الفهرس 
IntroductionOnly 14 pages are availabe for public view
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Abstract
Breast cancer is the most frequently diagnosed malignancy in women worldwide (Siegel et al., 2020). Although there is an increase in breast cancer incidence, breast cancer mortality is decreasing in the last years. This decrease in mortality is mainly caused by both the introduction of breast cancer screening and more extensive use of adjuvant systemic therapy (Barton et al.,2015). The treatment of breast cancer consists of two aspects. The first aspect is the loco-regional control, which is achieved by surgery and radiotherapy. The second part is the systemic control to treat or prevent distant metastases. It is either by chemotherapy, hormonal treatment or target therapy. (van Maaren et al., 2016). Androgen Receptor (AR) is the most commonly expressed hormone receptor in both invasive and metastatic breast cancers (Tang et al., 2012).AR seems to be associated with favorable clinicopathological features and a prognostic factor for better outcome in ER-α positive breast cancers (Tsang et al., 2014).However, its prognostic value in triple –negative breast cancers remains controversial (Huang et al., 2016). In a reported phase II trial, patients with ER-, PR-& AR + (by IHC) get a clinical benefit rate with the AR antagonist. Investigational clinical trials where AR antagonists are combined with other drugs in patients with this subtype are currently ongoing (Gucalp et al. 2013). Cyclin D1 is known to be a key mediator of cell-cycle progression (Arnold et al., 2005). It can rescue growth factor-deprived and antiestrogen-arrested cells from G1 to complete the cell cycle (Mochizuki et al., 2009).Several studies have shown that overexpressed cyclin D1 in breast cancer patients can bind directly to the ERs and propagate the downstream effects of estrogen in a CDK-independent and Rb-independent manner (Goldhirsch et al., 2013).Although evidence has shown that cyclin D1 is a good prognostic factor in ERα-positive breast cancers, its role in response to antiestrogen treatment seems to be inversed, leading to conflicting results regarding its role in pathogenesis and prognosis (McGhan et al., 2014). The p53 gene is located on the short arm of chromosome 17 and encodes a 375 amino acid nuclear phosphoprotein that prevents propagation of genetically altered cells (Shapira et al.,2013). Mutations within the p53 gene result in protein that is stabilized through posttranscriptional modification and accumulation within the cell nucleus (Dookeran et al.,2010). Mutations in the tumor suppressor gene p53 are present in 18%–25% of primary breast carcinomas (Zhu et al.,2013). Among the prognostic factors analyzed in studies focusing on breast cancer, an absence of p53 mutations appears to predict longer disease-free (DFS) and overall survival (OS) following primary therapy