McArthur, Heather

The treatment paradigm of stage II to III triple-negative breast cancer (TNBC) is rapidly evolving, with the recent incorporation of pembrolizumab to neoadjuvant chemotherapy improving disease outcomes. Nevertheless, almost one in five patients with early-stage TNBC will relapse in 5 years, underscoring an urgent need to identify and improve outcomes for those at high risk of recurrence. Novel therapeutic strategies including antibody-drug conjugates, anti-vascular endothelial growth factor therapies, dual immune checkpoint blockade, and locoregional therapies to augment the antitumor immune response are being investigated in clinical trials. Biomarker strategies including tumor infiltrating lymphocytes, immune signatures, and circulating tumor DNA are being explored to identify patients at a high risk of relapse and to predict treatment response. In this article, we review recent advances in the management of stage II to III TNBC, highlight emerging investigational therapies and combinations, and explore novel biomarker strategies aimed at personalizing the care for patients with stage II to III TNBC.

PURPOSE This guideline updates recommendations of the ASCO guideline on chemotherapy and targeted therapy for patients with human epidermal growth factor receptor 2–negative metastatic breast cancer (MBC) that is either endocrine-pretreated or hormone receptor (HR)–negative. METHODS An Expert Panel conducted a targeted systematic literature review guided by a signals approach to identify new, potentially practice-changing data that might translate into revised guideline recommendations. RESULTS The Expert Panel reviewed abstracts from the literature review and retained 14 articles. RECOMMENDATIONS Patients with triple-negative, programmed cell death ligand-1–positive MBC may be offered the addition of immune checkpoint inhibitor to chemotherapy as first-line therapy. Patients with triple-negative, programmed cell death ligand-1–negative MBC should be offered single-agent chemotherapy rather than combination chemotherapy as first-line treatment, although combination regimens may be offered for life-threatening disease. Patients with triple-negative MBC who have received at least two prior therapies for MBC should be offered treatment with sacituzumab govitecan. Patients with triple-negative MBC with germline BRCA mutations previously treated with chemotherapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. Patients with HR-positive human epidermal growth factor receptor 2–negative MBC for whom chemotherapy is being considered should be offered single–agent chemotherapy rather than combination chemotherapy, although combination regimens may be offered for highly symptomatic or life-threatening disease. Patients with HR-positive MBC with disease progression on an endocrine agent may be offered treatment with either endocrine therapy with or without targeted therapy or single-agent chemotherapy. Patients with HR-positive MBC with germline BRCA mutations no longer benefiting from endocrine therapy may be offered a poly (ADP-ribose) polymerase inhibitor rather than chemotherapy. No recommendation regarding when a patient's care should be transitioned to hospice or best supportive care alone is possible. Additional information is available at www.asco.org/breast-cancer-guidelines .