title: Combined Androgen and Estrogen Receptor Status in Breast Cancer: Treatment Prediction and Prognosis in a Population-Based Prospective Cohort.
abstract: OBJECTIVE
  To evaluate whether tumor androgen receptor (AR) expression was prognostic and/or predictive for endocrine treatment alone or in combination with estrogen receptor (ER). The AR has been hypothesized to have differential prognostic roles in breast cancer depending on tumor ER status, and to influence endocrine treatment response.
  
  
  METHODS
  A population-based prospective cohort of 1,026 patients diagnosed with primary invasive breast cancer in Lund, Sweden, between 2002 and 2012 was followed until June 2014. Associations between immunohistochemical AR expression in tumor tissue microarrays, patient and tumor characteristics, and AR genotypes were analyzed. Disease-free survival (DFS) by AR status, and combined ER/AR status was assessed in various treatment groups.
  
  
  RESULTS
  AR expression was assessable in 913 tumors. AR(+) tumors (85.0%) were associated with higher age (P = 0.036) and favorable tumor characteristics. The AR(+) status was a prognostic marker for DFS (LogRank P = 0.025). There was an interaction between AR and ER expression with respect to prognosis (adjusted P(interaction) ≤ 0.024). Tumors with discordant hormone receptor expressions (ER(+)AR(-) or ER(-)AR(+)) demonstrated worse prognosis compared with concordant tumor expressions (ER(+)AR(+) or ER(-)AR(-)) in multivariable models [adjusted HRs (95% confidence intervals); ≥ 1.99 (1.28-3.10), P ≤ 0.002]. ER(+)AR(-) indicated early treatment failure with aromatase inhibitors (AI) among chemonaïve patients aged 50 or older.
  
  
  CONCLUSIONS
  Prediction of breast cancer prognosis and treatment response was improved by combining AR and ER status. AR negativity predicted early treatment failure with AI but not tamoxifen, a finding that warrants confirmation in a randomized setting. Patients may benefit from anti-androgens or selective AR modulators.
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund, Sweden. Department of Plastic and Reconstructive Surgery, Skåne University Hospital, Malmö, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Elebro
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund, Sweden. Department of Oncology, Skåne University Hospital, Lund, Sweden.
authors.forename: Signe
authors.initials: S
authors.lastname: Borgquist
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Simonsson
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Markkula
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Surgery, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Ingvar
authors.affiliation: Lund University, CREATE Health and Department of Immunotechnology, Medicon Village, Lund, Sweden.
authors.forename: Carsten
authors.initials: C
authors.lastname: Rose
authors.affiliation: Lund University and Skåne University Hospital, Department of Clinical Sciences, Lund, Division of Oncology and Pathology, Lund, Sweden. helena.jernstrom@med.lu.se.
authors.forename: Helena
authors.initials: H
authors.lastname: Jernström
mesh_terms: D000368:Aged; D047072:Aromatase Inhibitors / Q000008:administration & dosage; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005828:Genetics, Population; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011944:Receptors, Androgen / Q000096:biosynthesis* / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics; D013548:Sweden; D017211:Treatment Failure
chemical_list: D047072:Aromatase Inhibitors; D014408:Biomarkers, Tumor; D018719:Erb-b2 Receptor Tyrosine Kinases; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; C410798:AR protein, human