Hennessy, Maeve A

Triple-negative breast cancer (TNBC) is an aggressive breast cancer subtype characterized by lack of estrogen receptor expression, progesterone receptor expression, and human epidermal growth factor 2 overexpression/amplification. Given its generally aggressive biology, current guidelines recommend systemic therapy for most patients, with anthracycline- and taxane-based regimens being historically preferred. However, the clinical outcomes of patients with stage I TNBC and the benefit (or lack thereof) of (neo)adjuvant chemotherapy have not been prospectively evaluated as this population has largely been excluded from prospective randomized clinical trials. As such, management decisions for stage I TNBC are typically extrapolated from trials enrolling patients with stage II or III TNBC or based on retrospective analyses. Currently, the primary factor influencing systemic therapy decisions is the anatomic stage, without other biomarkers clinically used to guide systemic therapy. This review summarizes the existing evidence supporting current and emerging systemic therapy strategies for stage I TNBC, with a special focus on treatment de-escalation and promising biomarkers that can advance personalized treatment selection.

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.

Triple-negative breast cancer (TNBC) is characterized by the lack of estrogen receptor (ER), progesterone receptor, and human epidermal growth factor receptor 2 overexpression. Historically, treatment options for TNBC have been limited, because of the absence of actionable targets. The addition of immune checkpoint inhibitors to chemotherapy improved outcomes for a subset of patients with metastatic PD-L1–positive disease; however, a critical need for more effective therapies remains. Antibody-drug conjugates (ADCs) have been a promising advance in the management of advanced TNBC and are reshaping the landscape as they move earlier into the treatment algorithm. A greater understanding of the molecular heterogeneity of TNBC has enabled the pursuit of more targeted and personalized therapeutic strategies. Despite this, TNBC continues to have the least favorable outcomes compared with other breast cancer subtypes. This review highlights current evidence and future challenges in advanced TNBC, including optimizing therapeutic sequencing and the ongoing need for predictive biomarkers and novel agents.