Efficacy, safety and biomarkers of neoadjuvant trastuzumab and pertuzumab combined with chemotherapy in Chinese patients with HER2-positive breast cancer: a multi-center retrospective cohort study

Objective: This multi-center real-world study aimed to evaluate the efficacy, safety, and neoadjuvant trastuzumab and pertuzumab combined with different chemotherapy regimens in Chinese patients with human epidermal growth factor receptor 2 (HER2) -positive breast cancer. Methods: A retrospective analysis was conducted on 557 patients treated at 15 institutions in China between January 2019 and December 2021. Patients were divided into three groups based on chemotherapy regimens: EC-THP (epirubicin, cyclophosphamide, docetaxel/paclitaxel protein-bound, trastuzumab, pertuzumab), TCbHP (docetaxel/paclitaxel protein-bound, carboplatin, trastuzumab, pertuzumab), and THP (docetaxel/paclitaxel protein-bound, trastuzumab, pertuzumab).The primary endpoint was total pathological complete response (tpCR), defined as the absence of invasive disease in both the breast and axillary lymph nodes (ypT0/is, ypN0).Secondary endpoints included apCR (ypN0), bpCR (ypT0/is), and safety. Propensity score overlap weighting was applied to minimize confounding factors. Results: Of the 557 patients included in the study, 341 (61.2%) achieved total pathological complete response (tpCR). The tpCR rate was significantly higher in the HER2-positive hormone receptor (HR)-negative group (183/242 patients, 75.6%) than in the HER2-positive HR-positive group (158/315 patients, 50.2%, P < 0.001), as well as bpCR was achieved in 188/241 patients (77.7%) in the HER2-positive HR-negative group compared to 164/315 patients (52.1%) in the HER2-positive HR-positive group ( P < 0.001), and apCR was achieved in 214/242 patients (88.4%) versus 240/315 patients (76.2%) respectively ( P < 0.001). After applying propensity score overlap weighting, no significant differences were observed among the three treatment regimen groups in tpCR (68.4% vs. 63.0% vs. 54.5%, P = 0.116), bpCR (71.3% vs. 64.0% vs. 59.6%, P = 0.198), or apCR (80.2% vs. 84.4% vs. 73.9%, P = 0.173). Gene analysis suggested favorable tpCR trends in patients with TP53, ERBB2, MYC, or CCND1 alterations, though not statistically significant. Most adverse events were grade 1–2, with anemia (254/557, 45.6%), leukopenia (147/557, 26.4%), and reduced ejection fraction (99/421, 23.4%) being the most common. No fatal toxicities were reported. Conclusions: Trastuzumab and pertuzumab combined with different chemotherapy regimens demonstrated high tpCR rates and manageable safety in HER2-positive breast cancer, particularly in HER2-positive HR-negative patients. The study supports the real-world efficacy of dual HER2-targeted neoadjuvant therapy, though further validation of biomarkers and long-term outcomes is needed.