Wednesday, September 18, 2019

Breast Cancer :: Health, Diseases

Breast Cancer as the most common cancer in Iranian women affects women at least one decade younger than their counterparts in developed countries. The highest frequency of malignancies has been observed in the 40-49 age groups [1]. It is commonly accepted that estrogen and its receptor have an important role in the pathogenesis of breast malignancies. Breast tumors are classified based on ER status to ER negative and ER positive tumors. About 40% of breast tumors are ER negative [2]. ER negative tumors in comparison to ER positive tumors tend to have worse prognosis and less likely to respond to endocrine therapy. This type of tumor is more prevalent in younger patients. Triple negative breast tumors (without ERÃŽ ± and PR expression and Her2 amplification) are the most clinically aggressive ones. Considering to the challenging nature of ERÃŽ ± negative tumors treatment, and their innate poor prognosis, clarification of the molecular mechanisms that control expression of ERÃŽ ± is essential. This knowledge may enable us to modify the situation as such to restore sensitivity to endocrine therapies which provide us with opportunities for new therapeutic options for ERÃŽ ±-breast tumors [3]. Despite many studies on the mechanisms of negativity of ER in breast tumors, many details still need to be clarified [4],[5].The loss of ERÃŽ ± expression in breast cancer may result from different underlying causes such as structural changes within the gene or transcriptional silencing [6]. Abnormalities such as point mutations, deletions, loss of heterozygosity or polymorphisms within the gene have not shown to be frequent enough to explain ER negativity phenotype[6] [7]. In breast tumors such as other types of cancer, epigenetic alterations are common and are related to gene expression modification[8]. It has been shown that tumor suppressor genes promoter methylation gives growth advantages to malignant cells[9]. Because of the potential reversible nature of epigenetic gene silencing, epigenetic mechanisms have been under intense investigations in recent years [4, 6, 10, 11]. Regarding to evidences which have been resulted from several in vitro (cell lines) and in vivo (animal models) studies, it has been shown that the inhibitors of DNA methyltransferase (DNMT) and histone deacetylase (HDAC) enzymes can reactivate ERÃŽ ± expression in ERÃŽ ± negative cells and restore response to endocrine therapy [12, 13]. These promising landscape encouraged researchers to focus on the relationship between ERÃŽ ±- phenotype and promoter methylation. However, heterogeneity of the cellular population in breast tumors and differences in

No comments:

Post a Comment

Note: Only a member of this blog may post a comment.