The real-world utility of homologous repair deficiency testing in BRCA1/2 wild-type high-grade serous carcinoma and the utility of MYC amplification as a potential surrogate marker.

Poly (ADP-ribose) polymerase inhibitors (PARPi) have advanced treatment for high-grade serous tubo-ovarian carcinoma (HGSC). Homologous recombination deficiency (HRD) is a useful biomarker of PARPi benefit but is not uniformly available. Our objective was to evaluate PARPi use in relation to HRD testing and other clinical factors and identify genetic features that may infer HRD status in BRCA1/2 wild-type (BRCA-wt) tumors. The main cohort included patients with HGSC in Alberta, Canada who underwent HRD testing between January 2023 and 2025. Data included demographics, PARPi use and effect, tumor mutations, and recurrence. Descriptive analyses compared niraparib use between HRD and HRP BRCA-wt patients. Separate BRCA-wt cohorts were used to validate HRD-predictive genetic features. In the main cohort, 96 patients underwent HRD testing: 33 HRD, 59 HRP, 4 inconclusive. HRD tumors were 3.5 times more likely than HRP tumors to receive niraparib (25/33 vs 13/59). Among niraparib-treated patients, 40% with HRD tumors remained on treatment vs 23% of HRP tumors. Among BRCA-wt HGSC, MYC amplification (≥5 copies) was more common in HRD than HRP tumors in both the main cohort (6/14, 43% vs 1/30, 3%; p = 0.00050) and the validation cohorts (18/33, 55% vs 6/57, 11%; p < 0.005). MYC amplification was associated with an 85% probability of HRD, 2.6-fold higher than the 33% HRD rate across all cohorts. Our findings support the value of HRD testing in risk-benefit assessment for niraparib use in HGSC. Clinical DNA panels that include MYC copy number may provide a surrogate estimate of HRD status.