Clinical Management of BRCA Mutation Carriers
The Prevention and Observation of Surgical End Points (PROSE) study group estimated the degree of breast cancer risk reduction after RRM in BRCA1/BRCA2 mutation carriers. The rate of breast cancer in 105 mutation carriers who underwent bilateral RRM was compared with that in 378 mutation carriers who did not choose surgery. Bilateral mastectomy reduced the risk of breast cancer after a mean follow-up of 6.4 years by approximately 90%.
Another study evaluated the effectiveness of contralateral RRM in affected women with hereditary breast cancer. In a group of 148 BRCA1 or BRCA2 mutation carriers, 79 of whom underwent RRM, the risk of contralateral cancer was reduced by 91% and was independent of the effect of risk-reducing oophorectomy. Survival was better among women undergoing RRM, but this result was apparently associated with higher mortality due to the index cancer or metachronous ovarian cancer in the group not undergoing surgery. More recently, data from ten European centers on 550 women indicated that RRM was highly effective.
Studies describing histopathologic findings in RRM specimens from women with BRCA1 or BRCA2 mutations have been somewhat inconsistent. In two series, proliferative lesions associated with an increased risk of breast cancer (lobular carcinomain situ, atypical lobular hyperplasia, atypical ductal hyperplasia, DCIS) were noted in 37% to 46% of women with mutations undergoing either unilateral or bilateral RRM.[50,51,52] In these series, 13% to 15% of patients were found to have previously unsuspected DCIS in the prophylactically removed breast. Among 47 cases of risk-reducing bilateral or contralateral mastectomies performed in known BRCA1 or BRCA2 mutation carriers from Australia, three (6%) cancers were detected at surgery. In a study from Sweden among 100 women with a hereditary risk of breast cancer, unsuspected lesions were found in 13 out of 50 BRCA1/BRCA2 mutation carriers. These findings were not replicated in a third retrospective cohort study. In this study, proliferative fibrocystic changes were noted in none of 11 bilateral mastectomies from patients with deleterious mutations and in only two of seven contralateral unilateral risk-reducing mastectomies in affected mutation carriers.
Although data are sparse, the evidence to date indicates that while a substantial proportion of women with a strong family history of breast cancer are interested in discussing RRM as a treatment option, uptake varies according to culture, geography, health care system, insurance coverage, provider attitudes, and other social factors. For example, in one setting where the providers made one to two field trips to family gatherings for family information sessions and individual counseling, only 3% of unaffected carriers obtained RRM within 1 year of follow-up. Among women at increased risk of breast cancer due to family history, fewer than 10% opted for mastectomy. Selection of this option was related to breast cancer-related worry as opposed to objective risk parameters (e.g., number of relatives with breast cancer). In contrast, in a Dutch study of highly motivated women being followed every 6 months at a high-risk center, more than half (51%) of unaffected carriers opted for RRM. Almost 90% of the RRM surgeries were performed within 1 year of DNA testing. In this study, those most likely to have RRM were women younger than 55 years and with children. In addition, self-perceived risk has been closely linked to interest in RRM.