The panel grounds the discussion in the biology and natural history of metastatic triple-negative breast cancer, framing it as a high-proliferation subtype prone to rapid resistance, in which the first-line setting offers an important opportunity to influence outcomes. Panelists outline a biomarker-driven treatment algorithm stratified by PD-L1 status, germline BRCA status, and prior early-stage therapy, touching on immune checkpoint inhibition, PARP inhibitors, platinum-based chemotherapy, and the role of antibody-drug conjugates across lines of therapy.

The panel reviews how the metastatic TNBC treatment paradigm has evolved, tracing TROP2-directed ADCs from later-line use into the first-line setting.

The panel discusses the rationale for using effective agents in the first-line metastatic setting rather than reserving them for later lines, considering the disease's aggressive course and limited expected survival alongside the trajectories seen in other breast cancer subtypes.

The panel addresses one of the more difficult challenges in metastatic TNBC: central nervous system involvement.

The panel turns to the design of two pivotal first-line trials, framing the discussion not as a head-to-head comparison but as a way to inform patient selection in clinic.

The panel takes a closer look at ASCENT-03, framing it as a study designed to test whether a TROP2-directed ADC could serve as a first-line alternative to chemotherapy.

The panel reviews the TROPION-Breast02 findings, offering equipoise alongside the prior discussion of ASCENT-03.

With both pivotal trials reviewed, the panel discusses how to reconcile the data when counseling an individual patient.

The panel explores how to assign value to different trial endpoints in an aggressive disease, discussing overall survival as the gold standard while considering how crossover and confounding factors complicate its interpretation, and where PFS2 fits as a measure that reflects benefit across lines of therapy.

The panel addresses one of the field's most pressing practical questions: what to offer after a first-line ADC, acknowledging that no prospective data yet exist to guide the decision.

The panel takes a deeper look at neutropenia, one of the adverse events of special interest with sacituzumab govitecan.

The panel reviews the distinct adverse event profile associated with datopotamab deruxtecan, moving from least to most common.

The panel discusses the notably low treatment discontinuation rates seen with ADCs in both pivotal trials compared with chemotherapy, and whether these reassuring numbers translate to real-world practice.

The panel explores the rationale and emerging data for combining ADCs with immunotherapy and other targeted agents.

In the program's closing segment, the panel shares practical pearls and reflections for clinicians.