Editor’s Note: The 2025 Second Forum on Innovative Anticancer Drug Clinical Research and the 9th East China Breast Cancer Salon, hosted by the Beijing Sci-Tech Medical Development Foundation and organized by the Academic Publishing Center of Jiangsu Provincial People’s Hospital, have recently concluded in Nanjing. At the meeting, Professor Min Yan from Henan Cancer Hospital delivered a presentation titled “A New Journey in Breast Cancer Treatment—The Rise and Potential of TROP2 ADCs.” Her talk provided a systematic overview of the latest advances and clinical value of TROP2-targeted ADCs in breast cancer, and discussed their potential to shape future treatment paradigms.
Oncology Frontier invited Professor Min Yan to share expert insights on the therapeutic advantages of TROP2, its application prospects in HR+/HER2– advanced breast cancer after CDK4/6 inhibitor resistance, and its role in promoting precision oncology in China.
01
Oncology Frontier: TROP2 has become one of the hottest ADC drug-development targets. In your view, what advantages does TROP2 offer in breast cancer compared with other targets?
Professor Min Yan:
TROP2 is widely expressed in breast cancer—whether in triple-negative breast cancer or HR+/HER2– disease, expression levels are high, with an overall expression rate exceeding 80%. Meanwhile, its expression in normal tissues is relatively low.
Because of this, in clinical practice, TROP2 testing is generally not required prior to treatment, and therapies can proceed without additional screening. New ADCs developed against this target have already shown promising therapeutic outcomes. Three such ADCs have been approved for indications in China and are undergoing further breast cancer–related clinical studies.
Evidence from current clinical research is quite consistent: these TROP2 ADCs demonstrate superior efficacy compared with physician’s-choice chemotherapy, establishing their value in clinical treatment.
02
Oncology Frontier: Treatment options for HR+/HER2– advanced breast cancer after progression on CDK4/6 inhibitors are limited. How do you evaluate the performance of TROP2 ADCs in this setting, and how might they influence therapeutic strategies in the post-CDK4/6 era?
Professor Min Yan:
For HR+/HER2– breast cancer, CDK4/6 inhibitors combined with endocrine therapy remain the standard first-line regimen. In later lines of treatment, there is no universally recognized standard. Therapeutic choices depend on factors such as genomic alterations, HER2 expression status, and other biomarkers.
One reason we lack a universal standard is that existing clinical studies cannot cover every potential therapeutic scenario. In recent years, TROP2 has become a research hotspot, and several TROP2-targeted ADCs have shown clinical promise. Three such ADCs now have supporting evidence in HR+/HER2– disease.
The earliest approved TROP2 ADC is sacituzumab govitecan (SG), with the TROPiCS-02 study providing strong evidence for its use in HR+/HER2– advanced breast cancer. Based on TB-01 results, datopotamab deruxtecan (Dato-Dxd) has also gained approval for this patient population. Most recently, at the 2024 ESMO Congress, the OptiTROP-Breast02 study evaluated luskansartuzumab, further confirming the value of TROP2 ADCs in HR+/HER2– disease.
All three ADCs consistently demonstrate that, after progression on CDK4/6 inhibitors, TROP2 ADCs outperform chemotherapy. Combined with earlier data in triple-negative breast cancer (TNBC), we now see that TROP2 ADCs provide meaningful clinical benefit across both HR+/HER2– and TNBC subtypes.
03
Oncology Frontier: The rise of TROP2 ADCs brings new treatment options and may reshape the overall management pathway of breast cancer. How do you think these agents will promote more precise and standardized breast cancer care in China?
Professor Min Yan:
Breast cancer management follows the principles of evidence-based medicine and stratified treatment. Take triple-negative breast cancer, for example: current first-line treatment involves chemotherapy combined with immunotherapy; if PD-L1 expression is negative, single-agent chemotherapy is used.
In later-line TNBC treatment, TROP2 ADCs have shown superior efficacy compared with chemotherapy. Newly released data in the first-line setting are also encouraging: regardless of PD-L1 status, TROP2 ADC monotherapy trends toward better outcomes than chemotherapy; in PD-L1–positive patients, TROP2 ADC plus immunotherapy also outperforms chemotherapy plus immunotherapy.
Looking ahead, TROP2 ADCs are poised to enter first-line therapy for TNBC, which would dramatically reshape current treatment paradigms. Guided by precision-treatment principles, these agents may even offer cure opportunities for select patients with recurrent or metastatic disease—ushering in an era of transformative therapy.
For HR+/HER2– breast cancer, the current standard first-line treatment remains CDK4/6 inhibitors plus endocrine therapy. As TROP2 ADCs move into the post-CDK4/6 setting, comparisons with other second-line options become crucial. These include: – endocrine therapy plus PIK3CA inhibitors for PIK3CA-mutant patients, – PARP inhibitors for BRCA-mutant patients, – AKT inhibitors plus endocrine therapy, – chemotherapy, and – anti-HER2 ADCs for HER2-low disease.
However, direct head-to-head comparisons are largely lacking. Most existing evidence comes from comparisons with chemotherapy or endocrine monotherapy. We urgently need high-quality randomized trials to define differential efficacy across options and ultimately establish a second-line standard of care.
At present, clinicians rely on expert consensus and clinical guidelines to prioritize treatment strategies. While helpful, these recommendations are not yet grounded in sufficiently strong evidence. Building such evidence will be a critical focus for future research.
About Professor Min Yan
Professor Min Yan Breast Cancer Department, Henan Cancer Hospital Deputy Director, Henan Breast Disease Diagnosis and Treatment Center
