approach to modeling breast cancer prognosis using large datasets containing genomic and clinical information and an online real-time leaderboard program used to speed feedback to the modeling team and to encourage each modeler to work towards achieving a higher ranked submission. We find that machine learning methods combined with molecular features selected based on expert prior knowledge can improve survival predictions compared to current best-in-class methodologies and that ensemble models trained across multiple user submissions systematically outperform individual models within the ensemble. We also find that model scores are highly consistent across multiple independent evaluations. This study serves as the pilot phase of a much larger competition open to the whole research community, with the goal of understanding general strategies for model optimization using clinical and molecular profiling data and providing an objective, transparent system for assessing prognostic models. PMID:23671412

  2. Improving breast cancer survival analysis through competition-based multidimensional modeling.

    PubMed

    Bilal, Erhan; Dutkowski, Janusz; Guinney, Justin; Jang, In Sock; Logsdon, Benjamin A; Pandey, Gaurav; Sauerwine, Benjamin A; Shimoni, Yishai; Moen Vollan, Hans Kristian; Mecham, Brigham H; Rueda, Oscar M; Tost, Jorg; Curtis, Christina; Alvarez, Mariano J; Kristensen, Vessela N; Aparicio, Samuel; Børresen-Dale, Anne-Lise; Caldas, Carlos; Califano, Andrea; Friend, Stephen H; Ideker, Trey; Schadt, Eric E; Stolovitzky, Gustavo A; Margolin, Adam A

    2013-01-01

    Breast cancer is the most common malignancy in women and is responsible for hundreds of thousands of deaths annually. As with most cancers, it is a heterogeneous disease and different breast cancer subtypes are treated differently. Understanding the difference in prognosis for breast cancer based on its molecular and phenotypic features is one avenue for improving treatment by matching the proper treatment with molecular subtypes of the disease. In this work, we employed a competition-based approach to modeling breast cancer prognosis using large datasets containing genomic and clinical information and an online real-time leaderboard program used to speed feedback to the modeling team and to encourage each modeler to work towards achieving a higher ranked submission. We find that machine learning methods combined with molecular features selected based on expert prior knowledge can improve survival predictions compared to current best-in-class methodologies and that ensemble models trained across multiple user submissions systematically outperform individual models within the ensemble. We also find that model scores are highly consistent across multiple independent evaluations. This study serves as the pilot phase of a much larger competition open to the whole research community, with the goal of understanding general strategies for model optimization using clinical and molecular profiling data and providing an objective, transparent system for assessing prognostic models.

  3. Matrix metalloproteinase genes are associated with breast cancer risk and survival: the Breast Cancer Health Disparities Study.

    PubMed

    Slattery, Martha L; John, Esther; Torres-Mejia, Gabriela; Stern, Mariana; Lundgreen, Abbie; Hines, Lisa; Giuliano, Anna; Baumgartner, Kathy; Herrick, Jennifer; Wolff, Roger K

    2013-01-01

    Matrix metalloproteinases (MMPs) contribute to cancer through their involvement in cancer invasion and metastasis. We evaluated genetic variation in MMP1 (9 SNPs), MMP2 (8 SNPs), MMP3 (4 SNPs), and MMP9 (3 SNPs) and breast cancer risk among Hispanic (2111 cases, 2597 controls) and non-Hispanic white (NHW) (1481 cases, 1586 controls) women in the Breast Cancer Health Disparities Study. Ancestral informative markers (n = 104) were assessed to determine Native American (NA) ancestry. MMP1 [4 single nucleotide polymorphisms (SNPs)] and MMP2 (2 SNPs) were associated with breast cancer overall. MMP1 rs996999 had strongest associations among women with the most NA ancestry (OR 1.61,95% CI 1.09,2.40) as did MMP3 rs650108 (OR 1.36, 95% CI 1.05,1.75) and MMP9 rs3787268 (OR 1.52, 95% CI 1.09,2.13). The adaptive rank truncated product (ARTP) showed a significant pathway p(artp)  value of 0.04, with a stronger association among women with the most NA ancestry (p(artp) = 0.02). Significant pathway genes using the ARTP were MMP1 for all women (p(artp) = 0.02) and MMP9 for women with the most NA ancestry (p(artp) = 0.024); MMP2 was borderline significant overall (p(artp) =0.06) and MMP1 and MMP3 were borderline significant for women with the most NA ancestry (p(artp) = 0.07 and 0.06 respectively). MMP1 and MMP2 were associated with ER+/PR+ and ER+/PR-tumors; MMP3 and MMP9 were associated with ER-/PR- tumors. The pathway was highly significant with survival (p(artp) = 0.0041) with MMP2 having the strongest gene association (p(artp) = 0.0007). Our findings suggest that genetic variation in MMP genes influence breast cancer development and survival in this genetically admixed population.

  4. Association of occult metastases in sentinel lymph nodes and bone marrow with survival of women with early-stage invasive breast cancer

    PubMed Central

    Giuliano, Armando E.; Hawes, Debra; Ballman, Karla V.; Whitworth, Pat W.; Blumencranz, Peter W.; Reintgen, Douglas S.; Morrow, Monica; Leitch, A. Marilyn; Hunt, Kelly K.; McCall, Linda M.; Abati, Andrea; Cote, Richard

    2017-01-01

    Context Immunochemical staining of sentinel lymph nodes (SLNs) and bone marrow identifies breast cancer metastases not seen with routine pathologic or clinical examination. Objective To determine the association between survival and metastases detected by immunochemical staining of SLNs and bone marrow from patients with early-stage breast cancer. Design, Setting, and Patients From May 1999 to May 2003, 126 sites in the American College of Surgeons Oncology Group Z0010 trial enrolled women with clinical T1–T2, N0, M0 invasive breast carcinoma in a prospective observational study. Interventions All patients underwent breast-conserving surgery and SLN dissection; bone marrow aspiration at the time of operation was initially optional and subsequently mandatory (March 2001). SLN specimens (hematoxylin-eosin negative) and bone marrow specimens were sent to a central laboratory for immunochemical staining; treating clinicians were blinded to results. Main Outcome Measures Overall survival (primary end point) and disease-free survival (a secondary end point). Results Of 5119 (98.3%) SLN specimens, 3904 (76.3%) were tumor-negative by hematoxylin-eosin staining. Of 3326 SLN specimens examined by immunohistochemistry, 349 (10.5%) were tumor-positive. Of 3413 bone marrow specimens examined by immunocytochemistry, 104 (3.0%) were positive. At a median follow-up of 6.3 years (through April 2010), 435 patients had died and 376 had disease recurrence. Immunohistochemical evidence of SLN metastases was not significantly associated with overall survival (5-year rates: 95.7% (95% CI, 95.0%–96.5%) for immunohistochemical positive and 95.1% (95% CI, 92.7%–97.5% for immunohistochemical negative disease, P=0.64), unadjusted hazard ratio [HR], 0.90; 95% confidence interval [CI], 0.59–1.39; P=.64). Bone marrow metastases were associated with decreased overall survival (5-year rates: 95.0% (95% CI, 94.3%–95.8%) and 90.1% (95% CI, 84.5%–96.1%), respectively (P=.01) (unadjusted

  5. Does the Intent to Irradiate the Internal Mammary Nodes Impact Survival in Women With Breast Cancer? A Population-Based Analysis in British Columbia

    SciTech Connect

    Olson, Robert A.; Woods, Ryan; Speers, Caroline; Lau, Jeffrey; Lo, Andrea; Truong, Pauline T.; Tyldesley, Scott; Olivotto, Ivo A.; Weir, Lorna

    2012-05-01

    Purpose: To determine the value of the intent to include internal mammary nodes (IMNs) in the radiation therapy (RT) volume for patients receiving adjuvant locoregional (breast or chest wall plus axillary and supraclavicular fossa) RT for breast cancer. Methods and Materials: 2413 women with node-positive or T3/4N0 invasive breast cancer, treated with locoregional RT from 2001 to 2006, were identified in a prospectively maintained, population-based database. Intent to include IMNs in RT volume was determined through review of patient charts and RT plans. Distant relapse free survival (D-RFS), breast cancer-specific survival (BCSS), and overall survival (OS) were compared between the two groups. Prespecified pN1 subgroup analyses were performed. Results: The median follow-up time was 6.2 years. Forty-one percent of study participants received IMN RT. The 5-year D-RFS for IMN inclusion and exclusion groups were 82% vs. 82% (p = 0.82), BCSS was 87% vs. 87% (p = 0.81), and OS was 85% vs. 83% (p = 0.06). In the pN1 subgroup, D-RFS was 90% vs. 88% (p = 0.31), BCSS was 94% vs. 92% (p = 0.18), and OS was 91% vs. 88% (p = 0.01). After potential confounding variables were controlled for, women who received IMN RT did not have significantly different D-RFS (hazard ratio [HR] = 1.02 (95% confidence interval [CI], 0.84-1.24; p = 0.85), BCSS (HR = 0.98 (95% CI, 0.79-1.22; p = 0.88), or OS (HR = 0.95; 95% CI, 0.78-1.15; p = 0.57). In the pN1 subgroup, IMN RT was associated with trends for improved survival that were not statistically significant: D-RFS (HR = 0.87; 95% CI, 0.63-1.22; p = 0.42), BCSS (HR = 0.85; 95% CI, 0.57-1.25; p = 0.39), and OS (HR = 0.78; 95% CI, 0.56-1.09; p = 0.14). Conclusions: After a median follow-up time of 6.2 years, although intentional IMN RT was not associated with a significant improvement in survival, this population-based study suggests that IMN RT may contribute to improved outcomes in selected patients with N1 disease.

  6. 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

  7. Netrin-1 expression confers a selective advantage for tumor cell survival in metastatic breast cancer

    PubMed Central

    Fitamant, Julien; Guenebeaud, Céline; Coissieux, Marie-May; Guix, Catherine; Treilleux, Isabelle; Scoazec, Jean-Yves; Bachelot, Thomas; Bernet, Agnès; Mehlen, Patrick

    2008-01-01

    Netrin-1, an axon navigation cue was proposed to play a crucial role during colorectal tumorigenesis by regulating apoptosis. The netrin-1 receptors DCC and UNC5H were shown to belong to the family of dependence receptors that share the ability to induce apoptosis in the absence of their ligands. Such a trait confers on these receptors a tumor suppressor activity. Expression of one of these dependence receptors at the surface of a tumor cell is indeed speculated to render this cell dependent on ligand availability for its survival, hence inhibiting uncontrolled cell proliferation or metastasis. Consequently, it is a selective advantage for a tumor cell to lose this dependence receptor activity, as previously described with losses of DCC and UNC5H expression in human cancers. However, the model predicts that a similar advantage may be obtained by gaining autocrine expression of the ligand. We describe here that, unlike human nonmetastatic breast tumors, a large fraction of metastatic breast cancers overexpress netrin-1. Moreover, we show that netrin-1-expressing mammary metastatic tumor cell lines undergo apoptosis when netrin-1 expression is experimentally decreased or when decoy soluble receptor ectodomains are added. Such treatments prevent metastasis formation both in a syngenic mouse model of lung colonization of a mammary cancer cell line and in a model of spontaneous lung metastasis of xenografted human breast tumor. Thus, netrin-1 expression observed in a large fraction of human metastatic breast tumors confers a selective advantage for tumor cell survival and potentially represents a promising target for alternative anticancer therapeutic strategies. PMID:18353983

  8. 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

  9. 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.

  10. 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

  11. Actigraphy-Measured Sleep Disruption as a Predictor of Survival among Women with Advanced Breast Cancer

    PubMed Central

    Palesh, Oxana; Aldridge-Gerry, Arianna; Zeitzer, Jamie M.; Koopman, Cheryl; Neri, Eric; Giese-Davis, Janine; Jo, Booil; Kraemer, Helena; Nouriani, Bita; Spiegel, David

    2014-01-01

    Background: Poor sleep, prevalent among cancer survivors, is associated with disrupted hormonal circadian rhythms and poor quality of life. Using a prospective research design, this study aimed to clarify the relationship between objective measures of sleep efficiency and sleep disruption with survival among women with advanced breast cancer. Method: We examined sleep quality and duration via wrist-worn actigraphy and sleep diaries for 3 days among 97 women in whom advanced breast cancer was diagnosed (age = 54.6 ± 9.8 years). Sleep efficiency was operationalized using actigraphy as the ratio of total sleep time to total sleep time plus wake after sleep onset. Results: As hypothesized, better sleep efficiency was found to predict a significant reduction in overall mortality (hazard ratio [HR], 0.96; 95% confidence interval [CI], 0.94–0.98; P < 0.001) at median 6 y follow-up. This relationship remained significant (HR, 0.94; 95% CI, 0.91–0.97; P < 0.001) even after adjusting for other known prognostic factors (age, estrogen receptor status, cancer treatment, metastatic spread, cortisol levels, and depression). Secondary hypotheses were also supported (after adjusting for baseline prognostic factors) showing that less wake after sleep onset (HR, 0.41; 95% CI, 0.25–0.67; P < 0.001), fewer wake episodes, (HR, 0.93; 95% CI, 0.88–0.98; P = 0.007); and shorter wake episode duration (HR, 0.29; 95% CI, 0.14–0.58; P < 0.001) also contributed to reductions in overall mortality. Conclusions: These findings show that better sleep efficiency and less sleep disruption are significant independent prognostic factors in women with advanced breast cancer. Further research is needed to determine whether treating sleep disruption with cognitive behavioral and/or pharmacologic therapy could improve survival in women with advanced breast cancer. Citation: Palesh O, Aldridge-Gerry A, Zeitzer JM, Koopman C, Neri E, Giese-Davis J, Jo B, Kraemer H, Nouriani B, Spiegel D

  12. Influence of socioeconomic factors on survival after breast cancer--a nationwide cohort study of women diagnosed with breast cancer in Denmark 1983-1999.

    PubMed

    Dalton, Susanne Oksbjerg; Ross, Lone; Düring, Maria; Carlsen, Kathrine; Mortensen, Preben Bo; Lynch, John; Johansen, Christoffer

    2007-12-01

    The reasons for social inequality in breast cancer survival are far from established. Our study aims to study the importance of a range of socioeconomic factors and comorbid disorders on survival after breast cancer surgery in Denmark where the health care system is tax-funded and uniform. All 25,897 Danish women who underwent protocol-based treatment for breast cancer in 1983-1999 were identified in a clinical database and information on socioeconomic variables and both somatic and psychiatric comorbid disorders was obtained from population-based registries. We used Cox proportional hazards models to estimate the association between socioeconomic position and overall survival and further to analyse breast cancer specific deaths in a competing risk set-up regarding all other causes of death as competing risks. The adjusted hazard ratio (HR) for death was reduced in women with higher education (HR, 0.91; 95% confidence interval (CI), 0.85-0.98), with higher income (HR, 0.93; 95% CI, 0.87-0.98) and with larger dwellings (HR, 0.90; 95% CI, 0.85-0.96 for women living in houses larger than 150 m(2)). Presence of comorbid disorders increased the HR. An interaction between income and comorbid disorders resulting in a 15% lower survival 10 year after primary surgery in poor women with low-risk breast cancer having comorbid conditions ( approximately 65%) compared to rich women with similar breast cancer prognosis and comorbid conditions ( approximately 80%) suggests that part of the explanation for the social inequality in survival after breast cancer surgery in Denmark lies in the access to and/or compliance with management of comorbid conditions in poorer women.

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

    PubMed

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

    2015-07-30

    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.

  14. TTK is a favorable prognostic biomarker for triple-negative breast cancer survival

    PubMed Central

    Xu, Qianqian; Xu, Yali; Pan, Bo; Wu, Liangcai; Ren, Xinyu; Zhou, Yidong; Mao, Feng; Lin, Yan; Guan, Jinghong; Shen, Songjie; Zhang, Xiaohui; Wang, Changjun; Zhong, Ying; Zhou, Liangrui; Liang, Zhiyong; Zhao, Haitao; Sun, Qiang

    2016-01-01

    Purpose Previous studies demonstrate that threonine and tyrosine kinase (TTK) is overexpressed in triple-negative breast cancer (TNBC), but there are conflicting results regarding its effect on TNBC survival. The purpose of this study was to assess the prognostic significance of TTK expression in primary TNBC. Results Of 169 consecutive cases eligible for this study, 164 included follow-up information. Cytoplasm and membrane TTK staining was observed in 99.4% of cases, while 5.9% displayed whole cell immunostaining. At a discriminating threshold of 55, elevated TTK expression was associated with prolonged disease free survival (DFS) (p < 0.001) and overall survival (OS) (p = 0.024) in primary TNBC and prolonged DFS in individual basal-like (p = 0.001) and non-basal-like (p = 0.001) TNBC subtypes. In addition, Cox regression analysis demonstrated that elevated TTK expression was an independent prognostic factor for DFS in TNBC (p < 0.001). Methods TTK expression of 169 samples was tested by immunohistochemistry (IHC). A receiver operating characteristic (ROC) curve was used to identify a cutpoint for TTK expression, which was analyzed for its association with patients' clinicopathological factors and survival using Chi-square, log-rank, and Cox regression analyses. Conclusions TTK is a favorable prognostic biomarker associated with TNBC survival. PMID:27833085

  15. 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

  16. 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.

  17. Blockade of PAR1 signaling with cell-penetrating pepducins inhibits Akt-survival pathways in breast cancer cells and suppresses tumor survival and metastasis

    PubMed Central

    Yang, Eric; Boire, Adrienne; Agarwal, Anika; Nguyen, Nga; O'Callaghan, Katie; Tu, Powen; Kuliopulos, Athan; Covic, Lidija

    2009-01-01

    Protease-activated receptor 1 (PAR1) is a G protein-coupled receptor that is not expressed in normal breast epithelia, but is up-regulated in invasive breast carcinomas. In the present study, we found that matrix metalloprotease-1 (MMP-1) robustly activates the PAR1-Akt survival pathway in breast carcinoma cells. This process is blocked by a cell-penetrating lipopeptide ‘pepducin’, P1pal-7, which is a potent inhibitor of cell viability in breast carcinoma cells expressing PAR1. Both a MMP-1 inhibitor and P1pal-7 significantly promote apoptosis in breast tumor xenografts and inhibit metastasis to the lungs by up to 88%. Dual therapy with P1pal-7 and taxotere inhibits the growth of MDA-MB-231 xenografts by 95%. Consistently, biochemical analysis of xenograft tumors treated with P1pal-7 or MMP-1 inhibitor demonstrated attenuated Akt activity. Ectopic expression of constitutively active Akt rescues breast cancer cells from the synergistic cytotoxicity of P1pal-7 and taxotere, suggesting that Akt is a critical component of PAR1-dependent cancer cell viability. Together, these findings indicate that blockade of MMP1-PAR1 signaling may provide a benefit beyond treatment with taxotere alone in advanced, metastatic breast cancer. PMID:19622769

  18. Sex of first child and breast cancer survival in young women.

    PubMed

    Olson, J C; Bogdan, G F; Tuthill, R W; Nasca, P C; Janerich, D T

    2001-05-01

    Two studies have reported that young women with breast cancer face increased risk of early mortality if their first child was male rather than female. An immunological mechanism has been suggested. We sought to confirm these results in a larger, historical cohort study of 223 parous women who were aged <45 years at breast cancer diagnosis during 1983-1987. Subjects were identified through the Maine Cancer Registry. Follow-up data were obtained from hospitals, physicians, and death certificates. Reproductive history data were obtained from the next of kin of the deceased women, birth certificates, physicians, hospitals, and lastly, subjects. With a 7-year follow-up, multivariate modeling found a lower mortality risk in women with a male first child (hazard ratio [HR] 0.51, 95% confidence interval [CI] 0.32-0.81, log-rank comparison). The survival advantage remained for at least 13 years in women with a male firstborn. Thus, previous studies were not confirmed. Mortality risk in young women with breast cancer is not increased by having borne a male first child rather than a female first child.

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

    PubMed

    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

    2013-07-01

    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.

  20. 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

  1. 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.

  2. Blood sampling in juvenile buff-breasted sandpipers: Movement, weight change and survival

    USGS Publications Warehouse

    Lanctot, Richard B.

    1994-01-01

    The effect of blood sampling on juvenile Buff-breasted Sandpipers (Tryngites subruficollis) was evaluated by comparing movements, mass, and survival of 10 broods (37 chicks) that were bled and eight broods (31 chicks) that were not bled. Blood was sampled from the jugular vein of chicks when they weighed 9.1 ± 0.9 g (x̄ ± SD) on or within 1 d of hatch. Chicks showed few short-term negative effects from blood sampling. Individual chicks suffered little physical injury, and five of eight chicks where injury occurred (i.e., hematomas formed) survived to fledging. Furthermore, bled broods gained mass at a comparable rate during the first 5 d post-hatch, and were resighted at similar frequencies as broods that were not bled. Bled broods moved slightly longer distances than control broods 1 d after hatch, however. This increased activity may have been stress-induced, but was only temporary; bled and control broods made similar long-term movements, and the probability of resighting was similar at fledging. With the proper precautions, it appears that Buff-breasted Sandpiper young can be safely sampled for blood at an early age without causing undue harm.

  3. Acetyl-CoA carboxylase alpha is essential to breast cancer cell survival.

    PubMed

    Chajès, Véronique; Cambot, Marie; Moreau, Karen; Lenoir, Gilbert M; Joulin, Virginie

    2006-05-15

    Activation of de novo fatty acid synthesis is a characteristic feature of cancer cells. We have recently described an interaction between acetyl-CoA carboxylase alpha (ACCalpha), a key enzyme in fatty acid synthesis, and BRCA1, which indicates a possible connection between lipid synthesis and genetic factors involved in susceptibility to breast and ovarian cancers. For this reason, we explored the role of ACCalpha in breast cancer cell survival using an RNA interference (RNAi) approach. We show that specific silencing of either the ACCalpha or the fatty acid synthase (FAS) genes in cancer cells results in a major decrease in palmitic acid synthesis. Depletion of the cellular pool of palmitic acid is associated with induction of apoptosis concomitant with the formation of reactive oxygen species (ROS) and mitochondrial impairment. Expression of a small interfering RNA (siRNA)-resistant form of ACCalpha mRNA prevented the effect of ACCalpha-RNAi but failed to prevent the effect of FAS gene silencing. Furthermore, supplementation of the culture medium with palmitate or with the antioxidant vitamin E resulted in the complete rescue of cells from both ACCalpha and FAS siRNA-induced apoptosis. Finally, human mammary epithelial cells are resistant to RNAi against either ACCalpha or FAS. These data confirm the importance of lipogenesis in cancer cell survival and indicate that this pathway represents a key target for antineoplastic therapy that, however, might require specific dietary recommendation for full efficacy.

  4. 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

  5. Breast cancer and leptomeningeal disease (LMD): hormone receptor status influences time to development of LMD and survival from LMD diagnosis.

    PubMed

    Yust-Katz, S; Garciarena, P; Liu, D; Yuan, Y; Ibrahim, N; Yerushalmi, R; Penas-Prado, M; Groves, M D

    2013-09-01

    Leptomeningeal disease (LMD) occurs in 5 % of breast cancer patients. The aim of this study was to identify risk factors related to survival and time to development of LMD in breast cancer patients. A retrospective analysis of breast cancer patients with LMD, evaluated in MDACC between 1995 and 2011. 103 patients with diagnosis of breast cancer and LMD were identified (one male). The median age at LMD diagnosis was 49.2 years. 78.2 % had invasive ductal carcinoma. Hormone receptors (HRs) were positive in 55.3 % of patients, 47.4 % were human epidermal growth factor receptor 2-positive and 22.8 % were triple negative. 52 % of the patients were treated with WBRT, 19 % with spinal radiation, 36 % with systemic chemotherapy and 55 % with intrathecal chemotherapy. Estimated median overall survival from time of breast cancer diagnosis was 3.66 years. Median survival from time of LMD diagnosis was 4.2 months. Time from breast cancer diagnosis to LMD was 2.48 years. In multivariate analysis, HR status and stage at diagnosis were significantly associated with time to LMD diagnosis (p < 0.05). In triple negative patients, time to LMD was shorter. In patients who were HR positive, time to LMD was longer. Survival from LMD diagnosis was significantly associated with both treatment, as well as positive HR status (multivariate analysis p < 0.05). In conclusion LMD has dismal prognosis in breast cancer patients. HR status contributes to time to LMD diagnosis and survival from LMD diagnosis. The impact of treatment aimed at LMD cannot be ascertained in our retrospective study due to the inherent bias associated with the decision to treat.

  6. Reproductive steroid hormones and recurrence-free survival in women with a history of breast cancer.

    PubMed

    Rock, Cheryl L; Flatt, Shirley W; Laughlin, Gail A; Gold, Ellen B; Thomson, Cynthia A; Natarajan, Loki; Jones, Lovell A; Caan, Bette J; Stefanick, Marcia L; Hajek, Richard A; Al-Delaimy, Wael K; Stanczyk, Frank Z; Pierce, John P

    2008-03-01

    Epidemiologic studies fairly consistently show in postmenopausal women that reproductive steroid hormones contribute to primary breast cancer risk, and this association is strongly supported by experimental studies using laboratory animals and model systems. Evidence linking sex hormone concentrations with risk for recurrence in women diagnosed with breast cancer is limited; however, beneficial effects of antiestrogenic therapy on recurrence-free survival suggest that these hormones affect progression and risk for recurrence. This study examined whether baseline serum concentrations of estradiol, testosterone, and sex hormone binding globulin were associated with recurrence-free survival in a nested case-control cohort of women from a randomized diet trial (Women's Healthy Eating and Living Study) who were followed for >7 years after diagnosis. In 153 case-control pairs of perimenopausal and postmenopausal women in this analysis, total estradiol [hazard ratio (HR), 1.41 per unit increase in log concentration; 95% confidence interval (95% CI), 1.01-1.97], bioavailable estradiol (HR, 1.26; 95% CI, 1.03-1.53), and free estradiol (HR, 1.31; 95% CI, 1.03-1.65) concentrations were significantly associated with risk for recurrence. Recurred women had an average total estradiol concentration that was double that of nonrecurred women (22.7 versus 10.8 pg/mL; P = 0.05). Testosterone and sex hormone binding globulin concentrations did not differ between cases and controls and were not associated with risk for recurrence. Although genetic and metabolic factors likely modulate the relationship between circulating sex hormones and risk, results from this study provide evidence that higher serum estrogen concentration contributes to risk for recurrence in women diagnosed with early stage breast cancer.

  7. 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

    2015-05-01

    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.

  8. 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

  9. Phosphorylated eIF2α predicts disease-free survival in triple-negative breast cancer patients.

    PubMed

    Guo, Liang; Chi, Yayun; Xue, Jingyan; Ma, Linxiaoxi; Shao, Zhiming; Wu, Jiong

    2017-03-15

    Phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), which functions as a marker of endoplasmic reticulum stress, has been reported to be associated with patient prognosis in various cancers. However, little is known about the prognostic value of p-eIF2α in breast cancer, particularly in different breast cancer subtypes. An immunohistochemistry screen for p-eIF2α was performed using a tissue microarray containing 233 tumors and paired peritumoral tissues from female patients diagnosed with breast cancer. The staining results were scored semiquantitatively, and the p-eIF2α expression level in breast cancer and its potential prognostic value were investigated. In this retrospective cohort study, we found that p-eIF2α levels were significantly upregulated in breast cancer (P < 0.001). p-eIF2α level was negatively correlated with lymph node status (P = 0.039). Survival analysis by Kaplan-Meier estimation and Cox regression showed that p-eIF2α level was correlated with better disease free survival (P = 0.026) and served as an independent prognostic factor (P = 0.046) in patients with triple-negative breast cancer. Our study revealed that p-eIF2α was upregulated in breast cancer and represented a novel predictor of prognosis in patients with triple-negative subtype.

  10. Phosphorylated eIF2α predicts disease-free survival in triple-negative breast cancer patients

    PubMed Central

    Guo, Liang; Chi, Yayun; Xue, Jingyan; Ma, Linxiaoxi; Shao, Zhiming; Wu, Jiong

    2017-01-01

    Phosphorylated eukaryotic translation initiation factor 2α (p-eIF2α), which functions as a marker of endoplasmic reticulum stress, has been reported to be associated with patient prognosis in various cancers. However, little is known about the prognostic value of p-eIF2α in breast cancer, particularly in different breast cancer subtypes. An immunohistochemistry screen for p-eIF2α was performed using a tissue microarray containing 233 tumors and paired peritumoral tissues from female patients diagnosed with breast cancer. The staining results were scored semiquantitatively, and the p-eIF2α expression level in breast cancer and its potential prognostic value were investigated. In this retrospective cohort study, we found that p-eIF2α levels were significantly upregulated in breast cancer (P < 0.001). p-eIF2α level was negatively correlated with lymph node status (P = 0.039). Survival analysis by Kaplan–Meier estimation and Cox regression showed that p-eIF2α level was correlated with better disease free survival (P = 0.026) and served as an independent prognostic factor (P = 0.046) in patients with triple-negative breast cancer. Our study revealed that p-eIF2α was upregulated in breast cancer and represented a novel predictor of prognosis in patients with triple-negative subtype. PMID:28294178

  11. 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

  12. BRCA mutations and survival in breast cancer: an updated systematic review and meta-analysis.

    PubMed

    Zhu, Yaning; Wu, Jian; Zhang, Chengwan; Sun, Suan; Zhang, Jian; Liu, Wenjie; Huang, Jian; Zhang, Zhihong

    2016-10-25

    BRCA mutations occur frequently in breast cancer (BC), but their prognostic impact on outcomes of BC has not been determined. We conducted an updated meta-analysis on the association between BRCA mutations and survival in patients with BC. Electronic databases were searched. The primary outcome measure was overall survival (OS), and the secondary outcome measures included breast cancer-specific survival (BCSS) and event-free survival (EFS). Hazard ratios (HR) and 95% confidence interval (CI) were abstracted and pooled with random-effect modeling. Data from 297, 402 patients with BC were pooled from 34 studies. The median prevalence rates of BRCA1 and BRCA2 mutations were 14.5% and 8.3%, respectively. BRCA mutations were associated with worse OS (BRCA1: HR = 1.69, 95% CI, 1.35 to 2.12, p < 0.001; BRCA2: HR = 1.50, 95% CI 1.03 to 2.19, p = 0.034). However, this did not translate into poor BCSS (BRCA1: HR = 1.14, 95% CI, 0.81 to 1.16, p = 0.448; BRCA2: HR = 1.16; 95% CI 0.82 to 1.66, p = 0.401) or EFS (BRCA1: HR = 1.10, 95% CI, 0.86 to 1.41, p = 0.438; BRCA2: HR= 1.09; 95% CI 0.81 to 1.47, p = 0.558). Several studies analyzed BRCA1 and BRCA2 mutations together and found no impact on OS (HR = 1.21; 95% CI, 0.73 to 2.00, p = 0.454) or EFS (HR = 0.94; 95% CI, 0.60 to 1.48, p = 0.787). BRCA1 and BRCA2 mutations were associated with poor OS in patients with BC, but had no significant impact on BCSS or EFS. An improved survival was observed in BC patients who had BRCA1 mutation and treated with endocrinotherapy. The results may have therapeutic and prognostic implications important for BRCA mutation carriers with BC.

  13. Patterns of metastasis and survival in breast cancer patients: a preliminary study in an Iranian population.

    PubMed

    Ziaei, Jamal Eivazi; Pourzand, Ali; Bayat, Amrollah; Vaez, Jalil

    2012-01-01

    Due to lack of sufficient data on characteristics of breast cancer patients and risk factors for developing metastasis in Iran this study was designed to understand clinical aspects impacting on survival. A cross-sectional study on breast cancer patients was conducted in an oncology clinic of the university hospital between 1995 and 2010. Data were retrieved from medical records and included age, menopausal status, tumor diameter, number of involved nodes, histopathological type, estrogen and progesterone receptor expression, c-erbB-2, primary and secondary metastasis sites, overall survival, disease free interval and type of chemotherapy protocol. The results were analyzed with SPSS 13 software.The mean age of the patients was 49.2 (27-89) years. The primary tumors were mainly ER positive (48%) and PR negative (49.3%). The status of lymph nodes dissected and examined in these patients was unknown in 19 patients (25.3%) while 18 patients (24%) had positive lymph nodes with no report on the number of involved nodes. All of the patients had received antracyclin based chemotherapy in an adjuvant or metastatic setting. Adjuvant hormonal therapy was administered to receptor positive patients. In average, overall survival after recurrence was 30 months (95%CI 24.605-35.325) for non-skeletal versus 42 months (95%CI 31.211-52.789) for skeletal metastasis (P= 0.002). The median survival was also greater for receptor positive patients; 39 months (95%CI 33.716-44.284) for PR+ versus 26 months (95%CI 19.210-32.790) for PR- (P=0.047) and 38 months (95%CI 32.908-43.092) for ER+ versus 27 months (95%CI 18.780-35.220) for ER- patients (P=0.016). No relation was found between site of first metastasis and hormone receptor, age, tumor diameter, DFI and menopausal status. Sites of metastasis were independent of age, size of the tumor, menopausal and hormone receptor status in this study. Overall survival provided significant relations with respect to receptor status and bone

  14. 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…

  15. The influence of nativity and neighborhoods on breast cancer stage at diagnosis and survival among California Hispanic women

    PubMed Central

    2010-01-01

    Background In the US, foreign-born Hispanics tend to live in socioeconomic conditions typically associated with later stage of breast cancer diagnosis, yet they have lower breast cancer mortality rates than their US-born counterparts. We evaluated the impact of nativity (US- versus foreign-born), neighborhood socioeconomic status (SES) and Hispanic enclave (neighborhoods with high proportions of Hispanics or Hispanic immigrants) on breast cancer stage at diagnosis and survival among Hispanics. Methods We studied 37,695 Hispanic women diagnosed from 1988 to 2005 with invasive breast cancer from the California Cancer Registry. Nativity was based on registry data or, if missing, imputed from case Social Security number. Neighborhood variables were developed from Census data. Stage at diagnosis was analyzed with logistic regression, and survival, based on vital status determined through 2007, was analyzed with Cox proportional hazards regression. Results Compared to US-born Hispanics, foreign-born Hispanics were more likely to be diagnosed at an advanced stage of breast cancer (adjusted odds ratio (OR) = 1.14, 95% confidence interval (CI): 1.09-1.20), but they had a somewhat lower risk of breast cancer specific death (adjusted hazard ratio (HR) = 0.94, 95% CI: 0.90-0.99). Living in low SES and high enclave neighborhoods was associated with advanced stage of diagnosis, while living in a lower SES neighborhood, but not Hispanic enclave, was associated with worse survival. Conclusion Identifying the modifiable factors that facilitate this survival advantage in Hispanic immigrants could help to inform specific interventions to improve survival in this growing population. PMID:21050464

  16. 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.

  17. Survival Prediction and Feature Selection in Patients with Breast Cancer Using Support Vector Regression

    PubMed Central

    Goli, Shahrbanoo; Faradmal, Javad; Mashayekhi, Hoda; Soltanian, Ali-Reza

    2016-01-01

    The Support Vector Regression (SVR) model has been broadly used for response prediction. However, few researchers have used SVR for survival analysis. In this study, a new SVR model is proposed and SVR with different kernels and the traditional Cox model are trained. The models are compared based on different performance measures. We also select the best subset of features using three feature selection methods: combination of SVR and statistical tests, univariate feature selection based on concordance index, and recursive feature elimination. The evaluations are performed using available medical datasets and also a Breast Cancer (BC) dataset consisting of 573 patients who visited the Oncology Clinic of Hamadan province in Iran. Results show that, for the BC dataset, survival time can be predicted more accurately by linear SVR than nonlinear SVR. Based on the three feature selection methods, metastasis status, progesterone receptor status, and human epidermal growth factor receptor 2 status are the best features associated to survival. Also, according to the obtained results, performance of linear and nonlinear kernels is comparable. The proposed SVR model performs similar to or slightly better than other models. Also, SVR performs similar to or better than Cox when all features are included in model. PMID:27882074

  18. Protein Intake and Breast Cancer Survival in the Nurses' Health Study.

    PubMed

    Holmes, Michelle D; Wang, Jun; Hankinson, Susan E; Tamimi, Rulla M; Chen, Wendy E

    2017-01-20

    Purpose Greater protein intake has been associated with better breast cancer survival in several prospective studies, including among 1,982 women in the Nurses' Health Study. We proposed to extend this previous finding. We hypothesized that protein, essential amino acid, branched-chain amino acid, and leucine intakes are associated with improved survival and that these associations are stronger in tumors expressing insulin receptor (IR). Patients and Methods We included 6,348 women diagnosed with stage I to III breast cancer between 1976 and 2004. There were 1,046 distant recurrences. Relative risks (RRs) and 95% CIs were calculated according to quintiles of updated postdiagnostic diet using adjusted Cox proportional hazards models based on follow-up until 2010. Results There was an inverse association between energy-adjusted protein intake and recurrence. Multivariable RRs for increasing quintiles of intake compared with the lowest were 0.95 (95% CI, 0.79 to 1.15), 0.92 (95% CI, 0.76 to 1.11), 0.75 (95% CI, 0.61 to 0.91), and 0.84 (95% CI, 0.69 to 1.03; trend P = .02). For animal protein intake, the RRs were 0.88 (95% CI, 0.73 to 1.06), 0.85 (95% CI, 0.70 to 1.02), 0.75 (95% CI, 0.62 to 0.92), and 0.78 (95% CI, 0.63 to 0.95; trend P = .003). Neither essential amino acids, branched-chain amino acids, nor any individual amino acid stood out as being the source of the association. The association also did not differ by IR status. There was no clear association with any protein-containing foods. Conclusion We found a modest survival advantage with higher intake of protein, regardless of IR status. There was no clear mechanism for this association, although it is consistent with prior studies. Our data suggest that there is likely no advantage for women with a history of breast cancer in restricting protein intake or protein-containing foods.

  19. 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

  20. Health-related quality of life as prognostic factor for response, progression-free survival, and survival in women with metastatic breast cancer.

    PubMed

    Svensson, Helene; Hatschek, Thomas; Johansson, Hemming; Einbeigi, Zakaria; Brandberg, Yvonne

    2012-06-01

    The purpose of this study was to, on an exploratory basis, investigate the role of health-related quality of life (HRQoL) at randomization as an independent prognostic factor for response to treatment, progression-free survival (PFS), and survival. In the TEX trial, 287 patients with locally advanced or distant metastatic breast cancer were randomized to either epirubicin and paclitaxel (ET) or epirubicin, paclitaxel, and capecitabine (TEX). Treatment was repeated every 3 weeks. The EORTC QLQ-C30 questionnaire was used to assess HRQoL before randomization. A total of 252 (88%) patients completed EORTC QLQ-C30 before randomization. Clinical conditions included in the multivariate model were age, number of metastases, ECOG performance status, time between diagnosis and randomization, and treatment arm. Univariate analysis revealed an association between prolonged survival and the HRQoL variables global health, physical functioning, role functioning, fatigue, and pain (P < 0.01). After controlling for clinical conditions, only fatigue remained statistically significant. No statistically significant relationships were found between HRQoL and PFS. In the analysis of the association between HRQoL and response to treatment, role functioning, social functioning, fatigue, nausea/vomiting, and appetite loss remained statistically significant. HRQoL variables could act as important predictors of response to treatment, progression-free survival, and overall survival in women with metastatic breast cancer.

  1. 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.

  2. Poorer breast cancer survival outcomes in males than females might be attributable to tumor subtype

    PubMed Central

    Zhu, Shan; Wu, Juan; Li, Xiang; Liu, Qian; Wei, Wen; Sun, Shengrong

    2016-01-01

    Background & Aims Substantial controversy exists regarding the differences in tumor subtypes between male breast cancer (MBC) and female breast cancer (FBC). This is the largest population-based study to compare MBC and FBC patients. Methods Using data obtained by the Surveillance, Epidemiology, and End Results (SEER) program from 2010-2012, a retrospective, population-based cohort study was conducted to investigate tumor subtype-specific differences in various characteristics, overall survival (OS) and breast cancer-specific mortality (BCSM) between males and females. Results In all, 181,814 BC patients (1,516 male and 180,298 female) were eligible for this study. The male patients were more likely to be black, older, and have lower histological grades, more advanced stages, larger tumors, more lymph node and distant metastases and human epidermal growth factor receptor 2 (HER2)-negative tumors (each p<0.05). A matched analysis showed that the 2-year OS was 91.2% and 93.7% and that the BCSM was 2.2% and 2.5% for male and female patients, respectively. The univariate analysis showed that male triple-negative (TN), hormone receptor (HoR)-positive/HER2-positive and HoR-positive/HER2-negative patients had poorer OS (p <0.01). Meanwhile, the HoR-positive/HER2-positive and TN subtypes were associated with a higher BCSM in MBC patients (p<0.01). The multivariate analysis revealed that TN MBC patients had poorer OS and BCSM (p<0.05). Simultaneously, the results showed that male patients in the HoR-positive/HER2-negative subgroup were less likely to die of BC when adjusting for other factors (p<0.05). Conclusions The analysis of 2-year OS and BCSM among the BC subtypes showed clear differences between MBC and FBC patients with the TN subtype; these differences warrant further investigation PMID:27655704

  3. Expression of Proteins Involved in Epithelial-Mesenchymal Transition as Predictors of Metastasis and Survival in Breast Cancer Patients

    DTIC Science & Technology

    2015-01-01

    Medical Data, University of Michigan School of Public Health Graduate Summer Session in Epidemiology). 5 Task 4 - Trainee has worked with a...Metastasis and Survival in Breast Cancer Patients PRINCIPAL INVESTIGATOR: Michelle Roberts CONTRACTING ORGANIZATION: Health Research Inc. Buffalo...Detrick, Maryland 21702-5012 DISTRIBUTION STATEMENT: X Approved for public release; distribution unlimited The views, opinions and/or findings

  4. Hemoglobin level trajectories in the early treatment period are related with survival outcomes in patients with breast cancer

    PubMed Central

    Lee, Chia-Lin; Tsai, Chun-Hao; Yeh, Dah-Cherng; Lin, Chi-Shy; Li, Yu-Fen; Tzeng, Huey-En

    2017-01-01

    Hemoglobin (Hb) levels are reportedly related with treatment outcomes and survival in patients of breast cancer. However, the long-term change in Hb levels after treatment and the effects of Hb on survival remain unknown. This retrospective cohort study enrolled 1931 breast cancer patients with pathological stage I-IV between 1/1/2003 and 12/31/2013. Latent class modeling was used to identify trajectories in monthly Hb levels over time. The primary endpoint was 10-year cancer-related death. We identified 5 distinct Hb trajectories: persistent anemia (5.6 %; n = 109), improved anemia (4.8 %, n = 93), mild anemia (21.0%; n = 406), low normal Hb (46.6 %; n = 899), and normal Hb (21.9%; n = 424). Compared with the normal-Hb group, trajectories with low Hb levels had worst 10-year survival. The adjusted hazard ratios were 1.79(95% CI, 0.91-3.53) for the improved anemia group, 1.09(95% CI, 0.68-1.74) for the mild anemia group, 1.06 (95% CI, 0.71-1.60) for the low normal Hb group, and 2.19(95% CI 1.28-3.75) for the persistent anemia group. Our findings show there are five Hb level trajectories during breast cancer treatment. The anemia Hb level trajectory during the first 12 months after treatment reflect the worst cancer-related 10-year survival in breast cancer patients. PMID:27906669

  5. Dietary lignan intakes in relation to survival among women with breast cancer: the Western New York Exposures and Breast Cancer (WEB) Study.

    PubMed

    McCann, Susan E; Thompson, Lilian U; Nie, Jing; Dorn, Joan; Trevisan, Maurizio; Shields, Peter G; Ambrosone, Christine B; Edge, Stephen B; Li, Hsin-Fang; Kasprzak, Christina; Freudenheim, Jo L

    2010-07-01

    Dietary lignan intakes have been associated with reduced breast cancer risks; however, no previous studies have investigated whether lignan intake might be associated with breast cancer survival. We examined the association of dietary lignan intakes with survival in 1122 women with primary, incident, histologically confirmed breast cancer identified between 1996 and 2001, and with vital status determined through December 31, 2006. Diet in the 12-24 months before diagnosis was assessed with an extensive food frequency questionnaire, and potential confounders assessed from an extensive epidemiologic interview and abstracted clinical data. Lignan intake was calculated using published food composition data. Hazard ratios (HR), and 95% confidence intervals (CIs) for dietary lignan intakes with all cause, and breast cancer mortality were estimated using Cox proportional hazards adjusting for age, education, race, total energy intake, tumor stage, and body mass index. Of the 1122 women with complete dietary data, 160 had died by the end of follow-up. Among postmenopausal women only, those in the highest versus lowest quartile of lignan intakes had a statistically significant reduction in the risk of all cause mortality (HR 0.49, 95% CI 0.26-0.91) and a significantly reduced risk of breast cancer mortality (HR 0.29, 95% CI 0.11-0.76). Higher intakes of dried beans (HR 0.61, 95% CI 0.36-1.03), but not fruits, vegetables, or grains, were also weakly associated with overall mortality. In summary, our results suggest that higher lignan intakes may be associated with improved survival among postmenopausal women with breast cancer.

  6. Long-term Survival after Lapatinib Rechallenge in Isolated Brain Metastasis of HER2-positive Breast Cancer

    PubMed Central

    Karagöz, Bülent; Özgün, Alpaslan; Emirzeoğlu, Levent; Tunçel, Tolga; Çelik, Serkan; Bilgi, Oğuz; Kara, Kemal

    2015-01-01

    Lapatinib is an effective drug in HER2-positive breast cancer. We present a case with successful treatment of lapatinib in brain metastasis of HER2+ breast cancer. Forty-eight years old woman was admitted our clinic with early breast cancer. In third years after adjuvant chemotherapy and trastuzumab, isolated and multiple brain metastasis were detected. After whole brain RT, lapatinib (with capecitabine for 10 months and with letrozole for 3 months) has been used. Volumetric reduction of lesions was achieved and symptoms disappeared. When lapatinib discontinued, brain metastasis relapses. Lapatinib plus capecitabine reinduction has been started. Totally, longer survival than 45 months was achieved after first brain metastasis detection. Because both combinations of lapatinib with capecitabine and letrozole were effective and reinduction treatment was successful, presented case has strongly supported activity of lapatinib treatment in brain metastasis of HER2+ breast cancer.

  7. Oestrogen receptors, nodes and stage as predictors of post-recurrence survival in 457 breast cancer patients.

    PubMed Central

    Shek, L. L.; Godolphin, W.; Spinelli, J. J.

    1987-01-01

    The relationship to survival after first recurrence of oestrogen receptor (ER), nodal status and TNM stage at diagnosis, and treatment for advanced disease was studied in 457 females whose primary breast cancer was diagnosed in 1975 to 1981. Receptor concentration was the most important predictor of post-recurrence survival, with some additional information conveyed by nodal status. ER predicted survival after recurrence independently of nodal status, clinical stage or mode of therapy. Response to endocrine therapy is only a facet of the generally favourable prognosis of ER positive patients, rather than the sole explanation. PMID:3435707

  8. 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

  9. Metastatic triple-negative breast cancer is dependent on SphKs/S1P signaling for growth and survival.

    PubMed

    Maiti, Aparna; Takabe, Kazuaki; Hait, Nitai C

    2017-04-01

    About 40,000 American women die from metastatic breast cancer each year despite advancements in treatment. Approximately, 15% of breast cancers are triple-negative for estrogen receptor, progesterone receptor, and HER2. Triple-negative cancer is characterized by more aggressive, harder to treat with conventional approaches and having a greater possibility of recurrence. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid signaling mediator has emerged as a key regulatory molecule in breast cancer progression. Therefore, we investigated whether cytosolic sphingosine kinase type 1 (SphK1) and nuclear sphingosine kinase type 2 (SphK2), the enzymes that make S1P are critical for growth and PI3K/AKT, ERK-MAP kinase mediated survival signaling of lung metastatic variant LM2-4 breast cancer cells, generated from the parental triple-negative MDA-MB-231 human breast cancer cell line. Similar with previous report, SphKs/S1P signaling is critical for the growth and survival of estrogen receptor positive MCF-7 human breast cancer cells, was used as our study control. MDA-MB-231 did not show a significant effect of SphKs/S1P signaling on AKT, ERK, and p38 pathways. In contrast, LM2-4 cells that gained lung metastatic phenotype from primary MDA-MB-231 cells show a significant effect of SphKs/S1P signaling requirement on cell growth, survival, and cell motility. PF-543, a selective potent inhibitor of SphK1, attenuated epidermal growth factor (EGF)-mediated cell growth and survival signaling through inhibition of AKT, ERK, and p38 MAP kinase pathways mainly in LM2-4 cells but not in parental MDA-MB-231 human breast cancer cells. Moreover, K-145, a selective inhibitor of SphK2, markedly attenuated EGF-mediated cell growth and survival of LM2-4 cells. We believe this study highlights the importance of SphKs/S1P signaling in metastatic triple-negative breast cancers and targeted therapies.

  10. Effects of multidisciplinary team working on breast cancer survival: retrospective, comparative, interventional cohort study of 13 722 women

    PubMed Central

    Allardice, Gwen M; George, W David; Burns, Harry J G; Morrison, David S

    2012-01-01

    Objectives To describe the effect of multidisciplinary care on survival in women treated for breast cancer. Design Retrospective, comparative, non-randomised, interventional cohort study. Setting NHS hospitals, health boards in the west of Scotland, UK. Participants 14 358 patients diagnosed with symptomatic invasive breast cancer between 1990 and 2000, residing in health board areas in the west of Scotland. 13 722 (95.6%) patients were eligible (excluding 16 diagnoses of inflammatory cancers and 620 diagnoses of breast cancer at death). Intervention In 1995, multidisciplinary team working was introduced in hospitals throughout one health board area (Greater Glasgow; intervention area), but not in other health board areas in the west of Scotland (non-intervention area). Main outcome measures Breast cancer specific mortality and all cause mortality. Results Before the introduction of multidisciplinary care (analysed time period January 1990 to September 1995), breast cancer mortality was 11% higher in the intervention area than in the non-intervention area (hazard ratio adjusted for year of incidence, age at diagnosis, and deprivation, 1.11; 95% confidence interval 1.00 to 1.20). After multidisciplinary care was introduced (time period October 1995 to December 2000), breast cancer mortality was 18% lower in the intervention area than in the non-intervention area (0.82, 0.74 to 0.91). All cause mortality did not differ significantly between populations in the earlier period, but was 11% lower in the intervention area than in the non-interventional area in the later period (0.89, 0.82 to 0.97). Interrupted time series analyses showed a significant improvement in breast cancer survival in the intervention area in 1996, compared with the expected survival in the same year had the pre-intervention trend continued (P=0.004). This improvement was maintained after the intervention was introduced. Conclusion Introduction of multidisciplinary care was associated with

  11. 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

  12. Long-term survival after high-dose chemotherapy followed by peripheral stem cell rescue for high-risk, locally advanced/inflammatory, and metastatic breast cancer.

    PubMed

    VanderWalde, A; Ye, W; Frankel, P; Asuncion, D; Leong, L; Luu, T; Morgan, R; Twardowski, P; Koczywas, M; Pezner, R; Paz, I B; Margolin, K; Wong, J; Doroshow, J H; Forman, S; Shibata, S; Somlo, G

    2012-08-01

    Patients with high-risk locally advanced/inflammatory and oligometastatic (≤3 sites) breast cancer frequently relapse or experience early progression. High-dose chemotherapy combined with peripheral stem cell rescue may prolong progression-free survival/relapse-free survival (PFS/RFS) and overall survival (OS). In this study, patients initiated high-dose chemotherapy with STAMP-V (carboplatin, thiotepa, and cyclophosphamide), ACT (doxorubicin, paclitaxel, and cyclophosphamide), or tandem melphalan and STAMP-V. Eighty-six patients were diagnosed with locally advanced/inflammatory (17 inflammatory) breast cancer, and 12 were diagnosed with oligometastatic breast cancer. Median follow-up was 84 months (range, 6-136 months) for patients with locally advanced cancer and 40 months (range, 24-62 months) for those with metastatic cancer. In the patients with locally advanced cancer, 5-year RFS and OS were 53% (95% CI, 41%-63%) and 71% (95% CI, 60%-80%), respectively, hormone receptors were positive in 74%, and HER2 overexpression was seen in 23%. In multivariate analysis, hormone receptor-positive disease and lower stage were associated with better 5-year RFS (60% for ER [estrogen receptor]/PR [progesterone receptor]-positive versus 30% for ER/PR-negative; P < .01) and OS (83% for ER/PR-positive versus 38% for ER/PR-negative; P < .001). In the patients with metastatic cancer, 3-year PFS and OS were 49% (95% CI, 19%-73%) and 73% (95% CI, 38%-91%), respectively. The favorable long-term RFS/PFS and OS for high-dose chemotherapy with peripheral stem cell rescue in this selected patient population reflect the relative safety of the procedure and warrant validation in defined subgroups through prospective, randomized, multi-institutional trials.

  13. 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

  14. An increased neutrophil-to-lymphocyte ratio predicts poorer survival following recurrence for patients with breast cancer

    PubMed Central

    Iwase, Toshiaki; Sangai, Takafumi; Sakakibara, Masahiro; Sakakibara, Junta; Ishigami, Emi; Hayama, Shouko; Nakagawa, Ayako; Masuda, Takahito; Tabe, Shunsuke; Nagashima, Takeshi

    2017-01-01

    The aim of the present study was to evaluate the association between changes in the neutrophil-to-lymphocyte ratio and the survival rate, as well as tumor subtype, in recurrent breast cancer. Patients with recurrent breast cancer following surgery were included in this study. NLR was calculated and compared between two time points: Pre-treatment and recurrence. The associations between the longitudinal NLR change, the NLR at the time of recurrence and overall survival following recurrence (OSrec) were evaluated. A total of 89 patients were evaluated. NLR increased by 0.59 at recurrence, as compared with the initial treatment (P<0.05). The triple negative (TN) type demonstrated 4.59 in NLR, which was the highest among the four subtypes at the time of recurrence (P<0.05). The highest change (an increase of 2.0) was observed in TN type cancer (P<0.05). Patients with high NLR upon recurrence demonstrated significantly shorter OSrec rates (P<0.05). On the other hand, patients with an NLR increased by more than a third quartile demonstrated a shorter OSrec rate (P=0.06). When adjusted by covariates, the NLR and tumor subtype were determined to be associated with OSrec (P<0.05). Therefore, an increased NLR predicts survival, even in patients with recurrent breast cancer, and the NLR is potentially useful as an inflammation marker for TN breast cancer.

  15. 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.

  16. The role of poverty rate and racial distribution in the geographic clustering of breast cancer survival among older women: a geographic and multilevel analysis.

    PubMed

    Schootman, Mario; Jeffe, Donna B; Lian, Min; Gillanders, William E; Aft, Rebecca

    2009-03-01

    The authors examined disparities in survival among women aged 66 years or older in association with census-tract-level poverty rate, racial distribution, and individual-level factors, including patient-, treatment-, and tumor-related factors, utilization of medical care, and mammography use. They used linked data from the 1992-1999 Surveillance, Epidemiology, and End Results (SEER) programs, 1991-1999 Medicare claims, and the 1990 US Census. A geographic information system and advanced statistics identified areas of increased or reduced breast cancer survival and possible reasons for geographic variation in survival in 2 of the 5 SEER areas studied. In the Detroit, Michigan, area, one geographic cluster of shorter-than-expected breast cancer survival was identified (hazard ratio (HR) = 1.60). An additional area where survival was longer than expected approached statistical significance (HR = 0.4; P = 0.056). In the Atlanta, Georgia, area, one cluster of shorter- (HR = 1.81) and one cluster of longer-than-expected (HR = 0.72) breast cancer survival were identified. Stage at diagnosis and census-tract poverty (and patient's race in Atlanta) explained the geographic variation in breast cancer survival. No geographic clusters were identified in the 3 other SEER programs. Interventions to reduce late-stage breast cancer, focusing on areas of high poverty and targeting African Americans, may reduce disparities in breast cancer survival in the Detroit and Atlanta areas.

  17. 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.

  18. Strigolactones: a novel class of phytohormones that inhibit the growth and survival of breast cancer cells and breast cancer stem-like enriched mammosphere cells.

    PubMed

    Pollock, C B; Koltai, H; Kapulnik, Y; Prandi, C; Yarden, R I

    2012-08-01

    Several naturally occurring phytohormones have shown enormous potential in the prevention and treatment of variety of different type of cancers. Strigolactones (SLs) are a novel class of plant hormones produced in roots and regulate new above ground shoot branching, by inhibiting self-renewal of undifferentiated meristem cells. Here, we study the effects of six synthetic SL analogs on breast cancer cell lines growth and survival. We show that SL analogs are able to inhibit proliferation and induce apoptosis of breast cancer cells but to a much lesser extent "non-cancer" lines. Given the therapeutic problem of cancer recurrence which is hypothesized to be due to drug resistant cancer stem cells, we also tested the ability of SL analogs to inhibit the growth of mammosphere cultures that are typically enriched with cancer stem-like cells. We show that SLs are potent inhibitors of self-renewal and survival of breast cancer cell lines grown as mammospheres and even a short exposure leads to irreversible effects on mammosphere dissociation and cell death. Immunoblot analysis revealed that SLs analogs induce activation of the stress response mediated by both P38 and JNK1/2 MAPK modules and inhibits PI3K/AKT activation. Taken together this study indicates that SLs may be promising anticancer agents whose activities may be achieved through modulation of stress and survival signaling pathways.

  19. Triple Receptor–Negative Breast Cancer: The Effect of Race on Response to Primary Systemic Treatment and Survival Outcomes

    PubMed Central

    Dawood, Shaheenah; Broglio, Kristine; Kau, Shu-Wan; Green, Marjorie C.; Giordano, Sharon H.; Meric-Bernstam, Funda; Buchholz, Thomas A.; Albarracin, Constance; Yang, Wei T.; Hennessy, Bryan T.J.; Hortobagyi, Gabriel N.; Gonzalez-Angulo, Ana Maria

    2009-01-01

    Purpose The goal of this study was to describe the effect of race on pathologic complete response (pCR) rates and survival outcomes in women with triple receptor–negative (TN) breast cancers. Patients and Methods Four hundred seventy-one patients with TN breast cancer diagnosed between 1996 and 2005 and treated with primary systemic chemotherapy were included. pCR was defined as no residual invasive cancer in the breast and axillary lymph nodes. Overall survival (OS) and recurrence-free survival (RFS) were estimated using the Kaplan-Meier product-limit method and compared between groups using the log-rank test. Cox proportional hazards models were fitted for each survival outcome to determine the relationship of patient and tumor variables with outcome. Results Median follow-up time was 24.5 months. One hundred patients (21.2%) were black, and 371 patients (78.8%) were white/other race. Seventeen percent of black patients (n = 17) and 25.1% of white/other patients (n = 93) achieved a pCR (P = .091). Three-year RFS rates were 68% (95% CI, 56% to 76%) and 62% (95% CI, 57% to 67%) for black and white/other patients, respectively, with no significant difference observed between the two groups (P = .302). Three-year OS was similar for the two racial groups. After controlling for patient and tumor characteristics, race was not significantly associated with RFS (hazard ratio [HR] = 1.08; 95% CI, 0.69 to 1.68; P = .747) or OS (HR = 1.08; 95% CI, 0.69 to 1.68; P = .735) when white/other patients were compared with black patients. Conclusion Race does not significantly affect pCR rates or survival outcomes in women with TN breast cancer treated in a single institution under the same treatment conditions. PMID:19047281

  20. The calpain system is associated with survival of breast cancer patients with large but operable inflammatory and non-inflammatory tumours treated with neoadjuvant chemotherapy.

    PubMed

    Storr, Sarah J; Zhang, Siwei; Perren, Tim; Lansdown, Mark; Fatayer, Hiba; Sharma, Nisha; Gahlaut, Renu; Shaaban, Abeer; Martin, Stewart G

    2016-07-26

    The calpains are a family of intracellular cysteine proteases that function in a variety of important cellular functions, including cell signalling, motility, apoptosis and survival. In early invasive breast cancer expression of calpain-1, calpain-2 and their inhibitor, calpastatin, have been associated with clinical outcome and clinicopathological factors.The expression of calpain-1, calpain-2 and calpastatin was determined using immunohistochemistry on core biopsy samples, in a cohort of large but operable inflammatory and non-inflammatory primary breast cancer patients treated with neoadjuvant chemotherapy. Information on treatment and prognostic variables together with long-term clinical follow-up was available for these patients. Diagnostic pre-chemotherapy core biopsy samples and surgically excised specimens were available for analysis.Expression of calpastatin, calpain-1 or calpain-2 in the core biopsies was not associated with breast cancer specific survival in the total patient cohort; however, in patients with non-inflammatory breast cancer, high calpastatin expression was significantly associated with adverse breast cancer-specific survival (P=0.035), as was low calpain-2 expression (P=0.031). Low calpastatin expression was significantly associated with adverse breast cancer-specific survival of the inflammatory breast cancer patients (P=0.020), as was low calpain-1 expression (P=0.003).In conclusion, high calpain-2 and low calpastatin expression is associated with improved breast cancer-specific survival in non-inflammatory large but operable primary breast cancer treated with neoadjuvant chemotherapy. In inflammatory cases, high calpain-1 and high calpastatin expression is associated with improved breast cancer-specific survival. Determining the expression of these proteins may be of clinical relevance. Further validation, in multi-centre cohorts of breast cancer patients treated with neoadjuvant chemotherapy, is warranted.

  1. Detection methods predict differences in biology and survival in breast cancer patients

    PubMed Central

    2012-01-01

    Background The aim of this study was to measure the biological characteristics involved in tumorigenesis and the progression of breast cancer in symptomatic and screen-detected carcinomas to identify possible differences. Methods For this purpose, we evaluated clinical-pathological parameters and proliferative and apoptotic activities in a series of 130 symptomatic and 161 screen-detected tumors. Results After adjustment for the smaller size of the screen-detected carcinomas compared with symptomatic cancers, those detected in the screening program presented longer disease-free survival (RR = 0.43, CI = 0.19-0.96) and had high estrogen and progesterone receptor concentrations more often than did symptomatic cancers (OR = 3.38, CI = 1.72-6.63 and OR = 3.44, CI = 1.94-6.10, respectively). Furthermore, the expression of bcl-2, a marker of good prognosis in breast cancer, was higher and HER2/neu expression was lower in screen-detected cancers than in symptomatic cancers (OR = 1.77, CI = 1.01-3.23 and OR = 0.64, CI = 0.40-0.98, respectively). However, when comparing prevalent vs incident screen-detected carcinomas, prevalent tumors were larger (OR = 2.84, CI = 1.05-7.69), were less likely to be HER2/neu positive (OR = 0.22, CI = 0.08-0.61) and presented lower Ki67 expression (OR = 0.36, CI = 0.17-0.77). In addition, incident tumors presented a shorter survival time than did prevalent ones (RR = 4.88, CI = 1.12-21.19). Conclusions Incident carcinomas include a variety of screen-detected carcinomas that exhibit differences in biology and prognosis relative to prevalent carcinomas. The detection method is important and should be taken into account when making therapy decisions. PMID:23244222

  2. 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.

  3. 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

  4. Overall survival differences between patients with inflammatory and noninflammatory breast cancer presenting with distant metastasis at diagnosis.

    PubMed

    Fouad, Tamer M; Kogawa, Takahiro; Liu, Diane D; Shen, Yu; Masuda, Hiroko; El-Zein, Randa; Woodward, Wendy A; Chavez-MacGregor, Mariana; Alvarez, Ricardo H; Arun, Banu; Lucci, Anthony; Krishnamurthy, Savitri; Babiera, Gildy; Buchholz, Thomas A; Valero, Vicente; Ueno, Naoto T

    2015-07-01

    Inflammatory breast cancer (IBC) is a rare and aggressive disease. Previous studies have shown that among patients with stage III breast cancer, IBC is associated with a worse prognosis than noninflammatory breast cancer (non-IBC). Whether this difference holds true among patients with stage IV breast cancer has not been studied. We tested the hypothesis that overall survival (OS) is worse in patients with IBC than in those with non-IBC among patients with distant metastasis at diagnosis (stage IV disease). We reviewed the records of 1504 consecutive patients with stage IV breast cancer (IBC: 206; non-IBC: 1298) treated at our institution from 1987 through 2012. Survival curves for IBC and non-IBC subcohorts were compared. The Cox proportional hazards model was used to determine predictors of OS. The median follow-up period was 4.7 years. IBC was associated with shorter median OS time than non-IBC (2.27 vs. 3.40 years; P = 0.0128, log-rank test). In a multicovariate Cox model that included 1389 patients, the diagnosis of IBC was a significant independent predictor of worse OS (hazard ratio = 1.431, P = 0.0011). Other significant predictors of worse OS included Black (vs. White) ethnicity, younger age at diagnosis, negative HER2 status, and visceral (vs. nonvisceral) site of metastasis. IBC is associated with shorter OS than non-IBC in patients with distant metastasis at diagnosis. The prognostic impact of IBC should be taken into consideration among patients with stage IV breast cancer.

  5. The role of the tumour inflammatory cell infiltrate in predicting recurrence and survival in patients with primary operable breast cancer.

    PubMed

    Mohammed, Zahra M A; Going, James J; Edwards, Joanne; McMillan, Donald C

    2012-12-01

    Although the first studies highlighting the importance of the tumour inflammatory cell infiltrate were reported more than 80 years ago, the prognostic value of this response in breast cancer is still controversial. With the realisation of the importance of the inflammatory response in determining tumour progression there has been renewed interest in establishing the relationship between the type, density and location of inflammatory cell infiltrate and survival in patients with primary operable breast cancer. The aim was to undertake a systematic review of the literature examining the evidence for the role of the tumour inflammatory cell infiltrate in predicting recurrence and survival in patients with primary operable breast cancer. A systematic review of published papers up to September 2011 was undertaken according to a pre-defined protocol (Fig. 1). A total of 66 independent studies (34,086 patients) were identified. It can be concluded from the review that despite the large number of studies and considerable effort over an extended period, the relationship between different aspects of tumour inflammatory cell infiltrate and outcome in primary operable breast cancer remains unclear. This is in large part due to the absence of methodological validation, underpowered studies (small sample size and sample subtype heterogeneity, insufficient follow-up) and the absence of validation datasets. Therefore, although there are tantalising examples of the potential of the tumour inflammatory cell infiltrate to improve risk stratification patients with operable breast cancer (personalised care), this has not yet been realised. Future studies with standardised methodology, large and homogenous groups, sufficient follow-up and validation datasets should be undertaken to unlock the potential of the tumour inflammatory infiltrate to predict outcome in patients with primary operable breast cancer.

  6. Long-term survival of a breast cancer patient with extensive liver metastases upon immune and virotherapy: a case report.

    PubMed

    Schirrmacher, Volker; Stücker, Wilfried; Lulei, Maria; Bihari, Akos-Sigmund; Sprenger, Tobias

    2015-01-01

    Liver metastases in breast cancer are associated with a poor prognosis. We report long-term survival of a patient with breast cancer and liver metastases. After operation the patient declined further standard therapy. Instead, she was treated with local hyperthermia, Newcastle disease virus and dendritic cell vaccination at the Immunological and Oncological Center Cologne (IOZK), Germany. A continuous high quality of life was reported and the patient survived more than 66 months after initial diagnosis. No recurrence or further metastases developed under treatment. Following treatment, a long-lasting tumor-reactive memory T-cell responsiveness could be documented. This possibly explains the favorable course of disease. Since this combination of therapies is not restricted to a particular tumor type, further exploration is warranted.

  7. 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).

  8. From surviving to thriving: a health and wellness colloquium for breast cancer survivors.

    PubMed

    Stoutenberg, Mark; Cutrono, Stacy; Perry, Arlette C

    2011-12-01

    Recent evidence demonstrates that exercise training can provide numerous physical and psychosocial benefits for breast cancer (BCa) survivors. However, educational training programs designed to disseminate exercise training information to survivors are scarce. The From Surviving to Thriving (FST) Colloquium was a one-and-a-half-day event that featured presentations on wellness topics from fitness and health to the latest research in nutrition and exercise. Attendees filled out demographic questionnaires and feedback surveys to assess the impact of the Colloquium. Overall, the FST Colloquium was well received by BCa survivors and health care providers (HCPs). The majority of BCa survivors (84.4%) and HCPs (93.3%) rated their Colloquium experience as very good. Prior to attending the Colloquium, only 8.9% of BCa survivors rated their self-perceived knowledge of exercise and nutrition as excellent. After participation in the Colloquium, this increased to 44.4%. The Colloquium was also successful in influencing planned and actual behavior changes in BCa survivors.

  9. 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

  10. Digoxin use after diagnosis of breast cancer and survival: a population-based cohort study.

    PubMed

    Karasneh, Reema A; Murray, Liam J; Mc Menamin, Úna C; Hughes, Carmel M; Cardwell, Chris R

    2015-06-01

    Digoxin has been shown to have an estrogenic effect and is associated with increased risk of gynecomastia and estrogen-sensitive cancers such as breast and uterus cancer. These findings, particularly recent observations of increased breast cancer risk, raise questions about the safety of digoxin use in breast cancer patients. Therefore, we investigated whether digoxin use after breast cancer diagnosis increased the risk of breast cancer-specific mortality in breast cancer patients. A cohort of 17,842 breast cancer patients newly diagnosed from 1998 to 2009 was identified from English cancer registries (from the National Cancer Data Repository). This cohort was linked to the UK Clinical Practice Research Datalink (to provide digoxin and other prescription records) and to the Office of National Statistics mortality data (to identify breast cancer-specific deaths). Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95 % confidence intervals (CIs) were calculated for the association between post-diagnostic exposure to digoxin and breast cancer-specific and all-cause mortality. In 17,842 breast cancer patients, there were 2219 breast cancer-specific deaths. Digoxin users appeared to have increased breast cancer-specific mortality compared with non-users (HR 1.73; 95 % CI 1.39-2.15) but this association was entirely attenuated after adjustment for potential confounders (adjusted HR 0.91; 95 % CI 0.72-1.14). In this large population-based breast cancer cohort study, there was little evidence of an increase in breast cancer-specific mortality with digoxin use after diagnosis. These results provide some reassurance that digoxin use is safe in breast cancer patients.

  11. The Enrichment of Survivin in Exosomes from Breast Cancer Cells Treated with Paclitaxel Promotes Cell Survival and Chemoresistance

    PubMed Central

    Kreger, Bridget T.; Johansen, Eric R.; Cerione, Richard A.; Antonyak, Marc A.

    2016-01-01

    The generation and release of membrane-enclosed packets from cancer cells, called extracellular vesicles (EVs), play important roles in propagating transformed phenotypes, including promoting cell survival. EVs mediate their effects by transferring their contents, which include specific proteins and nucleic acids, to target cells. However, how the cargo and function of EVs change in response to different stimuli remains unclear. Here, we discovered that treating highly aggressive MDAMB231 breast cancer cells with paclitaxel (PTX), a chemotherapy that stabilizes microtubules, causes them to generate a specific class of EV, namely exosomes, that are highly enriched with the cell survival protein and cancer marker, Survivin. Treating MDAMB231 cells with a variety of other chemotherapeutic agents, and inhibitors that block cell growth and survival, did not have the same effect as PTX, with the exception of nocodazole, another inhibitor of microtubule dynamics. Exosomes isolated from PTX-treated MDAMB231 cells strongly promoted the survival of serum-starved and PTX-treated fibroblasts and SKBR3 breast cancer cells, an effect that was ablated when Survivin was knocked-down from these vesicles using siRNA. These findings underscore how the enrichment of a specific cargo in exosomes promotes cell survival, as well as can potentially serve as a marker of PTX resistance. PMID:27941677

  12. Renal transplantation in children less than 5 years of age.

    PubMed Central

    Rizzoni, G; Malekzadeh, M H; Pennisi, A J; Ettenger, R B; Uittenbogaart, C H; Fine, R N

    1980-01-01

    19 young children (less than 5 years old) have received 31 renal transplants from 4 live relatives and 27 cadaver donors. The 2-year allograft survival rate for the patients receiving their 1st allograft from the 4 live donors was 75 +/- 22% while for the patients receiving their 1st allograft from 15 cadaver donors was 26 +/- 11%. 10 children are currently surviving with functioning allographs (7 cadavers and 3 live relatives); 4 have died and 5 are undergoing dialysis after the loss of at least one allograft. Despite the poor allograft survival rate the fact that 7 children are surviving with cadaver allografts indicates that the lack of a living related donor should not prevent transplants in young children. PMID:7002060

  13. 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

  14. 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.

  15. 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.

  16. The scaffold protein MEK Partner 1 is required for the survival of estrogen receptor positive breast cancer cells.

    PubMed

    Marina, Mihaela; Wang, Limin; Conrad, Susan E

    2012-07-09

    MEK Partner 1 (MP1 or MAPKSP1) is a scaffold protein that has been reported to function in multiple signaling pathways, including the ERK, PAK and mTORC pathways. Several of these pathways influence the biology of breast cancer, but MP1's functional significance in breast cancer cells has not been investigated. In this report, we demonstrate a requirement for MP1 expression in estrogen receptor (ER) positive breast cancer cells. MP1 is widely expressed in both ER-positive and negative breast cancer cell lines, and in non-tumorigenic mammary epithelial cell lines. However, inhibition of its expression using siRNA duplexes resulted in detachment and apoptosis of several ER-positive breast cancer cell lines, but not ER-negative breast cancer cells or non-tumorigenic mammary epithelial cells. Inhibition of MP1 expression in ER-positive MCF-7 cells did not affect ERK activity, but resulted in reduced Akt1 activity and reduced ER expression and activity. Inhibition of ER expression did not result in cell death, suggesting that decreased ER expression is not the cause of cell death. In contrast, pharmacological inhibition of PI3K signaling did induce cell death in MCF-7 cells, and expression of a constitutively active form of Akt1 partially rescued the cell death observed when the MP1 gene was silenced in these cells. Together, these results suggest that MP1 is required for pro-survival signaling from the PI3K/Akt pathway in ER-positive breast cancer cells.

  17. Prognostic factors predicting functional outcomes, recurrence-free survival, and overall survival after radiotherapy for metastatic spinal cord compression in breast cancer patients

    SciTech Connect

    Rades, Dirk . E-mail: Rades.Dirk@gmx.net; Veninga, Theo; Stalpers, Lukas J.A.; Schulte, Rainer; Hoskin, Peter J.; Poortmans, Philip; Schild, Steven E.; Rudat, Volker

    2006-01-01

    Purpose: To identify significant prognostic factors after irradiation of metastatic spinal cord compression (MSCC) in 335 breast cancer patients. Methods and Materials: The potential prognostic factors investigated included involved vertebra, other bone metastases, visceral metastases, performance status, pretreatment ambulatory status, time until motor deficits developed before RT, radiation schedule (shorter-course RT [one fraction of 8 Gy/five fractions of 4 Gy] vs. longer-course RT [10 fractions of 3 Gy/15 fractions of 2.5 Gy/20 fractions of 2 Gy), and the response to RT. Results: On multivariate analysis, better functional outcome was associated with slower development of motor deficits (p <0.001) and being ambulatory before RT (p <0.001). The overall recurrence rate of MSCC was greater if other bone metastases were present (p <0.001) and if shorter-course RT was used (p <0.001). In-field recurrences alone were more frequent after shorter-course RT (p = 0.008). Survival was negatively affected by the presence of visceral metastases (p <0.001), deterioration of motor function after RT (p <0.001), reduced performance status (p <0.001), and the rapid development of motor deficits (p = 0.044). Conclusion: Outcomes and survival after RT for MSCC in breast cancer patients are associated with several prognostic factors. Patients with poor expected survival may be treated with shorter-course RT to keep the overall treatment time short. If survival is expected to be relatively favorable, longer-course RT appears preferable, because it is associated with fewer MSCC recurrences.

  18. 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

  19. Breast cancer characteristics at diagnosis and survival among Arab-American women compared to European- and African-American women

    PubMed Central

    Alford, Sharon Hensley; Schwartz, Kendra; Soliman, Amr; Johnson, Christine Cole; Gruber, Stephen B.; Merajver, Sofia D.

    2009-01-01

    Background Data from Arab world studies suggest that Arab women may experience a more aggressive breast cancer phenotype. To investigate this finding, we focused on one of the largest settlements of Arabs and Iraqi Christians (Chaldeans) in the US, metropolitan Detroit- a SEER reporting site since 1973. Materials and Methods We identified a cohort of primary breast cancer cases diagnosed 1973–2003. Using a validated name algorithm, women were identified as being of Arab/Chaldean descent if they had an Arab last or maiden name. We compared characteristics at diagnosis (age, grade, histology, SEER stage, and marker status) and overall survival between Arab-, European-, and African-Americans. Results The cohort included 1,652 (2%) women of Arab descent, 13,855 (18%) African-American women, and 63,615 (80%) European-American. There were statistically significant differences between the racial groups for all characteristics at diagnosis. Survival analyses overall and for each SEER stage showed that Arab-American women had the best survival, followed by European-American women. African-American women had the poorest overall survival and were 1.37 (95% confidence interval: 1.23–1.52) times more likely to be diagnosed with an aggressive tumor (adjusting for age, grade, marker status, and year of diagnosis). Conclusion Overall, Arab-American women have a distribution of breast cancer histology similar to European-American women. In contrast, the stage, age, and hormone receptor status at diagnosis among Arab-Americans was more similar to African-American women. However, Arab-American women have a better overall survival than even European-American women. PMID:18415013

  20. Quantifying trade-offs: quality of life and quality-adjusted survival in a randomised trial of chemotherapy in postmenopausal patients with lymph node-negative breast cancer.

    PubMed

    Bernhard, J; Zahrieh, D; Coates, A S; Gelber, R D; Castiglione-Gertsch, M; Murray, E; Forbes, J F; Perey, L; Collins, J; Snyder, R; Rudenstam, C-M; Crivellari, D; Veronesi, A; Thürlimann, B; Fey, M F; Price, K N; Goldhirsch, A; Hürny, C

    2004-11-29

    We evaluated quality of life (QL) and quality-adjusted survival in International Breast Cancer Study Group Trial IX, a randomised trial including 1669 eligible patients receiving tamoxifen for 5 years or three prior cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) followed by 57 months tamoxifen. During the time with CMF toxicity (Tox), without symptoms and toxicity (TWiST), and following relapse (Rel), patients scored their QL indicators and a utility indicator for subjective health estimation between 'perfect' and 'worst' health. Scores were averaged within Tox, TWiST and Rel and transformed to utilities. Mean durations for the three transition times were weighted with utilities to obtain mean quality-adjusted TWiST (Q-TWiST). Patients receiving CMF reported significantly worse scores for most QL domains at month 3, but less hot flushes. After completing chemotherapy, there were no differences by treatment groups. Benefits evaluated by Q-TWiST favoured the additional chemotherapy. CMF provided 3 more months of Q-TWiST for patients with ER-negative tumours, but CMF provided no benefit in Q-TWiST for patients with ER-positive tumours. Q-TWiST analysis based on patient ratings is feasible in large-scale cross-cultural clinical trials.

  1. 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

  2. Tumor-infiltrating lymphocytes in breast cancer predict the response to chemotherapy and survival outcome: A meta-analysis

    PubMed Central

    Wang, Ke; Xu, Jianjun; Zhang, Tao; Xue, Dan

    2016-01-01

    Tumor-infiltrating lymphocytes (TILs) influence tumor prognosis and the chemotherapeutic response. Here, we quantified the clinical relevance of TILs, including the effect of TILs on lymphocyte subpopulations and assessed their consistency in breast cancer. We searched published literature from January 2000 to January 2016. The main parameters analyzed were pathological complete response (pCR) and survival outcome following chemotherapy in patients with breast cancer. Pooled odds ratio (OR) or relative risk (RR) values with 95% confidence intervals (CIs) were computed using random and fixed-effects models. Subgroup and heterogeneity analyses were also conducted. Twenty-three studies, which included 13,100 patients, met the inclusion criteria. The pooled results showed that TILs were associated with clinicopathological parameters of biologically aggressive phenotypes, such as high tumor grade or estrogen/progesterone receptor negativity, but they were not correlated with human epidermal growth factor receptor-2 expression. Moreover, a high TIL level was associated with a significantly improved pCR rate compared with a low TIL level (OR, 2.81; P < 0.001), particularly in the triple-negative breast cancer subtype (OR, 4.67; P < 0.001). An analysis of lymphocyte subpopulations showed that infiltration by CD8 lymphocytes, but not by CD4 lymphocytes and Foxp3 cells, was associated with a high pCR rate. Furthermore, a high TIL level was associated with significantly longer disease-free survival and overall survival. Our present meta-analysis indicates that an increased number of TILs predicted pCR to chemotherapy and improved survival. A high TIL level, characterized mainly by the infiltration of CD8 lymphocytes, is a strong predictive and prognostic factor. PMID:27329588

  3. Individualized Survival and Treatment Response Predictions in Breast Cancer Patients: Involvements of Phospho-EGFR and Phospho-Her2/neu Proteins

    PubMed Central

    Guo, Lan; Abraham, Jame; Flynn, Daniel C.; Castranova, Vincent; Shi, Xianglin; Qian, Yong

    2014-01-01

    Our robust prediction system for individual breast cancer patients combines three well-known machine-learning classifiers to provide stable and accurate clinical outcome prediction (N=269). The average performance of the selected classifiers is used as the evaluation criterion in breast cancer outcome predictions. A profile (incorporating histology, lymph node status, tumor grade, tumor stage, ER, PR, Her2/neu, patient’s age and smoking status) generated over 95% accuracy in individualized disease-free survival and treatment response predictions. Furthermore, our analysis demonstrated that the measurement of phospho-EGFR and phospho-Her2/neu is more powerful in breast cancer survival prediction than that of total EGFR and total Her2/neu (p < 0.05). The incorporation of hormone receptor status, Her2/neu, patient’s age and smoking status into the traditional pathologic markers creates a powerful standard to perform individualized survival and treatment outcome predictions for breast cancer patients. PMID:25558292

  4. 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

  5. Thromboxane A2 receptor (TBXA2R) is a potent survival factor for triple negative breast cancers (TNBCs)

    PubMed Central

    Orr, Katy; Buckley, Niamh E.; Haddock, Paula; James, Colin; Parent, Jean-Luc; McQuaid, Stephen; Mullan, Paul B.

    2016-01-01

    Triple Negative Breast Cancer (TNBC) is defined by the lack of ERα, PR expression and HER2 overexpression and is the breast cancer subtype with the poorest clinical outcomes. Our aim was to identify genes driving TNBC proliferation and/or survival which could represent novel therapeutic targets. We performed microarray profiling of primary TNBCs and generated differential genelists based on clinical outcomes following the chemotherapy regimen FEC (5-Fluorouracil/Epirubicin/Cyclophosphamide -‘good’ outcome no relapse > 3 years; ‘poor’ outcome relapse < 3 years). Elevated expression of thromboxane A2 receptor (TBXA2R) was observed in ‘good’ outcome TNBCs. TBXA2R expression was higher specifically in TNBC cell lines and TBXA2R knockdowns consistently showed dramatic cell killing in TNBC cells. TBXA2R mRNA and promoter activities were up-regulated following BRCA1 knockdown, with c-Myc being required for BRCA1-mediated transcriptional repression. We demonstrated that TBXA2R enhanced TNBC cell migration, invasion and activated Rho signalling, phenotypes which could be reversed using Rho-associated Kinase (ROCK) inhibitors. TBXA2R also protected TNBC cells from DNA damage by negatively regulating reactive oxygen species levels. In summary, TBXA2R is a novel breast cancer-associated gene required for the survival and migratory behaviour of a subset of TNBCs and could provide opportunities to develop novel, more effective treatments. PMID:27487152

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

    PubMed

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

    2015-12-22

    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.

  7. 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

  8. [A case of long-term survival of liver metastasis of breast cancer successfully treated with chemotherapy and endocrine therapy].

    PubMed

    Shiba, E; Koyama, H; Sasaki, Y; Iwanaga, T; Terasawa, T; Wada, A

    1985-09-01

    A 42-year-old woman was diagnosed as having hepatic metastasis two years after radical mastectomy for breast cancer. She was initially treated with oophorectomy and cytotoxic chemotherapy, which resulted in complete regression of the lesion within two years after the start of the treatment. She remained free of the disease until the fifth year thereafter, when she again developed a metastatic lesions in her liver. Since then, she has been treated sequentially with various kinds of chemotherapy and endocrine therapy with a certain degree of response to each treatment. She has survived 12 years and three months after the development of liver metastasis. This patient is the longest survivor of hepatic metastasis from breast cancer in the Japaneses literature.

  9. 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

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

    PubMed

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

    2015-11-18

    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.

  11. Progesterone receptor membrane component 1 promotes survival of human breast cancer cells and the growth of xenograft tumors

    PubMed Central

    Clark, Nicole C.; Friel, Anne M.; Pru, Cindy A.; Zhang, Ling; Shioda, Toshi; Rueda, Bo R.; Peluso, John J.; Pru, James K.

    2016-01-01

    ABSTRACT Triple negative breast cancers (TNBCs) are highly aggressive and grow in response to sex steroid hormones despite lacking expression of the classical estrogen (E2) and progesterone (P4) receptors. Since P4 receptor membrane component 1 (PGRMC1) is expressed in breast cancer tumors and is known to mediate P4-induced cell survival, this study was designed to determine the expression of PGRMC1 in TNBC tumors and the involvement of PGRMC1 in regulating proliferation and survival of TNBC cells in vitro and the growth of TNBC tumors in vivo. For the latter studies, the MDA-MB-231 (MDA) cell line derived from TNBC was used. These cells express PGRMC1 but lack expression of the classical P4 receptor. A lentiviral-based shRNA approach was used to generate a stably transfected PGRMC1-deplete MDA line for comparison to the PGRMC1-intact MDA line. The present studies demonstrate that PGRMC1: 1) is expressed in TNBC cells; 2) mediates the ability of P4 to suppress TNBC cell mitosis in vitro; 3) is required for P4 to reduce the apoptotic effects of doxorubicin in vitro; and 4) facilitates TNBC tumor formation and growth in vivo. Taken together, these findings indicate that PGRMC1 plays an important role in regulating the growth and survival of TNBC cells in vitro and ultimately in the formation and development of these tumors in vivo. Thus, PGRMC1 may be a therapeutic target for TNBCs. PMID:26785864

  12. Progesterone receptor membrane component 1 promotes survival of human breast cancer cells and the growth of xenograft tumors.

    PubMed

    Clark, Nicole C; Friel, Anne M; Pru, Cindy A; Zhang, Ling; Shioda, Toshi; Rueda, Bo R; Peluso, John J; Pru, James K

    2016-01-01

    Triple negative breast cancers (TNBCs) are highly aggressive and grow in response to sex steroid hormones despite lacking expression of the classical estrogen (E2) and progesterone (P4) receptors. Since P4 receptor membrane component 1 (PGRMC1) is expressed in breast cancer tumors and is known to mediate P4-induced cell survival, this study was designed to determine the expression of PGRMC1 in TNBC tumors and the involvement of PGRMC1 in regulating proliferation and survival of TNBC cells in vitro and the growth of TNBC tumors in vivo. For the latter studies, the MDA-MB-231 (MDA) cell line derived from TNBC was used. These cells express PGRMC1 but lack expression of the classical P4 receptor. A lentiviral-based shRNA approach was used to generate a stably transfected PGRMC1-deplete MDA line for comparison to the PGRMC1-intact MDA line. The present studies demonstrate that PGRMC1: 1) is expressed in TNBC cells; 2) mediates the ability of P4 to suppress TNBC cell mitosis in vitro; 3) is required for P4 to reduce the apoptotic effects of doxorubicin in vitro; and 4) facilitates TNBC tumor formation and growth in vivo. Taken together, these findings indicate that PGRMC1 plays an important role in regulating the growth and survival of TNBC cells in vitro and ultimately in the formation and development of these tumors in vivo. Thus, PGRMC1 may be a therapeutic target for TNBCs.

  13. Favourable ten-year overall survival in a Caucasian population with high probability of hereditary breast cancer

    PubMed Central

    2010-01-01

    Background The purpose of our study was to compare differences in the prognosis of breast cancer (BC) patients at high (H) risk or intermediate slightly (IS) increased risk based on family history and those without a family history of BC, and to evaluate whether ten-year overall survival can be considered a good indicator of BRCA1 gene mutation. Methods We classified 5923 breast cancer patients registered between 1988 and 2006 at the Department of Oncology and Haematology in Modena, Italy, into one of three different risk categories according to Modena criteria. One thousand eleven patients at H and IS increased risk were tested for BRCA1/2 mutations. The overall survival (OS) and disease free survival (DFS) were the study end-points. Results Eighty BRCA1 carriers were identified. A statistically significantly better prognosis was observed for patients belonging to the H risk category with respect to women in the IS and sporadic groups (82% vs.75% vs.73%, respectively; p < 0.0001). Comparing only BRCA1 carriers with BRCA-negative and sporadic BC (77% vs.77% vs.73%, respectively; p < 0.001) an advantage in OS was seen. Conclusions Patients belonging to a population with a high probability of being BRCA1 carriers had a better prognosis than those with sporadic BC. Considering these results, women who previously had BC and had survived ten years could be selected for BRCA1 analysis among family members at high risk of hereditary BC during genetic counselling. Since only 30% of patients with a high probability of having hereditary BC have BRCA1 mutations, selecting women with a long term survival among this population could increase the rate of positive analyses, avoiding the use of expensive tests. PMID:20219108

  14. 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.

  15. 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.

  16. Genetic variants in EBV reactivation-related genes and the risk and survival of breast cancer.

    PubMed

    Zhang, Wei; Zhang, Zheng-Zheng; Tang, Lu-Ying; Lin, Ying; Su, Feng-Xi; Xie, Xiao-Ming; Su, Xue-Fen; Ren, Ze-Fang

    2016-06-01

    Tumor susceptibility gene 101 (TSG101) and activating transcription factor 2 (ATF2) have been suggested to involve in the reactivation of EBV which has implications in the development and progression of breast cancer. Therefore, the polymorphisms of TSG101 and ATF2 may associate with breast cancer risk and prognosis. A case-control study with 1551 breast cancer cases and 1605 age-matched controls were conducted in Guangzhou, China. We have also successfully followed up 1168 cases until December 31, 2014. The variant allele of TSG101 rs2292179 was associated with a non-significant reduced risk of breast cancer, particularly among women with BMI < 24 (kg/m(2)) (P for interaction <0.05). For ATF2 rs3845744, the variant allele was also associated with a significantly reduced breast cancer risk [odds ratio (OR) (95 % confidence interval (CI)) 0.86 (0.74∼1.00)], and the association occurred among only postmenopausal women [OR (95 % CI) 0.69 (0.54∼0.88)] (P for interaction <0.05). Breast cancer risk was further reduced with the increasing numbers of the variant G alleles of the two polymorphisms (P for trend <0.05). We did not find an overall association of the two loci with breast cancer prognosis, while the hazard ratios of the two loci (AG/GG vs. AA) were significantly higher among postmenopausal women than premenopausal women (P = 0.046, 0.016 for TSG101 rs2292179 and ATF2 rs3845744, respectively). In summary, the variant alleles of TSG101 rs2292179 and ATF2 rs3845744 were associated with a reduced risk of breast cancer, particularly for subjects with BMI <24 (kg/m(2)) and postmenopausal women, respectively. The two SNPs and menopausal status may have a significant interaction on breast cancer progression.

  17. Smoking and survival after breast cancer diagnosis in Japanese women: A prospective cohort study.

    PubMed

    Kakugawa, Yoichiro; Kawai, Masaaki; Nishino, Yoshikazu; Fukamachi, Kayoko; Ishida, Takanori; Ohuchi, Noriaki; Minami, Yuko

    2015-08-01

    The results of previous studies investigating whether there is an association between active smoking and risk of death among breast cancer patients have been inconsistent. We investigated the association between active and passive smoking and risk of all-cause and breast cancer-specific death among female breast cancer patients in relation to menopausal and tumor estrogen/progesterone receptor (ER/PR) status. The present study included 848 patients admitted to a single hospital in Japan from 1997 to 2007. Active or passive smoking status was assessed using a self-administered questionnaire. The patients were followed until 31 December 2010. We used a Cox proportional-hazard model to estimate hazard ratios (HR). During a median follow-up period of 6.7 years, 170 all-cause and 132 breast cancer-specific deaths were observed. Among premenopausal patients, current smokers showed a non-significant higher risk of all-cause and breast cancer-specific death. A duration of smoking >21.5 years was positively associated with all-cause (HR = 3.09, 95% confidence interval [CI], 1.17-8.20) and breast cancer-specific death (HR = 3.35, 95% CI: 1.22-9.23, Ptrend  = 0.035) among premenopausal patients. In premenopausal patients with ER+ or PR+ tumors, there was some suggestion that a longer duration of smoking was associated with higher risk of all-cause and breast cancer-specific death. Passive smoking demonstrated no significant risk. Our results suggest that a longer duration of active smoking is associated with an increased risk of all-cause and breast cancer-specific death among premenopausal patients, possibly with hormonal receptor-positive tumors. Breast cancer patients should be informed about the importance of smoking cessation.

  18. Soviet business chaos seen lasting 5 years

    SciTech Connect

    Not Available

    1991-12-16

    This paper reports that companies seeking work in the collapsing Soviet Union can expect political uncertainty for another 5 years. PW discussed changes in the Soviet Union and offered advice on dealing with officials of the central government and Soviet republics at a recent meeting in Houston with executives of oil field service companies. That meeting preceded reports of the Russian federation, Ukraine, and Byelorussia agreeing to form a Slavic commonwealth.

  19. Significant survival improvement of patients with recurrent breast cancer in the periods 2001-2008 vs. 1992-2000

    PubMed Central

    2011-01-01

    Background It is unclear whether individualized treatments based on biological factors have improved the prognosis of recurrent breast cancer. The purpose of this study is to evaluate the survival improvement of patients with recurrent breast cancer after the introduction of third generation aromatase inhibitors (AIs) and trastuzumab. Methods A total of 407 patients who received first diagnosis of recurrent breast cancer and treatment at National Kyushu Cancer Center between 1992 and 2008 were retrospectively evaluated. As AIs and trastuzumab were approved for clinical use in Japan in 2001, the patients were divided into two time cohorts depending on whether the cancer recurred before or after 2001. Cohort A: 170 patients who were diagnosed between 1992 and 2000. Cohort B: 237 patients who were diagnosed between 2001 and 2008. Tumor characteristics, treatments, and outcome were compared. Results Fourteen percent of cohort A and 76% of cohort B received AIs and/or trastuzumab (P < 0.001). The median overall survival (OS) times after breast cancer recurrence were 1.7 years and 4.2 years for these respective cohorts (P < 0.001). Both the time period and treatment of AIs and/or trastuzumab for recurrent disease were significant prognostic factors in multivariate analysis (cohort B vs. cohort A: HR = 0.70, P = 0.01; AIs and/or trastuzumab for recurrent disease: yes vs. no: HR = 0.46, P < 0.001). When patients were categorized into 4 subgroups by the expression of hormone receptor (HR) and HER-2 status, the median OS times of the HR-positive/HER-2-negative, HR-positive/HER-2-positive, HR-negative/HER-2-positive, and HR-negative/HER-2-negative subtypes were 2.2, 2.4, 1.6, and 1.0 years in cohort A and 4.5, 5.1, 5.0, and 1.4 years in cohort B. Conclusions The prognosis of patients with recurrent breast cancer was improved over time following the introduction of AIs and trastuzumab and the survival improvement was apparent in HR- and/or HER-2-positive tumors. PMID:21453503

  20. 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

  1. A new era of improving progression-free survival with dual blockade in postmenopausal HR(+), HER2(-) advanced breast cancer.

    PubMed

    Jerusalem, Guy; Bachelot, Thomas; Barrios, Carlos; Neven, Patrick; Di Leo, Angelo; Janni, Wolfgang; de Boer, Richard

    2015-02-01

    Disease progression despite existing endocrine therapies remains a major challenge to the effective management of hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2-negative (HER2(-)), advanced breast cancer. Recent advances in elucidating the molecular mechanisms of disease progression have identified the existence of adaptive "cross-talk" between the estrogen receptor (ER) and various growth factor receptor and intracellular signaling pathways, allowing breast cancer cells to escape the inhibitory effects of endocrine therapy. These findings provide the clinical rationale for enhancing or extending endocrine sensitivity by combining endocrine therapy with a targeted agent against a compensatory pathway. In BOLERO-2, adding the mTOR inhibitor everolimus to endocrine therapy significantly improved progression-free survival (PFS) in patients with HR(+) advanced breast cancer previously treated with nonsteroidal aromatase inhibitor therapy. Notably, PFS benefits were comparable in subgroup analyses of first- and later-line settings. These results contrast with those of the large first-line HORIZON study, wherein adding the mTOR inhibitor temsirolimus to endocrine therapy did not improve PFS. Therefore, it is unclear whether a targeted agent should only be combined with endocrine therapy to restore endocrine sensitivity or whether it may also prevent or delay resistance in hormone-sensitive advanced breast cancer. Numerous additional targeted agents are currently being evaluated in combination with endocrine therapies, including PI3K, cyclin-dependent kinase 4/6, SRC, and histone deacetylase inhibitors. Appropriate patient selection based on prior treatment history will become increasingly important in maximizing the incremental benefit derived from these new agents combined with existing endocrine therapies in HR(+) advanced breast cancer.

  2. 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

  3. Lipid Raft Integrity Is Required for Survival of Triple Negative Breast Cancer Cells

    PubMed Central

    Badana, Anil; Chintala, Madhuri; Varikuti, Gayathri; Pudi, Nagaseshu; Kumari, Seema; Kappala, Vijaya Rachel

    2016-01-01

    Purpose Lipid rafts are cholesterol enriched microdomains that colocalize signaling pathways involved in cell proliferation, metastasis, and angiogenesis. We examined the effect of methyl-β-cyclodextrin (MβCD)-mediated cholesterol extraction on the proliferation, adhesion, invasion, and angiogenesis of triple negative breast cancer (TNBC) cells. Methods We measured cholesterol and estimated cell toxicity. Detergent resistant membrane (DRM) and non-DRM fractions were separated using the OptiPrep gradient method. Cell cycles stages were analyzed by flow cytometry, apoptosis was assessed using the TdT-mediated dUTP nick end-labeling assay, and metastasis was determined using a Matrigel invasion assay. Neo-vessel pattern and levels of angiogenic modulators were determined using an in vitro angiogenesis assay and an angiogenesis array, respectively. Results The present study found that the cholesterol-depleting agent MβCD, efficiently depleted membrane cholesterol and caused concentration dependent (0.1–0.5 mM) cytotoxicity compared to nystatin and filipin III in TNBC cell lines, MDA-MB 231 and MDA-MB 468. A reduced proportion of caveolin-1 found in DRM fractions indicated a cholesterol extraction-induced disruption of lipid raft integrity. MβCD inhibited 52% of MDA-MB 231 cell adhesion on fibronectin and 56% of MDA-MB 468 cell adhesion on vitronectin, while invasiveness of these cells was decreased by 48% and 52% respectively, following MβCD treatment (48 hours). MβCD also caused cell cycle arrest at the G2M phase and apoptosis in MDA-MB 231 cells (25% and 58% cells, respectively) and in MDA-MB 468 cells (30% and 38% cells, respectively). We found that MβCD treated cells caused a 52% and 58% depletion of neovessel formation in both MDA-MB 231 and MDA-MB 468 cell lines, respectively. This study also demonstrated that MβCD treatment caused a respective 2.6- and 2.5-fold depletion of tyrosine protein kinase receptor (TEK) receptor tyrosine kinase levels in both

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

    PubMed

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

    2015-10-06

    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.

  5. Aberrant DNA Double-strand Break Repair Threads in Breast Carcinoma: Orchestrating Genomic Insult Survival.

    PubMed

    Kumar, Azad; Purohit, Shruti; Sharma, Nilesh Kumar

    2016-12-01

    Breast carcinoma is a heterogeneous disease that has exhibited rapid resistance to treatment in the last decade. Depending genotype and phenotype of breast cancer, there are discernible differences in DNA repair protein responses including DNA double strand break repair. It is a fact that different molecular sub-types of breast carcinoma activate these dedicated protein pathways in a distinct manner. The DNA double-strand damage repair machinery is manipulated by breast carcinoma to selectively repair the damage or insults inflicted by the genotoxic effects of chemotherapy or radiation therapy. The two DNA double-strand break repair pathways employed by breast carcinoma are homologous recombination and non-homologous end joining. In recent decades, therapeutic interventions targeting one or more factors involved in repairing DNA double-strand breaks inflicted by chemo/radiation therapy have been widely studied. Herein, this review paper summarizes the recent evidence and ongoing clinical trials citing potential therapeutic combinatorial interventions targeting DNA double-strand break repair pathways in breast carcinoma.

  6. Psychological distress and coping in breast cancer patients and healthy women whose parents survived the Holocaust.

    PubMed

    Baider, Lea; Goldzweig, Gil; Ever-Hadani, Pnina; Peretz, Tamar

    2006-07-01

    Psychological distress levels of breast cancer patients whose parents were Holocaust survivors ('second-generation Holocaust' patients) were previously shown to be significantly higher than those of a matched group of patients with non-traumatized parents. In this study, we investigated whether this effect reflects only the generally higher distress levels of second-generation Holocaust women or whether breast cancer patients with traumatized parents also present lower adaptation abilities, which result in increased distress to the breast cancer diagnosis. We assessed psychological distress and measures of coping in 193 second-generation Holocaust patients diagnosed with breast cancer, 164 breast cancer patients with non-traumatized parents, 176 healthy second-generation Holocaust women, and 143 healthy women with non-traumatized parents. The main effect of cancer and the main effect of second-generation Holocaust survivor on psychological distress were found to be significant. These two factors (cancer x second generation) had a synergistic effect on the levels of depression and psychoticism. These results support the hypothesis that, at least on some psychological measures, the cumulative distressing effect of having traumatized parents and breast cancer diagnosis is higher than the effect of each factor alone.

  7. Aberrant DNA Double-strand Break Repair Threads in Breast Carcinoma: Orchestrating Genomic Insult Survival

    PubMed Central

    Kumar, Azad; Purohit, Shruti; Sharma, Nilesh Kumar

    2016-01-01

    Breast carcinoma is a heterogeneous disease that has exhibited rapid resistance to treatment in the last decade. Depending genotype and phenotype of breast cancer, there are discernible differences in DNA repair protein responses including DNA double strand break repair. It is a fact that different molecular sub-types of breast carcinoma activate these dedicated protein pathways in a distinct manner. The DNA double-strand damage repair machinery is manipulated by breast carcinoma to selectively repair the damage or insults inflicted by the genotoxic effects of chemotherapy or radiation therapy. The two DNA double-strand break repair pathways employed by breast carcinoma are homologous recombination and non-homologous end joining. In recent decades, therapeutic interventions targeting one or more factors involved in repairing DNA double-strand breaks inflicted by chemo/radiation therapy have been widely studied. Herein, this review paper summarizes the recent evidence and ongoing clinical trials citing potential therapeutic combinatorial interventions targeting DNA double-strand break repair pathways in breast carcinoma. PMID:28053956

  8. 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

  9. [Fissure sealants--5 years of use].

    PubMed

    Azul, A M

    1990-01-01

    This study assesses the caries prevalence, retention and cost-effectiveness of a pit and fissure sealant in a children population with 622 cases, 5 years after a single application of an auto-polymerized sealant to permanent molars. The status of the sealant and the presence of caries or restaurations on the sealed teeth was assessed. In a self-controlled group of children, the prevalence of disease (caries and restaurations) was also assessed in non-sealed teeth, for comparison. The sealant application was compared with Class I-restauration with amalgam for cost-effectiveness analysis.

  10. High expression of cholesterol biosynthesis genes is associated with resistance to statin treatment and inferior survival in breast cancer

    PubMed Central

    Kimbung, Siker; Lettiero, Barbara; Feldt, Maria; Bosch, Ana; Borgquist, Signe

    2016-01-01

    There is sufficient evidence that statins have a protective role against breast cancer proliferation and recurrence, but treatment predictive biomarkers are lacking. Breast cancer cell lines displaying diverse sensitivity to atorvastatin were subjected to global transcriptional profiling and genes significantly altered by statin treatment were identified. Atorvastatin treatment strongly inhibited proliferation in estrogen receptor (ER) negative cell lines and a commensurate response was also evident on the genome-wide transcriptional scale, with ER negative cells displaying a robust deregulation of genes involved in the regulation of cell cycle progression and apoptosis. Interestingly, atorvastatin upregulated genes involved in the cholesterol biosynthesis pathway in all cell lines, irrespective of sensitivity to statin treatment. However, the level of pathway induction; measured as the fold change in transcript levels, was inversely correlated to the effect of statin treatment on cell growth. High expression of cholesterol biosynthesis genes before treatment was associated with resistance to statin therapy in cell lines and clinical biopsies. Furthermore, high expression of cholesterol biosynthesis genes was independently prognostic for a shorter recurrence-free and overall survival, especially among ER positive tumors. Dysregulation of cholesterol biosynthesis is therefore predictive for both sensitivity to anti-cancer statin therapy and prognosis following primary breast cancer diagnosis. PMID:27458152

  11. Longitudinal biological exposure to carotenoids is associated with breast cancer-free survival in the Women's Healthy Eating and Living Study.

    PubMed

    Rock, Cheryl L; Natarajan, Loki; Pu, Minya; Thomson, Cynthia A; Flatt, Shirley W; Caan, Bette J; Gold, Ellen B; Al-Delaimy, Wael K; Newman, Vicky A; Hajek, Richard A; Stefanick, Marcia L; Pierce, John P

    2009-02-01

    In some cohort studies, a high-vegetable diet has been associated with greater likelihood of recurrence-free survival in women diagnosed with breast cancer. Carotenoids are obtained primarily from vegetables and fruit and they exhibit biological activities that may specifically reduce the progression of mammary carcinogenesis. The present analysis examines the relationship between plasma carotenoids at enrollment and 1, 2 or 3, 4, and 6 years and breast cancer-free survival in the Women's Healthy Eating and Living Study participants (N = 3,043), who had been diagnosed with early-stage breast cancer. The primary end point was time to a second breast cancer event (a recurrence or new primary breast cancer). An average carotenoid concentration over time was estimated for each participant as the average area under the plasma carotenoid curve formed by the plasma carotenoid concentrations at scheduled clinic visits. Multiple regression Cox proportional hazards analysis with adjustment for prognostic and other factors was used to examine the association between carotenoids and breast cancer-free survival. A total of 508 (16.7%) breast cancer events occurred over a median 7.12 years follow-up. Compared with the lowest tertile, the hazard ratio for the medium/high plasma carotenoid tertiles was 0.67 (95% confidence interval, 0.54-0.83) after adjustment. The interaction between the study group and tertile of average carotenoid concentration over time was not significant (P = 0.23). Higher biological exposure to carotenoids, when assessed over the time frame of the study, was associated with greater likelihood of breast cancer-free survival regardless of study group assignment.

  12. High expression of MnSOD promotes survival of circulating breast cancer cells and increases their resistance to doxorubicin

    PubMed Central

    Fu, Afu; Ma, Shijun; Wei, Na; Xuan Tan, Blanche Xiao; Tan, Ern Yu; Luo, Kathy Qian

    2016-01-01

    Understanding the survival mechanism of metastatic cancer cells in circulation will provide new perspectives on metastasis prevention and also shed new light on metastasis-derived drug resistance. In this study, we made it feasible to detect apoptosis of circulating tumor cells (CTCs) in real-time by integrating a fluorescence resonance energy transfer (FRET)-based caspase sensor into one in vitro microfluidic circulatory system, and two in vivo models: zebrafish circulation and mouse lung metastatic model. Our study demonstrated that fluid shear stresses triggered apoptosis of breast cancer cells in circulation by elevating the mitochondrial production of the primary free radical, superoxide anion. Cancer cells with high levels of manganese superoxide dismutase (MnSOD) exhibited stronger resistance to shear force-induced apoptosis and formed more lung metastases in mice. These metastasized cells further displayed higher resistance to chemotherapeutic agent doxorubicin, which also generates superoxide in mitochondria. Specific siRNA-mediated MnSOD knockdown reversed all three phenotypes. Our findings therefore suggest that MnSOD plays an important integrative role in supporting cancer cell survival in circulation, metastasis, and doxorubicin resistance. MnSOD can serve as a new biomarker for identifying metastatic CTCs and a novel therapeutic target for inhibiting metastasis and destroying doxorubicin-resistant breast cancer cells. PMID:27384484

  13. SPARC overexpression in primary tumors correlates with disease recurrence and overall survival in patients with triple negative breast cancer

    PubMed Central

    Zhu, Anjie; Yuan, Peng; Du, Feng; Hong, Ruoxi; Ding, Xiaoyan; Shi, Xiuqing; Fan, Ying; Wang, Jiayu; Luo, Yang; Ma, Fei; Zhang, Pin; Li, Qing; Xu, Binghe

    2016-01-01

    SPARC/osteonectin expression is reportedly altered in various malignancies. However, little is known regarding to the prognostic value of SPARC in triple-negative breast cancer (TNBC) patients. In this study, immunohistochemistry and immunoreactive scores (IRSs) were used to evaluate SPARC protein expression in primary tumors from 211 TNBC patients with up to 10 years of clinical follow-up data. High SPARC expression (IRS ≥3) was detected in 52.1% of primary tumors. Patients expressing high SPARC levels had worse disease-free survival (DFS) (HR=1.58, 95% CI: 1.01-2.47, P=0.044) and overall survival (OS) (HR=1.74, 95% CI: 1.06-2.85, P=0.029) than patients with lower SPARC levels. Furthermore, high SPARC expression was an independent prognostic factor for both DFS (HR=1.73, 95% CI: 1.10-2.73, P=0.018) and OS (HR=1.90, 95% CI: 1.14-3.16, P=0.014) in TNBC patients. These results suggest that increased SPARC expression may be an indicator of greater aggressiveness, and may serve as a prognostic factor for triple-negative breast cancer. PMID:27421134

  14. A Multiresolution Hazard Model for Multicenter Survival Studies: Application to Tamoxifen Treatment in Early Stage Breast Cancer

    PubMed Central

    BOUMAN, Peter; MENG, Xiao-Li; DIGNAM, James; DUKIĆ, Vanja

    2014-01-01

    In multicenter studies, one often needs to make inference about a population survival curve based on multiple, possibly heterogeneous survival data from individual centers. We investigate a flexible Bayesian method for estimating a population survival curve based on a semiparametric multiresolution hazard model that can incorporate covariates and account for center heterogeneity. The method yields a smooth estimate of the survival curve for “multiple resolutions” or time scales of interest. The Bayesian model used has the capability to accommodate general forms of censoring and a priori smoothness assumptions. We develop a model checking and diagnostic technique based on the posterior predictive distribution and use it to identify departures from the model assumptions. The hazard estimator is used to analyze data from 110 centers that participated in a multicenter randomized clinical trial to evaluate tamoxifen in the treatment of early stage breast cancer. Of particular interest are the estimates of center heterogeneity in the baseline hazard curves and in the treatment effects, after adjustment for a few key clinical covariates. Our analysis suggests that the treatment effect estimates are rather robust, even for a collection of small trial centers, despite variations in center characteristics. PMID:25620824

  15. Healthy Eating Index/Alternative Healthy Eating Index and Breast Cancer Mortality and Survival: A Systematic Review and Meta-analysis

    PubMed Central

    Pourmasoumi, Makan; Karimbeiki, Razieh; Vosoughi, Nooshin; Feizi, Awat; Ghiasvand, Reza; Barak, Farzane; Miraghajani, Maryam

    2016-01-01

    Objective: Breast cancer is the most common cancer in women worldwide. The effects of overall diet quality instead of single nutrients after breast cancer diagnosis on mortality have been a growing area of research interest. The aim of this systematic review was to investigate the relationship between the Healthy Eating Index (HEI)/the Alternative Healthy Eating Index (AHEI) and risk of breast cancer mortality or survival rates as a primary outcome, and some related inflammatory factors, as secondary outcomes among postdiagnosed women. Methods: This study methodology was performed based on the Preferred Reporting Item for Systematic Review and Meta-analysis statement recommendation and had been registered at PROSPERO (registration number: CRD42015015605). The systematic search was conducted in the electronic databases including PubMed, ISI, Scopus, Cochrane, and Google before July 2016. Researches that had not reported risk of breast cancer mortality or survival rates separately were excluded from the study. Similarly, this review excluded studies which only had examined the HEI or AHEI without reporting their association with the risk of mortality or survival rates. Results: After primary search, of 643 studies identified, 4 studies including eligible criteria were selected for the final assessment. All selected studies had been conducted in the USA and used self-report food-frequency questionnaire for diet quality assessment. In two studies HEI-2005, in one study AHEI, and in another study AHEI-2010 were applied. Meta-analysis result showed no significant association between these indexes and risk of breast cancer mortality/survival among women with this malignancy [relative risk: (RR) 1.04; 95% confidence interval (CI): 0.69–1.56; P = 0.87]. Conclusions: Regarding the adherence HEI/AHEI, we found no association between mentioned indexes and risk of mortality or survival from breast cancer in women with breast cancer. However, evidence in this field is limited

  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. 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

  18. Expression of melatonin receptors in triple negative breast cancer (TNBC) in African American and Caucasian women: relation to survival.

    PubMed

    Oprea-Ilies, Gabriela; Haus, Erhard; Sackett-Lundeen, Linda; Liu, Yuan; McLendon, Lauren; Busch, Robert; Adams, Amy; Cohen, Cynthia

    2013-02-01

    In the normal rodent breast, the pineal hormone melatonin controls the development of ductal and alveolar tissue. Melatonin counteracts tumor occurrence and tumor cell progression in vivo and in vitro in animal and human breast cancer cell cultures. It acts predominantly through its melatonin MT1 receptor. Our aim was to investigate the presence or absence of the MT1 melatonin receptor in the aggressive triple negative group of human breast carcinoma (TNBC) and its possible relationship to the course of the disease. A total of 167 patients with a ER-, PR-, Her-2/neu- phenotype in which tissue for receptor studies was available were examined. The MT1 receptor immunostain was evaluated semiquantitatively as staining intensity (0, 1, 2, 3), percentage of stained cells and the weighted index (WI) (staining intensity times percentage of stained cells). A score of WI < 60 was regarded as "negative". There was a striking difference in incidence of MT1 positivity and staining intensity between carcinomas in African American (AA) and Caucasian (C) women. The AA showed a higher incidence of MT1 negative tumors (41/84 = 48.8 % in AA, 6/51 = 11.8 % in C) and a lower average WI. MT1 positivity in TNBC was associated with a lower stage and a smaller tumor size at time of diagnosis. In multivariable survival analysis, MT1 negative TNBC in all cases regardless of race showed a significantly higher hazard ratio for disease progression, shorter progression free survival, and disease-related death, and shorter OS. This was especially pronounced in the AA group but did not reach statistical significance in the smaller group of C alone. These results suggest that melatonin or a melatonin receptor agonist may be useful biologic additions in the treatment of some forms of TNBC, especially in AA who generally show a more aggressive course of their disease.

  19. Pre-diagnostic acrylamide exposure and survival after breast cancer among postmenopausal Danish women.

    PubMed

    Olsen, Anja; Christensen, Jane; Outzen, Malene; Olesen, Pelle Thonning; Frandsen, Henrik; Overvad, Kim; Halkjær, Jytte

    2012-06-14

    Acrylamide is a probable human carcinogen, with industrial contact, tobacco smoking and foods processed at high temperatures as the main routes of exposure. In animal studies oral intake of acrylamide has been related to cancer development, with indications that the increased cancer occurrence especially regards endocrine related tumors. In human epidemiological studies, dietary exposure to acrylamide has also been suggested related to higher risk of endocrine related tumors, like estrogen sensitive breast cancer. The aim of the present study was to evaluate if pre-diagnostic acrylamide exposure, measured by acrylamide and glycidamide hemoglobin adducts (AA-Hb and GA-Hb), were associated to mortality in breast cancer cases. Among 24,697 postmenopausal women included into a Danish cohort between 1993 and 1997, 420 developed breast cancer before 2001 and 110 died before 2009. AA-Hb and GA-Hb concentrations measured in blood samples were related to mortality by Cox proportional hazard models. Estimates are given per 25 pmol/g globin higher levels. Among non-smokers, higher concentrations of GA-Hb were associated to a higher hazard rate of breast cancer specific mortality (HR (95% CI): 1.63 (1.06-2.51)), the hazard rate among women diagnosed with estrogen receptor positive tumors was (HR (95% CI): 2.23 (1.38-3.61)). For AA-Hb the tendency was similar, but only statistically significant among those with estrogen receptor positive tumors (HR (95% CI): 1.31 (1.02-1.69)). In conclusion, the present study indicates that pre-diagnostic exposure to acrylamide may be related to mortality among breast cancer patients and that this may especially concern the most endocrine related type of breast cancer.

  20. Long term survival of HER2-positive early breast cancer treated with trastuzumab-based adjuvant regimen: a large cohort study from clinical practice.

    PubMed

    Bonifazi, Martina; Franchi, Matteo; Rossi, Marta; Zambelli, Alberto; Moja, Lorenzo; Zambon, Antonella; Corrao, Giovanni; La Vecchia, Carlo; Zocchetti, Carlo; Negri, Eva

    2014-10-01

    Trastuzumab-based regimens for the adjuvant treatment of HER2-positive early breast cancer significantly prolonged overall survival (OS) and disease free survival (DFS) in large randomized trials, with sustained benefits at four-year follow-up. We assessed long-term survival estimates and predictors in a large cohort of Italian women with early breast cancer treated with trastuzumab in clinical practice. Through a record linkage between five regional healthcare databases, we identified women treated with trastuzumab for early breast cancer in Lombardy (2006-2009). DFS and OS were estimated using the Kaplan-Meier method, and independent predictors were assessed using proportional hazard models. 2046 women received trastuzumab in early breast cancer adjuvant setting. Overall, the proportion of patients surviving free of disease was 93.9% at one year, 85.8% at 2 years, 79.4% at 3 years, and 75.0% at 4 years. OS estimates were 98.7%, 95.4%, 91.5% and 89.4% at 1, 2, 3 and 4 years, respectively. Significant independent predictors of worse survival outcomes were age <40 or ≥70 years compared to age 40-69 years, positive nodal status, radical breast surgery, combination therapy with paclitaxel, having at least one comorbidity (i.e. diabetes, cardiovascular disease), and a trastuzumab-based regimen lasting less than six months. Long term survival rates of women treated with trastuzumab for early breast cancer in clinical practice were consistent with estimates from clinical trials testing the drug in the adjuvant setting.

  1. Epidermal growth factor regulates Mcl-1 expression through the MAPK-Elk-1 signalling pathway contributing to cell survival in breast cancer.

    PubMed

    Booy, E P; Henson, E S; Gibson, S B

    2011-05-19

    Myeloid cell leukaemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 family that is elevated in a variety of tumour types including breast cancer. In breast tumours, increased Mcl-1 expression correlates with high tumour grade and poor patient survival. We have previously demonstrated that Her-2 levels correspond to increased Mcl-1 expression in breast tumours. Epidermal growth factor (EGF) receptor signalling is frequently deregulated in breast cancer and leads to increased proliferation and survival. Herein, we determined the critical downstream signals responsible for the EGF mediated increase of Mcl-1 and their role in cell survival. We found that both Mcl-1 mRNA and protein levels are rapidly induced upon stimulation with EGF. Promoter analysis revealed that an Elk-1 transcription factor-binding site is critical for EGF activation of the Mcl-1 promoter. Furthermore, we found that knockdown of Elk-1 or inhibition of the Erk signalling pathway was sufficient to block EGF upregulation of Mcl-1 and EGF mediated cell survival. Using chromatin immunoprecipitation and biotin labelled probes of the Mcl-1 promoter, we found that Elk-1 and serum response factor are bound to the promoter after EGF stimulation. To determine whether Mcl-1 confers a survival advantage, we found that knockdown of Mcl-1 expression increased apoptosis whereas overexpression of Mcl-1 inhibited drug induced cell death. In human breast tumours, we found a correlation between phosphorylated Elk-1 and Mcl-1 protein levels. These results indicate that the EGF induced activation of Elk-1 is an important mediator of Mcl-1 expression and cell survival and therefore a potential therapeutic target in breast cancer.

  2. 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.

  3. 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…

  4. ERRα is a marker of tamoxifen response and survival in triple-negative breast cancer

    PubMed Central

    Manna, Subrata; Bostner, Josefine; Sun, Yang; Miller, Lance D.; Alayev, Anya; Schwartz, Naomi S.; Lager, Elin; Fornander, Tommy; Nordenskjöld, Bo; Yu, Jane J.; Stål, Olle; Holz, Marina K.

    2016-01-01

    Purpose Estrogen-related receptor alpha (ERRα) signaling has recently been implicated in breast cancer. We investigated the clinical value of ERRα in randomized cohorts of tamoxifen-treated and adjuvant-untreated patients. Experimental design Cox proportional hazards regression was used to evaluate the significance of associations between ERRα gene expression levels and patient DMFS in a previously published microarray dataset representing two thousand breast tumor cases derived from multiple medical centers worldwide. The 912 tumors used for immunostaining were from a tamoxifen-randomized primary breast cancer trial conducted in Stockholm, Sweden, during 1976–1990. Mouse model was used to study the effect of tamoxifen treatment on lung colonization of MDA-MB-231 control cells and MDA-MB-231 cells with stable knockdown of ERRα. The phenotypic effects associated with ERRα modulation were studied using immunoblotting analyses and wound healing assay. Results We found that in ER-negative and triple-negative breast cancer (TNBC) adjuvant-untreated patients, ERRα expression indicated worse prognosis and correlated with poor outcome predictors. However, in tamoxifen-treated patients, an improved outcome was observed with high ERRα gene and protein expression. Reduced ERRα expression was oncogenic in the presence of tamoxifen, measured by in vitro proliferation and migration assays and in vivo metastasis studies. Conclusion Taken together, these data show that ERRα expression predicts response to tamoxifen treatment, and ERRα could be a biomarker of tamoxifen sensitivity and a prognostic factor in TNBC. PMID:26542058

  5. The Impact of Diabetes Treatment on Survival in a Breast Cancer/Diabetes Model

    DTIC Science & Technology

    2008-10-09

    Epidemiological studies have identified that type 2 diabetes mellitus (DM2) is a significant risk factor for carcinogenesis and cancer death. A few...poster session. We have successfully bred the mouse model of HER2-positive breast cancer and diabetes mellitus , i.e., MMTV-ErbB2(neu): db/db. Based on

  6. Role of Autocrine Erythropoietin Signaling in the Survival of Human Breast Cancer Under Hypoxic Conditions

    DTIC Science & Technology

    2004-10-01

    per response, including the time for reviewing instructions, searching existing data sources, gathering and maintaining the data needed, and...completing and reviewing this collection of Information. Send comments regarding this burden estimate or any other aspect of this collection of information...previously untreated, unilateral breast cancer for the study, review the available histological sections and select the appropriate tissue blocks for

  7. 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

  8. Effect of pre-incubation conditions on growth and survival of Staphylococcus aureus in sliced cooked chicken breast.

    PubMed

    Rodriguez-Caturla, Magdevis Y; Valero Díaz, Antonio; Vallejo, Juan Luis Reyes; García-Gimeno, Rosa Ma; Cosano, Gonzalo Zurera

    2012-12-01

    In this work, the effect of pre-incubation conditions (temperature: 10, 15, 37 °C; pH 5.5, 6.5 and water activity, a(w): 0.997, 0.960) was evaluated on the subsequent growth, survival and enterotoxin production (SE) of Staphylococcus aureus in cooked chicken breast incubated at 10 and 20 °C. Results showed the ability of S. aureus to survive at 10 °C when pre-incubated at low a(w) (0.960) what could constitute a food risk if osmotic stressed cells of S. aureus which form biofilms survive on dried surfaces, and they are transferred to cooked meat products by cross-contamination. Regarding growth at 20 °C, cells pre-incubated at pH 5.5 and a(w) 0.960 had a longer lag phase and a slower maximum growth rate. On the contrary, it was highlighted that pre-incubation at optimal conditions (37 °C/pH 6.5/a(w) 0.997) produced a better adaptation and a faster growth in meat products what would lead to a higher SE production. These findings can support the adoption of management strategies and preventive measures in food industries leading to avoid growth and SE production in meat products.

  9. 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

  10. Modulation of breast cancer cell survival by aromatase inhibiting hop (Humulus lupulus L.) flavonoids.

    PubMed

    Monteiro, Rosário; Faria, Ana; Azevedo, Isabel; Calhau, Conceição

    2007-01-01

    Hop flavonoids are being regarded as attractive molecules to prevent or treat certain forms of cancer. Studies have focused mainly on xanthohumol, the most abundant prenylated chalcone existing in hops extract. However, during the production of beer, or after its ingestion, xanthohumol originates different metabolites, among which isoxanthohumol and 8-prenylnaringenin. The aim of this work was to study the effect of the prenylflavonoids xanthohumol, isoxanthohumol and 8-prenylnaringenin on the breast cancer Sk-Br-3 cell line proliferation, apoptosis and activity of the enzyme aromatase (estrogen synthase). Aromatase activity was determined by a tritiated water assay, cell proliferation was assessed by [(3)H]thymidine incorporation, sulforhodamine B protein measurement and Ki-67 immunostaining and apoptosis was determined by TUNEL. Our results show that all tested prenylflavonoids were able to inhibit aromatase activity and thus, estrogen formation. Additionally, breast cancer cell line proliferation was decreased and apoptosis induced by all three compounds. The presence of 17beta-estradiol in treatment medium was able to revert the effect of the prenylflavonoids on cellular proliferation. These observations strengthen the idea that hop flavonoids may have anti-breast cancer effects and shed new light on a possible mechanism of action by which these effects occur, namely through their ability to decrease estrogen synthesis.

  11. 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.

  12. Effect of refrigerated and frozen storage on the survival of Campylobacter jejuni in cooked chicken meat breast.

    PubMed

    Eideh, Ala'a M F; Al-Qadiri, Hamzah M

    2011-01-01

    This experimental work aimed to examine the survivability of Campylobacter jejuni in cooked chicken breast under several conditions: storage for 1, 3, and 7 d at refrigerated temperatures (4 °C) and for 20 d at frozen temperatures (-18 °C). In addition, storage at ambient temperature (26 to 28 °C) was involved. Chicken samples were inoculated with a mixed culture of C. jejuni strains (ATCC: 29428 and 33219) of known concentrations (50 and 500 CFU/g). Bacterial cells were recovered and enumerated using standard procedure (Preston method). Bacteria were not detected in the majority of samples stored at ambient temperature. Refrigeration reduced survivals in 95, 90, and 77.5% for samples inoculated with 500 CFU/g and kept for 1, 3, and 7 d, respectively. The maximum reduction reached 1 log(10) cycle for all refrigeration durations. It was observed that bacteria died in 17.5% of samples kept for 7 d at 4 °C. However, survivors in samples inoculated with 50 CFU/g were not detected in 50, 65, and 55% of samples kept for 1, 3, and 7 d, respectively. Freezing rendered survivors not detectable in 70% of samples inoculated with 50 CFU/g, while survived viable counts were reduced in 92.5% of samples inoculated with 500 CFU/g. These findings suggested that C. jejuni could be killed or just sublethally injured with or without reduction in viable counts under the investigated storage temperatures, which may indicate the ability of this bacterium to survive in chicken meat stored under refrigerated and frozen conditions.

  13. Proteomic Analyses Reveal High Expression of Decorin and Endoplasmin (HSP90B1) Are Associated with Breast Cancer Metastasis and Decreased Survival

    PubMed Central

    Dharsee, Moyez; Tran-Thanh, Danh; Ackloo, Suzanne; Zhu, Pei Hong; Sardana, Girish; Chen, Jian; Kupchak, Peter; Jacks, Lindsay M.; Miller, Naomi A.; Youngson, Bruce J.; Iakovlev, Vladimir; Guidos, Cynthia J.; Vallis, Katherine A.; Evans, Kenneth R.; McCready, David; Leong, Wey L.; Done, Susan J.

    2012-01-01

    Background Breast cancer is the most common malignancy among women worldwide in terms of incidence and mortality. About 10% of North American women will be diagnosed with breast cancer during their lifetime and 20% of those will die of the disease. Breast cancer is a heterogeneous disease and biomarkers able to correctly classify patients into prognostic groups are needed to better tailor treatment options and improve outcomes. One powerful method used for biomarker discovery is sample screening with mass spectrometry, as it allows direct comparison of protein expression between normal and pathological states. The purpose of this study was to use a systematic and objective method to identify biomarkers with possible prognostic value in breast cancer patients, particularly in identifying cases most likely to have lymph node metastasis and to validate their prognostic ability using breast cancer tissue microarrays. Methods and Findings Differential proteomic analyses were employed to identify candidate biomarkers in primary breast cancer patients. These analyses identified decorin (DCN) and endoplasmin (HSP90B1) which play important roles regulating the tumour microenvironment and in pathways related to tumorigenesis. This study indicates that high expression of Decorin is associated with lymph node metastasis (p<0.001), higher number of positive lymph nodes (p<0.0001) and worse overall survival (p = 0.01). High expression of HSP90B1 is associated with distant metastasis (p<0.0001) and decreased overall survival (p<0.0001) these patients also appear to benefit significantly from hormonal treatment. Conclusions Using quantitative proteomic profiling of primary breast cancers, two new promising prognostic and predictive markers were found to identify patients with worse survival. In addition HSP90B1 appears to identify a group of patients with distant metastasis with otherwise good prognostic features. PMID:22363530

  14. 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.

  15. Prediction of Recurrence and Survival for Triple-Negative Breast Cancer (TNBC) by a Protein Signature in Tissue Samples.

    PubMed

    Campone, Mario; Valo, Isabelle; Jézéquel, Pascal; Moreau, Marie; Boissard, Alice; Campion, Loic; Loussouarn, Delphine; Verriele, Véronique; Coqueret, Olivier; Guette, Catherine

    2015-11-01

    To date, there is no available targeted therapy for patients who are diagnosed with triple-negative breast cancers (TNBC). The aim of this study was to identify a new specific target for specific treatments. Frozen primary tumors were collected from 83 adjuvant therapy-naive TNBC patients. These samples were used for global proteome profiling by iTRAQ-OFFGEL-LC-MS/MS approach in two series: a training cohort (n = 42) and a test set (n = 41). Patients who remains free of local or distant metastasis for a minimum of 5 years after surgery were classified in the no-relapse group; the others were in the relapse group. OPLS and Kaplan-Meier analyses were performed to select candidate markers, which were validated by immunohistochemistry. Three proteins were identified in the training set and validated in the test set by Kaplan-Meier method and immunohistochemistry (IHC): TrpRS as a good prognostic markers and DP and TSP1 as bad prognostic markers. We propose the establishment of an IHC test to calculate the score of TrpRS, DP, and TSP1 in TNBC tumors to evaluate the degree of aggressiveness of the tumors. Finally, we propose that DP and TSP1 could provide therapeutic targets for specific treatments.

  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. The Cure: Design and Evaluation of a Crowdsourcing Game for Gene Selection for Breast Cancer Survival Prediction

    PubMed Central

    Loguercio, Salvatore; Griffith, Obi L; Nanis, Max; Wu, Chunlei; Su, Andrew I

    2014-01-01

    Background Molecular signatures for predicting breast cancer prognosis could greatly improve care through personalization of treatment. Computational analyses of genome-wide expression datasets have identified such signatures, but these signatures leave much to be desired in terms of accuracy, reproducibility, and biological interpretability. Methods that take advantage of structured prior knowledge (eg, protein interaction networks) show promise in helping to define better signatures, but most knowledge remains unstructured. Crowdsourcing via scientific discovery games is an emerging methodology that has the potential to tap into human intelligence at scales and in modes unheard of before. Objective The main objective of this study was to test the hypothesis that knowledge linking expression patterns of specific genes to breast cancer outcomes could be captured from players of an open, Web-based game. We envisioned capturing knowledge both from the player’s prior experience and from their ability to interpret text related to candidate genes presented to them in the context of the game. Methods We developed and evaluated an online game called The Cure that captured information from players regarding genes for use as predictors of breast cancer survival. Information gathered from game play was aggregated using a voting approach, and used to create rankings of genes. The top genes from these rankings were evaluated using annotation enrichment analysis, comparison to prior predictor gene sets, and by using them to train and test machine learning systems for predicting 10 year survival. Results Between its launch in September 2012 and September 2013, The Cure attracted more than 1000 registered players, who collectively played nearly 10,000 games. Gene sets assembled through aggregation of the collected data showed significant enrichment for genes known to be related to key concepts such as cancer, disease progression, and recurrence. In terms of the predictive

  18. Regulation of Survival by IKK(epsilon) in Inflammatory Breast Cancer Involves EpCAM

    DTIC Science & Technology

    2013-12-01

    responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms . Blood 115, 5232-5240 (2010). 28. J. S. Duncan, M. C. Whittle, K...H. Chen, D. Morosini, K. Bell, M. Alimzhanov, S. Ioannidis, P. McCoon, Z. A. Cao, H. Yu, R. Jove, M. Zinda, The JAK2 inhibitor AZD1480 potently...Frank, K. Polyak, The JAK2 /STAT3 signaling pathway is required for growth of CD44CD24 stem cell-like breast cancer cells in human tumors. The Journal

  19. 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

  20. Recent perspectives of breast cancer prognosis and predictive factors

    PubMed Central

    Cao, Su-Sheng; Lu, Cun-Tao

    2016-01-01

    Breast cancer is the most common type of cancer affecting women worldwide. Although there have been great improvements in treating the disease and at present between 80 and 90% of the women survive5-years after their primary diagnosis. However, due to the high incidence of the disease >450,000 women succumb to breast cancer annually worldwide. The majority of improvements in breast cancer survival may be explained through better knowledge of the development and progression of the disease. Consequently, the treatments employed have become more effective. Furthermore, continuous efforts are being made for the identification of novel and efficient biomarkers for the timely prognosis of breast cancer. The present review aims to examine recent perspectives of breast cancer prognosis and the predictive factors involved. PMID:27900052

  1. Adjuvant cytostatic therapy of breast cancer as an important factor in the postponing of a relapse and longer survival period.

    PubMed

    Stula, N

    1992-01-01

    This prospective clinical study shows the results of the adjuvant cytostatic therapy (ACT) in breast cancer applied to patients in the premenopausal age. Cyclophosphamide, methotrexate, 5-fluorouracil (CMF) group (70 patients): after operative and radiotherapeutic treatment the ACT is applied over the period of six months (six cycles). Control group (71 patients): only operative and radiotherapeutic treatment. Protocol of the ACT: cyclophosphamide, methotrexate, 5-fluorouracil (CMF) over 5 days with a 4-week break. Total 6 cycles. Control period: 10 years. Stratification of patients was made on the basis of the following risk factors: size of the tumour, number of positive lymph nodes of ipsilateral axilla, grade of the differentiation of the tumour, hormonal dependence of the tumour. Statistical method of analysis: actuary calculation, the Hi square test. The results show that the application of the ACT is statistically significant (P < 0.05) in regard to the disease-free interval. However, concerning the survival, the usefulness of its application is present but not statistically significant on the significance level of 5%. The usefulness of the ACT application as regards high risk factors (T3, T4 > or = 4 lymph nodes, grade of differentiation II, III, ER-PR-) is statistically significant (P < 0.05) both in regard to the DFI and survival. Regarding low risk factors the ACT application adversely influenced the results in the control group. This is probably the result of the ACT toxicity. The patients have a favourable prognosis in this subgroup in regard to the staging and biological nature of the tumour. The ACT in the premenopausal age of patients with high risk factors gives a significantly better results concerning the procrastination of relapse and the length of the survival period.

  2. High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti-HER2 therapy

    PubMed Central

    Aura, Claudia; Garrido-Castro, Ana; Vilaro, Marta; Peg, Vicente; Jimenez, José; Vicario, Rocio; Cecchi, Fabiola; Hoos, William; Burrows, Jon; Hembrough, Todd; Ferreres, Juan Carles; Perez-Garcia, José; Arribas, Joaquin; Cortes, Javier; Scaltriti, Maurizio

    2016-01-01

    Introduction Current methods to determine HER2 (human epidermal growth factor receptor 2) status are affected by reproducibility issues and do not reliably predict benefit from anti-HER2 therapy. Quantitative measurement of HER2 may more accurately identify breast cancer (BC) patients who will respond to anti-HER2 treatments. Methods Using selected reaction monitoring mass spectrometry (SRM-MS), we quantified HER2 protein levels in formalin-fixed, paraffin-embedded (FFPE) tissue samples that had been classified as HER2 0, 1+, 2+ or 3+ by immunohistochemistry (IHC). Receiver operator curve (ROC) analysis was conducted to obtain optimal HER2 protein expression thresholds predictive of HER2 status (by standard IHC or in situ hybridization [ISH]) and of survival benefit after anti-HER2 therapy. Results Absolute HER2 amol/μg levels were significantly correlated with both HER2 IHC and amplification status by ISH (p < 0.0001). A HER2 threshold of 740 amol/μg showed an agreement rate of 94% with IHC and ISH standard HER2 testing (p < 0.0001). Discordant cases (SRM-MS-negative/ISH-positive) showed a characteristic amplification pattern known as double minutes. HER2 levels >2200 amol/μg were significantly associated with longer disease-free survival (DFS) and overall survival (OS) in an adjuvant setting and with longer OS in a metastatic setting. Conclusion Quantitative HER2 measurement by SRM-MS is superior to IHC and ISH in predicting outcome after treatment with anti-HER2 therapy. PMID:26422389

  3. 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

  4. 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.

  5. The Effect of Tumor Subtype on Survival and the Graded Prognostic Assessment (GPA) for Patients with Breast Cancer and Brain Metastases

    PubMed Central

    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.; Chiang, Veronica; Knisely, Jonathan P.S.; Sperduto, Christina Maria; Lin, Nancy; Mehta, Minesh

    2011-01-01

    BACKGROUND 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 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 (MCR) 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 MCR 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 60–80. The median survival time (MST) overall was 13.8 months, and for GPA scores of 0–1.0, 1.5–2.0, 2.5–3.0 and 3.5–4.0 was 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 versus 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 of 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. PMID:21497451

  6. One-Carbon Metabolism and Breast Cancer Survival in a Population-Based Study

    DTIC Science & Technology

    2007-06-01

    association of one-carbon metabolism polymorphisms and overall survival was different by ER/PR status for several polymorphisms, i.e. MTHFR C677T (p...survival ER/PR status Chemotheray + - yes no Gene Genotype HR HR HR HR MTHFR 0 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref) (C677T) 1 1.47 0.61 1.13...0.86 P,int 0.05 0.55 MTHFR 0 1.00(ref) 1.00(ref) 1.00(ref) 1.00(ref) (A1208C) 1 1.27 0.66 1.22 0.91 P,int 0.13 0.64 TSTR 0 1.00(ref

  7. Reduced selenium-binding protein 1 in breast cancer correlates with poor survival and resistance to the anti-proliferative effects of selenium.

    PubMed

    Zhang, Sheng; Li, Feng; Younes, Mamoun; Liu, Hao; Chen, Changyi; Yao, Qizhi

    2013-01-01

    Supplemental dietary selenium is associated with reduced incidence of many cancers. The antitumor function of selenium is thought to be mediated through selenium-binding protein 1 (SELENBP1). However, the significance of SELENBP1 expression in breast cancer is still largely unknown. A total of 95 normal and tumor tissues assay and 12 breast cancer cell lines were used in this study. We found that SELENBP1 expression in breast cancer tissues is reduced compared to normal control. Low SELENBP1 expression in ER(+) breast cancer patients was significantly associated with poor survival (p<0.01), and SELENBP1 levels progressively decreased with advancing clinical stages of breast cancer. 17-β estradiol (E2) treatment of high SELENBP1-expressing ER(+) cell lines led to a down-regulation of SELENBP1, a result that did not occur in ER(-) cell lines. However, after ectopic expression of ER in an originally ER(-) cell line, down-regulation of SELENBP1 upon E2 treatment was observed. In addition, selenium treatment resulted in reduced cell proliferation in endogenous SELENBP1 high cells; however, after knocking-down SELENBP1, we observed no significant reduction in cell proliferation. Similarly, selenium has no effect on inhibition of cell proliferation in low endogenous SELENBP1 cells, but the inhibitory effect is regained following ectopic SELENBP1 expression. Furthermore, E2 treatment of an ER silenced high endogenous SELENBP1 expressing cell line showed no abolishment of cell proliferation inhibition upon selenium treatment. These data indicate that SELENBP1 expression is regulated via estrogen and that the cell proliferation inhibition effect of selenium treatment is dependent on the high level of SELENBP1 expression. Therefore, the expression level of SELENBP1 could be an important marker for predicting survival and effectiveness of selenium supplementation in breast cancer. This is the first study to reveal the importance of monitoring SELENBP1 expression as a

  8. 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

  9. Evaluating the Survival Benefit Following Ovarian Function Suppression in Premenopausal Patients with Hormone Receptor Positive Early Breast Cancer.

    PubMed

    Qiu, Lin; Fu, Fangmeng; Huang, Meng; Lin, Yuxiang; Chen, Yazhen; Chen, Minyan; Wang, Chuan

    2016-05-27

    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.

  10. Upper Limb Functionality and Quality of Life in Women with Five-Year Survival after Breast Cancer Surgery.

    PubMed

    Recchia, Thaís Lunardi; Prim, Amably Cristiny; Luz, Clarissa Medeiros da

    2017-03-01

    Objective To evaluate the correlation between upper limb functionality and quality of life in women with five-year survival following breast cancer surgical treatment. The secondary objective was to evaluate the function of the ipsilateral upper limb and the quality of life in relation to the type of surgery and the presence of pain. Methods The Disabilities of Arm, Shoulder and Hand (DASH), and the Functional Assessment of Cancer Therapy - Breast plus Arm Morbidity (FACTB + 4) questionnaires were used to evaluate upper limb function and quality of life respectively. Data distribution was verified by the Shapiro-Wilk test. Pearson's correlation coefficient was used for the parametric variables, and Spearman's rank correlation coefficient was used for the distribution of non-parametric variables. The statistical significance was set at 5% (p < 0.05). Results The study included 30 patients, with a mean age of 51.23 (±8.72) years. The most common complications were: pain (50%), adherence (33.3%), and nerve lesion (20.0%). There was a moderate negative correlation between the instruments DASH and FACTB + 4 (total score), r = -0.634, and a strong negative correlation between the DASH and the FACTB + 4 arm subscale, r = -0.829. The scores of both questionnaires showed significant difference on the manifestation of pain. However, there was no significant difference found when comparing the scores considering the type of surgery performed. Conclusions Five years after surgery, the patients showed regular functionality levels on the ipsilateral upper limb and decreased quality of life, especially in the group manifesting pain.

  11. HR+/Her2- breast cancer in pre-menopausal women: The impact of younger age on clinical characteristics at diagnosis, disease management and survival.

    PubMed

    De Camargo Cancela, Marianna; Comber, Harry; Sharp, Linda

    2016-12-01

    Young women (20-39 years-old) with breast cancer are diagnosed with more aggressive tumours and consequently have poorer survival. However, there is an evidence gap as to whether age has an independent effect on survival of pre-menopausal women diagnosed with HR+/Her2- tumours. The aim of this population-based study was to compare characteristics at diagnosis, determinants of treatment and survival in women aged 20-39 and 40-49 years diagnosed with HR+/Her2- tumours. From the National Cancer Registry Ireland, we identified women aged 20-49 diagnosed with a first invasive HR+/Her2- breast cancer during 2002-2008. Women aged 20-39 were compared to those aged 40-49 years. Poisson regression with robust error variance was used to explore the impact of age on treatment receipt. Associations between age and survival from all causes was investigated using Cox models. In multivariate models, women aged 20-39 significantly more often having no cancer-directed surgery (IRR=1.49, 95%CI 1.07, 2.08). In those having surgery, younger age was associated with significantly higher likelihood of receiving chemotherapy; age was not associated with receipt of adjuvant radiotherapy or endocrine therapy. Women aged 20-39 undergoing surgery were significantly more likely to die than women aged 40-49 (HR=1.84, 95%CI: 1.31, 2.59). Age is an independent prognostic factor in younger women diagnosed with HR+/Her2- breast cancer, supporting the hypothesis that breast cancer in women under 40 has more aggressive behaviour, even within HR+/Her2- tumours. Future research should explore the reasons for poorer survival in order to inform strategies to improve outcomes in this age group.

  12. Host Resistance and Survival in Carcinoma of Breast: A Study of 104 Cases of Medullary Carcinoma in a Series of 1,411 Cases of Breast Cancer Followed for 20 years*

    PubMed Central

    Bloom, H. J. G.; Richardson, W. W.; Field, J. R.

    1970-01-01

    This paper deals with a special type of mammary carcinoma, generally of high-grade malignancy, which carries a remarkably good prognosis—the so-called “medullary carcinoma of the breast with lymphoid infiltrate.” Probably the increased lymphoid tissue seen in these tumours is concerned with cell-mediated and humoral immunological reactions and reflects a strong host-defence mechanism which is responsible for the remarkably high survival rates following radical treatment. Since the evidence for host resistance to malignant disease is based largely on animal data, the opportunity to study a group of patients followed for 20 years, in whom this type of defence reaction appears to exist, is of considerable clinical interest. Among 1,411 cases of breast cancer there were 104 with medullary carcinoma (7·4%), for which the corrected 5- to 20-year survival rates have been calculated. After 20 years 74% of cases with operable medullary tumours were alive, compared with 14% of cases with similar stage non-medullary cancer. In the presence of histologically proved axillary metastases the 20-year survival rate was 61% for medullary cases, compared with only 13% for other types of breast cancer. In 30 cases of medullary cancer in which the axilla was free, the corrected 20-year survival rate was 95% following a combination of radical operation and radiotherapy. No evidence could be found that axillary dissection or postoperative irradiation is harmful to women with operable highly malignant breast cancer in whom a well-marked host resistance is thought to be present. A combination of radical mastectomy and postoperative irradiation appears to be the most effective treatment for such cases. The present grounds for rejecting a radical approach to treatment of breast cancer, based on current immunological considerations, are regarded as being quite inadequate. PMID:5448777

  13. One-Carbon Metabolism and Breast Cancer Survival in a Population-Based Study

    DTIC Science & Technology

    2005-06-01

    1. All genotype distributions at these three loci were in agreement with Hardy-Weinberg Equilibrium. In addition, genotyping for the MTHFR 677C>T...95%CI 1.04-2.06). MTHFR 677 C-- > T GENOTYPF AND BC SURV’,[VAL HR: 1.46 (1.04 -- 2.06) MTHFR 677 C->T Genotype------ TT or CT CC Overall survival ofthe...BC cases in the LIBCSP affected by MTHFR 677 C-.T genotypes: CC versus TT or CT c. Study associations of one-carbon metabolism (diet and polymorphism

  14. Dissecting the Molecular Mechanism of RhoC GTPase Expression in the Normal and Malignant Breast

    DTIC Science & Technology

    2011-09-01

    metastatic and, because of this disease’s rapid progression, the effectiveness of aggressive multimodality treatment is limited; the 5-year disease -free...aggressive multimodality treatment is limited; the 5-year disease -free, mean survival rate is less than 45%, making IBC the most lethal form of breast...of human diseases , most notably, cancer (Bracken and Helin, 2009; Margueron and Reinberg, 2011). Key components of the human PRC2 include the histone

  15. 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).

  16. Your Child's Development: 2.5 Years (30 Months)

    MedlinePlus

    ... Old Your Child’s Development: 2.5 Years (30 Months) KidsHealth > For Parents > Your Child’s Development: 2.5 Years (30 Months) A A A Are you amazed by the ... TOPIC Your Child's Checkup: 2.5 Years (30 Months) Home and Away: How to Keep Toddlers Active ...

  17. Annexin/S100A Protein Family Regulation through p14ARF-p53 Activation: A Role in Cell Survival and Predicting Treatment Outcomes in Breast Cancer

    PubMed Central

    Hatoum, Diana; Yagoub, Daniel; Ahadi, Alireza; Nassif, Najah T.; McGowan, Eileen M.

    2017-01-01

    The annexin family and S100A associated proteins are important regulators of diverse calcium-dependent cellular processes including cell division, growth regulation and apoptosis. Dysfunction of individual annexin and S100A proteins is associated with cancer progression, metastasis and cancer drug resistance. This manuscript describes the novel finding of differential regulation of the annexin and S100A family of proteins by activation of p53 in breast cancer cells. Additionally, the observed differential regulation is found to be beneficial to the survival of breast cancer cells and to influence treatment efficacy. We have used unbiased, quantitative proteomics to determine the proteomic changes occurring post p14ARF-p53 activation in estrogen receptor (ER) breast cancer cells. In this report we identified differential regulation of the annexin/S100A family, through unique peptide recognition at the N-terminal regions, demonstrating p14ARF-p53 is a central orchestrator of the annexin/S100A family of calcium regulators in favor of pro-survival functions in the breast cancer cell. This regulation was found to be cell-type specific. Retrospective human breast cancer studies have demonstrated that tumors with functional wild type p53 (p53wt) respond poorly to some chemotherapy agents compared to tumors with a non-functional p53. Given that modulation of calcium signaling has been demonstrated to change sensitivity of chemotherapeutic agents to apoptotic signals, in principle, we explored the paradigm of how p53 modulation of calcium regulators in ER+ breast cancer patients impacts and influences therapeutic outcomes. PMID:28068434

  18. Cyberknife Radiosurgery and Concurrent Intrathecal Chemotherapy for Leptomeningeal Metastases: Case Report of Prolonged Survival of a HER-2+ Breast Cancer Patient Status-Post Craniospinal Irradiation.

    PubMed

    Lekovic, Gregory; Drazin, Doniel; Mak, Albert C; Schwartz, Marc S

    2016-01-07

    Leptomeningeal disease (LMD) from breast cancer is usually a rapidly fatal condition, with median overall survival reported to be 15 weeks. Conventional treatment for LMD includes craniospinal irradiation and intrathecal (IT) methotrexate. However, the role of stereotactic radiation for leptomeningeal disease remains poorly defined. This case report describes our experience using Cyberknife radiosurgery to treat a 49-year-old female with HER-2+ breast cancer and focal/nodular leptomeningeal metastases that were refractory to craniospinal irradiation and concurrent IT chemotherapy. This combined approach--i.e., craniospinal irradiation, IT chemotherapy, and Cyberknife Radiosurgery for local, recurrent metastases--resulted in survival of 46 months with controlled disease. Based on our experience with this patient, we believe further consideration of radiosurgery for LMD is warranted.

  19. Cyberknife Radiosurgery and Concurrent Intrathecal Chemotherapy for Leptomeningeal Metastases: Case Report of Prolonged Survival of a HER-2+ Breast Cancer Patient Status-Post Craniospinal Irradiation

    PubMed Central

    Lekovic, Gregory; Mak, Albert C; Schwartz, Marc S

    2016-01-01

    Leptomeningeal disease (LMD) from breast cancer is usually a rapidly fatal condition, with median overall survival reported to be 15 weeks. Conventional treatment for LMD includes craniospinal irradiation and intrathecal (IT) methotrexate. However, the role of stereotactic radiation for leptomeningeal disease remains poorly defined. This case report describes our experience using Cyberknife radiosurgery to treat a 49-year-old female with HER-2+ breast cancer and focal/nodular leptomeningeal metastases that were refractory to craniospinal irradiation and concurrent IT chemotherapy. This combined approach--i.e., craniospinal irradiation, IT chemotherapy, and Cyberknife Radiosurgery for local, recurrent metastases--resulted in survival of 46 months with controlled disease. Based on our experience with this patient, we believe further consideration of radiosurgery for LMD is warranted.  PMID:26918221

  20. 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.

  1. The truncated somatostatin receptor sst5TMD4 stimulates the angiogenic process and is associated to lymphatic metastasis and disease-free survival in breast cancer patients

    PubMed Central

    Gahete, Manuel D.; Rincón-Fernández, David; Durán-Prado, Mario; Hergueta-Redondo, Marta; Ibáñez-Costa, Alejandro; Rojo-Sebastián, Alejandro; Gracia-Navarro, Francisco; Culler, Michael D.; Casanovas, Oriol; Moreno-Bueno, Gema; Luque, Raúl M.; Castaño, Justo P.

    2016-01-01

    The truncated somatostatin receptor sst5TMD4 is associated with poor prognosis in breast cancer and increases breast cancer cell malignancy. Here, we examined the cellular/molecular mechanisms underlying this association, aiming to identify new molecular tools to improve diagnosis, prognosis or therapy. A gene expression array comparing sst5TMD4 stably-transfected MCF-7 cells and their controls (empty-plasmid) revealed the existence of profound alterations in the expression of genes involved in key tumoral processes, such as cell survival or angiogenesis. Moreover, sst5TMD4-overexpressing MCF-7 and MDA-MB-231 cells demonstrated increased expression/production of pro-angiogenic factors and enhanced capacity to form mammospheres. Consistently, sst5TMD4-expressing MCF-7 cells induced xenografted tumors with higher VEGF levels and elevated number of blood vessels. Importantly, sst5TMD4 was expressed in a subset of breast cancers, where it correlated with angiogenic markers, lymphatic metastasis, and reduced disease-free survival. These results, coupled to our previous data, support a relevant role of sst5TMD4 in the angiogenic process and reinforce the role of sst5TMD4 in breast cancer malignancy and metastatic potential, supporting its possible utility to develop new molecular biomarkers and drug therapies for these tumors. PMID:27507050

  2. Common profiles of Notch signaling differentiate disease-free survival in luminal type A and triple negative breast cancer

    PubMed Central

    Orzechowska, Magdalena; Jędroszka, Dorota; Bednarek, Andrzej K

    2017-01-01

    Breast cancer (BC) is characterized by high heterogeneity regarding its biology and clinical characteristics. The Notch pathway regulates such processes as organ modeling and epithelial-to-mesenchymal transition (EMT). The aim of the study was to determine the effect of differential expression of Notch members on disease-free survival (DFS) in luminal type A (lumA) and triple negative (TN) BC. The differential expression of 19 Notch members was examined in a TCGA BC cohort. DFS analysis was performed using the log-rank test (p<0.05). Biological differences between DFS groups were determined with Gene Set Enrichment Analysis (GSEA) (tTest, FDR<0.25). Common expression profiles according to Notch signaling were examined using ExpressCluster (K-means, mean centered, Euclidean distance metric). The overexpression of HES1, LFNG and PSEN1 was found to be favorable for DFS in lumA, and lowered expression favorable for DFS in TN. GSEA analysis showed that differential Notch signaling is associated with cell cycle, tissue architecture and remodeling. Particularly, targets of E2F, early stage S phase transcription factor, were upregulated in the lumA unfavorable group and the TN favorable group differentiated on a basis of HES1 and PSEN1 expression. Summarizing, our analysis show significance of Notch signaling in BRCA progression through triggering EMT. Moreover, identification of numerous genes which overexpression is associated with disease recurrence may serve as a source of potential targets for a new anticancer therapy. PMID:27888801

  3. Patient Prognostic Score and Associations With Survival Improvement Offered by Radiotherapy After Breast-Conserving Surgery for Ductal Carcinoma In Situ: A Population-Based Longitudinal Cohort Study

    PubMed Central

    Freedman, Rachel A.; Vaz-Luis, Ines; Mallory, Melissa Anne; Wong, Stephanie M.; Aydogan, Fatih; DeSantis, Stephen; Barry, William T.; Golshan, Mehra

    2016-01-01

    Purpose Radiotherapy (RT) after breast-conserving surgery (BCS) is a standard treatment option for the management of ductal carcinoma in situ (DCIS). We sought to determine the survival benefit of RT after BCS on the basis of risk factors for local recurrence. Patients and Methods A retrospective longitudinal cohort study was performed to identify patients with DCIS diagnosed between 1988 and 2007 and treated with BCS by using SEER data. Patients were divided into the following two groups: BCS+RT (RT group) and BCS alone (non-RT group). We used a patient prognostic scoring model to stratify patients on the basis of risk of local recurrence. We performed a Cox proportional hazards model with propensity score weighting to evaluate breast cancer mortality between the two groups. Results We identified 32,144 eligible patients with DCIS, 20,329 (63%) in the RT group and 11,815 (37%) in the non-RT group. Overall, 304 breast cancer–specific deaths occurred over a median follow-up of 96 months, with a cumulative incidence of breast cancer mortality at 10 years in the weighted cohorts of 1.8% (RT group) and 2.1% (non-RT group; hazard ratio, 0.73; 95% CI, 0.62 to 0.88). Significant improvements in survival in the RT group compared with the non-RT group were only observed in patients with higher nuclear grade, younger age, and larger tumor size. The magnitude of the survival difference with RT was significantly correlated with prognostic score (P < .001). Conclusion In this population-based study, the patient prognostic score for DCIS is associated with the magnitude of improvement in survival offered by RT after BCS, suggesting that decisions for RT could be tailored on the basis of patient factors, tumor biology, and the prognostic score. PMID:26834064

  4. 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

  5. Prognosis of screen-detected breast cancers: results of a population based study

    PubMed Central

    Cortesi, Laura; Chiuri, Vincenzo E; Ruscelli, Silvia; Bellelli, Valeria; Negri, Rossella; Rashid, Ivan; Cirilli, Claudia; Fracca, Antonella; Gallo, Ennio; Federico, Massimo

    2006-01-01

    Background The reduced mortality rate from breast carcinoma among women offered screening mammography is demonstrated after 15–20 years of follow-up. However, the assessment of 5-year overall and event-free survival could represent an earlier measure of the efficacy of mammography screening program (MSP). Methods All cases of breast cancer diagnosed in the Province of Modena between years 1996 and 2000 in women aged 50 to 69 years, were identified through the Modena Cancer Registry (MCR). Stage of disease and treatment information were obtained from clinical records. All the events occurring up to June 30, 2003 were retrieved by experienced monitors. Five-year overall and event-free survival were the principal end-points of the study. Results During a 5-year period, 587 primary breast cancers were detected by the MSP and 471 primary breast cancers were diagnosed out of the MSP. The screen-detected breast cancers were smaller, more likely node negative, with low histological grade, low proliferative activity and positive receptors status. Furthermore, the breast cancer diagnosed through the MSP more frequently received a conservative surgery. The 5-year survival rate was 94% in the screen-detected group, versus 84% in the other group (p = 0.0001). The rate of 5-year event-free survival was 89% and 75% for the MSP participants and not participants, respectively (p = 0.0001). Conclusions Our data confirm a favourable outcome of screen-detected breast cancers in terms of five-year overall and event-free survival, which reflect the good quality assurance parameters of the MSP. Finally, a cancer registry should be implemented in every area covered by screening programs. PMID:16430776

  6. 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.

  7. Alcohol Consumption and Survival after a Breast Cancer Diagnosis: A Literature-Based Meta-analysis and Collaborative Analysis of Data for 29,239 Cases

    PubMed Central

    Ali, Alaa M.G.; Schmidt, Marjanka K.; Bolla, Manjeet K.; Wang, Qin; Gago-Dominguez, M.; Castelao, J. Esteban; Carracedo, Angel; Garzón, Victor Muñoz; Bojesen, Stig E.; Nordestgaard, Børge G.; Flyger, Henrik; Chang-Claude, Jenny; Vrieling, Alina; Rudolph, Anja; Seibold, Petra; Nevanlinna, Heli; Muranen, Taru A.; Aaltonen, Kirsimari; Blomqvist, Carl; Matsuo, Keitaro; Ito, Hidemi; Iwata, Hiroji; Horio, Akiyo; John, Esther M.; Sherman, Mark; Lissowska, Jolanta; Figueroa, Jonine; Garcia-Closas, Montserrat; Anton-Culver, Hoda; Shah, Mitul; Hopper, John L.; Trichopoulou, Antonia; Bueno-de-Mesquita, Bas; Krogh, Vittorio; Weiderpass, Elisabete; Andersson, Anne; Clavel-Chapelon, Françoise; Dossus, Laure; Fagherazzi, Guy; Peeters, Petra H.; Olsen, Anja; Wishart, Gordon C.; Easton, Douglas F.; Borgquist, Signe; Overvad, Kim; Barricarte, Aurelio; González, Carlos A.; Sánchez, María-José; Amiano, Pilar; Riboli, Elio; Key, Tim; Pharoah, Paul D.

    2015-01-01

    Background Evidence for an association of alcohol consumption with prognosis after a diagnosis of breast cancer has been inconsistent. We have reviewed and summarized the published evidence and evaluated the association using individual patient data from multiple case cohorts. Methods A MEDLINE search to identify studies published up to January 2013 was performed. We combined published estimates of survival time for “moderate drinkers” versus nondrinkers. An analysis of individual participant data using Cox regression was carried out using data from 11 case cohorts. Results We identified 11 published studies suitable for inclusion in the meta-analysis. Moderate post-diagnosis alcohol consumption was not associated with overall survival [HR, 0.95; 95% confidence interval (CI), 0.85–1.05], but there was some evidence of better survival associated with prediagnosis consumption (HR, 0.80; 95% CI, 0.73–0.88). Individual data on alcohol consumption for 29,239 cases with 4,839 deaths were available from the 11 case cohorts, all of which had data on estrogen receptor (ER) status. For women with ER-positive disease, there was little evidence that pre- or postdiagnosis alcohol consumption is associated with breast cancer–specific mortality, with some evidence of a negative association with all-cause mortality. On the basis of a single study, moderate postdiagnosis alcohol intake was associated with a small reduction in breast cancer–specific mortality for women with ER-negative disease. There was no association with prediagnosis intake for women with ER-negative disease. Conclusion There was little evidence that pre- or post-diagnosis alcohol consumption is associated with breast cancer–specific mortality for women with ER-positive disease. There was weak evidence that moderate post-diagnosis alcohol intake is associated with a small reduction in breast cancer–specific mortality in ER-negative disease. Impact Considering the totality of the evidence, moderate

  8. Breast awareness and screening.

    PubMed

    Harmer, Victoria

    Breast cancer is the most commonly diagnosed cancer in the UK. Breast awareness and screening, along with better treatment, can significantly improve outcomes, and more women than ever are now surviving the disease. This article discusses breast awareness and screening, symptoms and risk factors for breast cancer, and how nurses can raise breast awareness and screening uptake.

  9. 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.

  10. Up-regulation of cell cycle arrest protein BTG2 correlates with increased overall survival in breast cancer, as detected by immunohistochemistry using tissue microarray

    PubMed Central

    2010-01-01

    Background Previous studies have shown that the ADIPOR1, ADORA1, BTG2 and CD46 genes differ significantly between long-term survivors of breast cancer and deceased patients, both in levels of gene expression and DNA copy numbers. The aim of this study was to characterize the expression of the corresponding proteins in breast carcinoma and to determine their correlation with clinical outcome. Methods Protein expression was evaluated using immunohistochemistry in an independent breast cancer cohort of 144 samples represented on tissue microarrays. Fisher's exact test was used to analyze the differences in protein expression between dead and alive patients. We used Cox-regression multivariate analysis to assess whether the new markers predict the survival status of the patients better than the currently used markers. Results BTG2 expression was demonstrated in a significantly lower proportion of samples from dead patients compared to alive patients, both in overall expression (P = 0.026) and cell membrane specific expression (P = 0.013), whereas neither ADIPOR1, ADORA1 nor CD46 showed differential expression in the two survival groups. Furthermore, a multivariate analysis showed that a model containing BTG2 expression in combination with HER2 and Ki67 expression along with patient age performed better than a model containing the currently used prognostic markers (tumour size, nodal status, HER2 expression, hormone receptor status, histological grade, and patient age). Interestingly, BTG2 has previously been described as a tumour suppressor gene involved in cell cycle arrest and p53 signalling. Conclusions We conclude that high-level BTG2 protein expression correlates with prolonged survival in patients with breast carcinoma. PMID:20553615

  11. Does women's education affect breast cancer risk and survival? Evidence from a population based social experiment in education.

    PubMed

    Palme, Mårten; Simeonova, Emilia

    2015-07-01

    Breast cancer is a notable exception to the well documented positive education gradient in health. A number of studies have found that highly educated women are more likely to be diagnosed with the disease. Breast cancer is therefore often labeled as a "welfare disease". However, it has not been established whether the strong positive correlation holds up when education is exogenously determined. We estimate the causal effect of education on the probability of being diagnosed with breast cancer by exploiting an education reform that extended compulsory schooling and was implemented as a social experiment. We find that the incidence of breast cancer increased for those exposed to the reform.

  12. 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 Central

    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.

    2014-01-01

    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

  13. 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.

  14. 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.

  15. Regional recurrence in breast cancer patients with one to three positive axillary lymph nodes treated with breast-conserving surgery and whole breast irradiation

    PubMed Central

    Hirata, Kimiko; Yoshimura, Michio; Inoue, Minoru; Yamauchi, Chikako; Ogura, Masakazu; Toi, Masakazu; Suzuki, Eiji; Takeuchi, Megumi; Takada, Masahiro; Hiraoka, Masahiro

    2017-01-01

    Radiotherapy with breast-conserving therapy plays a crucial role in the treatment of early breast cancer. However, optimal radiotherapy targets have been controversial. We therefore evaluated regional recurrence in breast cancer patients with one to three positive lymph nodes (LNs) treated with breast-conserving surgery (BCS) followed by whole-breast irradiation (WBI). From 1993 to 2010, 121 breast cancer patients with one to three positive LNs who underwent BCS followed by WBI were analyzed. All patients underwent radiotherapy with two tangential fields to the whole breast. To evaluate the radiation dose to the axillary LNs, we contoured axillary LNs area and evaluated the dose–volumetric parameters. The median follow-up time was 112.4 months (range, 15.6–248.1 months). The 5-year overall survival and disease-free survival rates were 95.6% and 86.6%, respectively. The 5-year regional recurrence–free rate (RRFR) was 97.4%. During follow-up, six patients had regional recurrence. The pathological T stage was the factor best associated with the 5-year RRFR using the log-rank test, with 100.0% in the pT1 cohort versus 94.7% in the pT2–4 cohort (P < 0.01). The radiation dose to the axillary LNs did not contribute to the RRFR. In conclusion, while the pathological T stage was the prognostic factor best associated with regional recurrence, few regional recurrences were observed in early breast cancer patients with one to three LNs treated with BCS followed by WBI. Unintentional radiation doses to the axillary LNs using standard WBI were not related to the RRFR after axillary dissection. PMID:27422931

  16. 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.

  17. 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

  18. Better pathologic complete response and relapse-free survival after carboplatin plus paclitaxel compared with epirubicin plus paclitaxel as neoadjuvant chemotherapy for locally advanced triple-negative breast cancer: a randomized phase 2 trial

    PubMed Central

    Yin, Yi; Mo, Hongnan; Zhang, Bailin; Wang, Xiang; Li, Qing; Yuan, Peng; Wang, Jiayu; Zheng, Shan; Cai, Ruigang; Ma, Fei; Fan, Yin

    2016-01-01

    Background: No standard chemotherapy is used as neoadjuvant therapy in triple negative breast cancer (TNBC). This study has compared carboplatin plus paclitaxel with commonly used epirubicin plus paclitaxel as neoadjuvant chemotherapy (NAC) in TNBC. Results: 91 patients with a median age of 47 years (PC 47 patients, EP 44 patients) were enrolled. 65% of the patients were premenopausal. While the objective response rate was similar in the PC and EP arm (89.4% vs. 79.5%, P = 0.195), the pCR rate in the PC arm was significantly higher (38.6% vs. 14.0%, P = 0.014). The median follow-up time was 55.0 months. 5-year RFS were 77.6% and 56.2%, significantly higher in the PC arm, P = 0.043. No significant difference in OS was observed between the two arms (P = 0.350). Adverse events were similar, except for more thrombocytopenia in the PC arm (P = 0.001). Methods: Patients with stage II/III TNBC were randomized to receive either paclitaxel (175 mg/m2, day1) plus carboplatin (Area Under the Curve = 5, day2) (PC) or epirubicin (75mg/m2, day1) plus paclitaxel (175 mg/m2, day2) (EP) as NAC every three weeks for 4-6 cycles. The primary endpoint was rate of pathologic complete response (pCR).The secondary endpoints included relapse-free survival (RFS), overall survival (OS) and safety. Conclusions:This study suggested that the addition of carboplatin to paclitaxel was superior to the regimen of epirubicin plus paclitaxel as NAC for TNBC in terms of improving pCR rate and RFS. Further phase 3 study has already started. PMID:27447966

  19. High Expression of Three-Gene Signature Improves Prediction of Relapse-Free Survival in Estrogen Receptor-Positive and Node-Positive Breast Tumors

    PubMed Central

    Thakkar, Arvind; Raj, Hemanth; Ravishankar; Muthuvelan, Bhaskaran; Balakrishnan, Arun; Padigaru, Muralidhara

    2015-01-01

    The objective of the present study was to validate prognostic gene signature for estrogen receptor alpha-positive (ER03B1+) and lymph node (+) breast cancer for improved selection of patients for adjuvant therapy. In our previous study, we identified a group of seven genes (GATA3, NTN4, SLC7A8, ENPP1, MLPH, LAMB2, and PLAT) that show elevated messenger RNA (mRNA) expression levels in ERα (+) breast cancer patient samples. The prognostic values of these genes were evaluated using gene expression data from three public data sets of breast cancer patients (n = 395). Analysis of ERα (+) breast cancer cohort (n = 195) showed high expression of GATA3, NTN4, and MLPH genes significantly associated with longer relapse-free survival (RFS). Next cohort of ERα (+) and node (+) samples (n = 109) revealed high mRNA expression of GATA3, SLC7A8, and MLPH significantly associated with longer RFS. Multivariate analysis of combined three-gene signature for ERα (+) cohort, and ERα (+) and node (+) cohorts showed better hazard ratio than individual genes. The validated three-gene signature sets for ERα (+) cohort, and ERα (+) and node (+) cohort may have potential clinical utility since they demonstrated predictive and prognostic ability in three independent public data sets. PMID:26648682

  20. Lipin-1 regulation of phospholipid synthesis maintains endoplasmic reticulum homeostasis and is critical for triple-negative breast cancer cell survival.

    PubMed

    He, Jingquan; Zhang, Feng; Tay, Li Wei Rachel; Boroda, Salome; Nian, Weiqi; Levental, Kandice R; Levental, Ilya; Harris, Thurl E; Chang, Jeffrey T; Du, Guangwei

    2017-03-27

    Cancer cells reprogram their metabolism to increase the synthesis of macromolecules for rapid proliferation. Compared to fatty acids, much less is known about the synthesis of phospholipids, which is essential for membrane biogenesis in cancer cells. We found that LPIN1, which encodes lipin-1, a phosphatidic acid phosphatase (PAP) controlling the rate-limiting step in the phospholipid synthesis pathway, is highly up-regulated in basal-like triple-negative breast cancer (TNBC). Moreover, high LPIN1 expression correlates with the poor prognosis of these patients. Knockdown of LPIN1 increases apoptosis in basal-like TNBC cell lines, whereas it has minimal or less effect on normal human mammary gland epithelial cells (HMECs) and estrogen receptor-positive breast cancer cell lines. Fatty acid incorporation and lipidomics analyses showed that LPIN1 knockdown blocks phospholipid synthesis and changes membrane lipid compositions that ultimately induce the activation of 1 of the 3 branches of unfolded protein responses, the inositol-requiring enzyme-1α pathway. We also show for the first time, to our knowledge, that lipin-1 knockdown significantly inhibits tumor growth in vivo using an orthotopic xenograft breast mouse model. Our results suggest that lipin-1 is a potential target for cancer therapy.-He, J., Zhang, F., Tay, L. W. R., Boroda, S., Nian, W., Levental, K. R., Levental, I., Harris, T. E., Chang, J. T., Du, G. Lipin-1 regulation of phospholipid synthesis maintains endoplasmic reticulum homeostasis and is critical for triple-negative breast cancer cell survival.

  1. 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.

  2. Care and Survival of Mexican American Women with Node Negative Breast Cancer: Historical Cohort Evidence of Health Insurance and Barrio Advantages

    PubMed Central

    Richter, Nancy L.; Haji-Jama, Sundus; Luginaah, Isaac N.

    2013-01-01

    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. PMID:24155037

  3. Monitoring of Serum DNA Methylation as an Early Independent Marker of Response and Survival in Metastatic Breast Cancer: TBCRC 005 Prospective Biomarker Study.

    PubMed

    Visvanathan, Kala; Fackler, MaryJo S; Zhang, Zhe; Lopez-Bujanda, Zoila A; Jeter, Stacie C; Sokoll, Lori J; Garrett-Mayer, Elizabeth; Cope, Leslie M; Umbricht, Christopher B; Euhus, David M; Forero, Andres; Storniolo, Anna M; Nanda, Rita; Lin, Nancy U; Carey, Lisa A; Ingle, James N; Sukumar, Saraswati; Wolff, Antonio C

    2017-03-01

    Purpose Epigenetic alterations measured in blood may help guide breast cancer treatment. The multisite prospective study TBCRC 005 was conducted to examine the ability of a novel panel of cell-free DNA methylation markers to predict survival outcomes in metastatic breast cancer (MBC) using a new quantitative multiplex assay (cMethDNA). Patients and Methods Ten genes were tested in duplicate serum samples from 141 women at baseline, at week 4, and at first restaging. A cumulative methylation index (CMI) was generated on the basis of six of the 10 genes tested. Methylation cut points were selected to maximize the log-rank statistic, and cross-validation was used to obtain unbiased point estimates. Logistic regression or Cox proportional hazard models were used to test associations between the CMI and progression-free survival (PFS), overall survival (OS), and disease status at first restaging. The added value of the CMI in predicting survival outcomes was evaluated and compared with circulating tumor cells (CellSearch). Results Median PFS and OS were significantly shorter in women with a high CMI (PFS, 2.1 months; OS, 12.3 months) versus a low CMI (PFS, 5.8 months; OS, 21.7 months). In multivariable models, among women with MBC, a high versus low CMI at week 4 was independently associated with worse PFS (hazard ratio, 1.79; 95% CI, 1.23 to 2.60; P = .002) and OS (hazard ratio, 1.75; 95% CI, 1.21 to 2.54; P = .003). An increase in the CMI from baseline to week 4 was associated with worse PFS ( P < .001) and progressive disease at first restaging ( P < .001). Week 4 CMI was a strong predictor of PFS, even in the presence of circulating tumor cells ( P = .004). Conclusion Methylation of this gene panel is a strong predictor of survival outcomes in MBC and may have clinical usefulness in risk stratification and disease monitoring.

  4. Breast-conserving surgery in locally advanced breast cancer submitted to neoadjuvant chemotherapy. Safety and effectiveness based on ipsilateral breast tumor recurrence and long-term follow-up

    PubMed Central

    Carrara, Guilherme Freire Angotti; Scapulatempo-Neto, Cristovam; Abrahão-Machado, Lucas Faria; Brentani, Maria Mitzi; Nunes, João Soares; Folgueira, Maria Aparecida Azevedo Koike; da Costa Vieira, René Aloisio

    2017-01-01

    OBJECTIVE: To evaluate ipsilateral breast tumor recurrence after breast-conserving surgery for locally advanced breast cancer. METHODS: A retrospective observational cohort study was performed in patients with locally advanced breast cancer submitted to breast-conserving surgery after neoadjuvant chemotherapy based on an adriamycin-cyclophosphamide-paclitaxel regimen. We evaluated the clinical, pathologic, immunohistochemistry, and surgical factors that contribute to ipsilateral breast tumor recurrence and locoregional recurrence. A Kaplan-Meier analysis and Cox model were used to evaluate the main factors related to disease-free survival. RESULTS: Of the 449 patients who received neoadjuvant chemotherapy, 98 underwent breast-conserving surgery. The average diameter of the tumors was 5.3 cm, and 87.2% reached a size of up to 3 cm. Moreover, 86.7% were classified as clinical stage III, 74.5% had T3-T4 tumors, 80.5% had N1-N2 axilla, and 89.8% had invasive ductal carcinoma. A pathologic complete response was observed in 27.6% of the tumors, and 100.0% of samples had free margins. The 5-year actuarial overall survival rate was 81.2%, and the mean follow-up was 72.8 months. The rates of ipsilateral breast tumor recurrence and locoregional recurrence were 11.2% and 15.3%, respectively. Multifocal morphology response was the only factor related to ipsilateral breast tumor recurrence disease-free survival (p=0.04). A multivariate analysis showed that the pathologic response evaluation criteria in solid tumors (RECIST)-breast cutoff was the only factor related to locoregional recurrence disease-free survival (p=0.01). CONCLUSIONS: Breast-conserving surgery is a safe and effective therapy for selected locally advanced breast tumors. PMID:28355358

  5. The relationship between total and phosphorylated STAT1 and STAT3 tumour cell expression, components of tumour microenvironment and survival in patients with invasive ductal breast cancer

    PubMed Central

    Gujam, Fadia J.A.; McMillan, Donald C.; Edwards, Joanne

    2016-01-01

    The aim of the present study was to examine the relationship between tumour cell expression of total and phosphorylated STAT1 (ph-STAT1) and STAT3 (ph-STAT-3), components of tumour microenvironment and survival in patients with invasive ductal breast cancer. Immunohistochemical analysis of total and ph-STAT1, and STAT3 were performed on tissue microarray of 384 breast cancer specimens. Tumour cell expression of STAT1 and STAT3 at both cytoplasmic and nuclear locations were combined and identified as STAT1/STAT3 tumour cell expression. These results were related to cancer specific survival (CSS) and phenotypic features of the tumour and the host. High ph-STAT1 and ph-STAT3 tumour cell expression were associated with increased ER (both P≤0.001) and PR (both P <0.05), reduced tumour grade (P=0.015 and P<0.001 respectively) and necrosis (both P=0.001). Ph-STAT1 was associated with increased general inflammatory infiltrate (P=0.007) and ph-STAT3 was associated with lower CD4+ infiltration (P=0.024). In multivariate survival analysis, only high ph-STAT3 tumour cell expression was a predictor of improved CSS (P=0.010) independent of other tumour and host-based factors. STAT1 and STAT3 tumour cell expression appeared to be an important determinant of favourable outcome in patients with invasive ductal breast cancer. The present results suggest that STAT1 and STAT3 may affect disease outcome through direct impact on tumour cells, counteracting aggressive tumour features, as well as interaction with the surrounding microenvironment. PMID:27769057

  6. CD3+, CD4+ & CD8+ tumour infiltrating lymphocytes (TILs) are predictors of favourable survival outcome in infiltrating ductal carcinoma of breast

    PubMed Central

    Rathore, Ankita Singh; Kumar, Sandeep; Konwar, Rituraj; Makker, Annu; Negi, M.P.S.; Goel, Madhu Mati

    2014-01-01

    Background & objectives: Tumour infiltrating lymphocytes (TILs) represent the host immune response against cancer cells associated with good or bad prognosis in different tumour types. This study was undertaken to evaluate the significance of CD3+, CD4+ and CD8+ TILs in breast cancer tissues in relation to clinico-pathological variables and survival outcome. Methods: Immunohistochemistry (IHC) was performed with antibodies against CD3, CD4 and CD8 antigens on formalin-fixed paraffin-embedded tissue sections of 150 breast cancer patients. Intratumoural and stromal TIL counting was performed semiquantitatively. Results: The higher CD3+, CD4+ and CD8+ intratumoural and stromal counts showed independent and direct association with good prognosis. The prognostic predictor value of intratumoural counts was higher than stromal counts. The independent associations of intratumoural and stromal counts became more prominent when adjusted with stage and grade, respectively. Among intratumoural counts, the high (++/+++) CD4+ count (OR=3.85, 95% CI=3.28-16.71, P<0.001) showed the highest survival followed by CD3+ (OR=2.70, 95% CI=1.76-8.30, P=0.001) and CD8+ (OR=2.58, 95% CI=1.55-5.86, P=0.001) the least when compared to respective low (+) counts. In contrast, among stromal counts, the high CD8+ count (OR=3.13, 95% CI=2.20-9.57, P<0.001) showed the highest survival followed by CD4+ (OR=3.02, 95% CI=2.07-8.89, P<0.001) and CD3+ (OR=2.45, 95% CI=1.53-6.73, P=0.002) the least. Interpretation & conclusions: Our results suggest that intratumoural CD4+ and stromal CD8+ counts by immunohistochemistry may serve as an independent prognosticator for favourable outcome in breast cancer. PMID:25366203

  7. C-erbB-2 onco-protein expression in breast cancer: relationship to tumour characteristics and short-term survival in Universiti Kebansaan Malaysia Medical Centre.

    PubMed

    Sharifah, N A; Lee, B R; Clarence-Ko, C H; Tan, G C; Shiran, M S; Naqiyah, I; Rohaizak, M; Fuad, I; Tamil, A M

    2008-01-01

    Breast cancer is the commonest cancer affecting females in Malaysia, contributing 31% of all newly diagnosed cases amongst Malaysian women. The present retrospective cohort study evaluated the relationship between cerbB- 2 onco-protein overexpression with various tumour characteristics and survival rate of breast cancer patients treated at the Universiti Kebangsaan Malaysia Medical Centre (UKMMC) between 1996-2000. CerbB- 2 oncoprotein overexpression was determined by immunohistochemistry (IHC) and tumors showing 2+ positivity were verified by Fluorescence In Situ Hybridization (FISH). One hundred and seventy two patients were eligible for the study with a short-term follow-up (median) of 5.1 years. C-erbB-2 oncoprotein overexpression correlated with lymph node positivity, oestrogen receptor (ER) and progesterone receptor (PR) negativity. Univariate analyses showed shorter disease free survival (DFS) and overall survival (OS) in patients with cerbB- 2 oncoprotein overexpression, Malay ethnicity, higher tumour grade, lymph node positivity, ER and PR negativity. In a subgroup of patients with c-erbB-2 oncoprotein overexpression, a shorter OS was observed in those with lymph node positivity, ER and PR negativity. In multivariate prognostic analysis, lymph node status, ER status and tumour grading were the strongest independent prognostic factors for both OS and DFS. However, c-erbB-2 status was not a significantly independent prognostic factor, even in subsets with lymph node positive or negative group. C-erbB-2 oncoprotein overexpression correlated well with lymph node status, ER and PR. Shorter OS and DFS were significantly observed in patients with c-erbB-2 oncoprotein overexpression. Lymph node status, ER status and tumour grading were the only three independent prognostic factors for OS and DFS in this study. Although c-erbB-2 expression is obviously important from a biological standpoint, multivariate analysis showed that it is not an independent prognostic

  8. p85 protein expression is associated with poor survival in HER2-positive patients with advanced breast cancer treated with trastuzumab.

    PubMed

    Pavlakis, Kitty; Bobos, Mattheos; Batistatou, Anna; Kotoula, Vassiliki; Eleftheraki, Anastasia G; Stofas, Anastasios; Timotheadou, Eleni; Pentheroudakis, George; Psyrri, Amanda; Koutras, Angelos; Pectasides, Dimitrios; Papakostas, Pavlos; Razis, Evangelia; Christodoulou, Christos; Kalogeras, Konstantine T; Fountzilas, George

    2015-04-01

    To investigate the immunohistochemical expression of p85 in a cohort of trastuzumab-treated HER2-positive and HER2-negative metastatic breast cancer patients. The medical records of all patients with metastatic breast cancer treated with trastuzumab-based regimens between 1998 and 2010 were reviewed and clinical information was obtained. Formalin-fixed paraffin-embedded tumor tissue samples with adequate material were retrospectively collected from 183 patients. Samples were evaluated by immunohistochemistry for p85, estrogen receptors (ER), progesterone receptors (PgR), HER2, Ki67, PTEN and phosphorylated Akt (S473 and T308). HER2 status was studied by fluorescence in situ hybridization, as well. PIK3CA mutational status was also evaluated. Median follow-up for all patients was 72 months. Central re-evaluation for HER2 revealed only 111 HER2-positive cases, with the remaining 72 patients being HER2-negative. Median survival was longer in HER2-positive patients (50.7 months) compared to HER2-negative patients (36.6 months) both treated with trastuzumab, but this difference has not reached significance (p = 0.068). In total, 62% of the patients were found positive for p85, however the p85 protein was not found to be differentially expressed in HER2-positive versus HER2-negative cases. There were no significant associations between protein expression of p85 and any of the markers under study, or with time to progression. Positive p85 protein expression was however associated with poor survival in trastuzumab-treated HER2-positive patients. In our cohort of trastuzumab-treated HER2-positive breast cancer patients, positive p85 protein expression appears to be a prognostic factor of poor survival and, if validated, might have important implications in the treatment of such patients.

  9. Long-term survival of advanced triple-negative breast cancers with a dose-intense cyclophosphamide/anthracycline neoadjuvant regimen

    PubMed Central

    Giacchetti, S; Porcher, R; Lehmann-Che, J; Hamy, A-S; de Roquancourt, A; Cuvier, C; Cottu, P-H; Bertheau, P; Albiter, M; Bouhidel, F; Coussy, F; Extra, J-M; Marty, M; de Thé, H; Espié, M

    2014-01-01

    Background: Triple-negative (TN) breast cancers exhibit major initial responses to neoadjuvant chemotherapy, but generally have a poor outcome. Because of the lack of validated drug targets, chemotherapy remains an important therapeutic tool in these cancers. Methods: We report the survival of two consecutive series of 267 locally advanced breast cancers (LABC) treated with two different neoadjuvant regimens, either a dose-dense and dose-intense cyclophosphamide–anthracycline (AC) association (historically called SIM) or a conventional sequential association of cyclophosphamide and anthracycline, followed by taxanes (EC-T). We compared pathological responses and survival rates of these two groups and studied their association with tumours features. Results: Although the two regimens showed equivalent pathological complete response (pCR) in the whole population (16 and 12%), the SIM regimen yielded a non-statistically higher pCR rate than EC-T (48% vs 24%, P=0.087) in TN tumours. In the SIM protocol, DFS was statistically higher for TN than for non-TN patients (P=0.019), although we showed that the TN status was associated with an increased initial risk of recurrence in both regimens. This effect gradually decreased and after 2 years, TN was associated with a significantly decreased likelihood of relapse in SIM-treated LABC (hazard ratio (HR)=0.25 (95% CI: 0.07–0.86), P=0.028). Conclusions: AC dose intensification treatment is associated with a very favourable long-term survival rate in TN breast cancers. These observations call for a prospective assessment of such dose-intense AC-based regimens in locally advanced TN tumours. PMID:24569467

  10. Risk of regional recurrence in triple-negative breast cancer patients: a Dutch cohort study.

    PubMed

    van Roozendaal, Lori M; Smit, Leonie H M; Duijsens, Gaston H N M; de Vries, Bart; Siesling, Sabine; Lobbes, Marc B I; de Boer, Maaike; de Wilt, Johannes H W; Smidt, Marjolein L

    2016-04-01

    Triple-negative breast cancer is associated with early recurrence and low survival rates. Several trials investigate the safety of a more conservative approach of axillary treatment in clinically T1-2N0 breast cancer. Triple-negative breast cancer comprises only 15 % of newly diagnosed breast cancers, which might result in insufficient power for representative results for this subgroup. We aimed to provide a nationwide overview on the occurrence of (regional) recurrences in triple-negative breast cancer patients with a clinically T1-2N0 status. For this cohort study, 2548 women diagnosed between 2005 and 2008 with clinically T1-2N0 triple-negative breast cancer were selected from the Netherlands Cancer Registry. Follow-up data until 2014 were analyzed using Kaplan-Meier. Sentinel lymph node biopsy was performed in 2486 patients, and (completion) axillary lymph node dissection in 562 patients. Final pathologic nodal status was pN0 in 78.5 %, pN1mi in 4.5 %, pN1 in 12.3 %, pN2-3 in 3.6 %, and pNx in 1.1 %. During a follow-up of 5 years, regional recurrence occurred in 2.9 %, local recurrence in 4.2 % and distant recurrence in 12.2 %. Five-year disease-free survival was 78.7 %, distant disease-free survival 80.5 %, and 5-year overall survival 82.3 %. Triple-negative clinically T1-2N0 breast cancer patients rarely develop a regional recurrence. Their disease-free survival is more threatened by distant recurrence, affecting their overall survival. Consequently, it seems justified to include triple-negative breast cancer patients in randomized controlled trials investigating the safety of minimizing axillary staging and treatment.

  11. Latino Children's Body Mass Index at 2–3.5 Years Predicts Sympathetic Nervous System Activity at 5 Years

    PubMed Central

    Harley, Kim G.; Neilands, Torsten B.; Tambellini, Katelyn; Lustig, Robert H.; Boyce, W. Thomas; Eskenazi, Brenda

    2014-01-01

    Abstract Background: To understand whether the relationship between young children's autonomic nervous system (ANS) responses predicted their BMI, or vice versa, the association between standardized BMI (zBMI) at 2, 3.5, and 5 years of age and ANS reactivity at 3.5–5 years of age, and whether zBMI predicts later ANS reactivity or whether early ANS reactivity predicts later zBMI, was studied. Methods: Low-income, primarily Latino children (n=112) were part of a larger cohort study of mothers recruited during early pregnancy. Study measures included maternal prenatal weight, children's health behaviors (i.e., time watching television, fast food consumption, and time playing outdoors), children's height and weight at 2, 3.5, and 5 years, and children's ANS reactivity at 3.5 and 5 years. ANS measures of sympathetic nervous system (i.e., pre-ejection period) and parasympathetic nervous system (i.e., respiratory sinus arrhythmia) activity were monitored during rest and four challenges. Reactivity was calculated as the difference between mean challenge response and rest. Structural equation models analyzed the relationship between children's zBMI at 2, 3.5, and 5 years and ANS reactivity at 3.5 and 5 years, adjusting for mother's BMI, children's behaviors, and changes in height. Results: There was no association between zBMI and ANS cross-sectionally. Children with high zBMI at 2 or 3.5 years or large zBMI increases from 2 to 3.5 years of age had decreased sympathetic activity at 5 years. Neither sympathetic nor parasympathetic reactivity at 3.5 years predicted later zBMI. Conclusions: Increased zBMI early in childhood may dampen young children's SNS responses later in life. PMID:24745554

  12. Prognostic Factors of Survival in the Trastuzumab Era Among Women With Breast Cancer and Brain Metastases Who Receive Whole Brain Radiotherapy

    PubMed Central

    Dawood, Shaheenah; Gonzalez-Angulo, Ana M.; Albarracin, Constance; Yu, Tse Kuan; Hortobagyi, Gabriel N.; Buchholz, Thomas A.; Woodward, Wendy A.

    2011-01-01

    BACKGROUND The objective of this study was to review the outcome of women with breast cancer with known receptor status who were treated with whole brain radiotherapy for brain metastases and to determine factors that impact survival. METHODS A total of 223 women with breast cancer and brain metastases, who received whole brain radiotherapy, were identified. All women with HER-2–positive disease had received trastuzumab. Kaplan-Meier prodct limit method was used to determine overall survival (OS) estimates. Cox proportional hazards models were then fitted to explore the association of OS with various patient and tumor characteristics. RESULTS Median age at brain metastases diagnosis was 50 years. Sixty-seven (30.2%) patients had hormone receptor-positive/HER-2–negative disease, 101 (45.50%) had HER-2–positive disease, and 54 (24.3%) had triple receptor-negative disease. Median OS from brain metastases was 6 months, with 1-year survival of 30% (95% confidence interval [CI], 23%-36%). Women with hormone receptor-positive/HER-2–negative, HER-2–positive, and triple-negative tumors had median survivals of 5, 9, and 5 months, respectively (P =.0069). In the multivariate model, women with HER-2–positive disease had a significantly decreased risk of death compared with women with hormone receptor-positive/HER-2–negative disease (hazard ratio, 0.63; 95%CI, 0.42-0.94; P =.02). The risk of death among women with triple-negative disease compared with hormone receptor-positive/HER-2–negative disease was not significantly different (P =.54). Lower recursive partitioning analysis class and ≥30-gray brain radiation dose were also significantly associated with a decreased risk of death. CONCLUSIONS Breast tumor subtype has a significant prognostic role among women with breast cancer and brain metastases. In addition, in the trastuzumab era factors such as recursive partitioning analysis and adequate radiation dose continue to be important prognostic factors. PMID

  13. Body mass index and survival after diagnosis of invasive breast cancer: a study based on the Japanese National Clinical Database-Breast Cancer Registry.

    PubMed

    Kawai, Masaaki; Tomotaki, Ai; Miyata, Hiroaki; Iwamoto, Takayuki; Niikura, Naoki; Anan, Keisei; Hayashi, Naoki; Aogi, Kenjiro; Ishida, Takanori; Masuoka, Hideji; Iijima, Kotaro; Masuda, Shinobu; Tsugawa, Koichiro; Kinoshita, Takayuki; Nakamura, Seigo; Tokuda, Yutaka

    2016-06-01

    Few studies have reported the association between body mass index (BMI) and outcome among Asian breast cancer patients. We analyzed data for 20,090 female invasive breast cancer patients who had been followed-up for a median period of 6.7 years entered in the National Clinical Database-Breast Cancer Registry between 2004 and 2006. We used mainly the WHO criteria for BMI (kg/m(2) ) categories; <18.5 (underweight), ≥18.5-<21.8 (reference), ≥21.8-<25, ≥25-<30 (overweight), and ≥30 (obese). We divided normal weight patients into two subgroups because this category includes many patients compared to others. The timing of BMI measurement was not specified. The Cox proportional hazards model and cubic spline regression were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Smoking, alcohol, and physical activity were not controlled. A total of 1418 all-cause, 937 breast cancer-specific deaths, and 2433 recurrences were observed. Obesity was associated with an increased risk of all-cause (HR: 1.46; 95% CI: 1.16-1.83) and breast cancer-specific death (HR: 1.47; 95% CI: 1.11-1.93) for all patients, and with all-cause (HR: 1.47; 95% CI: 1.13-1.92) and breast cancer-specific death (HR: 1.58; 95% CI: 1.13-2.20) for postmenopausal patients. Being underweight was associated with an increased risk of all-cause death for all (HR: 1.41; 95% CI: 1.16-1.71) and for postmenopausal patients (HR: 1.45; 95% CI: 1.15-1.84). With regard to subtype and menopausal status, obesity was associated with an increased risk of breast cancer-specific death for all cases of luminal B tumor (HR: 2.59; 95% CI: 1.51-4.43; Pheterogeneity of Luminal B vs. Triple negative = 0.016) and for postmenopausal patients with luminal B tumor (HR: 3.24; 95% CI: 1.71-6.17). Being obese or underweight is associated with a higher risk of death among female breast cancer patients in Japan.

  14. Green tea catechins: Proposed mechanisms of action in breast cancer focusing on the interplay between survival and apoptosis.

    PubMed

    Yiannakopoulou, Eugenia Ch

    2014-02-01

    Recent data have shown strong chemopreventive and possibly cancer chemotherapeutic effects of green tea polyphenols against cancer. Despite advances in breast cancer treatment, mortality from breast cancer is still high. Undoubtedly novel treatment strategies are needed for chemoprevention of high risk women and for the treatment of receptor negative breast cancer. Green tea catechins have been shown to inhibit proliferation of breast cancer cells and to block carcinogenesis. This review attempts a critical presentation of the mechanisms of action of green tea catechins in breast cancer. Several mechanisms of action of green tea catechins in breast cancer have been proposed including modulation of extracellular signalling, induction of apoptosis through redox regulation, or through modulation of epigenetic alterations. A number of molecular targets of green tea catechins have been suggested i.e molecular chaperones, telomerase, apoptotic cascade. Although the molecular links among the proposed mechanisms of action of green tea catechins are often missing, it must be emphasized that all the proposed mechanisms indicate that green tea catechins inhibit growth and /or promote apoptosis. It would be interesting if future experimental trials could take into account that green tea catechins are multi-target agents and attempt to link every novel proposed target with the other already proposed targets of green tea catechins.

  15. Your Child's Development: 1.5 Years (18 Months)

    MedlinePlus

    ... Your 1- to 2-Year-Old Your Child's Development: 1.5 Years (18 Months) KidsHealth > For Parents > ... parts ("Where is your nose?") Movement and Physical Development runs walks up stairs with hand held throws ...

  16. Fitness and Your 4-to 5-Year Old

    MedlinePlus

    ... Old Feeding Your 1- to 2-Year-Old Fitness and Your 4- to 5-Year-Old KidsHealth > ... the risk of serious illnesses later in life. Fitness for Preschoolers Physical activity guidelines for preschoolers recommend ...

  17. General Principles for 5-year Regional Haze Progress Reports

    EPA Pesticide Factsheets

    This guidance document was developed by the U.S. EPA for EPA Regional Offices and states in preparing and reviewing the 5-year progress reports for the initial regional haze state implementation plans.

  18. Medical Care and Your 4- to 5-Year-Old

    MedlinePlus

    ... compared with other kids the same age and gender. The doctor will take a medical and family ... cooperatively with other kids understand the concept of gender identify colors Developmental milestones for 5-year-olds ...

  19. The Management and Outcomes of Male Breast Cancer

    PubMed Central

    Uslukaya, Ömer; Gümüş, Metehan; Gümüş, Hatice; Bozdağ, Zübeyir; Türkoğlu, Ahmet

    2016-01-01

    Objective Due to a lack of sufficient data, the treatment protocols for male breast cancer are usually the same as those used for female breast cancer. The aim of the current study was to present our clinical experience with male breast cancer. Materials and Methods The records of 37 patients who were treated for male breast cancer in our hospital between 2004 and 2014 were reviewed retrospectively. The data of patients were recorded and analyzed. Results The mean age of the patients was 63.03±12.36 years. Thirty-three patients (89.2%) had invasive ductal carcinoma, two (5.4%) had ductal carcinoma in situ, and two had invasive lobular carcinoma (5.4%). The most common molecular subtype was luminal A (17 cases, 45.9%). Twenty-nine patients with male breast cancer underwent mastectomy and two underwent breast conserving surgery. Axillary lymph node dissection was performed in 25 patients. The most common surgical procedure was modified radical mastectomy. Distant metastases were present in 17 (45.9%) patients. Overall, the 5-year survival was 60%. The 5-year survival was 100% for those with stage 0–I disease, 87% for stage II, and 42% for stage III. The 3-year survival was 14% for stage IV. Conclusion Patients with male breast cancer presented at an older age, a later stage, and with earlier metastasis. Early metastasis and death increases with increasing stage. Poor prognosis correlates with late admission. Data from different centers should be compiled and reviewed in order to determine a specific treatment protocol for male breast cancer; each paper published reveals new data. PMID:28331756

  20. 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.

  1. 5-Year Update Environmental Assessment for CV-22 Beddown

    DTIC Science & Technology

    2007-02-01

    Final 5-Year Update Environmental Assessment for CV-22 Beddown Hurlburt Field , Florida...SIGNIFICANT IMPACT 5-YEAR UPDATE CV-22 BEDDOWN HURLBURT FIELD , FL Agencies: The United States Air Force (USAF) and the United States Navy (Navy...the CV-22 Osprey at Hurlburt Field , Florida. The purpose of the Proposed Action is to: • Conduct IOT&E by testing the operation of the CV-22 in as

  2. Computer-aided Diagnosis-generated Kinetic Features of Breast Cancer at Preoperative MR Imaging: Association with Disease-free Survival of Patients with Primary Operable Invasive Breast Cancer.

    PubMed

    Kim, Jin Joo; Kim, Jin You; Kang, Hyun Jung; Shin, Jong Ki; Kang, Taewoo; Lee, Seok Won; Bae, Young Tae

    2017-03-02

    Purpose To retrospectively investigate the relationship between the kinetic features of breast cancer assessed with computer-aided diagnosis (CAD) at preoperative magnetic resonance (MR) imaging and disease-free survival in patients with primary operable invasive breast cancer. Materials and Methods This retrospective study was approved by the institutional review board. The requirement to obtain informed consent was waived. The authors identified 329 consecutive women (mean age, 52.9 years; age range, 32-88 years) with newly diagnosed invasive breast cancer who had undergone preoperative MR imaging and surgery between January 2012 and February 2013. All MR images were retrospectively reviewed by using a commercially available CAD system, and the following kinetic parameters were noted for each lesion: peak enhancement (highest pixel signal intensity in the first series obtained after administration of contrast material), angio-volume (total volume of the enhancing lesion), and delayed enhancement profiles (the proportions of washout, plateau, and persistently enhancing component within a tumor). Cox proportional hazards modeling was used to identify the relationship between CAD-generated kinetics and disease-free survival after adjusting for clinical-pathologic variables. Results A total of 36 recurrences developed at a median follow-up of 50 months (range, 15-55 months). CAD-measured peak enhancement at preoperative MR imaging enabled differentiation between patients with and patients without recurrence (area under the receiver operating characteristic curve = 0.728; 95% confidence interval [CI]: 0.676, 0.775; P < .001). Multivariate Cox analysis showed that a higher peak enhancement (hazard ratio [HR] = 1.001; 95% CI: 1.000, 1.002; P = .004), a higher washout component (HR = 1.029; 95% CI: 1.005, 1.054; P = .017), and lymphovascular invasion at histopathologic examination (HR = 3.011; 95% CI: 1.302, 6.962; P = .010) were associated with poorer disease

  3. The HER2 amplicon includes several genes required for the growth and survival of HER2 positive breast cancer cells.

    PubMed

    Sahlberg, Kristine Kleivi; Hongisto, Vesa; Edgren, Henrik; Mäkelä, Rami; Hellström, Kirsi; Due, Eldri U; Moen Vollan, Hans Kristian; Sahlberg, Niko; Wolf, Maija; Børresen-Dale, Anne-Lise; Perälä, Merja; Kallioniemi, Olli

    2013-06-01

    About 20% of breast cancers are characterized by amplification and overexpression of the HER2 oncogene. Although significant progress has been achieved for treating such patients with HER2 inhibitor trastuzumab, more than half of the patients respond poorly or become resistant to the treatment. Since the HER2 amplicon at 17q12 contains multiple genes, we have systematically explored the role of the HER2 co-amplified genes in breast cancer cell growth and their relation to trastuzumab resistance. We integrated aCGH data of the HER2 amplicon from 71 HER2 positive breast tumors and 10 cell lines with systematic functional RNA interference analysis of 23 core amplicon genes with several phenotypic endpoints in a panel of trastuzumab responding and non-responding HER2 positive breast cancer cells. Silencing of HER2 caused a greater growth arrest and apoptosis in the responding compared to the non-responding cell lines, indicating that the resistant cells are inherently less dependent on the HER2 pathway. Several other genes in the amplicon also showed a more pronounced effect when silenced; indicating that expression of HER2 co-amplified genes may be needed to sustain the growth of breast cancer cells. Importantly, co-silencing of STARD3, GRB7, PSMD3 and PERLD1 together with HER2 led to an additive inhibition of cell viability as well as induced apoptosis. These studies indicate that breast cancer cells may become addicted to the amplification of several genes that reside in the HER2 amplicon. The simultaneous targeting of these genes may increase the efficacy of the anti-HER2 therapies and possibly also counteract trastuzumab resistance. The observed additive effects seem to culminate to both apoptosis and cell proliferation pathways indicating that these pathways may be interesting targets for combinatorial treatment of HER2+ breast cancers.

  4. 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. PMID:27698913

  5. Two E-selectin ligands, BST-2 and LGALS3BP, predict metastasis and poor survival of ER-negative breast cancer.

    PubMed

    Woodman, Natalie; Pinder, Sarah E; Tajadura, Virginia; Le Bourhis, Xuefen; Gillett, Cheryl; Delannoy, Philippe; Burchell, Joy M; Julien, Sylvain

    2016-07-01

    Distant metastases account for the majority of cancer-related deaths in breast cancer. The rate and site of metastasis differ between estrogen receptor (ER)-negative and ER-positive tumours, and metastatic fate can be very diverse even within the ER-negative group. Characterisation of new pro-metastatic markers may help to identify patients with higher risk and improve their care accordingly. Selectin ligands aberrantly expressed by cancer cells promote metastasis by enabling interaction between circulating tumour cells and endothelial cells in distant organs. These ligands consist in carbohydrate molecules, such as sialyl-Lewis x antigen (sLex), borne by glycoproteins or glycolipids on the cancer cell surface. We have previously demonstrated that the molecular scaffold presenting sLex to selectins (e.g. glycolipid vs. glycoproteins) was crucial for these interactions to occur. Moreover, we reported that detection of sLex alone in breast carcinomas was only of limited prognostic value. However, since sLex was found to be carried by several glycoproteins in cancer cells, we hypothesized that the combination of the carbohydrate with its carriers could be more relevant than each marker independently. In this study, we addressed this question by analysing sLex expression together with two glycoproteins (BST-2 and LGALS3BP), shown to interact with E-selectin in a carbohydrate-dependent manner, in a cohort of 249 invasive breast cancers. We found both glycoproteins to be associated with distant metastasis risk and poorer survival. Importantly, concomitant high expression of BST-2 with sLex defined a sub-group of patients with ER-negative tumours displaying higher risks of liver and brain metastasis and a 3-fold decreased survival rate.

  6. Prognostic significance of uPA/PAI-1 level, HER2 status, and traditional histologic factors for survival in node-negative breast cancer patients

    PubMed Central

    Takac, Iztok

    2017-01-01

    Abstract Background The association of HER2 status with urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) levels raises the question whether uPA/PAI-1 level carries additional clinically relevant prognostic information independently from HER2 status. The aim of our study was to compare the prognostic value of uPA/PAI-1 level, HER2 status, and traditional prognostic factors for survival in node-negative breast cancer patients. Patients and methods A retrospective analysis of 858 node-negative breast cancer patients treated in Maribor University Clinical Center, Slovenia, in the years 2000–2009 was performed. Data were obtained from patient medical records. The median follow-up time was 100 months. Univariate and multivariate analyses of disease-free (DFS) and overall survival (OS) were performed using the Cox regression and the Cox proportional hazards model. Results In univariate analysis, age, tumor size, grade, lymphovascular invasion, HER2 status and UPA/PAI-1 level were associated with DFS, and age, tumor size, grade, and uPA/PAI-1 level were associated with OS. In the multivariate model, the most important determinants of DFS were age, estrogen receptor status and uPA/PAI-1 level, and the most important factors for OS were patient age and tumor grade. The HR for death from any cause in the multivariate model was 1.98 (95% CI 0.83–4.76) for patients with high uPA and/or PAI-1 compared to patients with both values low. Conclusions uPA/PAI-1 level clearly carries an independent prognostic value regardless of HER2 status in node-negative breast cancer and could be used in addition to HER2 and other markers to guide clinical decisions in this setting. PMID:28265234

  7. 2003-2013, a valuable study: Autologous tumor lysate-pulsed dendritic cell immunotherapy with cytokine-induced killer cells improves survival in stage IV breast cancer.

    PubMed

    Lin, Mao; Liang, Shuzhen; Jiang, Feng; Xu, Jiongyuan; Zhu, Weibing; Qian, Wei; Hu, Yong; Zhou, Zhanchun; Chen, Jibing; Niu, Lizhi; Xu, Kecheng; Lv, Youyong

    2017-03-01

    Dendritic cells (DCs) and cytokine-induced killer (CIK) cells have both shown activity as immunotherapy in some malignancies. Our aim was to prospective assess the effect of this immunotherapy in patients with stage IV breast cancer. Between Aug 2003 and Dec 2013, we collected 368 patients who met inclusion criteria and divided into immunotherapy group (treatment group: 188 patients) and chemotherapy group (control group: 180 patients). DCs were prepared from the mononuclear cells isolated from patients in the treatment group using IL-2/GM-CSF and were loaded with tumour antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies. After the patients had received low-dose chemotherapy, those in the treatment group also received the DC-CIK therapy, which was repeated four times in a fortnight to form one cycle. At least three cycles of DC-CIK therapy were given. Immune function was measured in treatment group patients' sera. Disease-free survival (DFS) and Overall survival (OS) after the diagnosis of stage IV breast cancer was assessed after a 10-year follow-up. The result demonstrated that immune function is obviously enhanced after DC-CIK therapy. By Cox regression analysis, DC-CIK therapy reduced the risk of disease progression (p<0.01) with an increased OS (p<0.01). After low-dose chemotherapy, active immunization with DC-CIK immunotherapy is a potentially effective approach for the control of tumour growth in stage IV breast cancer patients.

  8. A modified Weibull model for growth and survival of Listeria innocua and Salmonella Typhimurium in chicken breasts during refrigerated and frozen storage.

    PubMed

    Pradhan, A K; Li, M; Li, Y; Kelso, L C; Costello, T A; Johnson, M G

    2012-06-01

    The potential of food-borne pathogens to survive and grow during refrigerated and frozen storage has raised serious concerns over the safety of stored poultry products. In this study, the effect of refrigeration and freezing temperatures (-20, -12, 0, 4, and 8°C) on growth and survival of Listeria innocua and Salmonella enterica serovar Typhimurium in raw chicken breasts for storage times of 3, 7, 10, 14, and 21 d were investigated. A modified Weibull model was also developed to analyze the microbial behavior of both microorganisms in raw chicken breasts under different refrigerated storage conditions over time. The results showed that the bacterial loads of L. innocua at 4 and 8°C and Salmonella Typhimurium at 8°C were significantly different (P < 0.05) from those at other refrigerated and frozen storage temperatures over storage times. The loads of both bacteria at frozen storage temperatures did not change significantly over time. At a storage time of 7 d, the increase in bacterial loads of L. innocua at 4 and 8°C was 2.1 log cfu/g and 3.7 log cfu/g, respectively, and that of Salmonella Typhimurium at 8°C was 1.2 log cfu/g. The root mean square errors, median relative error, mean absolute relative error, and the plot of predicted versus observed bacterial loads showed a good performance of the model. The results from this study provided useful information regarding the behavior of Listeria and Salmonella in raw chicken breast meat during refrigerated and frozen storage, which would be helpful in giving insight over the safety of poultry products storage.

  9. Trabecular metal tibia still stable at 5 years

    PubMed Central

    Henricson, Anders; Rösmark, Dan; Nilsson, Kjell G

    2013-01-01

    Background and purpose Clinical results of total knee replacement (TKR) are inferior in younger patients, mainly due to aseptic loosening. Coating of components with trabecular metal (TM) is a new way of enhancing fixation to bone. We have previously reported stabilization of TM tibial components at 2 years. We now report the 5-year follow-up of these patients, including RSA of their TM tibial components. Patients and methods 22 patients (26 knees) received an uncemented TM cruciate-retaining tibial component and 19 patients (21 knees) a cemented NexGen Option cruciate-retaining tibial component. Follow-up with RSA, and clinical and radiographic examinations were done at 5 years. In bilaterally operated patients, the statistical analyses included only the first-operated knee. Results Both groups had most migration within the first 3 months, the TM implants to a greater extent than the cemented implants. After 3 months, both groups stabilized and remained stable up to the 5-year follow-up. Interpretation After a high initial degree of migration, the TM tibia stabilized. This stabilization lasted for at least 5 years, which suggests a good long-term performance regarding fixation. The cemented NexGen CR tibial components showed some migration in the first 3 months and then stabilized up to the 5-year follow-up. This has not been reported previously. PMID:23992142

  10. Expression of Proteins Involved in Epithelial-Mesenchymal Transition as Predictors of Metastasis and Survival in Breast Cancer Patients

    DTIC Science & Technology

    2013-11-01

    and monthly Breast Disease Site Research Group meetings. Attendance at the 2013 American Association for Cancer Research (AACR) Annual Meeting. Task...Hattori M, Yang H, Bos JL, Minato N (1999) Rap1 GTPase-activating protein SPA -1 negatively regulates cell adhesion. J Biol Chem 274:18463–18469 19... binding protein 1 (RBP1) and the mSin3 histone deacetylase complex and represses transcription. J Biol Chem 279:1562–1569 Breast Cancer Res Treat (2013) 139:873–885 885 123

  11. 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.

  12. HER-2/Neu overexpression does not predict response to neoadjuvant chemotherapy or prognosticate survival in patients with locally advanced breast cancer.

    PubMed

    Tulbah, Asma M; Ibrahim, Ezzeldin M; Ezzat, Adnan A; Ajarim, Dahish S; Rahal, Mohammed M; El Weshi, Amr N; Sorbris, Ralph

    2002-01-01

    Data about the prognostic and predictive value of HER-2/neu overexpression in patients with locally advanced breast cancer (LABC) treated with primary chemotherapy is limited. Therefore, this retrospective study was performed to examine this issue. Fifty-four consecutive patients with LABC were prospectively managed using a uniform multimodality approach. Response to neoadjuvant chemotherapy and survival were examined against HER-2/neu overexpression as determined by an immunohistochemistry method on formalin-fixed, paraffin-embedded samples of breast cancer using the commercially available, United States Food and Drug Administration-approved kit HercepTest (Dako Corp, Carpinteria, CA). The number of patients in each HercepTest immunostaining group were as follows; 0 in 12 patients (22%), 1+ in 8 (15%), 2+ in 12 (22%), and 3+ in 22 (41%). None of the clinical variables was significantly associated with HER-2/neu expression. After primary therapy, 22% of patients attained clinical complete response and an additional 70% achieved clinical partial response with an overall response rate of 92% (95% confidence interval: 100% to 79%). There was no significant correlation between clinical response and HercepTest positivity (p = 0.85). Of 52 patients with complete pathological data, there was no significant difference in HercepTest status between those who attained complete pathological response (46%) and those who did not (38%) (p = 0.74). Moreover, there was no significant difference in disease-free survival (75% vs 84%, [p = 0.26]) or overall survival (81% vs 84% [p = 0.31]) between those who overexpressed HER-2/neu and those with negative HercepTest, respectively. In patients with LABC, HER-2/neu overexpression determined using HercepTest assay and according to the manufacturer's approved guidelines failed to demonstrate a predictive or a prognostic role.

  13. 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.

  14. Rhinoscleroma in a 5-year-old Portuguese Child.

    PubMed

    Simão, Inês; Gaspar, Iuri; Faustino, Rosário; Brito, Maria João Rocha

    2014-07-01

    Rhinoscleroma is a chronic granulomatous infectious disease that is rare in Western Europe. We report the case of a 5-year-old Portuguese boy diagnosed with rhinoscleroma in the context of recurrent epistaxis. He had a 6-month course of antibiotic (amoxicillin plus clavulanate) therapy with full recovery.

  15. 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…

  16. The prognostic impact of age in different molecular subtypes of breast cancer.

    PubMed

    Liedtke, Cornelia; Rody, Achim; Gluz, Oleg; Baumann, Kristin; Beyer, Daniel; Kohls, Eva-Beatrice; Lausen, Kerstin; Hanker, Lars; Holtrich, Uwe; Becker, Sven; Karn, Thomas

    2015-08-01

    Breast cancer is a heterogeneous entity composed of distinct molecular subgroups with different molecular and clinical features. We analyzed the association between molecular breast cancer subgroups, age at diagnosis, and prognosis in a compilation of publicly available gene expression datasets. Affymetrix gene expression data (U133A or U133Plus2.0 arrays) of 4467 breast cancers from 40 datasets were compiled and homogenized. Breast cancer subgroups were defined based on expression of ESR1, PR, HER2, and Ki67. Event-free survival was calculated as recurrence-free survival or distant metastasis-free survival if recurrence-free survival was not available. Young age at diagnosis is associated with higher frequency of triple negative and HER2 subtypes and lower frequency of luminal A breast cancers. The 5-year event-free survival rates of patients aged less than 40, between 40 and 50, and >50 years were 54.3 ± 3.5, 68.5 ± 1.9, and 70.4 ± 1.3 %, respectively. When controlling for breast cancer subtype, we found that age <40 years remained significantly associated with poor prognosis in triple negative breast cancer. The effect was modest in luminal tumors and not found in HER2 subtype. Both subtypes and age retained their significances in multivariate analysis. Association of age at diagnosis with molecular breast cancer subtype contributes to its important role as prognostic factor among patients with breast cancer. Still, within the group of triple negative breast cancer, young age <40 years has a significant prognostic value which was retained in multivariate analysis.

  17. 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.

  18. Management of Adenoid Cystic Carcinoma of the Breast: A Rare Cancer Network Study

    SciTech Connect

    Khanfir, Kaouthar; Kallel, Adel; Villette, Sylviane; Belkacemi, Yazid; Vautravers, Claire; Nguyen, TanDat; Miller, Robert; Li Yexiong; Taghian, Alphonse G.; Boersma, Liesbeth; Poortmans, Philip; Goldberg, Hadassah; Vees, Hansjorg; Senkus, Elzbieta; Igdem, Sefik; Ozsahin, Mahmut; Jeanneret Sozzi, Wendy

    2012-04-01

    Background: Mammary adenoid cystic carcinoma (ACC) is a rare breast cancer. The aim of this retrospective study was to assess prognostic factors and patterns of failure, as well as the role of radiation therapy (RT), in ACC. Methods: Between January 1980 and December 2007, 61 women with breast ACC were treated at participating centers of the Rare Cancer Network. Surgery consisted of lumpectomy in 41 patients and mastectomy in 20 patients. There were 51(84%) stage pN0 and 10 stage cN0 (16%) patients. Postoperative RT was administered to 40 patients (35 after lumpectomy, 5 after mastectomy). Results: With a median follow-up of 79 months (range, 6-285), 5-year overall and disease-free survival rates were 94% (95% confidence interval [CI], 88%-100%) and 82% (95% CI, 71%-93%), respectively. The 5-year locoregional control (LRC) rate was 95% (95% CI, 89%-100%). Axillary lymph node dissection or sentinel node biopsy was performed in 84% of cases. All patients had stage pN0 disease. In univariate analysis, survival was not influenced by the type of surgery or the use of postoperative RT. The 5-year LRC rate was 100% in the mastectomy group versus 93% (95% CI, 83%-100%) in the breast-conserving surgery group, respectively (p = 0.16). For the breast-conserving surgery group, the use of RT significantly correlated with LRC (p = 0.03); the 5-year LRC rates were 95% (95% CI, 86%-100%) for the RT group versus 83% (95% CI, 54%-100%) for the group receiving no RT. No local failures occurred in patients with positive margins, all of whom received postoperative RT. Conclusion: Breast-conserving surgery is the treatment of choice for patients with ACC breast cancer. Axillary lymph node dissection or sentinel node biopsy might not be recommended. Postoperative RT should be proposed in the case of breast-conserving surgery.

  19. 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.

  20. Expression of Proteins Involved in Epithelial-Mesenchymal Transition as Predictors of Metastasis and Survival in Breast Cancer Patients

    DTIC Science & Technology

    2012-11-01

    ORGANIZATION: Health Research Inc. Buffalo NY 14263-0001 REPORT DATE: November 2012 TYPE OF REPORT: Annual Summary PREPARED FOR: U.S. Army...ORGANIZATION REPORT NUMBER Buffalo , NY 14263-0001 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10. SPONSOR/MONITOR’S...aggressive tumor characteristics and lymph node positive breast cancer at diagnosis between African - American and European-American women. Genotyping

  1. Breast Cancer Stem Cells Survive Periods of Farnesyl-Transferase Inhibitor-Induced Dormancy by Undergoing Autophagy

    PubMed Central

    Chaterjee, Moumita; van Golen, Kenneth L.

    2011-01-01

    A cancer stem cell has been defined as a cell within a tumor that possesses the capacity to self-renew and to cause the heterogeneous lineages of cancer cells that comprise the tumor. These tumor-forming cells could hypothetically originate from stem, progenitor, or differentiated cells. Previously, we have shown that breast cancer cells with low metastatic potential can be induced into a reversible state of dormancy by farnesyl transferase inhibitors (FTIs). Dormancy was induced by changes in RhoA and RhoC GTPases. Specifically, RhoA was found to be hypoactivated while RhoC was hyperactivated. In the current study we demonstrate that these dormant cells also express certain known stem cell markers such as aldehyde dehydrogenase I (ALDHI) and cluster of differentiation 44 (CD44). We also show that autophagy markers Atg5, Atg12, and LC3-B are expressed in these dormant stem cell-like breast cancer cells. Inhibiting autophagy by inhibitor 3-methyladenine (3-MA) blocked the process of autophagy reversing the dormant phenotype. Further, we show that c-jun NH2 terminal kinase (JNK/SAPK) is upregulated in these dormant stem cell-like breast cancer cells and is responsible for increasing autophagy. PMID:22046561

  2. General paediatric surgery for patients aged under 5 years: a 5-year experience at a district general hospital

    PubMed Central

    Gordon, AC

    2016-01-01

    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

  3. Methodological issues in estimating survival in patients with multiple primary cancers: an application to women with breast cancer as a first tumour

    PubMed Central

    Rosso, Stefano; Ricceri, Fulvio; Terracini, Lea; Zanetti, Roberto

    2009-01-01

    Background Comparing survival of patients with a single tumour and patients with multiple primaries poses different methodological problems. In population based studies, where we cannot rely on detailed clinical information, the issue is disentangling the share of survival probability from the first and second cancer, and their compounded effect. We examined three hypotheses: A) the survival probability since the first tumour does not change with the occurrence of a second tumour; B) the probability of surviving a tumour does not change with the presence of a previous primary; C) the probabilities of surviving two subsequent primary tumours are independent (additivity hypothesis on mortality rates). Methods We studied the survival probabilities modelling mortality rates according to hypotheses A), B) and C). Mortality rates were calculated using Aalen-Johansen estimators which allowed to discount for the lag-time survival before developing a second tumour. We applied this approach to a cohort of 436 women with breast cancer (BC) and a subsequent tumour in the resident population of Turin, Italy, between 1985 and 2002. Results We presented our results in term of a Standardised Mortality Ratio calculated (SMRAJ) after 10 years of follow-up. For hypothesis A we observed a significant excess mortality of 2.21 (95% C.I. 1.94 – 2.45). Concerning hypothesis B we found a not significant SMRAJ of 0.98 (95% C.I. 0.87 – 1.10). The additivity hypothesis (C) was not confirmed as it overestimated the risk of death, in fact SMRsAJ were all below 1: 0.75 (95% C.I. 0.66 – 0.84) for BC and all subsequent cancers, 0.72 (95% C.I. 0.55 – 0.94) for BC and colon-rectum cancer, 0.76 (95% C.I. 0.48 – 1.14) for BC and corpus uteri cancer (not significant). Conclusion This method proved to be useful in disentangling the effect of different subsequent cancers on mortality. In our application it shows a worse long-term mortality for women with two cancers than that with BC only

  4. 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.

  5. 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

  6. Basal-like Breast cancer DNA copy number losses identify genes involved in genomic instability, response to therapy, and patient survival.

    PubMed

    Weigman, Victor J; Chao, Hann-Hsiang; Shabalin, Andrey A; He, Xiaping; Parker, Joel S; Nordgard, Silje H; Grushko, Tatyana; Huo, Dezheng; Nwachukwu, Chika; Nobel, Andrew; Kristensen, Vessela N; Børresen-Dale, Anne-Lise; Olopade, Olufunmilayo I; Perou, Charles M

    2012-06-01

    Breast cancer is a heterogeneous disease with known expression-defined tumor subtypes. DNA copy number studies have suggested that tumors within gene expression subtypes share similar DNA Copy number aberrations (CNA) and that CNA can be used to further sub-divide expression classes. To gain further insights into the etiologies of the intrinsic subtypes, we classified tumors according to gene expression subtype and next identified subtype-associated CNA using a novel method called SWITCHdna, using a training set of 180 tumors and a validation set of 359 tumors. Fisher's exact tests, Chi-square approximations, and Wilcoxon rank-sum tests were performed to evaluate differences in CNA by subtype. To assess the functional significance of loss of a specific chromosomal region, individual genes were knocked down by shRNA and drug sensitivity, and DNA repair foci assays performed. Most tumor subtypes exhibited specific CNA. The Basal-like subtype was the most distinct with common losses of the regions containing RB1, BRCA1, INPP4B, and the greatest overall genomic instability. One Basal-like subtype-associated CNA was loss of 5q11-35, which contains at least three genes important for BRCA1-dependent DNA repair (RAD17, RAD50, and RAP80); these genes were predominantly lost as a pair, or all three simultaneously. Loss of two or three of these genes was associated with significantly increased genomic instability and poor patient survival. RNAi knockdown of RAD17, or RAD17/RAD50, in immortalized human mammary epithelial cell lines caused increased sensitivity to a PARP inhibitor and carboplatin, and inhibited BRCA1 foci formation in response to DNA damage. These data suggest a possible genetic cause for genomic instability in Basal-like breast cancers and a biological rationale for the use of DNA repair inhibitor related therapeutics in this breast cancer subtype.

  7. Prenatal Lead Exposure and Weight of 0- to 5-Year-Old Children in Mexico City

    PubMed Central

    Peterson, Karen E.; Sánchez, Brisa N.; Cantonwine, David; Lamadrid-Figueroa, Héctor; Schnaas, Lourdes; Ettinger, Adrienne S.; Hernández-Avila, Mauricio; Hu, Howard; Téllez-Rojo, Martha M.

    2011-01-01

    Background: Cumulative prenatal lead exposure, as measured by maternal bone lead burden, has been associated with smaller weight of offspring at birth and 1 month of age, but no study has examined whether this effect persists into early childhood. Objective: We investigated the association of perinatal maternal bone lead, a biomarker of cumulative prenatal lead exposure, with children’s attained weight over time from birth to 5 years of age. Methods: Children were weighed at birth and at several intervals up until 60 months. Maternal tibia and patella lead were measured at 1 month postpartum using in vivo K-shell X-ray fluorescence. We used varying coefficient models with random effects to assess the association of maternal bone lead with weight trajectories of 522 boys and 477 girls born between 1994 and 2005 in Mexico City. Results: After controlling for breast-feeding duration, maternal anthropometry, and sociodemographic characteristics, a 1-SD increase in maternal patella lead (micrograms per gram) was associated with a 130.9-g decrease in weight [95% confidence interval (CI), –227.4 to –34.4 g] among females and a 13.0-g nonsignificant increase in weight among males (95% CI, –73.7 to 99.9 g) at 5 years of age. These associations were similar after controlling for concurrent blood lead levels between birth and 5 years. Conclusions: Maternal bone lead was associated with lower weight over time among female but not male children up to 5 years of age. Given that the association was evident for patellar but not tibial lead levels, and was limited to females, results need to be confirmed in other studies. PMID:21715242

  8. The protective effect of longer duration of breastfeeding against pregnancy-associated triple negative breast cancer

    PubMed Central

    ElShmay, Wael M.

    2016-01-01

    Parity associated breast cancer (PABC) often diagnosed within the 2-5 years after a full term pregnancy. PABC is usually present with more advanced, poorly differentiated, high-grade cancers that show shorter time to progression and often of the triple negative breast cancer (TNBC) subtype. Data from around the world show that pregnancy-associated TNBC is independently associated with poor survival, underscoring the impact of the pregnant breast microenvironment on the biology and consequently the prognosis of these tumors. Although it is not yet clear, a link between pregnancy-associated TNBCs and lack or shorter duration of breastfeeding (not pregnancy per se) has been proposed. Here, we present epidemiological and experimental evidence for the protective effect of longer duration of lactation against pregnancy-associated TNBCs, and propose a putative molecular mechanism for this protective effect and its effect in eliminating any potential TNBC precursors from the breast by the end of the natural breast involution. PMID:27248476

  9. The vitamin D analogue EB 1089 prevents skeletal metastasis and prolongs survival time in nude mice transplanted with human breast cancer cells.

    PubMed

    El Abdaimi, K; Dion, N; Papavasiliou, V; Cardinal, P E; Binderup, L; Goltzman, D; Ste-Marie, L G; Kremer, R

    2000-08-15

    1,25-Dihydroxyvitamin D has potent antiproliferative and anti-invasive properties in vitro in cancer cells. However, its calcemic effect in vivo limits its therapeutic applications. Here, we report the efficacy of EB 1089, a low calcemic analogue of vitamin D, on the development of osteolytic bone metastases after intracardiac injection of the human breast cancer cell line MDA-MB-231 in nude mice. Animals injected with tumor cells were implanted simultaneously with osmotic minipumps containing either EB 1089 or vehicle. Both groups remained normocalcemic for the duration of the experiment. The total number of bone metastases, the mean surface area of osteolytic lesions, and tumor burden within bone per animal were markedly decreased in EB1089-treated mice. Furthermore, longitudinal analysis revealed that mice treated with EB1089 displayed a marked increase in survival and developed fewer bone lesions and less hind limb paralysis over time as compared with untreated animals. These results suggest that EB1089 may be beneficial in the prevention of metastatic bone lesions associated with human breast cancer.

  10. 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

  11. Onychomatricoma: A Case Report with 5-year Follow-up

    PubMed Central

    Ishida, Cleide Eiko; Gouveia, Bruna Melhoranse; Cuzzi, Tullia; Ramos-e-Silva, Marcia

    2016-01-01

    The authors present a case of onychomatricoma, a rare benign tumour of the nail matrix, first described by Baran and Kint in 1992. The lesion appeared on the proximal nail fold, covering half the nail of the second left finger. The nail was thickened and yellowish with longitudinal melanonychia. It was surgically removed with very satisfactory aesthetic results even after 5 years. A review on the subject is also presented. PMID:28163462

  12. Prognostic factors for patients with hepatic metastases from breast cancer.

    PubMed

    Wyld, L; Gutteridge, E; Pinder, S E; James, J J; Chan, S Y; Cheung, K L; Robertson, J F R; Evans, A J

    2003-07-21

    Median survival from liver metastases secondary to breast cancer is only a few months, with very rare 5-year survival. This study reviewed 145 patients with liver metastases from breast cancer to determine factors that may influence survival. Data were analysed using Kaplan-Meier survival curves, univariate and multivariate analysis. Median survival was 4.23 months (range 0.16-51), with a 27.6% 1-year survival. Factors that significantly predicted a poor prognosis on univariate analysis included symptomatic liver disease, deranged liver function tests, the presence of ascites, histological grade 3 disease at primary presentation, advanced age, oestrogen receptor (ER) negative tumours, carcinoembryonic antigen of over 1000 ng ml(-1) and multiple vs single liver metastases. Response to treatment was also a significant predictor of survival with patients responding to chemo- or endocrine therapy surviving for a median of 13 and 13.9 months, respectively. Multivariate analysis of pretreatment variables identified a low albumin, advanced age and ER negativity as independent predictors of poor survival. The time interval between primary and metastatic disease, metastases at extrahepatic sites, histological subtype and nodal stage at primary presentation did not predict prognosis. Awareness of the prognostic implications of the above factors may assist in selecting the most appropriate treatment for these patients.British Journal of Cancer (2003) 89, 284-290. doi:10.1038/sj.bjc.6601038 www.bjcancer.com

  13. Neutrophil to lymphocyte ratio (NLR) for prediction of distant metastasis-free survival (DMFS) in early breast cancer: a propensity score-matched analysis

    PubMed Central

    Orditura, Michele; Galizia, Gennaro; Diana, Anna; Saccone, Ciro; Cobellis, Luigi; Ventriglia, Jole; Iovino, Francesco; Romano, Ciro; Morgillo, Floriana; Mosca, Lavinia; Diadema, Maria Rosaria; Lieto, Eva; Procaccini, Eugenio; De Vita, Ferdinando; Ciardiello, Fortunato

    2016-01-01

    Objective To assess the correlation between presurgery neutrophil to lymphocyte ratio (NLR) and distant metastasis-free survival (DMFS) in patients with early breast cancer. Design Retrospective analysis. Participants 300 Caucasian patients with early (T1–2, N0–1, non-metastatic) breast cancer who were followed from July 1999 to June 2015 at our Institution. Main outcome measures Distant metastasis-free survival (DMFS). Results Of whole populations (300 patients), 134 and 166 patients were grouped as low and high NLR, respectively, on the basis of NLR value of 1.97, as established by receiver operating characteristic (ROC) curve analysis (area under curve (AUC)=0.625, p=0.0160). The DMFS rates for 1, 3, 6, 9, 12 and 15 years were better in low NLR patients (100%, 98.9%, 91.7%, 82.7%, 82.7%, 82.7%, respectively), than in high NLR patients (99.4%, 94.3%, 84.5%, 69.2%, 66.0%, 51.4%, respectively), with a statistically significant association. On multivariate analysis, premenopausal status (HR=2.78, 95% CI 1.36 to 5.67, p=0.0049), N1 stage (HR=2.31, 95% CI 1.16 to 4.60, p=0.0167) and a high NLR value (HR=2.64, 95% CI 1.22 to 5.638, p=0.0133) were shown to be independent prognostic factors related to poor recurrence rate. To avoid risk of confounding bias, a propensity score-matched analysis was performed and multivariate analysis according to the Cox model confirmed premenopausal status (HR=2.94, 95% CI 1.25 to 6.93, p=0.0136), N1 stage (HR=2.77, 95% CI 1.25 to 6.12, p=0.0117) and high NLR values (HR=2.52, 95% CI 1.11 to 5.73, p=0.0271), as independent prognostic variables of worse outcome. Conclusions This is the first study, to our knowledge, to show a significant correlation between high NLR and worse prognosis in Caucasian patients with early breast cancer by means of propensity score-matched analysis. Further well designed prospective trials with a large sample size are needed to verify our findings and to justify introducing NLR assessment in clinical

  14. 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

  15. 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.

  16. Modulation of the uptake of critical nutrients by breast cancer cells by lactate: Impact on cell survival, proliferation and migration.

    PubMed

    Guedes, Marta; Araújo, João R; Correia-Branco, Ana; Gregório, Inês; Martel, Fátima; Keating, Elisa

    2016-02-15

    This work aimed to characterize the uptake of folate and glucose by breast cancer cells and to study the effect of lactate upon the transport of these nutrients and upon cell viability, proliferation and migration capacity. Data obtained showed that: a) MCF7 cells uptake (3)H-folic acid ((3)H-FA) at physiological but not at acidic pH; b) T47D cells accumulate (3)H-FA and (14)C-5-methyltetrahydrofolate ((14)C-5-MTHF) more efficiently at acidic than at physiological pH; c) (3)H-deoxyglucose ((3)H-DG) uptake by T47D cells is sodium-independent, inhibited by cytochalasin B (CYT B) and stimulated by insulin. Regarding the effect of lactate, in T47D cells, acute (26 min) and chronic (24 h) exposure to lactic acid (LA) stimulated (3)H-FA uptake. Acute exposure to LA also stimulated (3)H-DG uptake and chronic exposure to LA significantly stimulated T47D cell migratory capacity. In conclusion, the transport of folates is strikingly different in two phenotypically similar breast cancer cell lines: MCF7 and T47D cells. Additionally, lactate seems to act as a signaling molecule which increases the uptake of nutrients and promotes the migration capacity of T47D cells.

  17. RAD51 inhibition in triple negative breast cancer cells is challenged by compensatory survival signaling and requires rational combination therapy

    PubMed Central

    Wiegmans, Adrian P.; Miranda, Mariska; Wen, Shu Wen

    2016-01-01

    The molecular rationale to induce synthetic lethality, by targeting defective homologous recombination repair in triple negative breast cancer (TNBC), has proven to have several shortcomings. Not meeting the expected minimal outcomes in clinical trials has highlighted common clinical resistance mechanisms including; increased expression of the target gene PARP1, increased expression or reversion mutation of BRCA1, or up-regulation of the compensatory homologous recombination protein RAD51. Indeed, RAD51 has been demonstrated to be an alternative synthetic lethal target in BRCA1-mutated cancers. To overcome selective pressure on DNA repair pathways, we examined new potential targets within TNBC that demonstrate synthetic lethality in association with RAD51 depletion. We confirmed complementary targets of PARP1/2 and DNA-PK as well as a new synthetic lethality combination with p38. p38 is considered a relevant target in breast cancer, as it has been implicated in resistance to chemotherapy, including tamoxifen. We show that the combination of targeting RAD51 and p38 inhibits cell proliferation both in vitro and in vivo, which was further enhanced by targeting of PARP1. Analysis of the molecular mechanisms revealed that depletion of RAD51 increased ERK1/2 and p38 signaling. Our results highlight a potential compensatory mechanism via p38 that limits DNA targeted therapy. PMID:27507046

  18. Olfactory Dysfunction Predicts 5-Year Mortality in Older Adults

    PubMed Central

    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. PMID:25271633

  19. 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.

  20. Treatment of Metastatic Breast Cancer in a Real-World Scenario: Is Progression-Free Survival With First Line Predictive of Benefit From Second and Later Lines?

    PubMed Central

    Bonotto, Marta; Gerratana, Lorenzo; Iacono, Donatella; Minisini, Alessandro Marco; Rihawi, Karim; Fasola, Gianpiero

    2015-01-01

    Introduction. Despite the availability of several therapeutic options for metastatic breast cancer (MBC), no robust predictive factors are available to help clinical decision making. Nevertheless, a decreasing benefit from first line to subsequent lines of treatment is commonly observed. The aim of this study was to assess the impact of benefit from first-line therapy on outcome with subsequent lines. Methods. We analyzed a consecutive series of 472 MBC patients treated with chemotherapy (CT) and/or endocrine therapy (ET) between 2004 and 2012. We evaluated progression-free survival (PFS) at first (PFS1), second, third, and fourth therapeutic lines, according to treatment (ET and/or CT) and tumor subtypes. Results. In the whole cohort, median overall survival was 34 months, and median PFS1 was 9 months. A 6-month benefit was shown by 289 patients (63.5%) at first line, 128 (40.5%) at second line, 76 (33.8%) at third line, and 34 (23.3%) at fourth line. Not having a 6-month benefit at PFS1 was associated with less chance of benefit at second line (odds ratio [OR]: 0.48; 95% confidence interval [CI]: 0.29–0.77, p = .0026) and at any line beyond first (OR: 0.39; 95% CI: 0.24–0.62, p < .0001). In the total series, after stratification for tumor subtypes, a strong predictive effect was observed among HER2-positive tumors (OR: 0.2; 95% CI: 0.05–0.73, p = .0152). Conclusion. Our results suggest that the absence of at least a 6-month benefit in terms of PFS with first-line therapy predicts a reduced probability of benefit from subsequent therapeutic lines, especially in HER2-positive disease. Implications for Practice: This study supports evidence showing that the absence of a 6-month benefit in terms of progression-free survival with first-line therapy predicts a lack of benefit from subsequent therapeutic lines in metastatic breast cancer. The random distribution of benefit experienced by a subset of the cohort further spurs an interest in identifying predictive

  1. 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

  2. Profilin-1 overexpression in MDA-MB-231 breast cancer cells is associated with alterations in proteomics biomarkers of cell proliferation, survival, and motility as revealed by global proteomics analyses.

    PubMed

    Coumans, Joëlle V F; Gau, David; Poljak, Anne; Wasinger, Valerie; Roy, Partha; Moens, Pierre D J

    2014-12-01

    Despite early screening programs and new therapeutic strategies, metastatic breast cancer is still the leading cause of cancer death in women in industrialized countries and regions. There is a need for novel biomarkers of susceptibility, progression, and therapeutic response. Global analyses or systems science approaches with omics technologies offer concrete ways forward in biomarker discovery for breast cancer. Previous studies have shown that expression of profilin-1 (PFN1), a ubiquitously expressed actin-binding protein, is downregulated in invasive and metastatic breast cancer. It has also been reported that PFN1 overexpression can suppress tumorigenic ability and motility/invasiveness of breast cancer cells. To obtain insights into the underlying molecular mechanisms of how elevating PFN1 level induces these phenotypic changes in breast cancer cells, we investigated the alteration in global protein expression profiles of breast cancer cells upon stable overexpression of PFN1 by a combination of three different proteome analysis methods (2-DE, iTRAQ, label-free). Using MDA-MB-231 as a model breast cancer cell line, we provide evidence that PFN1 overexpression is associated with alterations in the expression of proteins that have been functionally linked to cell proliferation (FKPB1A, HDGF, MIF, PRDX1, TXNRD1, LGALS1, STMN1, LASP1, S100A11, S100A6), survival (HSPE1, HSPB1, HSPD1, HSPA5 and PPIA, YWHAZ, CFL1, NME1) and motility (CFL1, CORO1B, PFN2, PLS3, FLNA, FLNB, NME2, ARHGDIB). In view of the pleotropic effects of PFN1 overexpression in breast cancer cells as suggested by these new findings, we propose that PFN1-induced phenotypic changes in cancer cells involve multiple mechanisms. Our data reported here might also offer innovative strategies for identification and validation of novel therapeutic targets and companion diagnostics for persons with, or susceptibility to, breast cancer.

  3. Association with pregnancy increases the risk of local recurrence but does not impact overall survival in breast cancer: A case-control study of 87 cases.

    PubMed

    Genin, A S; De Rycke, Y; Stevens, D; Donnadieu, A; Langer, A; Rouzier, R; Lerebours, F

    2016-12-01

    Pregnancy-associated breast cancer (PABC) constitutes 7% of all BCs in young women. The prognosis of PABC remains controversial. In this study, we evaluated the impact of the association of pregnancy with BC on the rates of overall survival (OS), disease free survival (DFS), and distant and local recurrence-free survival. We conducted a retrospective unicenter case-control study. We enrolled PABC patients treated at our institution between 1992 and 2009. For each case, 2 BC controls were matched for age and year of diagnosis. Univariate and multivariate analyses were performed to assess the parameters associated with prognosis. Eighty-seven PABC patients were enrolled and matched with 174 controls. The univariate analysis did not reveal any significant differences in OS, DFS or distant recurrence rates between the 2 groups. Pregnancy associated status, a tumor larger than T2 and neoadjuvant chemotherapy as the primary treatment were significantly associated with an increased risk of local relapse. The multivariate analysis showed that the pregnancy associated status and the tumor size were strong prognostic factors of local recurrence. Pregnancy associated status negates the prognostic value of tumor size, as both T0-T2 and T3-T4 PABC patients have the same poor prognosis as control BC patients with T3-T4 tumors. Interestingly, although PABC patients have more locally advanced tumors, they did not have a higher rate of radical surgery than the control BC patients. Pregnancy associated status is a strong prognostic factor of local relapse in BC. In PABC patients, when possible, radical surgery should be the preferred first treatment step.

  4. 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