Androgen receptor expression in triple-negative breast cancer

Dissertação de mestrado, Ciências Biomédicas, Departamento de Ciências Biomédicas e Medicina, Universidade do Algarve, 2014Worldwide, 3 million the women are diagnosed with breast cancer which is the most common malignancy in female gender. Breast Cancer is a heterogeneous disease and clinically it is evaluated using three markers: the estrogen receptor (ER), the progesterone receptor (PR) and the epidermal growth factor receptor type 2 (HER2). The tumors that do not express any of these receptors are called triple-negative breast cancers (TNBC). TNBC represent approximately 20% of BC. These tumors constitute an important clinical challenge, as they do not respond to endocrine treatment and to anti HER2 directed therapy. As a group they harbor an aggressive clinical phenotype with early development of visceral metastases and a poor long-term prognosis. The only systemic treatment for TNBC is chemotherapy. Numerous experiments and trials have been done to try to understand what is targetable in TNBC and if so, if the clinical trials achieve their endpoints. Today, the trend in clinical practice is individualized treatment based on molecular biology markers of tumor and patient. Lehmann et. al. attempted to characterize TNBC and put forward a microarray signature that divides these tumors in 6 groups, according to differential gene expression profiles: basal-like 1 (BL1); basal-like 2 (BL2); immunomodulatory (IM); mesenchymal (M); mesenchymal stem–like (MSL) and luminal androgen receptor (LAR). Androgen receptor is member of the steroid hormone receptor family, expressed in more than 70% of breast cancers and has been implicated in breast cancer pathogenesis. The role of AR is of particular interest in patients with TNBC. In this project, immunohistochemistry was used to characterize the AR expression in a consecutive cohort of TNBC cases from Hospital CUF Lisboa. The immunohistochemical panels of markers used to characterize this subgroup of breast cancer, along with AR, were the CK 5/6, p-cadherin, PHH3 and EGFR in an attempt to further characterize TNBC subtypes. Of all the TNBC cases, 56% (28/50) were CK5/6, 0; 22% (11/50) were CK5/6, 1+; 12% (6/50) were CK5/6, 2+; and 10% (5/50) were CK5/6, 3+. In 96% (48/50) the expression of p-cadherin was positive while only 4% (2/50) was negative. Regarding EGFR, 38% (19/50) were EGFR, 0; 26% (13/50) were EGFR, 1+; 24% (12/50) were EGFR, 2+; and 12% (6/50) were EGFR, 3+. The expression of AR was considered positive in 62% of cases of TNBC. We have known from the literature that AR status is a significant independent prognostic factor, although we cannot show this in this sample. In this study was not possible to implement the Lehmann classification because it was not possible to separate the different TNBC by Immunohistochemical staining into 6 different categories of the Lehmann classification. The functional role of AR in breast cancer remains unclear, further exploration of this area could expand the repertoire of potential treatments for patients with AR+ TNBC