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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2024年11月16日

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  • 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

摘要

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.