After a triple-negative breast cancer patient progresses on a first-line TROP2 antibody-drug conjugate (ADC), experts advise against immediately sequencing another ADC. Due to suspected cross-resistance, the recommended strategy is to return to traditional chemotherapy agents like taxanes or carboplatin, which remain effective options, before considering another ADC in later lines.

For first-line metastatic triple-negative breast cancer, determining PD-L1 status is the most critical first step, even in BRCA-positive patients. An immunotherapy-based regimen is preferred for PD-L1 positive cases to pursue the potential for a durable, complete response, deferring PARP inhibitors.

Patients with triple-negative breast cancer (TNBC) who recur after standard neoadjuvant chemo-immunotherapy (per the KEYNOTE-522 trial) represent a new, challenging population. There is virtually no clinical data to guide treatment, particularly on whether re-challenging with immunotherapy alongside an ADC is effective.

It is crucial to re-biopsy metastatic breast cancer upon progression because the tumor's fundamental biology can change. A patient initially diagnosed with ER-positive disease can develop triple-negative, PD-L1 positive disease, which opens up entirely new treatment options like immunotherapy and different ADCs.

For patients with otherwise well-controlled disease who develop isolated oligoprogression in the brain, evidence suggests a better survival outcome from adding local therapy (like SRS) and continuing the current effective systemic therapy, rather than switching the systemic regimen entirely.

A decade ago, metastatic triple-negative breast cancer (mTNBC) had a median survival of about one year. Today, the duration of response to modern antibody-drug conjugates (ADCs) in the first-line setting can be longer than what the entire overall survival used to be, highlighting a massive therapeutic advancement.

For patients on immunotherapy who develop an isolated site of progression while other lesions remain controlled, a practical strategy is to continue the checkpoint inhibitor and treat the single progressive site with localized therapy, such as radiation.

ADCs more frequently cause "oligoprogression," where most metastatic sites respond while only one or two progress. This allows for treating the progressing lesion with local therapy (e.g., radiotherapy) while continuing the systemic ADC, rather than abandoning an otherwise effective treatment.

Experts are more cautious about sequencing ADCs back-to-back in triple-negative breast cancer (TNBC) compared to less aggressive subtypes. A sobering 50% of TNBC patients do not receive treatment beyond the first line, making it critical to use the most effective therapy upfront rather than saving options for later.