Abstract
BACKGROUND: Neoadjuvant trastuzumab and pertuzumab combined with carboplatin and taxane (TCbHP) is the standard treatment for human epidermal growth factor receptor 2 (HER2)-positive breast cancer. However, limited clinical data and efficacy biomarkers for TCbHP have been reported in Chinese HER2-positive breast cancer patients. OBJECTIVES: This study aimed to observe the pathological complete response (pCR) rate in the cohort, with an exploratory analysis of efficacy-related biomarkers in a subset of patients. DESIGN: This was a prospective, observational, non-interventional cohort study. METHODS: Patients with HER2-positive breast cancer treated with TCbHP neoadjuvant therapy were prospectively collected. Exploratory genomic and transcriptomic biomarker analyses were performed in a subset of patients with available baseline tumour specimens retrospectively collected. RESULTS: A total of 252 patients with a median age of 48 years were enrolled. Patients with stage III were 69.4% (175/252), and clinical N3 patients accounted for 24.6% (62/252). Patients with hormone receptor (HR) positive were 62.7% (158/252). Total pCR rate was 55.2% (139/252). HR-negative and HR-positive rates were 72.3% (68/94) and 44.9% (71/158), respectively. Among neoadjuvant taxanes, including paclitaxel, docetaxel, and nab-paclitaxel, the pCR rates were 50.0% (57/114), 50.0% (41/82), and 73.2% (41/56), respectively. Multivariate logistic regression analyses showed that HR negativity, receiving nab-paclitaxel, HER2 3+, and cT1-2 were independent predictive factors of high pCR. Genomic and transcriptomic analyses were performed on baseline tumour specimens from 40 patients. Genomic analysis revealed lower pCR rates in patients with PIK3CA mutations (odds ratio = 13.47, p = 0.025) and SPOP amplification (p = 0.047) than in wild types. Transcriptomic analysis revealed that higher pCR rates were associated with elevated ERBB2 (p = 0.004) and CDK12 (p < 0.001) mRNA. CONCLUSION: Neoadjuvant trastuzumab and pertuzumab with carboplatin-based chemotherapy is the recommended regimen for Chinese patients with HER2-positive breast cancer, and nab-paclitaxel may be an optimal alternative taxane for TCbHP regimens. PIK3CA mutations may be predictive biomarkers for poor efficacy.