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

Autor:	Morgan RD; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom. robert.morgan7@nhs.net.; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom. robert.morgan7@nhs.net.; Manchester Academic Health Science Centre (MAHSC), Manchester, United Kingdom. robert.morgan7@nhs.net., Wang X; Clinical Outcome and Data Unit, The Christie NHS Foundation Trust, Manchester, United Kingdom., Barnes BM; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.; Manchester Academic Health Science Centre (MAHSC), Manchester, United Kingdom., Spurgeon L; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom., Carrot A; Centre pour l'lnnovation en Cancérologie de Lyon (CICLY), EA 3738, Université Claude Bernard University Lyon 1, Univ Lyon 1, Oullins-Pierre-Bénite, France., Netto D; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom., Hasan J; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom., Mitchell C; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom., Salih Z; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom., Desai S; Department of Histopathology, The Christie NHS Foundation Trust, Manchester, United Kingdom., Shaw J; Department of Histopathology, Manchester University NHS Foundation Trust, Manchester, United Kingdom.; Manchester Centre for Genomic Medicine, North West Genomic Laboratory Hub, Saint Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom., Winter-Roach B; Department of Gynaecological Surgery, The Christie NHS Foundation Trust, Manchester, United Kingdom., Schlecht H; Manchester Centre for Genomic Medicine, North West Genomic Laboratory Hub, Saint Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom., Burghel GJ; Manchester Academic Health Science Centre (MAHSC), Manchester, United Kingdom.; Manchester Centre for Genomic Medicine, North West Genomic Laboratory Hub, Saint Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom.; Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom., Clamp AR; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom.; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.; Manchester Academic Health Science Centre (MAHSC), Manchester, United Kingdom., Edmondson RJ; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.; Manchester Academic Health Science Centre (MAHSC), Manchester, United Kingdom.; Department of Gynaecological Surgery, Manchester University NHS Foundation Trust, Manchester, United Kingdom., You B; Centre pour l'lnnovation en Cancérologie de Lyon (CICLY), EA 3738, Université Claude Bernard University Lyon 1, Univ Lyon 1, Oullins-Pierre-Bénite, France.; Service d'oncologie médicale, Institut de Cancérologie des Hospices Civils de Lyon (IC-HCL), CITOHL, EPSILYON, Centre Hospitalier Lyon-Sud, Oullins-Pierre-Bénite, France., Evans DGR; Manchester Academic Health Science Centre (MAHSC), Manchester, United Kingdom.; Manchester Centre for Genomic Medicine, North West Genomic Laboratory Hub, Saint Mary's Hospital, Manchester University NHS Foundation Trust, Manchester, United Kingdom.; Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom., Jayson GC; Department of Medical Oncology, The Christie NHS Foundation Trust, Manchester, United Kingdom.; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.; Manchester Academic Health Science Centre (MAHSC), Manchester, United Kingdom., Taylor SS; Division of Cancer Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, United Kingdom.; Manchester Academic Health Science Centre (MAHSC), Manchester, United Kingdom.
Jazyk:	angličtina
Zdroj:	British journal of cancer [Br J Cancer] 2024 Dec; Vol. 131 (12), pp. 1919-1927. Date of Electronic Publication: 2024 Nov 16.
DOI:	10.1038/s41416-024-02874-6
Abstrakt:	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. Competing Interests: 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. (© 2024. The Author(s).)
Databáze:	MEDLINE
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