TAMPA – Women with BRCA1 mutations who undergo risk-reducing salpingo-oophorectomy may remain at risk for rare types of aggressive uterine cancer, according to preliminary findings from a prospective cohort study.
Of 525 women with BRCA1 or BRCA2 gene mutations who underwent risk-reducing salpingo-oophorectomy (RRSO) without hysterectomy and who were followed for a median of 5.8 years, 4 developed a high-risk uterine corpus cancer, including 2 who developed serous disease, 1 who developed carcinosarcoma, and 1 who developed leiomyosarcoma. All occurred in the 296 women in the study who had BRCA1 mutations, for a 2.1% 10-year risk of uterine cancer following RRSO in those women, Dr. Catherine Shu reported during a late-breaking abstract session at the annual meeting of the Society of Gynecologic Oncology.
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Even women who have undergone a salpingo-oophorectomy are at risk from high-risk aggressive uterine cancer caused by mutations of the BRCA1 or BRCA2 genes.
The expected number of these types of high-risk cancer in this population, based on age- and race-based Surveillance, Epidemiology, and End Results (SEER) data adjusted for prevalence of hysterectomy, was 0.28, for a highly significant ratio of observed to expected cancers (O/E) of 14.48 (P less than .001), said Dr. Shu, chief fellow in medical oncology at Memorial Sloan Kettering Cancer Center, New York.
One of the cases occurred among the 169 women in the study with no prior breast cancer (O/E, 16.7; P =.06), and three occurred among 356 with prior breast cancer (O/E, 14.01; P =.001). When stratified based on tamoxifen exposure, high-risk uterine cancer was observed in 2 of 131woman with exposure (O/E, 21.68; P =.004), and in 2 of 394 with no exposure (O/E, 10.87; P =.015), Dr. Shu said.
The women included in the study represented 79% of all women at Memorial Sloan Kettering Cancer Center who underwent genetic testing followed by risk-reducing surgery without hysterectomy from June 1, 1995, to Dec. 31, 2011. They had a mean age of 46.1 years.
The "time at risk" for participants began after both receipt of genetic testing results and RRSO, and the participants were followed annually by questionnaires and medical records review. Censoring events were hysterectomy, uterine cancer diagnosis, last follow-up, or death, Dr. Shu noted.
Importantly, no increased risk was seen for more common types of uterine cancer, including endometrioid, mucinous, adenocarcinoma, and not otherwise specified cancers.
Those who developed high-risk cancer were treated with chemotherapy and/or radiation, and all four were living at the time of Dr. Shu’s presentation, although one had metastatic disease.
Although this study is one of the largest prospective studies to date to look at the likelihood of high-risk uterine cancer among BRCA-positive patients who undergo RRSO without hysterectomy, it has a number of limitations, such as possible misclassification of rare uterine cancer subtypes in the SEER database and possible confounding by tamoxifen exposure. The findings require confirmation and should thus be considered preliminary, Dr. Shu said.
Indeed, it would be premature at this point to recommend routine hysterectomy along with RRSO women with BRCA1 mutations; the decision regarding hysterectomy at the time of RRSO may depend on the patient’s age, prior cancer history, and other risk factors, senior author Noah D. Kauff of Memorial Sloan Kettering Cancer Center, said in a press statement.
Currently, based on the fact that women with a BRCA1 mutation have a 39%-46% chance of developing ovarian cancer and 50%-85% chance of developing breast cancer, the National Comprehensive Cancer Network recommends RRSO between ages 35 years and 40 years, after childbearing is complete.
Hysterectomy at the time of RRSO is not recommended because of risks associated with the procedure, including bleeding and infection risks, as well the potential for long-term problems with bladder, bowel, and sexual function, and also because uterine cancers that develop after RRSO have been thought to generally be low risk, according to the press statement.
The current findings suggest this may not be the case,
Pending confirmation of the findings, women with BRCA1 gene mutations who are considering risk-reducing surgery should be advised that "this report suggests they may be at risk for rare types of aggressive uterine cancer," and the potential advantages and disadvantages of concomitant hysterectomy should be discussed, Dr. Kauff said.
Dr. Shu and Dr. Kauff reported having no disclosures.