Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer

Yimeng Chen; Xue Wang; Feng Du; Jian Yue; Yiran Si; Xiaochen Zhao; Lina Cui; Bei Zhang; Ting Bei; Binghe Xu; Peng Yuan

doi:10.20892/j.issn.2095-3941.2022.0525

Association between homologous recombination deficiency and outcomes with platinum and platinum-free chemotherapy in patients with triple-negative breast cancer

Cancer Biol Med. 2023 Mar 2;20(2):155-168. doi: 10.20892/j.issn.2095-3941.2022.0525.

Authors

Yimeng Chen^#¹, Xue Wang^#², Feng Du¹, Jian Yue², Yiran Si¹, Xiaochen Zhao³, Lina Cui³, Bei Zhang³, Ting Bei³, Binghe Xu¹, Peng Yuan²

Affiliations

¹ Department of Medical Oncology and Clinical Trial Center, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
² Department of VIP Medical Services, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China.
³ The Medical Department, 3D Medicines Inc., Shanghai 201114, China.

^# Contributed equally.

PMID: 36861447
PMCID: PMC9978893
DOI: 10.20892/j.issn.2095-3941.2022.0525

Abstract

Objective: The choice of chemotherapeutic regimen for triple-negative breast cancer (TNBC) remains controversial. Homologous recombination deficiency (HRD) has attracted increasing attention in informing chemotherapy treatment. This study was aimed at investigating the feasibility of HRD as a clinically actionable biomarker for platinum-containing and platinum-free therapy.

Methods: Chinese patients with TNBC who received chemotherapy between May 1, 2008 and March 31, 2020 were retrospectively analyzed with a customized 3D-HRD panel. HRD positivity was defined by an HRD score ≥ 30 or deleterious BRCA1/2 mutation. A total of 386 chemotherapy-treated patients with TNBC were screened from a surgical cohort (NCT01150513) and a metastatic cohort, and 189 patients with available clinical and tumor sequencing data were included.

Results: In the entire cohort, 49.2% (93/189) of patients were identified as HRD positive (40 with deleterious BRCA1/2 mutations and 53 with BRCA1/2 intact with an HRD score of ≥ 30). In the first-line metastatic setting, platinum therapy was associated with longer median progression-free survival (mPFS) than platinum-free therapy [9.1 vs. 3.0 months; hazard ratio (HR), 0.43; 95% confidence interval 0.22-0.84; P = 0.01]. Among HRD-positive patients, the mPFS was significantly longer in those treated with platinum rather than platinum-free therapy (13.6 vs. 2.0 months; HR, 0.11; P = 0.001). Among patients administered a platinum-free regimen, HRD-negative patients showed a PFS significantly superior to that of HRD-positive patients (P = 0.02; treatment-biomarker P-interaction = 0.001). Similar results were observed in the BRCA1/2-intact subset. In the adjuvant setting, HRD-positive patients tended to benefit more from platinum chemotherapy than from platinum-free chemotherapy (P = 0.05, P-interaction = 0.02).

Conclusions: HRD characterization may guide decision-making regarding the use of platinum treatment in patients with TNBC in both adjuvant and metastatic settings.

Keywords: BRCA; Homologous recombination deficiency; platinum; survival; triple-negative breast cancer.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adjuvants, Immunologic
Antineoplastic Agents* / therapeutic use
East Asian People
Homologous Recombination*
Humans
Platinum* / therapeutic use
Retrospective Studies
Triple Negative Breast Neoplasms* / drug therapy
Triple Negative Breast Neoplasms* / genetics

Substances

Adjuvants, Immunologic
Platinum
Antineoplastic Agents

Associated data

ClinicalTrials.gov/NCT01150513