Coexpression of androgen receptor and FOXA1 in nonmetastatic triple-negative breast cancer: ancillary study from PACS08 trial

Future Oncol. 2015;11(16):2283-97. doi: 10.2217/fon.15.102.

Abstract

Aim: Microarray studies identified a subgroup of molecular apocrine tumors (estrogen receptor [ER] negative/androgen receptor [AR] positive) that express luminal genes including FOXA1. FOXA1 may direct AR to sites normally occupied by ER in luminal tumors, inducing an estrogen-like gene program that stimulated proliferation.

Materials & methods: Expression of AR and FOXA1 was evaluated by immunohistochemistry in 592 patients with nonmetastatic triple-negative breast cancer (TNBC).

Results: Coexpression of AR and FOXA1 was found in 15.2% of patients. These tumors were more frequently lobular, found in older patients and exhibited a lower nuclear grade and a greater degree of node involvement. They less often exhibited lymphocytic infiltrate, pushing margins, syncytial architecture, central fibrosis or necrosis.

Conclusion: TNBC with coexpression of AR and FOXA1 seems to behave like luminal tumors with a morphological profile distinct from other TNBC. These biomarkers could be useful to identify a subgroup of TNBC and could have future therapeutic implications.

Keywords: FOXA1; androgen receptor; molecular apocrine tumors; triple-negative breast cancer.

Publication types

  • Clinical Trial, Phase III
  • Multicenter Study

MeSH terms

  • Adult
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use
  • Female
  • Gene Expression*
  • Hepatocyte Nuclear Factor 3-alpha / genetics*
  • Hepatocyte Nuclear Factor 3-alpha / metabolism
  • Humans
  • Immunohistochemistry
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Odds Ratio
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / genetics*
  • Triple Negative Breast Neoplasms / pathology*
  • Tumor Burden

Substances

  • AR protein, human
  • FOXA1 protein, human
  • Hepatocyte Nuclear Factor 3-alpha
  • Receptors, Androgen