Androgen receptor expression in a Sri Lankan patient cohort with early breast carcinoma

Abstract

Background: Androgen receptor (AR) expression is emerging as a prognostic biomarker in breast carcinoma (BCa). The study aimed to determine the prevalence of AR expression by immunohistochemical analysis among a cohort of Sri Lankan women with early BCa and to evaluate its association with clinicopathological features including immunohistochemical molecular subtype and early survival.

Method: We studied the clinical and pathological features and immunohistochemical profile of 141 women undergoing primary surgery for early BCa, followed by standard adjuvant therapy. AR status was assessed by immunohistochemistry in all cases. Overall survival (OS) and disease-free survival (DFS) was determined. The relationship between AR expression and clinical and pathological parameters and immunohistochemical molecular subtype was analyzed using Student T test and chi-square tests. Cox regression analysis was used to analyze the prognostic impact of AR expression.

Results: AR expression was seen in 40.8%(95%CI 33.10-49.07%) of the BCa study cohort. None of the clinical data studied showed a significant association with the AR status(p > 0.05). Ductal carcinoma in situ(p = 0.003), oestrogen receptor (ER) (p = 0.001) and progesterone receptor (PR) (p = 0.001) positivity and luminal IHC molecular subtype(p = 0.016) were significantly associated with AR-positive status. AR-negative status was significantly associated with tumour necrosis > 50%(p = 0.031), moderate to extensive lymphocytic infiltrate at the tumour margin(p = 0.025) and basal triple negative breast carcinoma(p = 0.016). The mean duration of patient follow-up was 46.70(95% CI 46.495-46.905) months (3.89 years). On univariate analysis, AR-positivity was associated with better OS among ER-positive tumours(p = 0.047), specifically in postmenopausal women (p = 0.030). In ER-negative tumours, AR positivity was associated with worse DFS (p = 0.036). On multivariate analysis, TNM stage and ER/AR status were predictive of survival. ER-positive/AR-positive (ER+/AR+) tumours demonstrated better OS than ER-positive/AR-negative (ER+/AR-) tumours(p = 0.015). ER-negative/AR-positive (ER-/AR+) tumours (p = 0.014) had a worse DFS than ER-negative/AR-negative (ER-/AR-) tumours.

Conclusions: AR prevalence obtained was low. AR positivity was associated with positivity for ER and PR. On multivariate analysis, apart from TNM stage only ER/AR status were predictive of OS and DFS, with concordant expression of ER/AR demonstrating a better, early survival.

Keywords: Androgen receptors; Breast carcinoma; Clinicopathological features; Prevalence; Prognosis; Sri Lanka.

Fig. 1

Immunohistochemical staining for AR in breast carcinoma

Fig. 2

Impact of menopausal state and ER/AR status on overall and disease free survival

Fig. 3

Impact of tumour grade and AR status on overall disease free survival according to tumour grade

Fig. 4

Impact of ER/AR status on overall and disease free survival