Decision-Making Regarding Prophylactic Mastectomy and Oophorectomy in Ashkenazi Jewish Women Seeking Genetic Testing for BRCA1/BRCA2 Mutations

Purpose: To analyze the use of genetic testing, prophylactic mastectomy, and oophorectomy among women with breast and/or ovarian cancer from families with a BRCA1 or BRCA2 mutation. Patients and Methods: We examined prospectively the use of BRCA1/BRCA2 testing in all women with a primary breast or ovarian cancer from a consecutive series of 112 high-risk families in which a BRCA1/BRCA2 mutation eventually was identified. The rate of prophylactic bilateral and contralateral mastectomy and prophylactic oophorectomy was analyzed in the women who carried a BRCA1/BRCA2 mutation and who had no metastatic disease at the time of the genetic test disclosure. We examined predictors for genetic test uptake and prophylactic surgery using univariate and multivariate analysis. Results: Overall, 192 of 220 women (87%) with primary tumors underwent genetic testing. Eleven of these 192 tested women (6%) appeared not to carry the family-specific BRCA1/BRCA2 mutation. Genetic testing occurred significantly more frequently at ages younger than 50 years (P = .04) and in persons with multiple primary tumors (P = .02). Among eligible women, 35 of 101 (35%) requested bilateral or contralateral mastectomy, and 47 of 95 (49%) requested oophorectomy. Women aged younger than 50 years and women who developed their first tumor after the initial identification of a BRCA1/BRCA2 mutation in the family were significantly (both P = .01) more likely to opt for prophylactic bilateral or contralateral mastectomy. Conclusion: In a clinical setting, we show a high demand for BRCA1/BRCA2 testing and for prophylactic surgery by women with breast and/or ovarian cancer from high-risk families.

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Racial differences in the use of contralateral prophylactic mastectomy among women undergoing BRCA1/BRCA2 genetic testing

Journal of Clinical Oncology ◽

10.1200/jco.2009.27.15_suppl.6542 ◽

2009 ◽

Vol 27 (15_suppl) ◽

pp. 6542-6542

Author(s):

K. Ready ◽

A. M. Gutierrez-Barrera ◽

J. Litton ◽

F. Meric-Bernstam ◽

A. M. Gonzalez-Angulo ◽

...

Keyword(s):

Genetic Testing ◽

African Americans ◽

Genetic Test ◽

Prophylactic Mastectomy ◽

Brca2 Mutation ◽

Contralateral Prophylactic Mastectomy ◽

Genetic Test Results ◽

Race Ethnicity ◽

Brca1 Brca2

6542 Background: Patients often use both positive and negative BRCA1/BRCA2 genetic test results to aid in surgical management decisions, but little is known about the existence of racial/ethnic differences in the use of genetic test results. The objective of this study was to evaluate differences in rates of contralateral prophylactic mastectomy (CPM) by race. Methods: A retrospective chart review was performed. Women with a personal history of breast cancer who underwent genetic testing for the BRCA1 and BRCA2 genes at our institution between 1996 and 2008 and were eligible for CPM were included in the study. Genetic test result, race/ethnicity as reported by the patient, years of follow-up since receipt of test result, and decision regarding CPM were recorded. Pearson chi square analyses and Fisher's exact tests were performed to test for significance. Results: 881 women were included in the study. Twenty percent (n = 180) were found to have a BRCA1 or BRCA2 mutation, while 80% (n = 701) were found to have an uninformative negative result. The study population was 87% (n = 771) Caucasian; 7% (n = 58) African American; and 6% (n = 52) Hispanic. Median follow up time was 3 years. There were no significant differences in either follow up time or percentages of BRCA positivity, based on race/ethnicity. Among those with a positive result, 45% (67/149) of Caucasians, 33% (5/15) of African Americans, and 50% (8/16) of Hispanics underwent CPM, but this was not statistically significant. Caucasians and Hispanics with positive results were significantly more likely than their counterparts with negative results to undergo CPM (Caucasians, 45%; 67/149 vs. 16%; 101/622; p<.001; Hispanics, 50%; 8/16 vs. 11%; 4/36; p = 0.004), but this same trend was not observed among African Americans (positive results, 33%; 5/15 vs. negative results, 14%; 6/43; p = 0.10). Conclusions: Among those with a BRCA1/BRCA2 mutation, there does not appear to be any significant difference in the use of CPM based on race/ethnicity. However, Caucasians and Hispanics appear to be more likely than African Americans to use the results of genetic testing to make surgical management decisions. No significant financial relationships to disclose.

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Population Testing for Cancer Predisposing BRCA1/BRCA2 Mutations in the Ashkenazi-Jewish Community: A Randomized Controlled Trial

JNCI Journal of the National Cancer Institute ◽

10.1093/jnci/dju379 ◽

2014 ◽

Vol 107 (1) ◽

Cited By ~ 68

Author(s):

Ranjit Manchanda ◽

Kelly Loggenberg ◽

Saskia Sanderson ◽

Matthew Burnell ◽

Jane Wardle ◽

...

Keyword(s):

Randomized Controlled Trial ◽

Jewish Community ◽

Controlled Trial ◽

Ashkenazi Jewish ◽

Randomized Controlled ◽

Brca2 Mutations ◽

Brca1 Brca2

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Contralateral prophylactic mastectomy in affected carriers of deleterious BRCA1 or BRCA2 mutations: Does timing of genetic testing matter?

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.10512 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 10512-10512

Author(s):

J. Tchou ◽

S. Sonnad ◽

M. Sargen ◽

B. Weber ◽

K. Nathanson ◽

...

Keyword(s):

Breast Cancer ◽

Genetic Testing ◽

Family History ◽

High Risk ◽

Clinical Characteristics ◽

Prophylactic Mastectomy ◽

Contralateral Prophylactic Mastectomy ◽

Breast Cancer Surgery ◽

Mutation Carriers ◽

Brca2 Mutations

10512 Introduction: Prophylactic mastectomy (PM) reduces breast cancer risk by >90% in women who are carriers of deleterious BRCA1 or BRCA2 mutations. Genetic testing prior to breast cancer surgery has been reported to affect PM decision in high-risk patients. The ideal timing of genetic testing as well as the clinical characteristics of affected mutation carriers electing PM remain unclear. This is a pilot study to identify significant clinical characteristics associated with affected carriers who had undergone PM. Methods: Retrospective chart review was performed on 103 breast cancer affected BRCA1 or BRCA2 mutation carriers that were seen at our high risk clinic who had undergone genetic testing between 1995 and 2005. Clinical characteristic, initial surgery treatment modalities, and dates of genetic testing and prophylactic mastectomy were collected and analyzed using the chi-square or Fisher exact tests. Results: Of the 103 affected mutation carriers, 30 (29%) underwent prophylactic mastectomy (PM) where as 73 (71%) did not (no PM). Ethnicity, age of diagnosis, tumor size, nodal status, family history and initial breast cancer surgery types (BCT vs. mastectomy) were not significantly different between the two groups. Of the 30 women who underwent PM, 19 (63%) vs. 9 (30%) underwent PM before and after their genetic testing respectively. Of the 19 women who had PM before their genetic testing, 4 (21%) had BCT as initial treatment whereas 15 (78.9%) had mastectomy as initial treatment and 9 of 15 (60%) had synchronous contralateral prophylactic mastectomy. For the 9 women who had PM after their genetic testing, 5 (56%) had BCT vs. 4 (44%) had mastectomy as their initial surgical treatment (p < 0.001). Conclusion: In this study, we found a significant correlation between the initial breast cancer surgical modality of mastectomy with women undergoing prophylactic mastectomy. The impact of family history of breast cancer does not appear to be significant. Physician recommendations or patient preference are unknown. Our data suggest that high risk women who elect mastectomy as their initial surgical management to treat their breast cancer are more likely to undergo prophylactic mastectomy regardless of knowledge of their mutation status. No significant financial relationships to disclose.

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Risk of having BRCA mutations in women with triple-negative breast cancer: A systematic review and meta-analysis.

Journal of Clinical Oncology ◽

10.1200/jco.2011.29.27_suppl.160 ◽

2011 ◽

Vol 29 (27_suppl) ◽

pp. 160-160 ◽

Cited By ~ 1

Author(s):

N. M. Tun ◽

G. M. Villani ◽

K. Ong

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Odds Ratio ◽

Triple Negative ◽

Meta Analysis ◽

Brca2 Mutation ◽

Ashkenazi Jewish ◽

Jewish Women ◽

Brca1 Mutations ◽

Brca2 Mutations

160 Background: Increased prevalence of BRCA1 mutations (BRCA1) has been associated with the occurrence of triple-negative breast cancer (TNBC) (estrogen receptor [ER]- and progesterone receptor [PR]-negative, HER2-negative) in independent clinical studies. However, BRCA2 mutation (BRCA2) has not been found to overrepresent in women with TNBC. We have performed a meta-analysis of these studies to provide further statistical evidence of the association between BRCA positivity and TNBC. Methods: A Medline search of the MeSH terms “BRCA”, “triple”, and “negative” yielded 37 articles. A search of ASCO abstracts yielded 18 relevant articles. Random effects model was used for analysis due to heterogeneity among the proportions of included studies (Cochran’s Q = 18.52 and 15.18, tau2 = 0.61 and 1.29, I2 = 73% and 80% for BRCA1 and BRCA2 respectively). Mantel-Haenszel method was applied to calculate the pooled event-based odds ratio (OR) with 95% confidence interval (CI). Results: 6 studies including 1,602 BC patients were eligible for analysis of BRCA1 and 4 studies including 1297 BC patients for BRCA2. 172 patients with BRCA1 mutations and 79 patients with BRCA2 mutations were analyzed. Among these 6 studies, 1 included Ashkenazi Jewish women exclusively and 1 included only women of Chinese descent. The overall prevalence of BRCA1 was 10.05% (172 out of 1,602), and for TNBC patients 21.94% (95 out of 433) with an odds ratio of 5.90 (CI: 2.75, 12.66, p < 0.00001). TNBC was not a risk for BRCA2 (OR = 0.67, CI: 0.19, 2.39, p = 0.53). Chinese women with TNBC did not have an elevated risk of BRCA1 (OR = 0.94, CI: 0.24, 3.66) in contrast to Jewish women with TNBC who had the highest risk of BRCA1 among the populations studied (OR = 21.79, CI: 9.03, 52.55). Conclusions: Women with TNBC carry a significantly high risk of having BRCA1 but not BRCA2 mutations. We recommend genetic testing for BRCA1 mutations in women with TNBC especially in Ashkenazi Jewish population. Further studies on Chinese population are needed to further establish the relationship between TNBC and BRCA1 mutations in this cohort.

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Personalized Decision Making on Genomic Testing in Early Breast Cancer: Expanding the MINDACT Trial with Decision-Analytic Modeling

Medical Decision Making ◽

10.1177/0272989x21991173 ◽

2021 ◽

pp. 0272989X2199117

Author(s):

Ewout W. Steyerberg ◽

Liesbeth C. de Wreede ◽

David van Klaveren ◽

Patrick M. M. Bossuyt

Keyword(s):

Breast Cancer ◽

Decision Making ◽

Genetic Testing ◽

Early Stage ◽

Pragmatic Trial ◽

Genomic Signature ◽

Genomic Testing ◽

Analytic Modeling ◽

Clinical Risk ◽

Genomic Test

Background Genomic tests may improve upon clinical risk estimation with traditional prognostic factors. We aimed to explore how evidence on the prognostic strength of a genomic signature (clinical validity) can contribute to individualized decision making on starting chemotherapy for women with breast cancer (clinical utility). Methods The MINDACT trial was a randomized trial that enrolled 6693 women with early-stage breast cancer. A 70-gene signature (Mammaprint) was used to estimate genomic risk, and clinical risk was estimated by a dichotomized version of the Adjuvant!Online risk calculator. Women with discordant risk results were randomized to the use of chemotherapy. We simulated the full risk distribution of these women and estimated individual benefit, assuming a constant relative effect of chemotherapy. Results The trial showed a prognostic effect of the genomic signature (adjusted hazard ratio 2.4). A decision-analytic modeling approach identified far fewer women as candidates for genetic testing (4% rather than 50%) and fewer benefiting from chemotherapy (3% rather than 27%) as compared with the MINDACT trial report. The selection of women benefitting from genetic testing and chemotherapy depended strongly on the required benefit from treatment and the assumed therapeutic effect of chemotherapy. Conclusions A high-quality pragmatic trial was insufficient to directly inform clinical practice on the utility of a genomic test for individual women. The indication for genomic testing may be far more limited than suggested by the MINDACT trial.

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