title: Androgen receptor expression in breast cancer in relation to molecular phenotype: results from the Nurses' Health Study.
abstract: Previous studies have demonstrated that androgen receptor is expressed in many breast cancers, but its expression in relation to the various breast cancer subtypes as defined by molecular profiling has not been studied in detail. We constructed tissue microarrays from 3093 breast cancers that developed in women enrolled in the Nurses' Health Study. Tissue microarray sections were immunostained for estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), cytokeratin 5/6, epidermal growth factor receptor (EGFR) and androgen receptor (ER). Immunostain results were used to categorize each cancer as luminal A or B, HER2 and basal like. The relationships between androgen receptor expression and molecular subtype were analyzed. Overall, 77% of the invasive breast carcinomas were androgen receptor positive. Among 2171 invasive cancers, 64% were luminal A, 15% luminal B, 6% HER2 and 11% basal like. The frequency of androgen receptor expression varied significantly across the molecular phenotypes (P<0.0001). In particular, androgen receptor expression was commonly observed in luminal A (91%) and B (68%) cancers, but was less frequently seen in HER2 cancers (59%). Despite being defined by the absence of ER and PR expression and being considered hormonally unresponsive, 32% of basal-like cancers expressed androgen receptor. Among 246 cases of ductal carcinoma in situ, 86% were androgen receptor positive, but the frequency of androgen receptor expression differed significantly across the molecular phenotypes (P=0.001), and high nuclear grade lesions were less likely to be androgen receptor positive compared with lower-grade lesions. Androgen receptor expression is most commonly seen in luminal A and B invasive breast cancers. However, expression of androgen receptor is also seen in approximately one-third of basal-like cancers, providing further evidence that basal-like cancers represent a heterogeneous group. Our findings raise the possibility that targeting the androgen receptor pathway may represent a novel therapeutic approach to the management of patients with basal-like cancers.
authors.affiliation: Department of Pathology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA. lcollins@bidmc.harvard.edu
authors.forename: Laura C
authors.initials: LC
authors.lastname: Collins
authors.forename: Kimberly S
authors.initials: KS
authors.lastname: Cole
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Marotti
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Stuart J
authors.initials: SJ
authors.lastname: Schnitt
authors.forename: Rulla M
authors.initials: RM
authors.lastname: Tamimi
mesh_terms: D000328:Adult; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology*; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000032:analysis / Q000096:biosynthesis; D008875:Middle Aged; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis; D011944:Receptors, Androgen / Q000032:analysis / Q000096:biosynthesis*; D011960:Receptors, Estrogen / Q000032:analysis / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000032:analysis / Q000096:biosynthesis; D046888:Tissue Array Analysis
chemical_list: D066246:ErbB Receptors; D007633:Keratins; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C512478:EGFR protein, human; C508053:ERBB2 protein, human