Germline BRCA1/2 status and chemotherapy response score in high-grade serous ovarian cancer

Abstract

BACKGROUND: High-grade serous ovarian cancer (HGSOC) can be treated with platinum-based neoadjuvant chemotherapy (NACT) and delayed primary surgery (DPS). Histopathological response to NACT can be assessed using Böhm's chemotherapy response score (CRS). We investigated whether germline BRCA1/2 (gBRCA1/2) genotype associated with omental CRS phenotype. METHODS: A retrospective study of patients with newly diagnosed FIGO stage IIIC/IV HGSOC prescribed NACT and tested for gBRCA1/2 pathogenic variants (PVs) between September 2017 and December 2022 at The Christie Hospital. The Cox proportional hazards model evaluated the association between survival and key clinical factors. The chi-square test assessed the association between CRS3 (no/minimal residual tumour) and gBRCA1/2 status. RESULTS: Of 586 eligible patients, 393 underwent DPS and had a CRS reported. Independent prognostic factors by multivariable analysis were gBRCA1/2 status (PV versus wild type [WT]), CRS (3 versus 1 + 2), surgical outcome (complete versus optimal/suboptimal) and first-line poly (ADP-ribose) polymerase-1/2 inhibitor maintenance therapy (yes versus no) (all P < 0.05). There was a non-significant trend for tumours with a gBRCA2 PV having CRS3 versus WT (odds ratio [OR] = 2.13, 95% confidence intervals [CI] 0.95-4.91; P = 0.0647). By contrast, tumours with a gBRCA1 PV were significantly less likely to have CRS3 than WT (OR = 0.35, 95%CI 0.14-0.91; P = 0.0291). CONCLUSIONS: Germline BRCA1/2 genotype was not clearly associated with superior omental CRS. Further research is required to understand how HGSOC biology defines CRS.