Androgen receptor in breast cancer: expression in estrogen receptor-positive tumors and in estrogen receptor-negative tumors with apocrine differentiation

Mod Pathol. 2010 Feb;23(2):205-12. doi: 10.1038/modpathol.2009.159. Epub 2009 Nov 6.


Androgens exert growth inhibitory effects on estrogen receptor and progesterone receptor-negative breast cancer cell lines that show androgen receptor expression. These laboratory findings may be translated into inexpensive alternative therapies for hormone receptor-negative invasive breast cancers. Our aim was to systematically evaluate androgen receptor expression by immunohistochemistry in invasive breast cancers. Androgen receptor (clone AR441, Dako) expression was analyzed on 189 well-characterized consecutive invasive breast carcinomas represented with threefold redundancy on tissue microarrays. Androgen receptor expression was semi-quantitated using a histochemical score-like method and a score >10 was considered positive. Of the 189 consecutive invasive breast cancers, 151 (80%) were positive and 38 (20%) were negative for androgen receptor. The majority (95%) of estrogen receptor-positive tumors were also androgen receptor positive. Of the estrogen receptor-negative tumors, androgen receptor reactivity was seen in 3 of 30 (10%) triple-negative cases and in 5/8 (63%) estrogen receptor-negative/progesterone receptor-negative/HER2+ cases. Six of eight estrogen receptor-negative/androgen receptor-positive cases showed apocrine differentiation. Androgen receptor expression in estrogen receptor-positive cases was associated with smaller tumor size (P=0.0001), lower Nottingham grade (P=0.002) and less frequent tumor cell necrosis (P=0.0001). Androgen receptor expression in estrogen receptor-negative tumors was associated with lower Nottingham grade (P=0.005) and apocrine differentiation (P=0.039). In conclusion, most estrogen receptor-positive breast tumors also express androgen receptor. Androgen receptor expression in estrogen receptor-negative/progesterone receptor-negative/HER2+ tumors (which commonly show apocrine differentiation) and a subset of triple - negative apocrine tumors suggest that these tumors together comprises the 'molecular apocrine' group described previously. However, these findings should be further confirmed on larger series of triple-negative and estrogen negative/progesterone negative/HER2+ tumors. Androgen receptor-targeted therapy in estrogen/progesterone receptor-negative tumors may provide an inexpensive alternative to usual high-dose chemotherapy with or without trastuzumab.

MeSH terms

  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Differentiation
  • Female
  • Humans
  • Immunohistochemistry
  • Receptor, ErbB-2 / biosynthesis
  • Receptor, ErbB-2 / genetics
  • Receptors, Androgen / biosynthesis*
  • Receptors, Androgen / genetics
  • Receptors, Estrogen / biosynthesis
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / biosynthesis
  • Receptors, Progesterone / genetics
  • Tissue Array Analysis


  • Biomarkers, Tumor
  • Receptors, Androgen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Receptor, ErbB-2