Real-World Eligibility for Germline Multigene Panel Testing in Breast Cancer: An Evaluation of Current Testing...

Background: Germline multigene testing is increasingly integrated into breast cancer care, but the ability of current eligibility frameworks to identify pathogenic variant carriers remains uncertain in real-world cohorts. Methods: This retrospective observational study included 556 patients with histologically confirmed breast cancer who underwent germline multigene testing at a single oncology center. Testing eligibility was retrospectively assessed according to NCCN criteria, ESMO-based recommendations, and the ASBrS universal-testing recommendations. Family history up to third-degree relatives and surgical data were evaluated. Results: Pathogenic variants were identified in 137 patients (24.6%), while variants of uncertain significance were reported in 310 patients (55.8%). NCCN criteria were fulfilled by 135 of 137 patients with pathogenic variants (98.5%), indicating high sensitivity but limited discriminatory capacity, as eligibility was also frequent among patients without pathogenic variants. ESMO-based criteria were met by 94 mutation-positive patients (68.6%) and were significantly associated with pathogenic variant status (p < 0.001; OR = 3.08, 95% CI: 2.05-4.65). Notably, 42.3% of pathogenic-variant-positive patients reported no family history of malignancy. Prophylactic surgery was documented in only 16.8% of patients with pathogenic variants. Conclusions: NCCN criteria captured nearly all mutation-positive patients; ESMO-based criteria were more selective. The findings support broader access to germline testing before surgery.