A small study has found an increased risk for serous or serous-like endometrial carcinoma among women with BRCA1 mutations after undergoing risk-reducing salpingo-oophorectomy without hysterectomy.
A small study has found an increased risk for serous or serous-like endometrial carcinoma among women with BRCA1 mutations after undergoing risk-reducing salpingo-oophorectomy (RRSO) without hysterectomy. However, the study, published in JAMA Oncology, showed no overall increased risk for uterine cancer after RRSO.
According to the study, 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% of uterine cancer cases, but more than 40% of deaths due to the disease.
Researchers led by Noah D. Kauff, MD, of the Duke University Health System in North Carolina, conducted a study that included 1,083 women with BRCA1 (n = 627), BRCA2 (n = 453), or both (n = 3) mutations who underwent RRSO without a prior or concomitant hysterectomy. Women were identified between 1995 and 2011 at nine academic centers.
Among this group of patients, eight incident uterine cancers were found (compared with 4.3 expected for an observed to expected [O:E] ratio of 1.9; P = .09). Five of the 627 women with BRCA1 disease and three of the 453 women with BRCA2 disease developed uterine cancer. In addition, the researchers observed five cases of serous and/or serous-like endometrial carcinoma; four in BRCA1 disease and one in BRCA2 disease.
“In our study, all three BRCA1-associated serous/serous-like carcinomas with available tissue showed clear loss of BRCA1 protein expression,” the researchers wrote. “In two cases, we also demonstrated that loss of the wild-type BRCA1 allele was the likely cause. In the third case, the mechanism for protein expression loss was not elucidated.”
These carcinomas occurred between 7.2 and 12.9 years after the RRSO procedure (BRCA1 O:E = 22.2, P < .001; BRCA2 O:E = 6.4, P = .15).
“With use of these data, the estimated risk for developing serous/serous-like carcinoma through age 70 years for a BRCA1-positive woman undergoing RRSO at age 45 years was 2.6%, assuming a constant annual risk, and 4.7%, assuming a constant relative risk compared with SEER rates,” the researchers wrote.
In an editorial that accompanied the article, Charles A. Leath, MD, MSPH, Warner K. Huh, MD, and Ronald D. Alvarez, MD, of the University of Alabama at Birmingham, called the findings “provocative.”
“Although the study by Kauff et al suffers from a small number of cases, it does add to the literature linking the presence of a BRCA mutation, in particular BRCA1 mutations, with a small but not null risk of endometrial cancer,” they wrote. “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. Perhaps it is time to consider that the line for risk-reducing gynecologic surgery in patients with BRCA mutations not stop at the ovaries and fallopian tubes. Thus, concomitant hysterectomy with RRSO, when performed with a minimally invasive surgical approach, particularly for women with a BRCA1 mutation, should be able to be performed with minimum morbidity and allow for use of estrogen-only hormone therapy after surgery, if needed.”