Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers.

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 follow-up (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 predicted that six to nine breast cancers should have developed among the mutation carriers, which translates into a risk reduction, after bilateral prophylactic mastectomy, of 89.5%-100% (95% confidence interval = 41.4% to 100%). CONCLUSIONS: Prophylactic mastectomy is associated with a substantial reduction in the incidence of subsequent breast cancer not only in women identified as being at high risk on the basis of a family history of breast cancer but also in known BRCA1 or BRCA2 mutation carriers.

Efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.

PURPOSE: To estimate the efficacy of contralateral prophylactic mastectomy in women with a personal and family history of breast cancer. PATIENTS AND METHODS: We followed the course of 745 women with a first breast cancer and a family history of breast and/or ovarian cancer who underwent contralateral prophylactic mastectomy at the Mayo Clinic between 1960 and 1993. Family history information and cancer follow-up information were obtained from the medical record, a study-specific questionnaire, and telephone follow-up. Life-tables for contralateral breast cancers, which consider age at first breast cancer, current age, and type of family history, were used to calculate the number of breast cancers expected in our cohort had they not had a prophylactic mastectomy. RESULTS: Of the 745 women in our cohort, 388 were premenopausal (age < 50 years) and 357 were post- menopausal. Eight women developed a contralateral breast cancer. Six events were observed among the premenopausal women, compared with 106.2 predicted, resulting in a risk reduction of 94.4% (95% confidence interval [CI], 87.7% to 97.9%). For the 357 postmenopausal women, 50.3 contralateral breast cancers were predicted, whereas only two were observed, representing a 96.0% risk reduction (95% CI, 85.6% to 99.5%). CONCLUSION: The incidence of contralateral breast cancer seems to be reduced significantly after contralateral prophylactic mastectomy in women with a personal and family history of breast cancer.

Long-term satisfaction and psychological and social function following bilateral prophylactic mastectomy.

CONTEXT: Prophylactic mastectomy is a preventive option for women who wish to reduce their risk of breast cancer. There has been concern about possible negative psychological sequelae following this procedure. However, few data are available regarding long-term satisfaction and psychological and social function following this procedure. OBJECTIVE: To evaluate patients' long-term satisfaction and psychological and social function following prophylactic mastectomy. DESIGN, SETTING, AND PARTICIPANTS: Descriptive study of all women known to be alive (n = 609) who had a family history of breast cancer and elected to undergo bilateral prophylactic mastectomy at a large, tertiary US health care clinic between 1960 and 1993, 94% (n = 572) of whom completed a study questionnaire. MAIN OUTCOME MEASURES: Satisfaction with procedure and effects on psychological and social function, based on responses to the study-specific questionnaire. RESULTS: Mean time from prophylactic mastectomy to last follow-up was 14.5 years. Most women (70%) were satisfied with the procedure; 11% were neutral; and 19% were dissatisfied. Among the psychological and social variables, the most striking finding was that 74% reported a diminished level of emotional concern about developing breast cancer. The majority of women reported no change/favorable effects in levels of emotional stability (68%/23%), level of stress (58%/28%), self-esteem (69%/13%), sexual relationships (73%/4%), and feelings of femininity (67%/8%). Forty-eight percent reported no change in their level of satisfaction with body appearance; 16% reported favorable effects. However, 9%, 14%, 18%, 23%, 25%, and 36% reported negative effects in these 6 variables, respectively. CONCLUSIONS: This study suggests that positive outcomes following prophylactic mastectomy include decreased emotional concern about developing breast cancer and generally favorable psychological and social outcomes. These must be weighed against the irreversibility of the decision, potential problems with implants and reconstructive surgery, and occurrence of adverse psychological and social outcomes in some women. JAMA. 2000;284:319-324