Androgen receptor expression and response to chemotherapy in breast cancer patients treated in the neoadjuvant TECHNO and PREPARE trial

Br J Cancer. 2019 Dec;121(12):1009-1015. doi: 10.1038/s41416-019-0630-3. Epub 2019 Nov 15.

Abstract

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

Methods: AR mRNA expression was analysed by RT-qPCR in breast cancer patients treated in the neoadjuvant TECHNO (n = 118, HER2-positive) and PREPARE trial (n = 321, HER2-positive and -negative). In addition, mRNA expression of the AR transcript variants 1 (AR1) and 2 (AR2) was measured.

Results: Regarding subtypes, high AR mRNA levels were frequent in HER2-positive (61.3%, 92/150) and luminal tumours (60.0%, 96/160) but almost absent in triple-negative tumours (4.3%, 3/69) (p < 0.0001). Overall, high AR mRNA levels were found to be associated with lower pathological complete remission (pCR) rates (OR 0.77 per unit, 95% CI 0.67-0.88, p = 0.0002) but also with better prognosis in terms of longer disease-free survival (DFS) (HR 0.57, 95% CI 0.39-0.85, p = 0.0054) and overall survival (OS) (HR 0.43, 95% CI, 0.26-0.71, p = 0.0011). In the PREPARE trial, a survival difference for patients with high and low AR1 mRNA levels could only be seen in the standard chemotherapy arm but not in the dose-dense treatment arm (OS: HR 0.41; 95% CI 0.22-0.74 vs. HR 1.05; 95% CI 0.52-2.13; p = 0.0459).

Conclusions: We provide evidence that AR mRNA predicts response to chemotherapy in breast cancer patients.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Adult
  • Breast Neoplasms / blood
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Disease-Free Survival
  • Epirubicin / administration & dosage
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Middle Aged
  • Neoadjuvant Therapy
  • Prognosis*
  • Protein Isoforms / blood
  • RNA, Messenger / genetics*
  • Receptor, ErbB-2 / genetics
  • Receptors, Androgen / blood
  • Receptors, Androgen / genetics*
  • Trastuzumab / administration & dosage

Substances

  • AR protein, human
  • Protein Isoforms
  • RNA, Messenger
  • Receptors, Androgen
  • Epirubicin
  • Receptor, ErbB-2
  • Trastuzumab