A large hereditary cancer study supports National Comprehensive Cancer Network guidance to consider risk-reducing salpingo-oophorectomy (RRSO) between ages 45 and 50 years for women with BRIP1, RAD51C, or RAD51D mutations, Lydia Usha, MD, said at the annual meeting of the Society of Gynecologic Oncology.
The average ages for an ovarian cancer diagnosis were 56 years for women with RAD51D mutations, 61 years for RAD51C mutations, and 64 years for BRIP1 mutations, said Dr. Usha of Rush Medical College, Chicago. When appropriate, delaying RRSO “avoids the psychosocial and medical complications of premature menopause,” she said.
Historically, the NCCN has recommended RRSO for women with mutations of BRCA1, BRCA2, and the mismatch repair genes MLH1, MSH2, MSH6, and PMS2, Dr. Usha noted. But more recent studies have also implicated less common mutations of BRIP1, RAD51C, and RAD51D, leading the NCCN to add these mutations and to recommend that affected women consider RRSO when they are 45-50 years old. However, typical ages for ovarian cancer diagnosis for these rarer mutations were unknown, Dr. Usha said. Therefore, she and her associates studied data from 345,667 women who were tested with a 25-gene hereditary cancer panel between 2013 and 2016.
Among all women, mutation prevalence was 0.3% for BRIP1, 0.1% for RAD51C and RAD51D, 1.2% for BRCA1, and 1.3% for BRCA2 mutations, Dr. Usha reported. Among 18,719 women who had a personal history of ovarian cancer, the most common mutation was BRCA1 (3.5%), followed by BRCA2 (2.7%). In contrast, the combined prevalence of BRIP1, RAD51C, and RAD51D mutations among cancer patients was only 1.6%.
Cancer prevalence was highest among women who had mutations of RAD51C (22%), followed by RAD51D (19%), BRCA1 and BRIP1 (16% in each case), and BRCA2 (11%). Thus, while BRIP1 and RAD51D mutations were uncommon, their presence signified an ovarian cancer risk that was similar to that with BRCA1 mutations, and a greater risk than with BRCA2, Dr. Usha said.
The average ages for ovarian cancer diagnosis were 64 years for BRIP1, 61 years for RAD51C, 60 years for BRCA2, 56 years for RAD51C, and 54 years for BRCA1. “More than 80% of women with ovarian cancer who had a mutation in BRIP1, RAD51C, or BRCA2 were diagnosed after age 50,” Dr. Usha noted. These findings support considering RRSO closer to age 45 years for RAD51D mutation carriers and closer to age 50 years for women with pathogenic variants of BRIP1, added discussant Kari Ring, MD, of the University of Virginia, Charlottesville.
Mutation type did not significantly correlate with ethnicity or type of ovarian cancer, Dr. Usha noted. “Collectively, these findings may aid clinical decisions about the medical management of women with mutations in these genes,” she said. “Our data may also assist with reproductive decisions, such as age of childbearing.”
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