Contralateral Breast Cancer Risk in BRCA1 and BRCA2 Mutation Carriers

Purpose To estimate the risk for contralateral breast cancer in members of BRCA1- and BRCA2-positive families and to determine predictive risk factors. Patients and Methods A retrospective, multicenter, cohort study was performed from 1996 until 2008 and comprised 2,020 women with unilateral breast cancer (index patients, n = 978; relatives, n = 1.42) from 978 families who had a BRCA1 or BRCA2 mutation. Cox regression analysis was applied to assess the association of age at first breast cancer with time from first to contralateral breast cancer, stratified by the affected BRCA gene. Results The cumulative risk for contralateral breast cancer 25 years after first breast cancer was 47.4% (95% CI, 38.8% to 56.0%) for patients from families with BRCA1 or BRCA2 mutations. Members of families with BRCA1 mutations had a 1.6-fold (95% CI, 1.2-fold to 2.3-fold) higher risk of contralateral breast cancer than members of families with BRCA2 mutations. Younger age at first breast cancer was associated with a significantly higher risk of contralateral breast cancer in patients with BRCA1 mutation, and a trend was observed in patients with BRCA2 mutation. After 25 years, 62.9% (95% CI, 50.4% to 75.4%) of patients with BRCA1 mutation who were younger than 40 years of age at first breast cancer developed contralateral breast cancer, compared with only 19.6% (95% CI, 5.3% to 33.9%) of those who were older than 50 years of age at first breast cancer. Conclusion Contralateral breast cancer risk depends on age at first breast cancer and on the affected BRCA gene, and this risk should be considered in treatment planning.

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Effects of chemotherapy on contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers: A nationwide cohort study

The Breast ◽

10.1016/j.breast.2021.12.007 ◽

2021 ◽

Author(s):

Delal Akdeniz ◽

Mark van Barele ◽

Bernadette A.M. Heemskerk-Gerritsen ◽

Ewout W. Steyerberg ◽

Michael Hauptmann ◽

...

Keyword(s):

Breast Cancer ◽

Cohort Study ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Contralateral Breast Cancer ◽

Brca2 Mutation ◽

Contralateral Breast ◽

Brca1 And Brca2 ◽

Mutation Carriers

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Contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers in a large cohort of unselected Chinese breast cancer patients

International Journal of Cancer ◽

10.1002/ijc.32918 ◽

2020 ◽

Vol 146 (12) ◽

pp. 3335-3342

Author(s):

Liming Su ◽

Ye Xu ◽

Tao Ouyang ◽

Jinfeng Li ◽

Tianfeng Wang ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Cancer Patients ◽

Contralateral Breast Cancer ◽

Brca2 Mutation ◽

Contralateral Breast ◽

Large Cohort ◽

Breast Cancer Patients ◽

Brca1 And Brca2

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The association between Polygenic Risk Scores and contralateral breast cancer risk in BRCA1 and BRCA2 mutation carriers: Analyses in the CIMBA consortium

European Journal of Cancer ◽

10.1016/s0959-8049(18)30269-7 ◽

2018 ◽

Vol 92 ◽

pp. S10

Author(s):

A. Van den Broek ◽

M.E. Robson ◽

J. Vos ◽

J.L. Bernstein ◽

K. Offit ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Contralateral Breast Cancer ◽

Brca2 Mutation ◽

Contralateral Breast ◽

Risk Scores ◽

Brca1 And Brca2 ◽

Polygenic Risk ◽

Mutation Carriers

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

Journal of Clinical Oncology ◽

10.1200/jco.2010.34.4440 ◽

2011 ◽

Vol 29 (34) ◽

pp. 4505-4509 ◽

Cited By ~ 32

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.

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Contralateral Breast Cancer in BRCA1 and BRCA2 Mutation Carriers

Journal of Clinical Oncology ◽

10.1200/jco.2004.04.033 ◽

2004 ◽

Vol 22 (12) ◽

pp. 2328-2335 ◽

Cited By ~ 441

Author(s):

Kelly Metcalfe ◽

Henry T. Lynch ◽

Parviz Ghadirian ◽

Nadine Tung ◽

Ivo Olivotto ◽

...

Keyword(s):

Breast Cancer ◽

Contralateral Breast Cancer ◽

Brca Mutation ◽

Brca1 Mutation ◽

Brca2 Mutation ◽

Contralateral Breast ◽

Second Primary ◽

Brca1 And Brca2 ◽

Breast Cancer Death ◽

Actuarial Risk

Purpose To estimate the risk of contralateral breast cancer in BRCA1 and BRCA2 carriers after diagnosis and to determine which factors are predictive of the risk of a second primary breast cancer. Patients and Methods Patients included 491 women with stage I or stage II breast cancer, for whom a BRCA1 or BRCA2 mutation had been identified in the family. Patients were followed from the initial diagnosis of cancer until contralateral mastectomy, contralateral breast cancer, death, or last follow-up. Results The actuarial risk of contralateral breast cancer was 29.5% at 10 years. Factors that were predictive of a reduced risk were the presence of a BRCA2 mutation (v BRCA1 mutation; hazard ratio [HR], 0.73; 95% CI, 0.47 to 1.15); age 50 years or older at first diagnosis (v ≤ 49 years; HR, 0.63; 95% CI, 0.36 to 1.10); use of tamoxifen (HR, 0.59; 95% CI, 0.35 to 1.01); and history of oophorectomy (HR, 0.44; 95% CI, 0.21 to 0.91). The effect of oophorectomy was particularly strong in women first diagnosed prior to age 49 years (HR, 0.24; 95% CI, 0.07 to 0.77). For women who did not have an oophorectomy or take tamoxifen, the 10-year risk of contralateral cancer was 43.4% for BRCA1 carriers and 34.6% for BRCA2 carriers. Conclusion The risk of contralateral breast cancer in women with a BRCA mutation is approximately 40% at 10 years, and is reduced in women who take tamoxifen or who undergo an oophorectomy.

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BRCA1 and BRCA2 Mutation Frequency in Women Evaluated in a Breast Cancer Risk Evaluation Clinic

Journal of Clinical Oncology ◽

10.1200/jco.2002.20.4.994 ◽

2002 ◽

Vol 20 (4) ◽

pp. 994-999 ◽

Cited By ~ 28

Author(s):

Helen A. Shih ◽

Fergus J. Couch ◽

Katherine L. Nathanson ◽

M. Anne Blackwood ◽

Timothy R. Rebbeck ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Risk Evaluation ◽

Brca2 Mutation ◽

Brca1 And Brca2 ◽

Brca1 Mutations ◽

Brca2 Mutations ◽

Brca1 And Brca2 Mutations

PURPOSE: To determine the prevalence of BRCA1 and BRCA2 mutations in families identified in a breast cancer risk evaluation clinic. PATIENTS AND METHODS: One hundred sixty-four families seeking breast cancer risk evaluation were screened for coding region mutations in BRCA1 and BRCA2 by conformation-sensitive gel electrophoresis and DNA sequencing. RESULTS: Mutations were identified in 37 families (22.6%); 28 (17.1%) had BRCA1 mutations and nine (5.5%) had BRCA2 mutations. The Ashkenazi Jewish founder mutations 185delAG and 5382insC (BRCA1) were found in 10 families (6.1%). However, 6174delT (BRCA2) was found in only one family (0.6%) despite estimates of equal frequency in the Ashkenazi population. In contrast to other series, the average age of breast cancer diagnosis was earlier in BRCA2 mutation carriers (32.1 years) than in women with BRCA1 mutations (37.6 years, P = .028). BRCA1 mutations were detected in 20 (45.5%) of 44 families with ovarian cancer and 12 (75%) of 16 families with both breast and ovarian cancer in a single individual. Significantly fewer BRCA2 mutations (two [4.5%] of 44) were detected in families with ovarian cancer (P = .01). Eight families had male breast cancer; one had a BRCA1 mutation and three had BRCA2 mutations. CONCLUSION: BRCA1 mutations were three times more prevalent than BRCA2 mutations. Breast cancer diagnosis before 50 years of age, ovarian cancer, breast and ovarian cancer in a single individual, and male breast cancer were all significantly more common in families with BRCA1 and BRCA2 mutations, but none of these factors distinguished between BRCA1 and BRCA2 mutations. Evidence for reduced breast cancer penetrance associated with the BRCA2 mutation 6174delT was noted.

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