biostudies-literatureUnknown7(2)Huang JThis study aimed to evaluate the efficacy and safety of triple human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab, pertuzumab, and pyrotinib (TPPy) versus dual HER2 blockade with trastuzumab and pertuzumab (TP) in the neoadjuvant treatment of HER2-positive breast cancer. Patients with stage II-III HER2-positive breast cancer were randomized (1:1) to receive TPPy or TP alongside weekly nab-paclitaxel for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/isN0). Exploratory biomarker and pathway analysis was done to identify patients benefiting from pyrotinib. A total of 109 patients were enrolled, and 108 received treatment: 55 in the TPPy group and 53 in the TP group. The tpCR rate was 65.5% (95% confidence interval [CI]: 51.4%-77.8%) in the TPPy group, and 60.4% (95% CI: 46.0%-73.5%) in the TP group (<i>p</i> = 0.585). In the TPPy group, 52 (94.5%) and 23 (41.8%) patients experienced dose interruption and discontinuation, respectively. The most common grade ≥3 adverse events in the TPPy and TP groups were diarrhea (58.1% vs. 0%) and neutropenia (23.6% vs. 15.1%). In conclusion, triple HER2 blockade did not improve tpCR rates compared with dual blockade but was associated with greater toxicity, particularly diarrhea.MedComme70611https://www.ebi.ac.uk/biostudies/studies/S-EPMC12812331biostudies-literatureTriple HER2 Blockade With Trastuzumab, Pertuzumab, and Pyrotinib Versus Dual HER2 Blockade in the Neoadjuvant Treatment of HER2-Positive Breast Cancer: A Randomized, Phase II Study.PMC12812331Ren WWu JShen KLi JHuang JZhu YHe JHong JWang HTong YYu JHuang OLi YChen WGao WChen XShi HZhu SfalseTriple HER2 Blockade With Trastuzumab, Pertuzumab, and Pyrotinib Versus Dual HER2 Blockade in the Neoadjuvant Treatment of HER2-Positive Breast Cancer: A Randomized, Phase II Study.This study aimed to evaluate the efficacy and safety of triple human epidermal growth factor receptor 2 (HER2) blockade with trastuzumab, pertuzumab, and pyrotinib (TPPy) versus dual HER2 blockade with trastuzumab and pertuzumab (TP) in the neoadjuvant treatment of HER2-positive breast cancer. Patients with stage II-III HER2-positive breast cancer were randomized (1:1) to receive TPPy or TP alongside weekly nab-paclitaxel for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/isN0). Exploratory biomarker and pathway analysis was done to identify patients benefiting from pyrotinib. A total of 109 patients were enrolled, and 108 received treatment: 55 in the TPPy group and 53 in the TP group. The tpCR rate was 65.5% (95% confidence interval [CI]: 51.4%-77.8%) in the TPPy group, and 60.4% (95% CI: 46.0%-73.5%) in the TP group (<i>p</i> = 0.585). In the TPPy group, 52 (94.5%) and 23 (41.8%) patients experienced dose interruption and discontinuation, respectively. The most common grade ≥3 adverse events in the TPPy and TP groups were diarrhea (58.1% vs. 0%) and neutropenia (23.6% vs. 15.1%). In conclusion, triple HER2 blockade did not improve tpCR rates compared with dual blockade but was associated with greater toxicity, particularly diarrhea.2026-01-01T00:00:00Z2026 Feb2026-06-30T03:31:28.852Z2026-06-30T03:21:23.959ZS-EPMC128123314155604010.1002/mco2.70611