Drs. Reshma Mahtani, Heather McArthur, and Anne O’Dea discuss new first-line treatment options for PD-L1–negative metastatic triple-negative breast cancer presented at ESMO 2025 and SABCS updates. They review results from ASCENT-03, showing improved progression-free survival with sacituzumab govitecan vs chemotherapy, and TROPION-Breast02, which demonstrated significant PFS and overall survival benefits with datopotamab deruxtecan. The panel explores how these data may shift practice toward ADC-based first-line therapy, while also addressing sequencing strategies and differences in toxicity profiles that may guide treatment selection. Sponsored By Gilead.