Breast Cancer Prognosis in BRCA1 and BRCA2 Mutation Carriers: An International Prospective Breast Cancer Family Registry Population-Based Cohort Study

2012 ◽  
Vol 30 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Pamela J. Goodwin ◽  
Kelly-Anne Phillips ◽  
Dee W. West ◽  
Marguerite Ennis ◽  
John L. Hopper ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Distant Recurrence ◽  
Population Based ◽  
Cancer Prognosis ◽  
Univariable Analysis ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Sporadic Disease

Purpose To compare breast cancer prognosis in BRCA1 and BRCA2 mutation carriers with that in patients with sporadic disease. Patients and Methods An international population-based cohort study was conducted in Canada, the United States, and Australia of 3,220 women with incident breast cancer diagnosed between 1995 and 2000 and observed prospectively. Ninety-three had BRCA1 mutations; 71, BRCA2 mutations; one, both mutations; 1,550, sporadic breast cancer; and 1,505, familial breast cancer (without known BRCA1 or BRCA2 mutation). Distant recurrence and death were analyzed. Results Mean age at diagnosis was 45.3 years; mean follow-up was 7.9 years. Risks of distant recurrence and death did not differ significantly between BRCA1 mutation carriers and those with sporadic disease in univariable and multivariable analyses. Risk of distant recurrence was higher for BRCA2 mutation carriers compared with those with sporadic disease in univariable analysis (hazard ratio [HR], 1.63; 95% CI, 1.02 to 2.60; P = .04). Risk of death was also higher in BRCA2 carriers in univariable analysis (HR, 1.81; 95% CI, 1.15 to 2.86; P = .01). After adjustment for age, tumor stage and grade, nodal status, hormone receptors, and year of diagnosis, no differences were observed for distant recurrence (HR, 1.00; 95% CI, 0.62 to 1.61; P = 1.00) or death (HR, 1.12; 95% CI, 0.70 to 1.79; P = .64). Conclusion Outcomes of BRCA1 mutation carriers were similar to those of patients with sporadic breast cancer. Worse outcomes in BRCA2 mutation carriers in univariable analysis seem to reflect the presence of more adverse tumor characteristics in these carriers. Similar outcomes were identified in BRCA2 carriers and those with sporadic disease in multivariable analyses.

scholarly journals Oral Contraceptive Use and Breast Cancer Risk: Retrospective and Prospective Analyses From a BRCA1 and BRCA2 Mutation Carrier Cohort Study

2018 ◽  
Vol 2 (2) ◽  
Author(s):  
Lieske H Schrijver ◽  
Håkan Olsson ◽  
Kelly-Anne Phillips ◽  
Mary Beth Terry ◽  
David E Goldgar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Oral Contraceptive ◽  
Contraceptive Use ◽  
Cox Regression ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Brca1 And Brca2 ◽  
Full Cohort ◽  
Mutation Carriers ◽  
Prospective Analyses

Abstract Background For BRCA1 and BRCA2 mutation carriers, the association between oral contraceptive preparation (OCP) use and breast cancer (BC) risk is still unclear. Methods Breast camcer risk associations were estimated from OCP data on 6030 BRCA1 and 3809 BRCA2 mutation carriers using age-dependent Cox regression, stratified by study and birth cohort. Prospective, left-truncated retrospective and full-cohort retrospective analyses were performed. Results For BRCA1 mutation carriers, OCP use was not associated with BC risk in prospective analyses (hazard ratio [HR] = 1.08, 95% confidence interval [CI] = 0.75 to 1.56), but in the left-truncated and full-cohort retrospective analyses, risks were increased by 26% (95% CI = 6% to 51%) and 39% (95% CI = 23% to 58%), respectively. For BRCA2 mutation carriers, OCP use was associated with BC risk in prospective analyses (HR = 1.75, 95% CI = 1.03 to 2.97), but retrospective analyses were inconsistent (left-truncated: HR = 1.06, 95% CI = 0.85 to 1.33; full cohort: HR = 1.52, 95% CI = 1.28 to 1.81). There was evidence of increasing risk with duration of use, especially before the first full-term pregnancy (BRCA1: both retrospective analyses, P < .001 and P = .001, respectively; BRCA2: full retrospective analysis, P = .002). Conclusions Prospective analyses did not show that past use of OCP is associated with an increased BC risk for BRCA1 mutation carriers in young middle-aged women (40–50 years). For BRCA2 mutation carriers, a causal association is also not likely at those ages. Findings between retrospective and prospective analyses were inconsistent and could be due to survival bias or a true association for younger women who were underrepresented in the prospective cohort. Given the uncertain safety of long-term OCP use for BRCA1/2 mutation carriers, indications other than contraception should be avoided and nonhormonal contraceptive methods should be discussed.

Is mammography adequate for screening BRCA mutation carriers with low breast density?

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10014-10014 ◽  
Author(s):  
R. Bigenwald ◽  
E. Warner ◽  
A. Gunasekara ◽  
K. Hill ◽  
P. Causer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Density ◽  
Brca Mutation ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Brca1 And Brca2 ◽  
Younger Women ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

10014 Background: Several large observational studies have demonstrated that magnetic resonance imaging (MRI) is much more sensitive than M (sensitivity 71–96% vs. 28–43%) for screening women > age 25 at high risk for hereditary breast cancer. However, MRI is much more costly and less specific than M. The extent to which the low sensitivity of M in these studies is due to the greater average breast density of younger women is unknown. Accordingly, we sought to determine the sensitivity of M and MRI according to breast density for the detection of breast cancer in a screening study of BRCA mutation carriers. Methods: Breast density was measured on the screening mammogram of the contralateral breast for all women who developed in-situ or invasive breast cancer on study. Density was measured in 2 ways: qualitatively according to the four categories characterized by the BIRADS system: 1) mostly fatty, 2) scattered fibroglandular tissue, 3) heterogeneously dense, 4) extremely dense; and semi-quantitatively using computer-aided techniques with subsequent classification as: A) ≤10%, B) 11–25%, C) 26%-50%, or D) >50% density. Results: Between 11/97 and 06/05 a total of 39 cases (12 in-situ and 27 invasive) were found in 36 mutation carriers (19 BRCA1 and 17 BRCA2). Mean age of the women with cancer was 48 (range 34 to 64). Average semi-quantitative breast density for BRCA1 mutation carriers was 28% and for BRCA2 was 27%. Sensitivity of M vs. MRI for in-situ cases was 25% vs. 83%, and for invasive cases was 30% vs. 93%. Sensitivities for BRCA1 and BRCA2 mutation carriers were similar. For BIRADS 1 to 4 respectively M detected 1/3 (33%), 5/11 (45%), 4/22 (18%), and 1/3 (33%) of cases; and for density groups A to D respectively detected 2/6 (33%), 7/15 (47%), 1/11 (9%) and, 1/7 (14%). Conclusion: Although there was a trend towards decreasing mammographic sensitivity with increasing density, even among BRCA mutation carriers with low breast density mammography is an inadequate screening tool. No significant financial relationships to disclose.

scholarly journals Estrogen Receptor Status Oppositely Modifies Breast Cancer Prognosis in BRCA1/BRCA2 Mutation Carriers Versus Non-Carriers

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 738 ◽  
Author(s):  
Michal Vocka ◽  
Martina Zimovjanova ◽  
Zuzana Bielcikova ◽  
Petra Tesarova ◽  
Lubos Petruzelka ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor Status ◽  
Brca2 Mutation ◽  
Disease Free Survival ◽  
Cancer Prognosis ◽  
Brca1 And Brca2 ◽  
Risk Of Death ◽  
Mutation Carriers ◽  
Er Positive ◽  
Brca1 Brca2

Breast cancer (BC) prognosis in BRCA1 and BRCA2 mutation carriers has been reported contradictorily, and the significance of variables influencing prognosis in sporadic BC is not established in BC patients with hereditary BRCA1/BRCA2 mutations. In this retrospective cohort study, we analyzed the effect of clinicopathological characteristics on BC prognosis (disease-free survival [DFS] and disease-specific survival [DSS]) in hereditary BRCA1/BRCA2 mutation carriers. We enrolled 234 BRCA1/BRCA2 mutation carriers and 899 non-carriers, of whom 191 carriers and 680 non-carriers, with complete data, were available for survival analyses. We found that patients with ER-positive tumors developed disease recurrence 2.3-times more likely when they carried a BRCA1/BRCA2 mutation (23/60; 38.3% ER-positive carriers vs. 74/445; 16.6% ER-positive non-carriers; p < 0.001). ER-positive mutation carriers also had a 3.4-times higher risk of death due to BC compared with ER-positive non-carriers (13/60; 21.7% vs. 28/445; 6.3%; p < 0.001). Moreover, prognosis in ER-negative BRCA1/BRCA2 mutation carriers was comparable with that in ER-positive non-carriers. Our study demonstrates that ER-positivity worsens BC prognosis in BRCA1/BRCA2 mutation carriers, while prognosis for carriers with ER-negative tumors (including early-onset) is significantly better and comparable with that in ER-positive, older BC non-carriers. These observations indicate that BRCA1/BRCA2 mutation carriers with ER-positive BC represent high-risk patients.

Tamoxifen As Chemoprevention in BRCA1 and BRCA2 Mutation Carriers With Breast Cancer: A Pilot Survey of Physicians

2003 ◽  
Vol 21 (23) ◽  
pp. 4322-4328 ◽  
Author(s):  
Beth N. Peshkin ◽  
Claudine Isaacs ◽  
Clinton Finch ◽  
Sheryl Kent ◽  
Marc D. Schwartz
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Mutation Carrier ◽  
Treatment Guidelines ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Breast Cancer Patients ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Er Positive

Purpose: To assess physician recommendations about the use of tamoxifen in premenopausal BRCA1 and BRCA2 mutation carriers. Methods: We mailed surveys to a stratified random sample of 1,286 physicians selected from the San Antonio Breast Cancer Symposium mailing list. Eligible participants were physicians whose practice consisted of ≥ 10% breast cancer patients. Participants were asked to complete a three-part, 10-minute questionnaire. Demographics and responses to hypothetical patient vignettes were analyzed. Results: Of potentially eligible participants, 27% responded to the survey, and 260 participants were included in the final analysis. Physicians did not distinguish between BRCA1 and BRCA2 status in making recommendations about tamoxifen to breast cancer patients; however, in an unaffected woman, they were more likely to recommend tamoxifen to a BRCA2 mutation carrier than to a BRCA1 mutation carrier (73% v 57%; P < .0001). In newly diagnosed breast cancer patients, physicians were much more likely to recommend tamoxifen to an estrogen receptor (ER)–positive mutation carrier versus an ER-negative carrier (94% v 27%; P < .0001). When the mutation carrier was diagnosed 10 years ago, physicians were still much more likely to recommend tamoxifen if the tumor was ER-positive versus ER-negative (79% v 35%; P < .0001). Conclusion: Physicians’ recommendations about tamoxifen use in mutation carriers with a history of breast cancer seem to be heavily dependent on ER status. This finding suggests that among mutation carriers, physicians are influenced by adjuvant treatment guidelines more so than the potential role that tamoxifen might play in the reduction of risk for contralateral breast cancer.

scholarly journals The Influence of Number and Timing of Pregnancies on Breast Cancer Risk for Women With BRCA1 or BRCA2 Mutations

2018 ◽  
Vol 2 (4) ◽  
Author(s):  
Mary Beth Terry ◽  
Yuyan Liao ◽  
Karin Kast ◽  
Antonis C Antoniou ◽  
Jasmine A McDonald ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Retrospective Cohort ◽  
Proportional Hazards ◽  
Brca1 Mutation ◽  
Brca2 Mutation ◽  
Cox Proportional Hazards ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Cox Proportional Hazards Models ◽  
Brca1 Carriers

Abstract Background Full-term pregnancy (FTP) is associated with a reduced breast cancer (BC) risk over time, but women are at increased BC risk in the immediate years following an FTP. No large prospective studies, however, have examined whether the number and timing of pregnancies are associated with BC risk for BRCA1 and BRCA2 mutation carriers. Methods Using weighted and time-varying Cox proportional hazards models, we investigated whether reproductive events are associated with BC risk for mutation carriers using a retrospective cohort (5707 BRCA1 and 3525 BRCA2 mutation carriers) and a prospective cohort (2276 BRCA1 and 1610 BRCA2 mutation carriers), separately for each cohort and the combined prospective and retrospective cohort. Results For BRCA1 mutation carriers, there was no overall association with parity compared with nulliparity (combined hazard ratio [HRc] = 0.99, 95% confidence interval [CI] = 0.83 to 1.18). Relative to being uniparous, an increased number of FTPs was associated with decreased BC risk (HRc = 0.79, 95% CI = 0.69 to 0.91; HRc = 0.70, 95% CI = 0.59 to 0.82; HRc = 0.50, 95% CI = 0.40 to 0.63, for 2, 3, and ≥4 FTPs, respectively, Ptrend < .0001) and increasing duration of breastfeeding was associated with decreased BC risk (combined cohort Ptrend = .0003). Relative to being nulliparous, uniparous BRCA1 mutation carriers were at increased BC risk in the prospective analysis (prospective hazard ration [HRp] = 1.69, 95% CI = 1.09 to 2.62). For BRCA2 mutation carriers, being parous was associated with a 30% increase in BC risk (HRc = 1.33, 95% CI = 1.05 to 1.69), and there was no apparent decrease in risk associated with multiparity except for having at least 4 FTPs vs. 1 FTP (HRc = 0.72, 95% CI = 0.54 to 0.98). Conclusions These findings suggest differential associations with parity between BRCA1 and BRCA2 mutation carriers with higher risk for uniparous BRCA1 carriers and parous BRCA2 carriers.

scholarly journals Second primary breast cancer in BRCA1 and BRCA2 mutation carriers: 10-year cumulative incidence in the Breast Cancer Family Registry

2015 ◽  
Vol 151 (3) ◽  
pp. 653-660 ◽  
Author(s):  
Tehillah S. Menes ◽  
Mary Beth Terry ◽  
David Goldgar ◽  
Irene L. Andrulis ◽  
Julia A. Knight ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cumulative Incidence ◽  
Primary Breast Cancer ◽  
Brca2 Mutation ◽  
Second Primary ◽  
Brca1 And Brca2 ◽  
Breast Cancer Family ◽  
Cancer Family ◽  
Mutation Carriers

scholarly journals The frequency and outcome of breast cancer risk-reducing surgery in finnish BRCA1 and BRCA2 mutation carriers

2013 ◽  
Vol 103 (1) ◽  
pp. 34-40 ◽  
Author(s):  
L. Koskenvuo ◽  
C. Svarvar ◽  
S. Suominen ◽  
K. Aittomäki ◽  
T. Jahkola
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Brca2 Mutation ◽  
Brca1 And Brca2 ◽  
Mutation Carriers ◽  
Risk Reducing

scholarly journals Breast Cancer Risk for Noncarriers of Family-Specific BRCA1 and BRCA2 Mutations: Findings From the Breast Cancer Family Registry

2011 ◽  
Vol 29 (34) ◽  
pp. 4505-4509 ◽  
Author(s):  
Allison W. Kurian ◽  
Gail D. Gong ◽  
Esther M. John ◽  
David A. Johnston ◽  
Anna Felberg ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Brca2 Mutation ◽  
Population Based ◽  
Brca1 And Brca2 ◽  
Breast Cancer Family ◽  
Cancer Family ◽  
Brca2 Mutations ◽  
Brca1 And Brca2 Mutations

Purpose Women with germline BRCA1 and BRCA2 mutations have five- to 20-fold increased risks of developing breast and ovarian cancer. A recent study claimed that women testing negative for their family-specific BRCA1 or BRCA2 mutation (noncarriers) have a five-fold increased risk of breast cancer. We estimated breast cancer risks for noncarriers by using a population-based sample of patients with breast cancer and their female first-degree relatives (FDRs). Patients and Methods Patients were women with breast cancer and their FDRs enrolled in the population-based component of the Breast Cancer Family Registry; patients with breast cancer were tested for BRCA1 and BRCA2 mutations, as were FDRs of identified mutation carriers. We used segregation analysis to fit a model that accommodates familial correlation in breast cancer risk due to unobserved shared risk factors. Results We studied 3,047 families; 160 had BRCA1 and 132 had BRCA2 mutations. There was no evidence of increased breast cancer risk for noncarriers of identified mutations compared with FDRs from families without BRCA1 or BRCA2 mutations: relative risk was 0.39 (95% CI, 0.04 to 3.81). Residual breast cancer correlation within families was strong, suggesting substantial risk heterogeneity in women without BRCA1 or BRCA2 mutations, with some 3.4% of them accounting for roughly one third of breast cancer cases. Conclusion These results support the practice of advising noncarriers that they do not have any increase in breast cancer risk attributable to the family-specific BRCA1 or BRCA2 mutation.

Sign in / Sign up

Export Citation Format

Share Document