Efficacy of Bilateral Prophylactic Mastectomy in BRCA1 and BRCA2 Gene Mutation Carriers

Abstract

Background:In women with a family history of breast cancer, bilateral prophylactic mastectomy is associated with a decreased risk of subsequent breast cancer of approximately 90%. We examined the association between bilateral prophylactic mastectomy and breast cancer risk in women at high risk for breast cancer who also had mutations in BRCA1 and BRCA2 genes. Methods: We obtained blood samples from 176 of the 214 high-risk women who participated in our previous retrospective cohort study of bilateral prophylactic mastectomy. We used conformation-sensitive gel electrophoresis and direct sequence analysis of the blood specimens to identify women with mutations in BRCA1 and BRCA2. The carriers' probabilities of developing breast cancer were estimated from two different penetrance models. Results: We identified 26 women with an alteration in BRCA1 or BRCA2. Eighteen of the mutations were considered to be deleterious and eight to be of uncertain clinical significance. None of the 26 women has developed breast cancer after a median of 13.4 years of followup (range, 5.8-28.5 years). Three of the 214 women are known to have developed a breast cancer after prophylactic mastectomy. For two of these women, BRCA1 and BRCA2 screening was negative, and no blood specimen was available for the third. Estimations of the effectiveness of prophylactic mastectomy were performed, considering this woman as both a mutation carrier and a noncarrier. These calculations

Angelina Jolie’s faulty gene: newspaper coverage of a celebrity’s preventive bilateral mastectomy in Canada, the United States, and the United Kingdom

“…Research has shown that although prophylactic mastectomy substantially reduces (by ~90%) the incidence of subsequent breast cancer in women at high risk on the basis of a family history or due to BRCA1/2 mutations, it should not be seen as a panacea for breast cancer. 37 Moreover, physicians do not always agree that mastectomy is the best prevention method and may instead advise very close monitoring (e.g., periodic mammograms and regular clinical breast examinations) or prescribe medications (such as tamoxifen or raloxifene) that decrease the risks of developing breast cancer. 38 Future research should explore whether the press coverage of Jolie's preventive mastectomy resulted in increased demand and utilization of BRCA1/2 testing and preventive mastectomies.…”

Looking different, feeling different: women’s reactions to risk-reducing breast and ovarian surgery

“…Although BRCA1 and BRCA2 mutation carriers' cancer risks are increased [2,3], evidence suggests that these risks can be managed effectively [4][5][6][7]. While ovarian screening in high-risk groups is not effective, breast cancer screening is indicated and there is evidence of increased sensitivity of magnetic resonance imaging (MRI) for detecting malignancies in younger BRCA carriers [8,9], compared to mammography.…”

Evaluation of models to predict BRCA germline mutations

“…Identification of these individuals before they present with cancer is important since prophylactic surgery can reduce morbidity and mortality in these individuals (Struewing et al, 1995;Rebbeck et al, 1999;Hartmann et al, 1999;Hartmann et al, 2001;Meijers-Heijboer et al, 2001;Kauff et al, 2002;Rebbeck et al, 2004). Unfortunately, genetic testing is expensive, family history of breast cancer is common and BRCA mutations are rare (Ford et al, 1994;Peto et al, 1999;Antoniou et al, 2002).…”