Uterine serous carcinoma and germline genetic testing: patterns of referral, completion and pathogenic variant detection

Background

Current guidelines recommend consideration of germline genetic testing for patients with uterine serous carcinoma (USC) but real-world data are limited on completion rates of testing and pathogenic variant (PV) identification. This study aimed to evaluate the rate of genetic testing referral and completion in a cohort of patients with USC, determine the prevalence of clinically meaningful PVs found on testing and explore factors associated with genetics referral and testing completion.

Methods

We retrospectively examined the medical records of all individuals diagnosed with USC between 2019 and 2024 seen at a single academic cancer centre. Outcomes of interest included referral for germline genetic testing, completion of testing and testing results.

Results

Of 131 individuals included, 5 (3.8%) had prior genetic testing and only 45 (34.4%) were recommended to undergo genetic testing or referred to cancer genetics. Younger individuals and those with a personal history of cancer other than USC or family history of breast or ovarian cancer were more likely to be referred. Nine (26.5%) of 34 individuals who completed germline testing had a PV identified in a cancer-related gene, including BRCA1, BRCA2, BRIP1, CHEK2, MSH6, PMS2 and ATM. Only a personal history of cancer other than USC was independently associated with the discovery of a PV on germline genetic testing. In those without a prior personal history of cancer, the PV prevalence was 5.6%.

Conclusions

Given the high prevalence of PVs in this population, germline genetic testing for all patients diagnosed with USC can provide clinically meaningful benefit but is currently underused in practice.