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Due to the nature of tamoxifen as a competitive ER ligand, this increase in estrogen levels is liable to interfere with the antiestrogenic efficacy of tamoxifen. [85] The effects of tamoxifen on breast cancer Ki-67 expression , sex hormone-binding globulin (SHBG) levels, and IGF-1 levels are dose-dependent across a dosage range of 1 to 20 mg ...
Tamoxifen is a pure antiestrogenic trans-isomer and has differential actions at estrogen target tissues throughout the body. Tamoxifen is selectively antiestrogenic in the breast but estrogen-like in bones and endometrial cancer. [26] Tamoxifen undergo phase I metabolism in the liver by microsomal cytochrome P450 (CYP) enzymes.
Estrogen deprivation therapy, also known as endocrine therapy, is a form of hormone therapy that is used in the treatment of breast cancer.Modalities include antiestrogens or estrogen blockers such as selective estrogen receptor modulators (SERMs) such as tamoxifen, selective estrogen receptor degraders such as fulvestrant, and aromatase inhibitors such as anastrozole and ovariectomy.
All of the forms of estrogen found in the human body are able to bind to estrogen receptors (ER) present on cells. This initiates transcription in these cells, resulting in control of gene expression. [12] Treatment strategies that work by blocking the effect of estrogen on breast cancer are referred to as endocrine (or hormone) therapies.
Antiestrogens, also known as estrogen antagonists or estrogen blockers, are a class of drugs which prevent estrogens like estradiol from mediating their biological effects in the body. They act by blocking the estrogen receptor (ER) and/or inhibiting or suppressing estrogen production .
Some members of this family, such as tamoxifen, are actually partial agonists, which can actually increase estrogen receptor signalling in some tissues, such as the endometrium. Tamoxifen is currently first-line treatment for nearly all pre-menopausal women with hormone receptor-positive breast cancer. [1]
Sivifene (A-007) was initially thought to be a SERM due to its structural similarity to tamoxifen but it was subsequently found not to bind to the estrogen receptor (ER). [8] Tesmilifene (DPPE; YMB-1002, BMS-217380-01) is also structurally related to tamoxifen but similarly does not bind to the ER and is not a SERM. [9] [10]
Staging breast cancer is the initial step to help physicians determine the most appropriate course of treatment. As of 2016, guidelines incorporated biologic factors, such as tumor grade, cellular proliferation rate, estrogen and progesterone receptor expression, human epidermal growth factor 2 (HER2) expression, and gene expression profiling into the staging system.