Clinical Management of BRCA Mutation Carriers
To understand the role of germline BRCA1/BRCA2 mutations in determining outcome among women treated conservatively for breast cancer, the records of AJ women treated with lumpectomy and radiation therapy for invasive breast cancer were reviewed. Archival pathology material was obtained for analysis of the three founder AJ mutations. Deleterious BRCA mutations were found in 56 (11.3%) of the cases. The rate of ipsilateral cancer for founder mutation carriers was 12% at 10 years compared with 8% for women without mutations (not statistically significant). Women with founder AJ mutations were more than three times more likely than women without mutations to develop contralateral cancer, 27% versus 8% (P = .0001). The same investigators also described a separate case series of 87 women with BRCA mutations who were treated with breast- conserving surgery. They reported a 12.6% rate of ipsilateral breast cancer at a median of 51.8 months, and a 23% rate of contralateral breast cancer at a median of 67.4 months. No control group was included.
A case-control study from the Netherlands compared women with hereditary breast cancer (identified as either BRCA1/BRCA2 positive, or by a strong family history) with women without hereditary breast cancer for treatment outcome after breast conservation therapy. Although rates of ipsilateral breast recurrence were similar at 2 years following diagnosis, by 5 years the rate was twice as high in the hereditary cases (14% vs. 7%) and remained twice as high at 10 and 15 years after diagnosis (30% and 49% in the hereditary group, and 16% and 20% in the sporadic group).
A multi-institution retrospective cohort study compared outcomes after breast conserving treatment between women with known BRCA1/BRCA2 mutations and those whose family history was not suggestive of a hereditary pattern of breast cancer. At 10 years, overall rates of ipsilateral breast cancer were not significantly different. However, BRCA1/BRCA2 mutation status was significantly associated with a risk of ipsilateral breast cancer when those carriers who underwent oophorectomy were removed from the analysis (7.8% for noncarriers vs. 16.3% for carriers). The 10-year estimates for contralateral breast cancer were 3% for noncarriers and 26% for carriers. One study reported an approximately 40% risk of contralateral breast cancer in BRCA mutation carriers, a risk that is reduced by taking tamoxifen or undergoing oophorectomy.
A study of selected patients diagnosed with breast cancer at age 42 years or younger who had undergone conservative therapy were offered genetic testing for BRCA1/BRCA2 mutations. Of 127 participants, 22 were found to have deleterious mutations. At a median of 12.7 years of follow-up, the rate of ipsilateral events was 49% in the mutation carriers and 21% in the noncarriers (P = .007). Clinical and pathological features of the ipsilateral tumors were more consistent with second primaries than with local recurrence. Similarly, the rate of contralateral cancers was 42% in the carriers and 9% in the noncarriers (P = .001). This study has been criticized as having an unacceptable rate of ipsilateral events overall, calling into question the adequacy of the local-regional treatment.