Targeting low-risk triple-negative breast cancer: a review on de-escalation strategies for a new era.

Abstract

Triple-negative breast cancer (TNBC) is a subtype of breast cancer lacking estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression. Comprising 15-20% of breast cancers, TNBC is typically high-grade, affects younger women, and has a poor prognosis. However, TNBC is heterogeneous, encompassing different molecular subtypes and histological types with distinct molecular drivers, prognoses, and treatment responses. Among these, a subset of low-risk diseases associated with a lower risk of recurrence led to the exploration of de-escalation strategies. This review presents the clinicopathological characteristics of special TNBC with a better prognosis that could be spared from aggressive systemic treatment. We searched the PubMed database for articles that could support treatment de-escalation using the keywords "early-stage", "TNBC", and "low-risk". This article addresses four subgroups of low-risk TNBC: special histological types, tumors with high tumor-infiltrating lymphocytes (TILs), low Ki-67 levels, and early-stage tumors that achieved pathological complete response (pCR). The discussion explores the optimization of treatment options ranging from the omission of any systemic treatment to anthracycline-free possibilities and/or immunotherapies. Identifying these tumors can help personalize treatment, reduce costs and unnecessary toxicity, and contribute to a better quality of life for patients with favorable prognoses. Further studies should explore reliable biomarkers to identify these low-risk diseases precisely.