New Strategies in Breast Cancer: Immunotherapy

Abstract

More than 70% of breast cancers contain lymphocytic infiltration in the stroma, and preclinical studies suggest that immunoediting and partial control of cancer progression by the local immune microenvironment operate in most breast cancers. Consistent with this hypothesis, a large number of studies demonstrated a favorable prognostic and chemotherapy response predictive role for immune infiltration in breast cancer. The evidence is particularly strong for triple-negative and HER2-positive cancers. The development of clinically effective immune checkpoint inhibitors now provides an opportunity to test the therapeutic potential of augmenting the local antitumor immune response. Several phase I clinical trials using single-agent anti-PD-1 and anti-PD-L1 antibodies demonstrated objective tumor response rates, with remarkably durable responses, in heavily pretreated, metastatic, triple-negative cancers and somewhat lower responses in estrogen receptor-positive cancers. Currently, close to 50 ongoing, or soon to open, clinical trials evaluate the role of this new treatment modality in breast cancer. Clin Cancer Res; 22(9); 2105-10. ©2016 AACR.

Figure 1

Immunoediting during tumor evolution. All clinically apparent early breast cancers are already partially edited or not immunogenic enough since the elimination phase (A) has failed. Tumors in the equilibrium phase (B) are likely represented in the high immune infiltration group. Recurrences in this group are at least in part due to subsequent immune escape. Tumors with low immune infiltration may include cancers with intrinsicly low immunogenicity and cancers that have effectively escaped from immune surveillance (C, D). Abbreviations: DC, dendritic cells; MDSC, myeloid-derived suppressor cells; TAM1, tumor-associated macrophages M1 or classically activated; TAM2, tumor-associated macrophages M2 or alternatively activated.