Oophorectomy Value Varies by BRCA Type

ATLANTA—The risk reduction for breast and ovarian cancer associated with salpingo-oophorectomy (SO) in high-risk women varies according to the type of BRCA mutation, Noah D. Kauff, MD, of the Clinical Genetics Service, Memorial Sloan-Kettering Cancer Center, reported at the American Society of Clinical Oncology (ASCO) 42nd Annual Meeting (abstract 1003).^{"In the largest prospective follow-up study to date, risk-reducing surgery significantly reduced the risk of BRCA-associated gynecologic cancers in both BRCA1 and BRCA2 mutation carriers as well as breast cancer risk in BRCA2 mutation carriers. . . . We need to stratify for BRCA mutation type in these two related but distinct cancer syndromes," Dr. Kauff said.}

The study was undertaken, he said, because previous studies were limited by short follow-up or other methodological problems, and were not powered to examine differences in outcome between carriers of BRCA1 and BRCA2.

The researchers updated and combined follow-up data from two large cohorts of BRCA carriers. Patients were prospectively followed for a minimum of 6 months, and 1,080 mutation carriers were initially eligible for study inclusion. After various exclusions, 871 patients were in the study cohort, enrolled from 11 centers (597 with breast tissue at risk). Dr. Kauff said that 546 of these women elected risk-reduction surgery a median of 5 months from receipt of BRCA test results.

During a mean follow-up of 40 months, among BRCA1 mutation carriers, the investigators observed 12 gynecologic cancers in 198 women electing surveillance (10 ovarian, 1 fallopian tube, 1 primary peritoneal), compared with 3 gynecologic cancers (all primary peritoneal) in 352 women electing risk-reduction SO. Among BRCA2 mutation carriers, there were 2 gynecologic cancers (both ovarian) in the surveillance group (n = 127) vs none in the surgery group (n = 194).

For BRCA1 and BRCA2 groups combined, SO was associated with an 89% reduction in risk of gynecologic cancer (P < .001). When stratified by mutation type, the risk reduction was 87% for BRCA1 mutation carriers (P = .002) and 100% for BRCA2 mutation carriers (see Table).

With a mean follow-up of 35 months, among BRCA1 mutation carriers, there were 19 breast cancers in the 178 patients who did not have surgery vs 15 in the 190 women who had SO. In BRCA2 mutation carriers, there were 9 breast cancers in the nonsurgery group (n = 116) vs 4 in the surgery group (n = 113).

For BRCA1 and BRCA2 groups combined, salpingo-oophorectomy was associated with a 47% reduction in risk of breast cancer (P = .038). "BRCA2 carriers had a 72% reduction in the risk of subsequent breast cancer from risk-reduction surgery [P = .036], and BRCA1 mutation carriers, approximately a 39% risk reduction, which was not statistically significant [P = .16]," Dr. Kauff said.

Effects of ER Status

The researchers also did an exploratory analysis of the effects of SO on ER-positive vs ER-negative breast cancer. Dr. Kauff noted that BRCA2 carriers are much more likely to have ER-positive disease than BRCA1 carriers. The analysis (BRCA1 and 2 combined) showed a strong trend associating SO with protection against ER-positive disease, about a 78% risk reduction. "There was no evidence of benefit from SO for the prevention of ER-negative disease in the 24 women with invasive cancer for whom ER status was known," he said.