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, fallopian tube, and primary peritoneal cancers (collectively referred to as ovarian cancers), influencing treatment selection and response to PARP inhibitors. For patients undergoing neoadjuvant chemotherapy (NAC) followed by interval debulking surgery (IDS), clinicians have two opportunities to obtain tumor samples: before and after NAC. This study aimed to compare pre- and post-NAC samples to assess the impact of chemotherapy on HR status. Methods Between 2020 and 2023, 128 patients with ovarian cancer were treated at our institution. Among them, 24 underwent NAC followed by IDS. Tumor samples were analyzed using the Myriad myChoice® assay to determine genomic instability scores (GIS) and BRCA mutation status. Results Post-NAC HR status was unavailable in 8 of 24 patients (33%) due to insufficient or degraded samples. Among the 15 patients with paired pre- and post-NAC samples, BRCA mutation status remained unchanged. However, GIS scores were significantly reduced in HR-deficient (HRD) tumors after NAC, whereas HR-proficient (HRP) tumors showed no significant change. Notably, two patients converted from HRD to HRP status, with GIS decreasing from 51 to 34 in one and from 49 to 41 in the other, crossing the HRD threshold of 42. Conclusions NAC can reduce GIS and alter HR status in HRD tumors. Although post-NAC assessment may help refine treatment strategies after IDS, tissue availability is often limited. Moreover, conversion from HRD to HRP status following NAC may restrict eligibility for HR-targeted therapies.