Germline Genetic Testing in Breast and Gynecologic Cancers: Evaluating Age at Diagnosis as a Determinant

Background: Breast cancer and gynecological malignancies, including cervical, ovarian, and endometrial cancers, remain leading causes of cancer incidence and mortality among women worldwide. This study investigated hereditary predisposition rates in women diagnosed with breast or gynecological cancer, focusing on the effect of age on pathogenic/likely pathogenic (P/LP) variant detection. We sought to determine whether younger age at diagnosis should be used as a criterion for patient selection for genetic testing. Methods: A total of 9084 consecutive females with breast cancer or gynecological tumors underwent NGS-based genetic testing (53 cancer-relevant genes) at Genekor laboratory from 2020-2026. Multivariable logistic regression evaluated factors associated with P/LP variant detection, adjusting for tumor type and family history. Results: Overall P/LP prevalence was approximately 20% (one in five patients), with tumor-specific rates of 19.24% in breast cancer, 27.59% in ovarian cancer, and 26.67% in endometrial cancer. P/LP prevalence declined significantly with age from 24.37% in patients <40 years to 15.90% in those ≥70 years, while VUS remained stable (40-43%). P/LP patients had earlier diagnosis (median 45 vs 46 years, p<0.001), driven predominantly by high-risk genes (13.87% in <40y vs 7.11% in ≥70y). BRCA1 showed stronger age enrichment than BRCA2 (8.14% vs 3.16% in <40y; median diagnosis 43 vs 45 years). Age remained independently associated with P/LP detection in multivariable analysis, with an 18% reduction in odds per 10-year increase for any P/LP (OR 0.82, 95% CI 0.78-0.86) and a stronger 28% reduction for high-risk variants (OR 0.72, 95% CI 0.67-0.78). Family history also independently predicted P/LP detection (OR 1.40, 95% CI 1.19-1.66). Conclusions: While younger patients have a higher prevalence of high-risk variants, clinically actionable findings were identified across all age groups, including patients ≥70 years These findings indicate that focusing on age to determine eligibility for genetic testing is insufficient. Expanding testing accessibility to individuals regardless of their age at diagnosis may enhance the identification of genetic cancer risk and optimize patient management.