Women harboring BRCA1 or BRCA2 genetic variants had a moderate, 3% lifelong risk for developing serous endometrial carcinomas after risk-reducing salpingo-oophorectomy, according to results of a prospective study.
Serous endometrial carcinoma risk appeared more common among BRCA1 carriers, suggesting they could be at higher risk, the research showed.
Previous research demonstrated an association between BRCA1 and BRCA2 carriers and risk for serous endometrial carcinoma.
Saule, MD, from the department of genetics at Institut Curie in Paris, France, and colleagues sought to determine the incidence of serous endometrial carcinoma among a prospective cohort of 369 women carrying a germline BRCA1 (n = 238) or BRCA2 (n = 131) variant.
All patients underwent risk-reducing salpingo-oophorectomy by laparoscopy at Institut Curie. Median age at laparoscopy was 47.22 years (interquartile, 1.29) among BRCA1 carriers and 52.75 years (interquartile, 6.83) among BRCA2 carriers.
Saule and colleagues used the French national estimates of cancer incidence from 2012 as a reference population to measure expected incidence. Researchers assumed 10% of all endometrial carcinomas were serous.
Two cases of endometrial carcinoma occurred over 1,779 woman-years follow-up — both cases were serous — compared with an expected 0.062 incidence (P < .001).
The standardized incidence ratio for serous subtype was 32.2 (95% CI, 11.5-116.4) — which researchers noted appeared higher than expected — although the standardized incidence ratio for uterine cancer did not reach statistical significance.
Both women with serous endometrial carcinoma — detected at stage IVb for both patients — had familial history of breast and ovarian cancer. Researchers reported an age at onset of 51 years for one patient and 66 years for the second patient.
Both patients carried BRCA1 mutations, and their tumors showed loss of heterozygosity at the BRCA1 locus. Researchers determined the BRCA1 gene was inactive in both tumors, signaling its “agreement with its role in serous uterine carcinogenesis.”
Five women with BRCA1 or BRCA2 variants received treatment with tamoxifen, but neither of the two women with serous endometrial carcinoma had been exposed to tamoxifen.
“The increased risk [for] undifferentiated endometrial carcinomas associated with tamoxifen may have been a confounding factor and may explain different risk estimates,” the researchers wrote.
Researchers calculated a 3% lifelong risk for serous endometrial carcinoma by age 70 years among BRCA1/BRCA2 carriers currently aged 40 years. The researchers deemed this risk moderate and noted it appeared similar to 25-year risk estimates from previous research.
“Precise estimates of serous endometrial carcinoma risks and studies regarding the benefit of serous endometrial carcinoma early diagnosis on prognosis are not sufficient at the present time to make recommendations regarding risk-reducing salpingo-oophorectomy-associated prophylactic hysterectomy,” the researchers wrote. “However, prophylactic hysterectomy should be discussed with informed women, especially when they have relatives with ovarian and fallopian tube cancer and they do not present with comorbidities and thrombogenic factors.” – by Melinda Stevens
Disclosures: The authors report no relevant financial disclosures.