Abstract
Background: Platinum-based agents may benefit patients with triple-negative breast cancer (TNBC) whose tumors are dysfunctional in DNA repair mechanisms associated with the homologous recombination repair (HRR) genes. The purpose of this meta-analysis was to assess the values of BRCA1/2 and homologous recombination deficiency (HRD) in the prediction of the pathological complete response (pCR) rates of patients with TNBC treated with platinum-based neoadjuvant chemotherapy (NAC). Patients and Methods: Patients with TNBC with BRCA or HRD status from platinum-based NAC trials were analyzed. The odds ratios (ORs) with 95% confidence intervals (CI) for the identified studies were calculated. Results: 13 eligible studies between January 2000 and September 2021 were included through systematic literature searches of Embase, PubMed, Cochrane, and Web of Science databases. In 12 trials with BRCA status, 629 of 1266 (49.7%) patients with TNBC achieved pCR with platinum-based NAC, including 134 out of 222 (60.4%) BRCA1/2-mutated patients and 495 out of 1044 (47.4%) BRCA wildtype patients (OR, 1.62; 95% CI, 1.20–2.20). The prevalence of HRD was higher than BRCA1/2 mutations in patients with TNBC (69.2% vs. 17.5%). In six trials with HRD information, pCR rates of HRD-positive patients with TNBC were significantly higher than those of HRD-negative patients with TNBC (241/412, 58.5% vs. 60/183, 32.8%, OR, 3.01; 95% CI, 2.07–4.39, p < 0.001). Conclusions: BRCA1/2-mutated and HRD-positive patients with TNBC could benefit from platinum-based NAC. In the future, a prospective study using unified HRD testing criteria is warranted for further investigation.
Highlights
Triple-negative breast cancer (TNBC) refers to a molecular subtype of breast cancer (BC) with negative estrogen receptor, progesterone hormone receptor, and negative human epidermal growth factor receptor 2, accounting for 15–20% of breast tumors [1]
Of 1266 patients studied, 629 (49.7%) patients with triple-negative breast cancer (TNBC) achieved pathological complete response (pCR) after platinum-based neoadjuvant chemotherapy (NAC), and the pCR rates were 60.4% (134/222) and 47.4% (495/1044) in available BRCA1/2-mutated and BRCA wildtype patients, respectively (OR, 1.62; 95% confidence intervals (CI), 1.20–2.20)
The positive homologous recombination deficiency (HRD) was defined as ≥42, which was derived from the quantitative sum of the telomeric allelic imbalance (TAI), large-scale state transition (LST), and loss of heterozygosity (LOH) scores
Summary
Triple-negative breast cancer (TNBC) refers to a molecular subtype of breast cancer (BC) with negative estrogen receptor, progesterone hormone receptor, and negative human epidermal growth factor receptor 2, accounting for 15–20% of breast tumors [1]. The benefit of platinum-based regimens in patients with earlystage TNBC is controversial because no significant benefits in DFS and overall survival (OS) were observed [4,5]. The rate of BRCA1/2 mutations was 15–20% in patients with TNBC, which was higher than in other subtypes of BC [11,12,13]. Previous studies demonstrated that HRD, in addition to being a predictor of PFS and OS of patients who would benefit from platinumbased chemotherapy, is a major indicator for platinum-sensitive drugs in patients with ovarian cancer [20]. The purpose of this meta-analysis was to assess the values of BRCA 1/2 and HRD in the prediction of the pCR rates of patients with TNBC receiving platinum-based NAC
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