Endometrial Cancer and BRCA Mutations: A Systematic Review

Abstract

This systematic review identifies, evaluates, and summarises the findings of all relevant individual studies on the prevalence of BRCA mutation (BRCAm) in endometrial cancer patients and the incidence of endometrial cancer in BRCAm women patients. Consequently, the benefits and limits of a prophylactic hysterectomy at the time of the risk-reducing salpingo-oophorectomy are analysed and discussed. A systematic literature search was performed in the databases of PubMed, Cochrane, and Web of Science until May 2022; 13 studies met the eligibility criteria. Overall, 1613 endometrial cancer patients from 11 cohorts were tested for BRCA1/2 mutation. BRCA1/2m were identified in 4.3% of women with endometrial cancer (70/1613). BRCA1m was the most represented (71.4%) pathogenic variant. Alongside, a total of 209 BRCAm carriers from 14 studies were diagnosed with endometrial cancer. Only 5 out of 14 studies found a correlation between BRCAm and an increased risk of endometrial cancer. Nevertheless, two studies found a statistical difference only for BRCA1m women. The present systematic review does not provide strong evidence in favour of performing routine hysterectomy at the time of risk-reducing salpingo-oophorectomy; however, it provides epidemiological data that can be useful for counselling patients in order to offer a tailored approach.

Risk-Reducing Breast and Gynecological Surgery for BRCA Mutation Carriers: A Narrative Review

“…Among breast cancer survivors (not screened for germline mutations), increased risks of developing uterine or ovarian cancer higher than 150% and 40%, respectively, have been observed compared to the general population [ 64 ]. A recent review found that BRCA mutations were identified in 4.3% of women with endometrial cancer [ 65 ]. Moreover, a genomic mutation study that evaluated BRCA-associated mutational and transcriptomic profiles demonstrated the prognostic role of BRCA pathogenetic variants in patients affected by endometrial carcinoma, reporting lower levels of immune cell infiltration, higher expression of immunosuppressive checkpoint molecules, and worse prognoses in the presence of BRCA-associated mutations compared with wild-type BRCA [ 66 ].…”

“…The same differences were confirmed in an independent Australian cohort [ 97 ]. A recent systematic review did not provide strong evidence in favor of performing a routine hysterectomy at the time of the risk-reducing surgery [ 65 ], but these conclusions should be revised after the publication of new evidence [ 67 , 69 , 70 , 72 ]. Undoubtedly, prophylactic hysterectomy, due to its costs and potential complications (bleeding, infection, organ lesions, and vaginal cuff dehiscence), should be individually balanced with the potential increased risk of uterine cancer in this population.…”

NRG‐GY012: Randomized phase 2 study comparing olaparib, cediranib, and the combination of cediranib/olaparib in women with recurrent, persistent, or metastatic endometrial cancer

“…Across EC histologies and molecular subgroups, common genomic events have the potential to produce HRD. Germline pathogenic variants in HRR genes, including BRCA 1/2 , BRIP1 , and RAD51C , have been reported in EC 11–15 . A systematic review identified gBRCA1/2 pathogenic variants in up to 4.3% of ECs 12 .…”

“…Germline pathogenic variants in HRR genes, including BRCA1/2, BRIP1, and RAD51C, have been reported in EC. [11][12][13][14][15] A systematic review identified gBRCA1/2 pathogenic variants in up to 4.3% of ECs. 12 Molecular profiles (NGS600) from 1475 ECs demonstrated pathogenic variants in HRR genes in 34.4% of cancers.…”

“…[11][12][13][14][15] A systematic review identified gBRCA1/2 pathogenic variants in up to 4.3% of ECs. 12 Molecular profiles (NGS600) from 1475 ECs demonstrated pathogenic variants in HRR genes in 34.4% of cancers. 16 Genome-wide LOH (>16%) was identified in 24% of copy number high (CNH) EC, although this fell to 3% across the other molecular subgroups.…”