新兴生物标志物预测乳腺癌免疫治疗反应

PURPOSE OF REVIEW: Summarize and update the most recent evidence on biomarkers of immunotherapy response in breast cancer including currently used and investigational markers. RECENT FINDINGS: Currently, immune checkpoint inhibitors (ICIs) are approved only for patients with triple negative breast cancers (TNBC); however, ICIs are actively investigated in all breast cancer subtypes. Because only a subset of patients derives clinical benefit from ICIs, predictive biomarkers are crucial for rational treatment selection. In metastatic TNBC, PD-L1 positivity of the tumor and/or immune cells defines the patient population eligible for ICI therapy; however, it is an imperfect biomarker, and its expression does not always correlate with ICI benefit.

Other biomarkers such as high tumor mutation burden (TMB) and microsatellite instability (MSI)-High status also serve as tumor-agnostic indicators of ICI response. In early-stage TNBC, ICI benefit appears to be independent of PD-L1 expression. Higher tumor infiltrating lymphocytes (TILs) are generally associated with improved ICI responses.

Gene expression signatures are emerging as novel predictors of ICI response. The indications for ICIs in breast cancer are rapidly increasing. Currently available biomarkers fall short of accurately predicting which patients will benefit most from ICI therapy, highlighting the need for further research for more rational selection of patients to maximize efficacy and limit toxicities.