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

Robert D. Morgan, Xin Wang, Bethany M. Barnes, Laura Spurgeon, Aurore Carrot, Daniel Netto, Jurjees Hasan, Claire Mitchell, Zena Salih, Sudha Desai, Joseph Shaw, Brett Winter-Roach, Helene Schlecht, George J. Burghel, Andrew R. Clamp, Richard J. Edmondson, Benoit You, D. Gareth R. Evans, Gordon C. Jayson, Stephen S. Taylor

Research output: Contribution to journalArticlepeer-review

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.
Original languageEnglish
JournalBritish Journal of Cancer
Early online date16 Nov 2024
DOIs
Publication statusE-pub ahead of print - 16 Nov 2024

Keywords

  • Ovarian cancer
  • BRCA1
  • BRCA2
  • chemotherapy response score

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