Steroid Hormone Receptor and Infiltrating Immune Cell Status Reveals Therapeutic Vulnerabilities of ESR1-Mutant Breast Cancer.

ABSTRACT: Mutations in ESR1 that confer constitutive estrogen receptor alpha (ER) activity in the absence of ligand are acquired by ≥40% of metastatic breast cancers (MBC) resistant to adjuvant aromatase inhibitor (AI) therapy. To identify targetable vulnerabilities in MBC, we examined steroid hormone receptors and tumor-infiltrating immune cells in metastatic lesions with or without ER mutations. ER and progesterone receptor (PR) were significantly lower in metastases with wild-type (WT) ER compared with those with mutant ER, suggesting that metastases that evade AI therapy by mechanism(s) other than acquiring ER mutations lose dependency on ER and PR. Metastases with mutant ER had significantly higher T regulatory and Th cells, total macrophages, and programmed death ligand-1 (PD-L1)-positi

SUBMITTER: Williams MM 

PROVIDER: S-EPMC7854521 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature