Dynamic changes in homologous recombination status before and after chemotherapy in advanced ovarian, fallopian tube, and primary peritoneal cancers

OBJECTIVE: Homologous recombination (HR) status plays a pivotal role in the management of advanced ovarian cancers, particularly in guiding the use of PARP inhibitors. In patients receiving neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS), tumor samples are available both before and after chemotherapy. This study evaluated the impact of NAC on HR status using paired pre- and post-NAC samples. METHODS: Between 2020 and 2023, 128 patients with ovarian cancer were treated at our institution; 24 underwent NAC followed by IDS. Genomic instability scores (GIS) and tumor BRCA (tBRCA) mutation status were assessed using the Myriad myChoice® assay. Paired analyses included cases with both pre- and post-NAC samples. RESULTS: Post-NAC HR assessment was unavailable in 8 of 24 patients (33%) due to insufficient or degraded tumor tissue. Paired HR status evaluation was therefore feasible in 15 patients. Among these paired evaluable cases, tBRCA mutation status remained unchanged. GIS scores significantly decreased in HR-deficient (HRD) tumors, whereas no significant change was observed in HR-proficient (HRP) tumors. The median ΔGIS was − 6, indicating a reduction after NAC. Two patients converted from HRD to HRP status after NAC, crossing the HRD threshold of 42. CONCLUSIONS: Our findings suggest that NAC may reduce GIS and alter HR status in HRD tumors. Limited tissue availability after NAC poses a practical challenge for HR assessment, and HRD-to-HRP conversion may affect eligibility for HR-targeted therapies. These findings support performing HRD testing prior to chemotherapy whenever feasible.