A new approach is changing how metastatic triple-negative breast cancer (mTNBC) is treated. Experts are now focusing on TROP2-targeted antibody-drug conjugates (ADCs) as a first-line therapy instead of traditional chemotherapy. Recent clinical studies suggest these targeted drugs can help patients live longer and delay disease progression.
Three major Phase 3 trials reported in 2025 support this shift. The TROPION-Breast02 trial showed that datopotamab deruxtecan (Dato-DXd) significantly improved progression-free survival and overall survival compared with chemotherapy in patients with PD-L1–negative disease. The ASCENT-03 trial found that sacituzumab govitecan improved progression-free survival in a similar group of patients, although overall survival data are still being analyzed. Another study, ASCENT-04, showed that combining sacituzumab govitecan with pembrolizumab improved progression-free survival in patients whose tumors were PD-L1 positive.
Because of these consistent results, treatment guidelines are beginning to recommend TROP2-targeted ADCs as a preferred first-line option for many patients with metastatic triple-negative breast cancer. However, for about 10% of patients who carry BRCA1/2 or PALB2 mutations, PARP inhibitors may still be considered first because they may offer quality-of-life benefits. Researchers are now studying whether ADCs could also be used in earlier stages of breast cancer and in new drug combinations.