Platinum-Based Neoadjuvant Chemotherapy for Breast Cancer With BRCA Mutations: A Meta-Analysis

Abstract

Background: Triple-negative breast cancer (TNBC) is one of the most aggressive subtypes of breast cancer and the major phenotype of BRCA related hereditary breast cancer. Platinum is a promising chemotherapeutic agent for TNBC. However, its efficacy for breast cancer with BRCA germline mutation remains inconclusive. Here we present a meta-analysis to evaluate the effect of platinum agents for breast cancer patients with BRCA mutation in neoadjuvant setting.

Materials and methods: Pubmed, Embase, and Cochrane Central Register of Controlled Trials databases were searched for relevant studies on neoadjuvant platinum treatment and BRCA related breast cancer. Fixed- and random-effect models were adopted for meta-analyses. Heterogeneity investigation was conducted by sensitivity and subgroup analyses. Publication bias was evaluated by funnel plot and Begg's test.

Results: In all, five studies with 363 patients were included for meta-analysis. The pooled pathological complete response (pCR) rates were 43.4% (59/136) and 33.9% (77/227) for platinum and control groups, respectively. Adding platinum to neoadjuvant regimen did not significantly improved pCR rate (odds ratio [OR]: 1.340, 95% confidence interval [CI] = 0.677-2.653, p = 0.400). Sensitivity analyses also revealed platinum did not significantly increase pCR rate in either TNBC or HER2- patients (TNBC subgroup: OR: 1.028, 95% CI = 0.779-1.356, p = 0.846; HER2- subgroup: OR: 0.935, 95% CI = 0.716-1.221, p = 0.622).

Conclusions: Our meta-analysis suggested that the addition of platinum to neoadjuvant chemotherapy did not significantly improve pCR rate for patients with BRCA mutations. Further large-scale randomized control trial with survival data may provide more robust evidence on therapeutic value of platinum for breast cancer neoadjuvant treatment.

Keywords: BRCA gene; breast cancer; neoadjuvant chemotherapy; pathological complete response; platinum.

Figure 1

Flowchart of articles reviewed and included in meta-analysis. pCR, pathological complete response; RCB, Residual cancer burden.

Figure 2

Forest plot of OR for pCR rate.

Figure 3

Sensitivity analyses of HER2- and TNBC patients: (A) HER2-; (B) TNBC.

Figure 4

Subgroup analyses according to study design, quality assessment and BRCA mutation status: (A) Prospective cohort studies with low quality score and only BRCA1 mutated patients were included. (B) Randomized controlled trials with high quality score and both BRCA 1 and 2 mutated patients were included.

Figure 5

Subgroup analyses according to study population, experiment regimen and platinum usage: (A) Studies that included BRCA mutated patients as subgroup and used combination regimen with carboplatin. (B) Studies that the whole cohort was BRCA mutated patients and used single agent regimen with cisplatin.