BRCA1 Mutations Linked to Increased Risk of Serous, Serous-Like Endometrial Cancer

Increased risk for aggressive serous/serous-like endometrial cancer was increased in women with BRCA1 mutations, although the overall risk for uterine cancer after risk-reducing salpingo-oophorectomy (RRSO) to remove the fallopian tube and ovary was not increased, according to a new study published online by JAMA Oncology.1
RRSO is part of the standard treatment for women with BRCA mutations but the role of accompanying hysterectomy remains controversial. Clarifying the issue is relevant because serous/serous-like subtypes account for only about 10 percent of uterine cancer cases but more than 40 percent of deaths due to the disease.
Noah D. Kauff, M.D., of the Duke University Health System, Durham, N.C., and coauthors looked at the risk of uterine cancer after RRSO in women with mutations in the BRAC1 and BRCA2 gene. The study included 1,083 women without a prior or associated hysterectomy; 67.1 percent had a history of breast cancer and 29.4 percent of 928 women with data available had used tamoxifen.
Researchers documented eight uterine cancers among the 1,083 women. Five of 627 women with BRAC1 mutations developed uterine cancer and three of 453 women with BRCA2 mutations developed uterine carcinoma.
Five serous/serous-like endometrial carcinomas were observed about seven to 13 years after RRSO (4 in women with BRCA1mutations and one in a woman with BRCA2 mutations). In 4 of 5 serous/serous-like cancers, the women had prior breast cancer, three of whom used tamoxifen, according to the results.
The authors estimate a 2.6 percent risk of developing serous/serous-like carcinoma through age 70 for a women with BRCA1 mutation undergoing RRSO at age 45.
“These results suggest that BRCA1+ women undergoing RRSO without hysterectomy remain at increased risk for serous/serous-like endometrial carcinoma,” the author wrote.
They note that although their work is the largest prospective study to date, relatively few cancer cases were observed.
“Although instability in the estimated magnitude of this risk remains, we believe that the possibility of this cancer should be considered when discussing the advantages and risks of hysterectomy at the time of RRSO in BRCA1+ women,” the authors conclude.
“Although the study by Kauff et al suffers from a small number of cases, it does add to the literature linking the presence of BRCA mutation, in particular BRCA1 mutations, with a small but not null risk of endometrial cancer. Of concern is many of these uterine cancers are of serous histology, which is known to harbor worse outcomes even when diagnosed with early-stage disease,” Ronald D. Alvarez, M.D., M.B.A., of the University of Alabama at Birmingham, and coauthors write in a related editorial.2
1. JAMA Oncol. Published online June 30, 2016. doi:10.1001/jamaoncol.2016.1820. 
2. JAMA Oncol. Published online June 30, 2016. doi:10.1001/jamaoncol.2016.1773.