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. 2024 Dec;131(12):1919-1927.
doi: 10.1038/s41416-024-02874-6. Epub 2024 Nov 16.

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

Robert D Morgan  1   2   3 , Xin Wang  4 , Bethany M Barnes  5   6 , Laura Spurgeon  7 , Aurore Carrot  8 , Daniel Netto  7 , Jurjees Hasan  7 , Claire Mitchell  7 , Zena Salih  7 , Sudha Desai  9 , Joseph Shaw  10   11 , Brett Winter-Roach  12 , Helene Schlecht  11 , George J Burghel  6   11   13 , Andrew R Clamp  7   5   6 , Richard J Edmondson  5   6   14 , Benoit You  8   15 , D Gareth R Evans  6   11   13 , Gordon C Jayson  7   5   6 , Stephen S Taylor  5   6
Affiliations

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

Robert D Morgan et al. Br J Cancer. 2024 Dec.

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.

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Conflict of interest statement

Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The study was approved by the Quality Improvement & Clinical Audit Committee at The Christie NHS Foundation Trust. The Genetic Variants in Gynaecological Cancer database has been approved by The Christie NHS Foundation Trust. The study was performed in line with the principles of the Declaration of Helsinki. Informed consent was obtained from all subjects involved in the study.

Figures

Fig. 1
Fig. 1. CONSORT diagram.
Key: C1 cycle 1, CT computed tomography, CRS chemotherapy response score, DPS delayed primary surgery, NACT neoadjuvant chemotherapy.
Fig. 2
Fig. 2. Kaplan–Meier curves for progression-free survival (PFS) and overall survival (OS) in CRS groups.
a, c show Kaplan–Meier curves for PFS (a) and OS (c) for CRS1 versus CRS2 versus CRS3; b, d show Kaplan–Meier curves for PFS (b) and OS (d) for CRS1+2 versus CRS3.
Fig. 3
Fig. 3
Chemotherapy response score reported for patients with a germline BRCA1/2 pathogenic variant.
See this image and copyright information in PMC

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