Androgen receptor expression is a predictive marker in chemotherapy-treated patients with endocrine receptor-positive primary breast cancers

J Cancer Res Clin Oncol. 2013 May;139(5):809-16. doi: 10.1007/s00432-013-1382-8. Epub 2013 Feb 8.

Abstract

Purpose: The androgen receptor (AR) is intensively discussed as a prognostic and/or predictive marker in breast cancer patients.

Methods: We evaluated the value of AR mRNA expression with the Affymetrix HG-U 133A array in 3 different cohorts: a cohort of breast cancer patients who received adjuvant treatment (cohort A; n = 165), a cohort of untreated breast cancer patients (cohort B; n = 200) and a cohort of chemotherapy-treated breast cancer patients with estrogen receptor (ER)-positive tumors (cohort C; n = 223).

Results: AR mRNA expression was associated with lower grading (Grades 1 and 2) as well as ER and progesterone receptor (PgR) positivity in all cohorts. In the treated cohort (cohort A), low androgen receptor expression was associated with shorter event-free survival (OR 2,34, 95 % CI 1.01-5.43, p = 0.047) which was not seen in the untreated cohort B. Subgroup analysis revealed that shorter survival of patients with low AR mRNA expression was observed mainly in the ER-positive subgroup of patients treated with adjuvant chemotherapy. In the validation cohort C we could confirm a benefit of chemotherapy for the group of tumors with high AR mRNA expression (5-year event-free survival (EFS) 74 % versus 57 %, p = 0.013). In this cohort, low AR mRNA expression was associated with shorter event-free survival also in multivariate analysis (OR 2.86, 95 % CI 1.29-6.35, p = 0.010) adjusted for HER2, ki-67, tumor size, age and tumor grade.

Conclusions: We provide evidence that AR expression is associated with chemotherapy responsiveness in ER-positive patients.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Agents, Hormonal / therapeutic use
  • Biomarkers, Tumor / genetics*
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Prognosis
  • Receptor, ErbB-2 / genetics
  • Receptors, Androgen / genetics*
  • Receptors, Estrogen / genetics
  • Receptors, Progesterone / genetics

Substances

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