Facing the conundrum: which first-line therapy should be used for patients with metastatic triple-negative breast cancer carrying germline mutation?

Pembrolizumab combined with chemotherapy has been established as the preferred first-line therapy for treating metastatic triple-negative breast cancer (mTNBC) with programmed cell death ligand-1 (PD-L1)-positive disease since its approval for that indication. However, the optimal sequencing of therapy remains an unanswered question for a subset of mTNBC patients who harbor germline breast cancer gene 1/2 (; ) mutation. This article aims to offer insights into the optimal therapy sequencing for mTNBC patients with mutations and its impact on clinical decision-making. The perspective offered is based on the best currently available data and propose a practical algorithm to guide the management of this subgroup in the frontline setting.