SAN ANTONIOWomen 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 23rd 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
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.