The Importance of a Family History of Breast Cancer in Predicting the Presence of a BRCA Mutation

39 Background: The rate of women undergoing contralateral prophylactic mastectomy (CPM) has increased significantly over the past decade. Large population studies have examined factors associated with the use of CPM. We studied the factors associated with CPM within our institution. Methods: A 30-question validated survey was mailed to all patients who underwent mastectomy from 1972 to 2011 and are currently receiving treatment or surveillance at our institution. Responses were analyzed to determine the factors predictive of CPM. Multivariate logistic regression methods were used to calculate odds ratios (OR) and 95% confidence intervals (CI) for possible associations between exposures (including age at surgery, marital status, education, race, family history of breast cancer, and BRCA genetic mutation (BRCA mutation) and likelihood of CPM. Results: 368 of 691 surveys were returned. Younger age was statistically significantly associated with increased likelihood of CPM (p-trend < 0.001). Caucasian patients were 4 times as likely to undergo CPM compared to non-Caucasian patients (OR 3.95, 95%CI=1.89-8.23). Patients with a family history of breast cancer were 3 times as likely to undergo CPM as compared with those with no family history (OR 3.38, 95%CI=1.4-8.16). Married patients were also 3 times as likely to undergo CPM compared with unmarried patients (OR 3.00, 95%CI=1.39-6.52). Reporting a BRCA mutation was highly correlated with younger age, positive family history, higher level of education and marital status. Conclusions: When faced with the decision of whether to undergo a CPM, patients must assess both objective future risks and subjective feelings about those risks. These results suggest that the decision to undergo CPM is associated with known risk factors for the development of contralateral cancer such as younger age and positive breast cancer family history. In addition, multiple demographic factors including Caucasian race and married status increased the likelihood of choosing CPM. This may relate to social support as well socioeconomic status. Further exploration into societal factors that impact CPM use is warranted.

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Association of family history and location of BRCA1 and BRCA2 mutations in triple-negative breast cancer patients.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e12588 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e12588-e12588

Author(s):

Yen Yen Tan ◽

Daniela Muhr ◽

Christine Rappaport-Fuerhauser ◽

Daphne Gschwantler-Kaulich ◽

Christoph Grimm ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Brca Mutation ◽

Brca1 Mutation ◽

Age At Onset ◽

Family History Of Cancer ◽

The Family ◽

Brca1 Carriers ◽

History Of ◽

History Of Cancer

e12588 Background: We assessed the prevalence of family history and its association with germline BRCA1/2mutation status/location and age at onset in triple-negative breast cancer (TNBC) patients. Methods: 266 patients with TNBC < 60 years unselected for family history of cancer were enrolled and germline DNA was sequenced to identify mutations. Family pedigrees were prospectively collected from these patients. Logistic regression was used to investigate family history and its association with mutation type/location and age at onset. ROC curves were constructed to determine good predictors of BRCAmutations. Results: BRCA mutations were identified in 18.0% of all patients (15.0% BRCA1, 3.0% BRCA2). BRCA1 carriers have a significantly earlier age at onset than non-mutation carriers (40 vs 49 years; p < .001). While 39/124 (31.4%) patients with family history of cancer carried a BRCA1/2 mutation, 9/142 (6.3%) BRCA carriers had no family history of cancer. BRCA1 carriers with ≥1BC in the family are commonly identified in the breast cancer cluster regions (53.1%). BRCA2 carriers more commonly cluster within the ovarian cancer regions. Of note, this difference was not statistically significant. Women with mutations in BRCA1 OCCR are diagnosed at a younger age. TNBC diagnosed ≤45 years with ≥1BC and ≥1OC in the family are good predictors of BRCA1 mutation (AUC 0.867). Conclusions: Young women with TNBC and a family history of BC and OC are likely to have a BRCA mutation. Specific BRCA mutation locations may add to the identification of a subgroup of TNBC patients with a relatively higher risk of subsequent ovarian cancer. Identification of high-risk TNBC patients with BRCA1 mutation will enable clinicians to optimize cancer management for this phenotype, but will require further validation in larger studies.

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Family history of breast cancer in non-BRCA male breast cancer: A case-control study.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.15_suppl.e13032 ◽

2017 ◽

Vol 35 (15_suppl) ◽

pp. e13032-e13032

Author(s):

Gregory Sampang Calip ◽

Katherine Rebecca Exten ◽

Garth H Rauscher ◽

Krystal Brown ◽

Ryan Bernhisel ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Cancer Risk ◽

Case Control Study ◽

Brca Mutation ◽

Case Control ◽

Cancer Risk Counseling ◽

Mmr Genes ◽

History Of ◽

Control Study

e13032 Background: Approximately 85% of male breast cancer (MBC) patients test negative for a BRCA mutation, and the role of genetic predisposition is unclear. Cancer risk counseling for unaffected relatives of BRCA-negative MBC patients relies on accurate cancer risk estimates, but there is limited data on the risk of breast cancer (BC) for relatives of these men. We characterized the association between MBC and family history of BC in patients who test negative for BRCA mutations in order to facilitate cancer risk counseling and to explore the possibility of unidentified MBC susceptibility alleles. Methods: We performed a case-control study of patients who had full length sequencing and large-rearrangement analysis for germline mutations in BRCA1/2 or the mismatch repair (MMR) genes at a commercial laboratory from 2006-2012. Cases were MBC patients who tested negative for a BRCA1/2 mutation (n = 3,647); controls were male colon cancer patients who tested negative for mutations in MMR genes (n = 4,269). Information on family history of BC was ascertained from test request forms completed by the ordering healthcare provider at the time of testing. Unconditional multivariable logistic regression models estimated odds ratios (OR) and 95% confidence intervals (CI) for associations between family history of BC in first- (FDR) and second-degree relatives (SDR) and MBC with adjustment for potential confounders (age, ethnicity, year of testing). Results: Compared to controls, MBC cases had higher odds of BC in a FDR or SDR (OR = 4.7; 95% CI 4.1, 5.3). Associations were strongest for family history of BC in 1 female FDR (OR = 3.9; 95% CI: 3.3, 4.6), ≥2 female FDR (OR = 7.5; 95% CI 5.0, 11.4), BC in a FDR < 45 years old (for cases diagnosed < 45, OR = 6.9; 95% CI 3.9, 12.4), a male FDR or SDR with BC (OR = 17.9; 95% CI 7.6, 42.1), and both a male and female FDR or SDR with BC (OR = 15.7; 95%CI 4.4, 55.3). Conclusions: MBC patients who test negative for a BRCA mutation have significantly higher odds of reporting family members affected by breast cancer, particularly with affected FDR < 45 years old, multiple affected relatives, and male relatives with BC. This data can guide risk counseling in MBC families, and suggests the existence of unidentified MBC susceptibility alleles.

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Assessment of breast cancer risk in BRCA carriers with ovarian cancer: Evaluation of data from longitudinal observation.

Journal of Clinical Oncology ◽

10.1200/jco.2019.37.15_suppl.e13062 ◽

2019 ◽

Vol 37 (15_suppl) ◽

pp. e13062-e13062

Author(s):

Tamar Safra ◽

Barliz Waissengrin ◽

Deanna Gerber ◽

Rinat Bernstein Molho ◽

Amnon Amit ◽

...

Keyword(s):

Breast Cancer ◽

Ovarian Cancer ◽

Family History ◽

Prophylactic Mastectomy ◽

Brca Mutation ◽

Ashkenazi Jews ◽

Luminal A ◽

Luminal B ◽

History Of

e13062 Background: To confirm data from older studies reporting reduced risks of breast cancer (BC) in BRCA mutated (BRCA+) ovarian cancer (OC) patients and to re-evaluate BC surveillance and/or prophylactic mastectomy in OC patients. Methods: Data on 430 BRCA+ mutation carriers diagnosed with OC between 2000 and 2017 in 6 medical centers (one in the USA and five in Israel) were analyzed. Data included demographics, breast surveillance type, family history, BRCA mutation types, timing of BC diagnosis (before or after OC diagnosis) and family history of cancer. Results: Median age at diagnosis of OC was 55.4 years (range, 31.3-90) and median follow-up was 4.6 years. Most patients were BRCA1 (66.6%), and 35.7% had 185delAG. Most patients (68.4%) were Ashkenazi Jews, 27.4% had a family history of BC and 16.5% were diagnosed with BC before OC. Five percent developed BC following OC diagnosis with a median time to BC diagnosis of 68 months (range, 11-210). Of those diagnosed with BC, 50% had triple-negative BC, 40% had luminal B ER+, PR-, Her2-neg and 10% had luminal A -ER+, PR+, her2-neg. There was a non-significant increase in BC after OC, and in BC prior to OC diagnosis; there was no correlation of BC with family history. No definite deaths from BC were recorded. Conclusions: The incidence of BC after OC diagnosis in the BRCA+ population at a median follow-up of 4.6 years is consistent with prior series. Prophylactic bilateral Surveillance measures should be re-evaluated in this population and may only be needed in long-term disease-free survivors and/or subpopulations to be identified. Clinical trial information: 07-146.

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A 35-Year-Old Woman with a Strong Family History of Breast Cancer Not Linked to BRCA Mutation

Office Gynecology ◽

10.1017/9781108227469.044 ◽

2019 ◽

pp. 132-135

Author(s):

Natalie A. Bowersox

Keyword(s):

Breast Cancer ◽

Family History ◽

Brca Mutation ◽

Strong Family History ◽

History Of

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MR-guided intervention in women with a family history of breast cancer

Yearbook of Diagnostic Radiology ◽

10.1016/s0098-1672(08)70045-6 ◽

2007 ◽

Vol 2007 ◽

pp. 58-59

Author(s):

R.L. Birdwell

Keyword(s):

Breast Cancer ◽

Family History ◽

History Of

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Family history of breast cancer and local recurrence after breast conserving therapy

European Journal of Cancer ◽

10.1016/s0959-8049(98)80040-3 ◽

1998 ◽

Vol 34 ◽

pp. S12

Author(s):

C.T.M. Brekelmans ◽

A.C. Voogd ◽

G. Botke ◽

A.N. van Geel ◽

P. Rodrigus ◽

...

Keyword(s):

Breast Cancer ◽

Family History ◽

Local Recurrence ◽

Breast Conserving Therapy ◽

History Of

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A Group Therapy Approach to Facilitate Integration of Risk Information for Women at Risk for Breast Cancer

The Canadian Journal of Psychiatry ◽

10.1177/070674379804300405 ◽

1998 ◽

Vol 43 (4) ◽

pp. 375-380 ◽

Cited By ~ 17

Author(s):

Mary Jane Esplen ◽

Brenda Toner ◽

Jonathan Hunter ◽

Gordon Glendon ◽

Kate Butler ◽

...

Keyword(s):

Breast Cancer ◽

At Risk ◽

Family History ◽

Group Therapy ◽

Perceived Risk ◽

Positive Family History ◽

Risk Information ◽

Degree Relative ◽

Therapy Approach ◽

History Of

Objective: To describe and illustrate elements of a group counselling approach designed to enhance the communication of risk information on breast cancer (BC) to women with a family history of this disease. Breast cancer is a leading cause of female cancer death. The most important risk factor for BC is a positive family history in at least 1 first-degree relative, and approximately one-third of women with BC have a family history of the disease. Recent evidence suggests that there is a significant psychological impact associated with having a family history of BC, and this may influence the psychological adjustment and response to being counselled for personal risk. New counselling approaches are required. Method: This paper describes a group therapy approach that incorporates principles of supportive-expressive therapy designed to address the emotional impact of being at risk for BC and to promote accuracy of perceived risk. The key elements of the intervention are described along with clinical illustrations from groups that are part of an ongoing study to develop and standardize the group therapy. Conclusion: Qualitative data from the groups suggest that this model of therapy is both feasible and effective.

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