Homologous recombination deficiency predicts the response to platinum-based neoadjuvant chemotherapy in early-stage triple-negative breast cancer patients: a systematic review and meta-analysis

Liulu Zhang; Yuanqi Chen; Min-Yi Cheng; Xiaosheng Zhuang; Jiachen Zou; Dannuo Wei; Ying-Yi Lin; Yi Zhang; Kun Wang

doi:10.1177/17588359221096253

Homologous recombination deficiency predicts the response to platinum-based neoadjuvant chemotherapy in early-stage triple-negative breast cancer patients: a systematic review and meta-analysis

Ther Adv Med Oncol. 2022 May 7:14:17588359221096253. doi: 10.1177/17588359221096253. eCollection 2022.

Authors

Liulu Zhang¹, Yuanqi Chen¹, Min-Yi Cheng¹, Xiaosheng Zhuang², Jiachen Zou¹, Dannuo Wei³, Ying-Yi Lin¹, Yi Zhang¹, Kun Wang⁴

Affiliations

¹ Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
² Department of Cell and Molecular Biology, School of Life Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong.
³ Department of Social Work & Social Administration, The University of Hong Kong, Pokfulam, Hong Kong.
⁴ Department of Breast Cancer, Cancer Center, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, 106 Zhongshan Er Road, Yuexiu District, Guangzhou 510080, China.

Abstract

Background: Recent studies have shown that homologous recombination deficiency (HRD) may be correlated with the pathological complete response (pCR) rate. This meta-analysis aimed to determine the predictive value of HRD for the pCR rate in patients with triple-negative breast cancer (TNBC) receiving platinum-based neoadjuvant chemotherapy (NCT).

Methods: Published articles were searched in the PubMed, Embase, Medline, Web of Science, and Cochrane databases up to 1 June 2021, and studies reporting the pCR rate for HRD carriers on platinum-based NCT were selected. Odds ratios (ORs) with 95% confidence intervals (CIs) were determined for the pCR rate, clinical response rate, and Grade 3 or higher adverse events (AEs) using the random-effects model. Bias risk was evaluated using the Cochrane Collaboration tool (PROSPERO, registration number CRD42021249874).

Results: Seven studies were eligible. The results showed that HRD carriers had higher pCR rates than non-HRD carriers across all treatment arms (OR = 3.84, 95% CI = [1.93, 7.64], p = 0.0001). Among HRD carriers, the pCR rate was higher in patients on platinum-based NCT than in 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. Among HRD carriers, the pCR rates in the mutant and wild-type breast cancer susceptibility gene (BRCA) groups did not differ significantly (OR = 2.00, 95% CI = [0.77, 5.23], p = 0.16), but HRD carriers with wild-type BRCA had a significant advantage over non-HRD carriers on platinum-based NCT (OR = 3.64, 95% CI = [1.83, 7.21], p = 0.0002).

Conclusion: HRD is an effective predictor of increased pCR rates in platinum-based NCT, especially in wild-type BRCA patients. Adding platinum to NCT for non-HRD carriers can increase the incidence of AEs but may not improve the therapeutic effect.

Keywords: homologous recombination deficiency; platinum-based chemotherapy; triple-negative breast cancer.