BRCA1 mutation increased risk for rare uterine cancers after salpingo-oophorectomy

Women who harbored BRCA1 mutations were at an increased risk for developing rare, aggressive forms of uterine cancer after undergoing risk-reducing salpingo-oophorectomy, according to results of a prospective cohort study presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer in Tampa, Fla.

“While the absolute risk is still relatively low, it is much higher than we would have expected for these aggressive uterine cancers,” researcher Noah D. Kauff, MD, director of ovarian cancer screening and prevention of the gynecology service at Memorial Sloan-Kettering Cancer Center, said in a press release.

Kauff and colleagues evaluated data from 525 women with BRCA mutations who were undergoing risk-reducing salpingo-oophorectomy without concomitant hysterectomy.

Of these women, 168 had no history of breast cancer and 357 had a history of prior breast cancer. Most women (n=296; 56%) carried BRCA1 mutation, 226 (43%) had BRCA2 mutations and three (0.6%) harbored both.

Median follow-up was 5.8 years (range, 0.1-16.9).

Overall, four women were diagnosed with uterine cancer during 3,292 woman-years of follow-up.

Researchers used age- and race-specific, hysterectomy-adjusted SEER data to determine the expected uterine cancer incidence (2.23). They calculated a 1.8 observed-to-expected ratio (P=.19).

Although the expected number of low-risk uterine cancers was 1.95, no women were diagnosed with low-risk uterine cancer (P=.14).

All four uterine cancer cases were high risk — including two serous, one carcinosarcoma and one leiomyosarcoma — and were diagnosed among women with BRCA1 mutations 1.4 to 12.9 years after salpingo-oophorectomy. The expected number of high-risk uterine cases was 0.28, equating to a 14.48 observed-to-expected ratio (P˂.001).

Women with BRCA1 mutations were at a 2.1% increased risk for high-risk uterine cancers within 10 years after salpingo-oophorectomy, which is 26 times the risk of the general population.

Among the women diagnosed with high-risk uterine cancer, one had no prior breast cancer (expected, 0.06; observed-to-expected, 16.7; P=.06) and three had a history of breast cancer (expected, 0.22; observed-to-expected, 14.01; P=.001). Of these four women, two had been treated with tamoxifen (expected, 0.092; observed-to-expected, 21.68; P=.004) and two had not been treated with tamoxifen (expected, 0.184; observed-to-expected, 10.87; P=.015).

“Doctors should let their patients with BRCA1 mutations know that this report suggests they may be at risk for rare types of aggressive uterine cancer,” Kauff said. “Whether or not a woman decides to have a hysterectomy at time of risk-reducing salpingo-oophorectomy may depend on her age, prior cancer history and other risk factors.”

For more information:

Shu CA. Abstract #LBA-5. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; March 22-24, 2014; Tampa, Fla.

Disclosure: See the study for a full list of the researchers’ relevant financial disclosures.