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Immune Checkpoint Blockade in Hormone Receptor-Positive Breast Cancer: Resistance Mechanisms and Future Perspectives

      Highlights

      • Immune checkpoint blockade has demonstrated poor results in hormone-receptor positive breast cancer.
      • Signaling through estrogen receptor produces immune suppressive changes in the breast tumor microenvironment.
      • Combinatorial approaches appear to augment antitumor responses in patients with hormone-receptor positive disease.

      Abstract

      Anti-programmed cell death protein 1 immunotherapy has been incorporated in the treatment algorithm of triple-negative breast cancer (TNBC). However, clinical trial results for patients with hormone receptor (HR)-positive disease appear less compelling. HR-positive tumors exhibit lower levels of programmed death-ligand 1 expression in comparison with their triple-negative counterparts. Moreover, signaling through estrogen receptor alters the immune microenvironment, rendering such tumors immunologically “cold.” To explain differential responses to immune checkpoint blockade, this review interrogates differences between HR-positive and TNBC. Starting from distinct genomic features, we further present disparities concerning the tumor microenvironment and finally, we summarize early-phase clinical trial results on promising novel immunotherapy combinations.

      Keywords

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