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Prevalence of pathogenic germline variants and indications for testing in a diverse community-based endometrial
Elizabeth Suh-Burgmann1, Holly Finertie2, Yun-Yi Hung2
1Division of Gynecologic Oncology, The Permanente Medical Group, United States of America; Division of Research, Kaiser Permanente Northern California, United States of America.
Objective:
To assess the prevalence of pathogenic germline variants (gPVs) and indications for testing in a diverse community-based endometrial cancer population.
Methods:
Among patients diagnosed from 2016 to 2022, the prevalence of gPVs was determined and detection rates compared by indication. Propensity score weighting was used to estimate gPV prevalence in the overall endometrial cancer cohort.
Results:
Among 10,233 women, 1487 (14.5%) underwent germline testing: at diagnosis for 997 (67%), recurrence for 90 (6.1%), diagnosis of breast, colon, or lung cancer for 71 (4.8%), and at another time for 329 (22%). Among those tested, 251 (16.9%, 95% CI: 15.0-18.9%) tested positive, including 64 (4.3%, 95% CI: 3.4-5.5%) with variants related to homologous recombination deficiency (HRD) (BRCA1, BRCA2, ATM, BRIP1, RAD51C, RAD51D, and PALB), and 134 (9.0%, 95% CI: 7.6-10.6%) with Lynch syndrome related mutations (MSH6, PMS2, MLH1, MLH2, or EPCAM). Testing at diagnosis accounted for 74% of patients found to have gPVs, including 89.6% patients with Lynch and 54.7% patients with HRD-related variants. The estimated prevalence of gPVs in the overall endometrial cancer population was 11.9% (95% CI: 9.6-14.6%), including 1.7% (95% CI: 1.4-2.2%) with Lynch and 4.7% (95% CI: 3.3-6.7%) with HRD-related variants. Rates of gPVs did not differ by race, but Lynch variants were more common in Asian patients.
Conclusion:
In a population-based endometrial cancer cohort, the estimated prevalence of gPVs was 11.9%, including 1.7% with Lynch and 4.7% with HRD-related variants. Testing at diagnosis accounted for 3 out of 4 positive cases, including most Lynch but only half of HRD-related variants. Lynch related gPVs were more common among Asian patients.