Lumpectomy Not Contraindicated in BRCA-Linked Cancer

SAN ANTONIO—Women with breast cancer associated with germline BRCA1 or BRCA2 mutations can undergo breast-conserving surgery, if they so desire, since their risk of ipsilateral breast cancer recurrence is only slightly increased, according to a study from Memorial Sloan-Kettering Cancer Center presented at the 23^rd Annual San Antonio Breast Cancer Symposium.

Mark Robson, MD, of the Clinical Genetics Service, Memorial Sloan-Kettering, reported the results from a retrospective study of 466 Ashkenazi Jewish women undergoing breast-conserving therapy for 502 cancers at Memorial Sloan-Kettering and Jewish General Hospital of McGill University from 1980 to 1995.

The intent of the study was to determine clinical outcomes in women with BRCA mutations.

Among the 466 women, 53 (11.4%) were found to have a BRCA1 or BRCA2 mutation. BRCA1 mutations were almost five times more prevalent than BRCA2 mutations. BRCA-associated cancers were more likely to be diagnosed before the age of 50 (63% vs 27%, P < .001), but tumor stage was not different from that of breast cancers not associated with BRCA mutations.

After a median follow-up of 103 months, ipsilateral breast cancers occurred in 8 (12%) of 65 BRCA-associated breast cancers and 34 (7.8%) of 437 non-BRCA-associated cancers, giving a hazard ratio of 1.5 (95% CI: 0.7 to 3.4) for ipsilateral recurrence among women with BRCA mutations.

The risk of ipsilateral recurrence at 5 years was 13% for women who had BRCA-associated breast cancers vs 7% for women with non-BRCA disease (P = .07).

The most significant predictor of ipsilateral recurrence was age less than 50 (P < .0007), Dr. Robson said. "There is an increased risk of ipsilateral disease in women with mutations, but it is not independent of age," he noted.

Contralateral breast cancer, after 106 months median follow-up, occurred in 33% of women with a BRCA mutation and 7% of women without the mutation, producing a relative risk of 4.4 for women with BRCA1 mutations (P < .0001) and 3.5 for women with BRCA2 mutations (P < .09), he said.

Overall survival was 77% at 5 years for women with mutations and 91% for women without. Survival at a median follow-up of 106 months was 61% vs 81%, respectively (P < .001). Any BRCA mutation, therefore, carried a hazard ratio of 2.2 for death (P = .004), he reported.

Dr. Robson summarized the findings as follows: "BRCA mutations were not independently associated with an increased risk of metachronous ipsilateral cancer, but they did increase the risk of contralateral disease. BRCA1, especially, is independently associated with a worse overall survival."

He said the practice at Memorial Sloan-Kettering is to identify at-risk women, counsel them, and help them work through their options. "While we do not formally recommend prophylactic mastectomy, we support a woman’s decision to have this procedure," he commented.