Editor's Note: Breast cancer remains a leading malignancy threatening women’s health, and optimizing treatment strategies continues to be a major focus of research. Neoadjuvant therapy, especially for HER2-positive breast cancer, plays a key role in improving survival outcomes and quality of life. The 47th San Antonio Breast Cancer Symposium (SABCS) will take place from December 10 to 13, 2024, in San Antonio, Texas. Professor Wenbin Zhou and his team from Jiangsu Province Hospital will present a study (Poster Abstract No: P3-11-24) evaluating the efficacy of pyrotinib combined with trastuzumab and nab-paclitaxel in HER2-positive breast cancer. The results demonstrate an impressive pathological complete response (tpCR) rate in HER2-enriched patients, with good tolerability and controllable safety. This innovative therapy offers new hope for HER2-positive breast cancer patients and supports precision treatment strategies.

• Research Title：Pyrotinib, Trastuzumab, and Nab-Paclitaxel as Neoadjuvant Therapy for HER2-Enriched Early or Locally Advanced Breast Cancer: A Multicenter, Single-Arm, Phase II Trial

The primary significance of de-escalated neoadjuvant therapy is to reduce chemotherapy-related toxic side effects while maximizing the advantages of targeted therapies, improving patient tolerance and overall quality of life. This approach represents an essential direction in the development of individualized and precision cancer treatments. Previous studies, such as WSG-ADAPT, PHERGAIN, and the recently reported HELEN-006 trial, have explored de-escalation strategies in HER2-positive early breast cancer. In the HELEN-006 study, the tpCR rate was 66.3% (220/332, 95% CI: 61.2%–71.4%) in the nab-paclitaxel group, compared to 57.6% (194/337, 95% CI: 52.3%–62.9%) in the docetaxel-carboplatin group. These findings align with the current study, demonstrating that nab-paclitaxel monotherapy is not inferior to a dual-drug chemotherapy regimen.

Molecular subtyping represents a major breakthrough in precision therapy for breast cancer. Breast cancer is highly heterogeneous, and prognosis can vary significantly even among patients with the same clinical stage receiving identical treatment. Gene-based molecular subtyping is closely linked to treatment outcomes. For instance, the PAMELA trial, which utilized PAM50 molecular subtyping, demonstrated the highest tpCR rates in HER2-enriched patients receiving dual-targeted neoadjuvant therapy. Similarly, the PerELISA study confirmed the correlation between PAM50 molecular subtypes and treatment efficacy, highlighting the importance of selecting targeted therapies based on specific gene profiles to maximize therapeutic benefit.

Pyrotinib is a small-molecule pan-tyrosine kinase inhibitor that irreversibly binds to EGFR, HER2, and HER4, blocking downstream signaling pathways and inhibiting tumor cell growth. In contrast, trastuzumab targets HER2 receptors on the tumor cell surface, blocking HER2 dimerization and suppressing tumor growth. Pyrotinib and trastuzumab together form a novel dual-targeted approach that complements and enhances anti-tumor efficacy, potentially improving pCR rates and overcoming resistance.

The current results show that the combination of nab-paclitaxel, trastuzumab, and pyrotinib achieved a tpCR rate of 56.3% in HER2-enriched patients, with good tolerability overall. These findings underscore the higher sensitivity of HER2-enriched patients to dual anti-HER2 therapies and suggest that chemotherapy intensity may be appropriately reduced in this subgroup to balance efficacy and toxicity.

Wenbin Zhou

Deputy Director, Breast Center, Jiangsu Province Hospital Chief Physician, PhD Supervisor, Jiangsu Distinguished Young Scholar Secretary-General, Breast Health Committee, China Maternal and Child Health Association Youth Member, Breast Cancer Group, Chinese Society of Clinical Oncology Committee Member, Breast Surgery Branch, Jiangsu Medical Association Secretary, Breast Surgery Branch, Jiangsu Medical Doctor Association First/Corresponding Author of papers in Nature Communications, Med, Cell Molecular Immunology, Advanced Science, Radiology, and JAMA Network Open Principal Investigator for multiple National Natural Science Foundation and provincial-level projects Editorial Board Member, Chinese Journal of Endoscopic Surgery