Advancing ADC Strategies in Triple-Negative Breast Cancer: Addressing Unmet Needs and Emerging Combination

Triple-negative breast cancer (TNBC) remains a challenging subtype with significant unmet therapeutic needs. Optimizing ADC-based treatments offers a promising approach to improve outcomes in this patient population. Emerging evidence supports combination strategies that pair ADCs with immunotherapy, such as PD-L1 inhibitors, with early studies like ASCENT-04 (SG plus pembrolizumab) and TROPION-BREAST03 (Dato-Dxd with durvalumab) demonstrating encouraging activity. Additional combinations with targeted agents, including PARP inhibitors and CDK4/6 inhibitors, are under investigation, aiming to enhance efficacy while maintaining manageable toxicity. These strategies leverage complementary mechanisms of action and potential synergistic effects, addressing tumor heterogeneity and resistance pathways. Ongoing research and clinical trials are expected to refine sequencing, identify predictive biomarkers, and integrate ADCs into combination regimens, ultimately expanding therapeutic options and improving outcomes for patients with advanced TNBC.