AR is a ligand-dependent transcription factor; its expression on BCa is known to be linked with improved survival [10], [11] and [12]. Hu et al. assessed AR status in a large (n = 1467) cohort of patients with BCa; they found 91% and 86% 5-year survival in patients with AR-positive and AR-negative tumors, respectively [11], whereas other studies have not found a similar association with survival [13] and [14]. AR expression has been observed in approximately 40% to 80% of BCas [11], [15], [16], [17], [18] and [19]. Although a significant number of patients with BCa anti-PD-1 antibody inhibitor express AR, the underlying molecular mechanisms of AR signaling pathway in BCa biology have not been intensely

studied, and the role of AR on survival in patients with BCa needs further delineation. Protein kinase B (more commonly referred as Akt) is a serine/threonine kinase, which plays a role in BCa growth by promoting cell survival and inhibiting this website cell death [20] and [21] and is being considered as a potential target for BCa therapy [22] and [23], whereas PTEN, a well-recognized

tumor suppressor gene, negatively regulates Akt and has been shown to inhibit BCa growth [24] and [25]. Nagata and colleagues reported loss of PTEN in 50% of patients with BCa [26]. AR has been shown to increase PTEN expression by activating its promoter that in turn lowers Akt activity and decreases cellular proliferation in BCa [27]. Wang et al. also reported that AR increases PTEN

expression Org 27569 and inhibits Akt phosphorylation in BCa cells [28]. PTEN is a positive modulator, whereas Akt is a negative modulator of AR transcriptional activity. The cross talk of AR signaling with Akt and PTEN that may have clinical significance in the development of BCa has not been well studied, though the expression of Akt and PTEN in BCa tissue has been reported [29], [30] and [31]. To our knowledge, to date, no studies have been undertaken examining the expression of AR, active form of Akt (pAkt), and stable form of PTEN (pPTEN) on BCa in a cohort of Pakistani women. In this study, our aim was to determine the immunohistochemical expression of AR, pAkt, and pPTEN in Pakistani women with invasive BCa and their role as potential prognostic markers. We also examined the significance of AR expression on patient’s survival after stratifying by ER, pAkt, and pPTEN status and endocrine treatment. A total of 1103 patients were diagnosed with invasive BCa and treated at the section of breast diseases, Aga Khan University Hospital (Karachi, Pakistan), during 2002 to 2011. From a total of 1103 cases, 200 were selected for this study on the basis of the following criteria: 1) availability of formalin-fixed paraffin-embedded (FFPE) tissue blocks, 2) sufficient representative area of primary tumor in FFPE blocks, and 3) complete follow-up data.