Biomarker-Driven Treatment Selection: From Testing to Treatment Decisions

Biomarker testing remains a cornerstone of treatment decision-making in first-line mTNBC, particularly as new therapeutic options emerge. PD-L1 status continues to play a critical role in identifying patients who may benefit from the addition of immunotherapy to ADCs such as sacituzumab govitecan or datopotamab deruxtecan. The latter is currently being studied in combination with durvalumab in a phase 3 trial within the TROPION program, reflecting a growing interest in evaluating immunotherapy-ADC combinations regardless of PD-L1 status.

In addition to PD-L1, BRCA mutation status also remains clinically relevant. Although only a small proportion of patients with mTNBC harbor BRCA mutations, identifying these individuals is essential, as they may benefit from PARP inhibitor therapy at some point during the disease course. Looking ahead, the goal is to expand biomarker testing beyond these 2 factors to identify which patients are most likely to respond to specific ADCs. This approach could further refine and personalize treatment strategies in a disease known for its heterogeneity and aggressive behavior.

Preliminary data from trials such as ASCENT suggest that patients with tumors expressing higher levels of Trop-2—a target of sacituzumab govitecan—may experience improved response rates, though this trend has not been consistent across all studies. Still, the development of a predictive biomarker for ADC response could significantly enhance treatment precision. Ideally, future biomarker panels will help distinguish which patients derive the greatest benefit from therapies such as sacituzumab govitecan or datopotamab deruxtecan, enabling clinicians to better match each patient with the most effective and least toxic option available in the evolving mTNBC treatment landscape.