Abstract
OBJECTIVE: To characterize age-related variations in germline pathogenic variants (gPVs) in patients with high-grade serous ovarian cancer (HGSOC). METHODS: Patients with HGSOC who underwent clinical tumor-normal sequencing of ≥76 genes from 1/1/2015-11/15/2022, were included. Clinical variables including age at diagnosis were collected. Logistic regression models were built to examine associations between gPV, age, and clinical variables. RESULTS: Of 1231 patients, median age at diagnosis was 63 years (range, 33-93); 163 patients (13 %) were diagnosed at age ≤ 49, 739 (60 %) between ages 50-69, and 329 (27 %) at age ≥ 70 years. gPVs were observed in 68 (42 %), 200 (27 %), and 52 patients (16 %) respectively, p < 0.001. Compared to patients diagnosed between ages 50-69, those diagnosed at age ≥ 70 were less likely to have a gPV (OR: 0.58; 95 % CI: 0.38-0.86) and those diagnosed at age ≤ 49 were more likely to have a gPV (OR: 1.78; 95 % CI: 1.18-2.68), after adjustment for genetic ancestry and NCI Comorbidity Index. Seven of 67 patients (10 %) diagnosed at age ≥ 80 years had a gPV, including 2 in OC-related genes (BRCA2, PALB2). Twelve of 21 patients (57 %) diagnosed at age ≤ 39 years had a gPV, all in OC-related genes. No differences in genetics follow-up or poly (ADP-ribose) polymerase inhibitor use were observed by age (p > 0.05). CONCLUSION: Although gPV rates varied by age with the highest rates observed in patients with early-onset OC, rates were high (≥10 %) in all age groups, with similar genetics follow-up and implementation of targeted therapies. Universal genetic testing is important for all patients with OC regardless of age.