2. Academic Validation
  3. Effect of AR antagonist combined with PARP1 inhibitor on sporadic triple-negative breast cancer bearing AR expression and methylation-mediated BRCA1 dysfunction

Effect of AR antagonist combined with PARP1 inhibitor on sporadic triple-negative breast cancer bearing AR expression and methylation-mediated BRCA1 dysfunction

  • Biomed Pharmacother. 2019 Mar;111:169-177. doi: 10.1016/j.biopha.2018.11.136.
Meixiang Sang 1,  Lingjiao Meng 2,  Cuicui Ma 3,  Sihua Liu 2,  Meijie Sang 4,  Sheng Chang 2,  Fei Liu 2,  Yishui Lian 2,  Cuizhi Geng 5
Affiliations

Affiliations

  • 1 Research Center and Tumor Research Institute, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China. Electronic address: mxsang@hotmail.com.
  • 2 Research Center and Tumor Research Institute, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China.
  • 3 Breast Disease Diagnostic and Therapeutic Center, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China.
  • 4 Department of Surgical Nursing, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, China.
  • 5 Research Center and Tumor Research Institute, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China; Breast Disease Diagnostic and Therapeutic Center, The Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050017, China. Electronic address: cuizhigeng@hotmail.com.
PMID: 30580238 DOI: 10.1016/j.biopha.2018.11.136
Abstract

Triple-negative breast Cancer (TNBC) patients usually present worse clinical outcomes due to their high heterogeneity. The purpose of our study is to investigate the prognostic role of AR and BRCA1 expression in sporadic TNBC patients, and effect of AR blockade and PARP1 Inhibitor for TNBC patients who characterized by positive-AR expression and BRCA1 inactivation or dysfunction. In our present study, we found that AR is expressed in 43.6% and 34.0% of TNBC tissues, when 1% or 10% staining was used as the threshold for AR positivity, respectively. When 1% staining was used as the threshold, AR expression indicates a poor disease-free survival (DFS) of TNBC patients. TNBC patients with negative BRCA1 show a poor DFS, and BRCA1 suppression is associated with the methylation status of its promoter. Interestingly, BRCA1-/AR + TNBC patients have shorter DFS than other TNBC patients regardless of the threshold for AR positivity. AR antagonists MDV3100 enhances the PARP1 Inhibitor Olaparib-mediated decrease of cell viability in AR-positive/BRCA1-inactivated cells in vitro and in vivo. Our results suggested that combination of AR blockade and PARP1 Inhibitor may be a potential strategy for sporadic TNBC patients who characterized by positive-AR expression and BRCA1 inactivation or dysfunction.

Keywords

Androgen receptor; BRCA1; Enzalutamide; Olaparib; Triple-negative breast cancer.

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