Abstract
BackgroundAn association between BRCA pathogenic variants and an increased endometrial cancer risk, specifically serous-like endometrial cancer, has been postulated but remains unproven, particularly for BRCA2 carriers. Mechanistic evidence is lacking, and any link may be related to tamoxifen exposure or testing bias. Hysterectomy during risk-reducing bilateral salpingo-oophorectomy is, therefore, of uncertain benefit. Data from a large, prospective cohort will be informative. MethodsData on UK BRCA pathogenic variant carriers were interrogated for endometrial cancer diagnoses. Standardised incidence ratios (SIRs) were calculated in four distinct cohorts using national endometrial cancer rates; either from 1/1/1980 or age 20, prospectively from date of personal pathogenic variant report, date of family pathogenic variant report or date of risk-reducing salpingo-oophorectomy. Somatic BRCA sequencing of 15 serous endometrial cancers was performed to detect pathogenic variants. ResultsFourteen cases of endometrial cancer were identified in 2609 women (1350 BRCA1 and 1259 BRCA2), of which two were prospectively diagnosed. No significant increase in either overall or serous-like endometrial cancer risk was identified in any of the cohorts examined (SIR = 1.70, 95% confidence interval = 0.74–3.33; no cases of serous endometrial cancer diagnosed). Results were unaffected by the BRCA gene affected, previous breast cancer or tamoxifen use. No BRCA pathogenic variants were detected in any of the serous endometrial cancers tested. ConclusionsWomen with a BRCA pathogenic variant do not appear to have a significant increased risk of all-type or serous-like endometrial cancer compared with the general population. These data provide some reassurance that hysterectomy is unlikely to be of significant benefit if performed solely as a preventive measure.
Highlights
Since the publication of a number of reports describing diagnoses of serous endometrial cancer in BRCA1 pathogenic variant carriers of Ashkenazi Jewish heritage [1e3], there has been interest in a potential association between the BRCA pathogenic variants and an increased risk of endometrial cancer
Whilst several prospective studies have examined the incidence of endometrial cancer after risk-reducing salpingooophorectomy (RRSO) in BRCA1 and BRCA2 pathogenic variant carriers compared with the general population, they have failed to consider the impact of the procedure on the rate of endometrial cancer within this specific population [12,13]
This study, sought to determine whether BRCA pathogenic variants are associated with an increased risk of endometrial cancer compared with the general population using a large, well-described cohort of BRCA1 and BRCA2 pathogenic variant carriers with prospective follow-ups
Summary
Since the publication of a number of reports describing diagnoses of serous endometrial cancer in BRCA1 pathogenic variant carriers of Ashkenazi Jewish heritage [1e3], there has been interest in a potential association between the BRCA pathogenic variants and an increased risk of endometrial cancer. Limitations of the studies performed to date are that they have often been purely retrospective, have included only small numbers of BRCA pathogenic variant carriers, those with BRCA2 pathogenic variants, and have frequently omitted to undertake expert pathological review of the tumour tissue to ensure accurate subtyping. They have often had short follow-up durations of only 5e6 years, which, when applied to a cohort with a median age of 40e50 years, means that they have limited power to detect endometrial cancer cases which predominately occur in older women.
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