Germline landscape of high grade serous ovarian cancer across age groups: Is age just a number?
To characterize age-related variations in germline pathogenic variants (gPVs) in patients with high-grade serous ovarian cancer (HGSOC). 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. 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). 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.