Homologous Recombination Deficiency Predicts Response to Platinum-Based Neoadjuvant Chemotherapy in Early-Stage Triple-Negative Breast Cancer Patients: A Systematic Review and Meta-Analysis

Abstract

Background: Recent studies showed homologous recombination deficiency (HRD) status may correlate with pathological complete response (pCR) rate. However, whether HRD specifically predicts platinum chemotherapy efficacy or predicts pCR benefit irrespective of treatment regimen remains unclear. Methods: This meta-analysis aimed to determine the predictive value of HRD on pCR in patients with triple-negative breast cancer (TNBC) receiving platinum-based neoadjuvant chemotherapy (NCT). Published articles were searched on PubMed, Embase, Medline, Web of Science, and Cochrane database up to June 1, 2021 and studies reporting pCR rate for HRD carriers on platinum-based NCT selected. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined for pCR, clinical response rates and grade 3 or higher adverse events (AEs) using the random-effects model. Bias risk was evaluated using Cochrane Collaboration’s tool. Findings: Seven studies were eligible. Results showed that HRD carriers had higher pCR rates than non-HRD carriers across all treatment arms (OR 3.35, 95% CI 1.93 – 5.81, p < 0.01). In HRD carriers, pCR rate was higher in patients on platinum-based NCT relative to those without platinum exposure (OR 1.95, 95% CI 1.17 – 3.23, p = 0.01). We did not observe marked pCR improvements in non-HRD carriers. PCR rates in breast cancer susceptibility gene (BRCA) mutant relative to the BRCA wild-type group did not differ significantly in HRD carriers on platinum-based NCT (OR 1.84, 95% CI 0.84 – 4.02, p = 0.12). Interpretation: HRD carriers correlated with higher pCR in TNBC patients on platinum-based NCT irrespective of BRCA status. In non-HRD carriers, adding platinum to NCT was associated with elevated AEs rather than improved therapeutic effect. Registration Information: PROSPERO, registration number CRD420212498740. Funding Information: This study was supported by grants from National Natural Science Foundation of China (82171898)，Science and Technology Planning Project of Guangzhou City (202002030236), Beijing Medical Award Foundation(YXJL-2020-0941-0758), Science and Technology Special Fund of Guangdong Provincial People's Hospital (No.Y012018218), CSCO-Hengrui Cancer Research Fund (Y-HR2016-067), Medical Scientific Research Foundation of Guangdong Province (B2021406), and Guangdong Provincial Department of Education Characteristic Innovation Project（2015KTSCX080. Declaration of Interests: We declare no competing interests.