Clinical repositioning and individualized treatment strategies of trastuzumab-emtansine for HER2-positive breast cancer in the trastuzumab deruxtecan era_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

HE Shini ¹ , CHU Jie ¹ , LI Ruiqi ² , YOU Jiangxue ¹ , LIU Xin ³ , SONG Ying ⁴ ,  TIAN Chao ⁵

1. School of Medicine, University of Electronic Science and Technology of China, Chengdu 610054, P. R. China;
2. Department of Breast Surgery, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan 646099, P. R. China;
3. Department of Thyroid and Breast Surgery, Chengdu Seventh People’s Hospital (Affiliated Cancer Hospital of Chengdu Medical College), Chengdu 610041, P. R. China;
4. Department of Breast Surgery, Mianyang Cancer Hospital, Mianyang, Sichuan 621000, P. R. China;
5. Department of Breast Surgery, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, University of Electronic Science and Technology of China, Chengdu 610041, P. R. China;

Corresponding?author：

TIAN Chao, Email: hxtc2000@163.com

Keywords：

human epidermal growth factor receptor 2-positive breast cancer; trastuzumab emtansine; trastuzumab deruxtecan; combination therapy; de-escalation therapy; antibody-drug conjugates; precision medicine

DOI：

10.7507/1007-9424.202604123

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Objective To analyze the clinical repositioning and individualized treatment strategies of trastuzumab emtansine (T-DM1) in human epidermal growth factor receptor 2 (HER2)-positive breast cancer in the era of trastuzumab deruxtecan (T-DXd). Methods The latest evidence-based data for T-DM1 were systematically reviewed to identify two optimized clinical approaches: intensified combination therapy and de-escalation. For advanced and brain metastastic HER2-positive breast cancer, the synergistic antitumor efficacy of T-DM1 combined with tyrosine kinase inhibitors, along with data from pivotal trials such as HER2CLIMB-02, was analyzed. For early-stage HER2-positive breast cancer, the feasibility of chemotherapy-free de-escalation regimens was evaluated based on the WSG-ADAPT trial and other relevant studies. Results The differentiated value of T-DM1 is defined by its lower risk of interstitial lung disease and established long-term survival benefit, as evidenced by the 7-year invasive disease-free survival (iDFS) rate of 80.8% reported in the KATHERINE trial. Regarding intensified combinations, exploratory analyses of the KATE2 trial revealed synergistic potential of T-DM1 plus immune checkpoint inhibitors in the programmed death-ligand 1-positive subgroup. In patients with brain metastastatic HER2-positive, the HER2CLIMB-02 study confirmed a median progression-free survival benefit by adding tucatinib to T-DM1 [HR (95%CI)=0.64 (0.46, 0.89)]. In terms of de-escalation, the WSG-ADAPT trial reported a 5-year iDFS rate of 92.1% with chemotherapy-free regimens in molecularly selected populations. Additionally, the “decoupling” of pathological complete response from long-term outcomes observed in the KRISTINE trial provides biological rationale for de-escalation strategies, interpreted through the lenses of immune memory and senescence-associated tumor cell fate. Moreover, the sequential switching strategy—grounded in the non-cross-resistant payload mechanism—and the clinical accessibility brought by T-DM1’s inclusion in China’s National Reimbursement Drug List serve as additional dimensions supporting its clinical repositioning. Conclusions In the era of T-DXd, clinical decision-making regarding T-DM1 for HER2-positive breast cancer is shifting toward risk-stratified, precision-based management. The core strategic framework comprises an intensified combination pathway for patients with brain metastases and a de-escalation pathway for those with toxicity-driven de-escalation. However, specific implementation still requires comprehensive evaluation tailored to individual patient characteristics, biomarker profiles, and drug accessibility.

Citation： HE Shini, CHU Jie, LI Ruiqi, YOU Jiangxue, LIU Xin, SONG Ying, TIAN Chao. Clinical repositioning and individualized treatment strategies of trastuzumab-emtansine for HER2-positive breast cancer in the trastuzumab deruxtecan era. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2026, 33(7): 959-968. doi: 10.7507/1007-9424.202604123 Copy

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Clinical repositioning and individualized treatment strategies of trastuzumab-emtansine for HER2-positive breast cancer in the trastuzumab deruxtecan era

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