Androgen receptor expression in male breast cancer predicts inferior outcome and poor response to tamoxifen treatment

Eur J Endocrinol. 2014 Oct;171(4):527-33. doi: 10.1530/EJE-14-0278. Epub 2014 Jul 28.

Abstract

Objective: Androgen receptor (AR) plays an important role in male breast cancer (MBC). Additionally, endocrine therapy is the most important treatment in oestrogen receptor (ER)-positive advanced breast cancer. This study was aimed to investigate the role of AR in MBC treatment and prognosis and to analyse the relationship between AR and the effect of tamoxifen treatment in MBC patients.

Methods: AR protein levels and other tumour characteristics (e.g. expression of ER (ESR1), PR (PGR), AR, HER2 (ERBB2) and Ki-67 (MKI67)) in breast cancer tissue from 102 MBC patients were determined using immunohistochemical analysis. Additionally, the relationship between AR status and clinicopathological features was analysed using the χ(2)-test. Association with survival was initially analysed using the Kaplan-Meier method and the log-rank test, and Cox regression analysis was used to adjust for other prognostic indicators.

Results: High expression of AR was not correlated with T-stage, histological grade, HER2 status and the status of other sex hormone receptors, but was associated with lymph node metastases (P=0.032). AR-positive patients showed significantly shorter 5-year overall survival (OS) rates (P=0.045) and 5-year disease-free survival (DFS) rates (P=0.026) than AR-negative patients. By contrast, for patients who received tamoxifen therapy, AR-negative patients showed a higher clinical benefit rate than AR-positive patients (P=0.025). Additionally, the median TTP and OS were significantly different (P=0.02 for TTP; P=0.029 for OS).

Conclusions: AR expression correlates strongly with both OS and DFS in patients with MBC. AR-positive patients can predict a poorer clinical outcome than AR-negative patients after adjuvant tamoxifen therapy.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents, Hormonal / therapeutic use*
  • Biomarkers, Tumor / analysis*
  • Breast Neoplasms, Male / chemistry
  • Breast Neoplasms, Male / drug therapy*
  • Breast Neoplasms, Male / pathology*
  • Chemotherapy, Adjuvant
  • Disease-Free Survival
  • Estrogen Antagonists / therapeutic use
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Ki-67 Antigen / analysis
  • Male
  • Middle Aged
  • Neoplasm Staging
  • Predictive Value of Tests
  • Receptor, ErbB-2 / analysis
  • Receptors, Androgen / analysis*
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Tamoxifen / therapeutic use*
  • Treatment Outcome

Substances

  • AR protein, human
  • Antineoplastic Agents, Hormonal
  • Biomarkers, Tumor
  • Estrogen Antagonists
  • Ki-67 Antigen
  • Receptors, Androgen
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tamoxifen
  • ERBB2 protein, human
  • Receptor, ErbB-2