2025 Round-Up: Human Epidermal Growth Factor Receptor 2-Positive Early Breast Cancer

Treatment of early breast cancer (eBC) is continuing to advance, and pivotal Phase III trial data released at the San Antonio Breast Cancer Symposium (SABCS) 2025 signal a potential reshaping of clinical management for patients with human epidermal growth factor receptor 2-positive (HER2+) high-risk disease. In the pivotal DESTINY-Breast05 study, trastuzumab deruxtecan (T-DXd) showed statistically significant and clinically meaningful improvement in invasive disease-free survival (IDFS) versus trastuzumab emtansine (T-DM1) in the post-neoadjuvant residual disease setting. Additional results from the DESTINY-Breast05 interim analysis, presented at SABCS, confirmed that this survival advantage was consistent regardless of patients’ prior neoadjuvant chemotherapy (NACT) or HER2 status. In the DESTINY-Breast 11 study, neoadjuvant treatment with T-DXd followed by paclitaxel, trastuzumab, and pertuzumab (THP) yielded a high pathological complete response rate (pCR) of 67.3% in high-risk HER2+ eBC. The most recent data from this study, presented at SABCS, highlighted T-DXd’s manageable safety profile and improvements in key patient-reported outcomes (PRO) compared with dose-dense doxorubicin plus cyclophosphamide and THP (ddAC-THP). In DESTINY-Breast11, T-DXd demonstrated reduced toxicity compared to ddAC-THP, and was associated with a lower patient-reported treatment burden and improved physical functioning.