Endocrine therapy for tumors can be traced back to the late 19th century. In 1896, Beaton reported 2 cases of advanced breast cancer patients with symptom relief after removal of ovaries, and in 1941, Huggins and Hodges achieved good results in the treatment of prostate cancer by removing testes. At present, endocrine therapies have become an important tool in the treatment of tumors. In addition to gynecological tumors such as ovarian cancer that can be treated with progesterone, breast cancer and prostate cancer are also commonly treated with endocrine drugs. Among several advances in endocrine therapy, the main one is the discovery of hormone receptors, which reveals the principle that hormones act through receptors to produce biological effects, laying a theoretical foundation for endocrine therapy. Endocrine therapy has the advantages of convenient drug administration, less adverse effects and long-lasting therapeutic effect. In particular, in the past 10 years, estrogen receptor (ER) and progesterone receptor (PR) measurements have been carried out in China to select suitable treatment targets and further improve the therapeutic effect. I. Principle of hormone action Current endocrine therapy involves changes in the concentration or activity of steroid hormones (steroid hormones), except for thyroid hormone control of thyroid cancer. Steroid hormones, including estrogens, progestins, androgens and adrenocorticotropic hormones, all share a common basic structure, the steroid nucleus. Steroid hormones are lipid-soluble and readily cross the cell membrane to enter the cell. After their receptors bind to the hormones entering the target cells in the cytosol, their conformations change, some of them polymerize, and some of them thus remove the small molecule inhibitors originally present on the receptors, thus forming active complexes, which are then transferred into the nucleus to regulate nucleic acid metabolism, mainly activating the DNA transcription process and inducing the production of new proteins and enzymes, and finally exerting various biological effects. At present, this “three-step theory” of steroid hormone mechanism of action proposed by Jensen et al. has been widely accepted. Some scholars also believe that the receptor exists only in the nucleus of the cell based on the experimental results, thus proposing the “one-step theory” of steroid hormone action principle. Therefore, there is still a debate about the real mechanism of hormone action in the cell, which needs to be further elucidated. Hormones and hormone receptors 1. Estrogen and estrogen receptors Estrogen is mainly secreted by the ovaries, and the adrenal cortex also produces a small amount of hormones. Under normal conditions, estrogen promotes breast development. Lacassagne confirmed in animal experiments that estrogen can induce mammary carcinoma in mice, but if the pituitary gland is removed beforehand, mammary carcinoma will not occur. In rats, mammary carcinoma was induced with methylcholanthrene. If the ovaries, adrenal glands and pituitary gland are removed, the cancer can shrink or even regress, and estrogen administration does not cause deterioration. In breast cancer patients, the removal of the ovaries and adrenal glands eliminates the source of estrogen and the breast cancer is expected to improve, but if physiological doses of estrogen are given, the cancer will reappear and progress. All these data indicate that estrogen has a breast cancer-causing effect, and its effect must pass through the pituitary gland to be realized. Progesterone and progesterone receptors Progesterone is secreted by the ovaries and can also be converted from progesterone secreted by the adrenal cortex. Progesterone mainly acts on the endometrium and uterine muscle, and promotes the development of mammary glands with the cooperation of estrogen. Like androgens, it is a hormone that promotes anabolic metabolism. It has a more complex effect on water and salt metabolism and has an antagonistic effect on aldosterone. Progesterone has an antagonistic function against estrogen and is thought to have a protective effect in the incidence of breast cancer. Progesterone also converts proliferating endometrium into mature secretory endometrium, and cancer rarely occurs in endometrium that is cyclically acted upon by progesterone. The progesterone receptor (PR) is the end product of estradiol action, and the complex of estradiol and the receptor moves into the nucleus of the cell in its entirety, leading to the presence of PR through gene transcription. The effectiveness of endocrine therapy can be more accurately estimated in breast cancer patients by testing both ER and PR, while the effectiveness of endocrine therapy is 50%-60% in ER positive patients and more than 77% in both ER and PR positive patients. The efficiency of endocrine therapy for both ER and PR positive tumors is 10 times higher than that for both ER and PR negative tumors, which are mostly of better differentiated pathological types, while 50% of receptor negative tumors are poorly differentiated. Androgens and androgen receptors are mainly synthesized and secreted by the testes, and a small amount of testosterone is also secreted by the adrenal glands and ovaries. Androgens reach the target organs through blood circulation, and their main function is to stimulate the development of male sexual organs and maintain their functions, and to stimulate the emergence of male secondary sexual characteristics and maintain them in a normal state, in addition, they also have obvious effects on the central nervous system and metabolism, and mainly promote the synthesis of proteins. 4. Glucocorticoids and their receptors are secreted by the adrenal cortex, which are not only effective in the treatment of acute leukemia and chronic lymphocytic leukemia and can effectively control the disease, but are also the basic components in the combined chemotherapy of multiple myeloma, malignant lymphoma and breast cancer. Glucocorticoids work through glucocorticoid receptors. The relationship between hormones and tumors Certain tumors partially or fully retain hormone receptors in the cancer process, and their growth and division are influenced by the hormonal environment, and endocrine therapy is effective, which are called hormone-dependent tumors; while another type of tumors lack hormone receptors, and their growth and division are not influenced by the hormonal environment, and endocrine therapy is often ineffective, which are called non-hormone-dependent tumors. In terms of the relationship between estrogen and progesterone and tumors, the presence or absence of ER and PR is the key to determine the dependence of the tumor on estrogen and progesterone, and cannot be based on the origin of the tissue alone. In other words, tumors originating from estrogen and progestin target tissues lacking ER and PR will lack hormone dependence, while tumors from non-estrogenic organs containing ER and PR will indicate hormone dependence, and anti-estrogen therapy will inhibit its development. According to the hormone receptor theory of tumor, the determination of hormone receptor (ER, PR or AR) should be performed before endocrine therapy. For patients with ER and PR positive tumors, anti-estrogen therapy should be administered; for patients with AR positive tumors, anti-androgen therapy should be administered. 1. Anti-estrogen therapy: (1) Section endocrine therapy: mainly ovariectomy; pituitary tumor resection has similar efficacy to adrenalectomy creation, but it is not commonly used. (2) Endocrine therapy in internal medicine; including androgen therapy, anti-estrogen therapy, anti-estrogen therapy and glucocorticoid therapy. (2) Anti-androgen therapy: (1) Surgical endocrine therapy: orchiectomy is commonly used; pituitary resection and adrenalectomy are now eliminated because of trauma and poor results. (2) Internal endocrine therapy: including estrogen therapy, anti-androgen therapy and glucocorticoid application.