Androgen receptor expression as a prognostic and predictive marker in triple-negative breast cancer patients

Abstract

Purpose: It is clear that triple-negative breast cancer (TNBC) tumors are heterogeneous group, but clinically important sub-sets have begun to emerge. We investigate the immunohistochemical expression of androgen receptor (AR) among those hormonal insensitive groups which have only the option of chemotherapy. Exploiting this knowledge for therapy has been challenging.
Patients & methods: Seventy seven patients with TNBC subtype, treated from January 2009 until February 2011 were evaluated for AR expression where AR-positive expression group (P10% nuclear stained cells) was conducted to receive anti-androgen therapy post adjuvant chemotherapy (Bicalutamide ‘‘Casodex’’) 50 mg, once daily with or without meals at the same time each day, to date. AR expression was correlated with other prognostic factors and survival (disease free survival (DFS) and overall survival (OS)). Cox proportional hazard model was used to assess variables in the multivariate analysis.
Results: The median age in the present study was 35.6 year (19–63 years). The median follow-up period was 24 months (3–60 months). AR-positive expression in the present study was (21n77) 27.27% correlated with clinical outcomes, for recurrent event (n=4, 19.05%), (P=0.000, HR 12.750, Cl 95% 3.668–44.318) and for death event, no body died in AR positive expression group (P=0.000, HR 0.644, Cl 95% 0.533–0.779). Improved survival with AR-positive expression group for 2-year and 3-year DFS was 85% and 78% respectively with (P=<0.001, Cl 95% 39.17– 51.39) and for OS at 2-year and 3-year was 100% (P=0.0005). In univariate and multivariate analysis, AR positive expression with anti-androgen therapy in TNBC patients in our present study had retained their independent prognostic value for DFS (P=0.0006, HR 4.659, Cl 95% 1.553– 13.977). Bicalutamide was well-tolerated therapy with no grade 3/4 treatment-related adverse events.
Conclusions: Bicalumide is well tolerated in AR positive TNBC subtype patients and could offer an alternative to cytotoxic chemotherapy in those patients with better OS and DFS.

Keywords: Triple-negative breast cancer; Androgen receptor immuno- histochemistry; Anti-androgen therapy