Progesterone (PR)There are three isoforms of PR which are PR-A, PR-B and PR-C. PR-A is a truncated N-terminal that is crucial for uterine development and reproductive function. PR-B is necessary for normal development of the mammary gland and PR-C, lacking classical transcriptional activity, functions instead as a dominant inhibitor of uterine PR-B in the myometrium during labor. (Carol A. Lange et al 2008) The active involves binding with the ovarian steroid ligand, PR gene expression regulated by ligand-activated transcription factors can bind directly and indirectly to DNA. The three PR isoforms are a single gene located in chromosome 11 that undergoes transcription via the alternative promoters and internal translation start site. In the absence of PRs, PRs are involved in several chaperone molecules required for correct protein folding and constitute a cluster of stable PR-hsp90 herterocomplexes, competent for ligand binding. After binding to the PR, the receptor undergoes restructuring and dissociation of the hsp. Receptor activation will bind directly to the specific PR response element. By directly or indirectly binding to DNA, PRs will regulate the basal transcription machinery in conjunction with coregulatory molecules of nuclear receptors. (Carol A. Lange et al 2008) Estrogen (ER) Estrogen is a modulator of cell growth and differentiation in the mammary gland. . It mediates most of the function through two members of the nuclear receptor superfamily, ERα and ERβ. These receptors are hormone-dependent transcriptional regulators that, in the presence of appropriate ligands, bind to DNA EREs or interact with proteins in other pathways and affect the transcription of specific genes (...... middle of the article ..... .cer primarily targeting the ER signaling pathway either by reducing estrogen level, antagonizing ER function with antiestrogens such as tamoxifen or downregulating estrogen levels of ER with pure anti-estrogens such as fulvestrant (Faslodex (Rachel Schiff et al 2003). Tamoxifen is commonly used and is a non-steroidal SERM, which will inhibit the growth of breast cancer by competitive blockade of the ER , thereby inhibiting estrogen-induced growth (Elisavet Paplomata et al 2013) Tamoxifen is effective in most patients, but there is a complication that causes ER that does not respond to tamoxifen to lead to resistance. tamoxifen. Some patients who initially respond to tamoxifen will have acquired tumor resistance leading to tumor progression and death. When the patient develops resistance to tamoxifen, treatment should be stopped immediately. (Rachel Schiff et al. 2003)