Submit Manuscript  

Article Details


Efficacy and Safety of Targeting Androgen Receptor in Advanced Breast Cancer: A Systematic Review

[ Vol. 15 , Issue. 3 ]

Author(s):

Loay Kassem, Kyrillus S. Shohdy*, Nafie F. Makady, Dalal S. Salem, Nadia Ebrahim and Mostafa Eldaly   Pages 197 - 206 ( 10 )

Abstract:


Background: Androgen receptor (AR) upstreams complex signaling pathways that regulate cell proliferation and contribute to breast tumorignensis. Several clinical trials were initiated to investigate the clinical relevance of targeting AR especially in hormone-receptor-negative breast cancer.

Methods: The search was performed in PubMed and the meeting libraries of ASCO, ESMO, SABCS, ImpakT congresses from January 2005 to July 2017. The following key words were used: Breast cancer, Androgen receptor, androgen agonist/antagonist, Flutamide, Abiraterone, Bicalutamide, Enzalutamide, Enobosarm, selective androgen receptor modulator.

Results: Screening of title/abstracts yielded a total of 20 relevant results. Of those, twelve studies were found eligible: eleven clinical trials along with one case report. Response rates ranged from 0 to 12% while clinical benefit rates reached up to 35% in 2 studies (with enzalutamide and enobosarm). Progression-free survival ranged from 2.8 to 4.5 months. The most widely used cutoff for AR expression was 10%. High expression of AR was associated with more clinical benefit. Regarding safety, anti-androgens were generally well tolerated with hot flushes, elevated transaminases and fatigue being the most commonly reported across all agents.

Conclusion: Androgen receptor pathway targeting in advanced breast cancer remains a valid option with reasonable clinical benefit in non-selected patients. Future studies are needed to define an AR addicted cohort with better responses and outcome.

Keywords:

Breast cancer, androgen receptor, efficacy, safety, antiandrogens, signaling pathways.

Affiliation:

Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Cairo, Clinical Oncology Department, Kasr Alainy School of Medicine, Cairo University, Cairo

Graphical Abstract:



Read Full-Text article