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Hormones in Breast Carcinogenesis (pp. 121-134) $100.00
Authors:  (Veronika Brychtova, Roman Hrstka, Regional Centre for Applied Molecular Oncology, Masaryk Memorial Cancer Institute, Brno, Czech Republic)
Abstract:
The influence of hormones in oncogenic cascade is obvious. Approximately one half of newly diagnosed female cancers are hormone-dependent, namely breast, ovarian and endometrial tumours. Female breast cancer incidence rates vary substantially worldwide with women in North America and Northern Europe at highest risk. The level of endogenous oestrogen and time of exposition in women seems to play a role in determining the risk, which can also be confirmed by the higher ratio of breast cancer in women to men. On the basis of experimental, epidemiologic and clinical studies, the ovarian hormones, estradiol and progesterone, influence normal breast cell growth and development and are therefore strongly implicated in the aetiology of human breast cancer.
The particular molecular mechanism of action of both hormones in carcinogenesis is being extensively studied. Mechanisms of action of oestrogen are various. The originally described pathway includes the classical interaction of ligand-bound oestrogen receptor dimers with oestrogen-responsive elements in promoter region of target genes that promote growth of mammary epithelium. The main downstream mediators of oestrogen action include epidermal growth factor, transforming growth factors alpha and beta, platelet-derived growth factor, insulin–like growth factors I and II. Besides this classical pathway there has been documented non-transcriptional effect of oestrogen which acts through activation of mitogen-activated protein kinases. The role of progesterone in breast cancer is less understood, however progestin stimulation of breast cancer motility and invasion has been demonstrated.
Despite the indisputable contribution of hormone receptors to neoplastic development, hormone receptor positive breast cancers are very pliable to respond to endocrine therapy and oestrogen and progesterone receptor expression is an important predictor of response to hormonal therapy, which is the most important therapeutic approach in hormone receptor positive breast cancers. However up to half of patients relapse despite adjuvant hormonal therapy and resistance to anti-hormonal drugs unavoidably develops. Identification of resistance mechanism may enable development of new pharmaceutical compounds targeted at key molecules of therapy resistance pathways. 


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Hormones in Breast Carcinogenesis (pp. 121-134)