Outcomes of patients with HER2-negative metastatic breast cancer after platinum- and non-platinum-based first-line chemotherapy among patients with and without pathogenic germline BRCA1/2 mutations

Br J Cancer. 2022 Nov;127(11):1963-1973. doi: 10.1038/s41416-022-02003-1. Epub 2022 Oct 7.

Abstract

Background: The efficacy and added benefit of platinum-based chemotherapy (PtCT) for metastatic breast cancer (MBC) remain unclear in patients with and without germline BRCA1 or BRCA2 mutations (gBRCA1/2m and gBRCA1/2wt, respectively).

Methods: We selected from the French national real-world multicentre ESME cohort (2008-2016) all patients with HER2-negative MBC with known gBRCA1/2 status at first-line chemotherapy initiation. Using multivariable Cox models, we compared the outcome (progression-free (PFS) and overall survival (OS)) of first-line PtCT and non-PtCT regimens based on the patients' gBRCA1/2 status and tumour subtype.

Results: Patients who received PtCT had more aggressive tumour features. In the multivariable analysis, first-line PtCT was associated with better adjusted PFS and OS in gBRCA1/2m carriers (N = 300), compared with non-PtCT (HR 0.54, 95% CI 0.4-0.73, P < 0.001, and HR 0.70, 95% CI 0.49-0.99, P = 0.047, respectively). Conversely, outcomes were similar in gBRCA1/2wt patients (N = 922) treated with PtCT and non-PtCT, whatever the tumour subtype. Landmark analyses at months 3 and 6 post treatment initiation supported these results.

Conclusions: In this pre-PARP inhibitor real-world cohort, PFS and OS were better after PtCT than non-PtCT in patients with gBRCA1/2m, but not in those with gBRCA1/2wt. These results emphasise the need of early gBRCA1/2 testing in patients with MBC.

Clinical trial number: NCT03275311.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents* / therapeutic use
  • BRCA1 Protein / genetics
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / pathology
  • Female
  • Germ Cells
  • Humans
  • Mutation
  • Platinum / therapeutic use

Substances

  • Antineoplastic Agents
  • BRCA1 Protein
  • BRCA1 protein, human
  • Platinum

Associated data

  • ClinicalTrials.gov/NCT03275311