Recent Advancements in Immunotherapy for the Treatment of Metastatic Breast Cancer.

Abstract

Breast cancer (BC) is the most prevalent malignancy among women in the United States, affecting approximately 13% of the female population. While advancements in treatment strategies have improved survival rates, significant challenges remain due to tumor heterogeneity, metastatic progression, and acquired resistance to therapy. Recent studies have highlighted the potential of immunotherapy in managing various solid tumors, including BC. This growing interest stems from increasing recognition of the immune system's role in both normal breast tissue and BC development, leading to extensive clinical investigations into BC immunotherapy and its tumor immune landscape. Despite its promise, immunotherapy for BC faces hurdles such as low tumor immunogenicity, inadequate T-cell infiltration, and a highly immunosuppressive tumor microenvironment (TME), which limit its efficacy. Among the available approaches, PD-1/PD-L1 inhibitors have shown clinical benefit in a subset of metastatic BC patients, particularly those with PD-L1-positive tumors, triple-negative BC (TNBC), or high tumor-infiltrating lymphocyte (TIL) levels. Notably, atezolizumab and pembrolizumab have demonstrated durable responses in metastatic TNBC, underscoring their therapeutic potential. Current research is focused on developing combination immunotherapy strategies that can overcome resistance, enhance response rates, and convert non-responders to therapy-sensitive cases. A key area of investigation involves identifying biomarkers that can predict immunotherapy responsiveness, guide salvage therapy in progressive disease, and optimize personalized treatment combinations. This review explores the latest advancements and future directions in BC immunotherapy, including novel combination strategies with vaccines and chemotherapeutics aimed at improving treatment efficacy and patient survival outcomes.