INTRODUCTION

As early as the 19th century, investigators began to recognize the importance of hormonal suppression in the treatment of breast cancer. In 1896, George Beatson observed an association between surgical removal of the ovaries and reduction in some of the breast tumors (Beatson, 1896). Since that time, investigators have attempted to suppress estrogen through many different avenues. Because hormonal therapies are very specific in their ability to block specific receptors and various feedback loops, these therapies were the first form of targeted therapy. Although hormone therapy was first used in the treatment of breast cancer, it was quickly added to the treatment regimens of prostate, endometrial, and ovarian cancers. Tumor growth that is stimulated by testosterone or estrogen can be suppressed by blocking these hormones from communicating with the cancer cells.

ADRENOCORTICOIDS

Adrenocorticoids are mainly responsible for the control of glucose metabolism, gluconeogenesis, and immune systems regulation. The major forms of adrenocorticoids are cortisol and corticosterone. Adrenocorticoids are manufactured in the adrenal cortex and regulated through the action of adrenocorticotropic hormone (ACTH). ACTH is produced in the anterior pituitary. The regulation of ACTH depends on a precise sensitive balance between serum levels and stimulation from the nervous system. The feedback effects are mediated from the nervous system. The most commonly used corticosteroids in clinical practices are cortisone acetate, hydrocortisone, prednisolone, methylprednisolone, and dexamethasone. Studies of tissue culture demonstrated that lymphoid cells are most sensitive to glucocorticoids and resulted in a great decrease in deoxyribonucleic acid, ribonucleic acid, and protein synthesis (Cohen, 1989). Adrenocorticoids or glucocorticoids inhibit lymphocyte proliferation by encouraging apoptosis (Cohen, 1989). These agents are used commonly in acute lymphoblastic leukemia, chronic lymphocytic leukemia, Hodgkin disease, non-Hodgkin lymphoma, and multiple myeloma. In addition, the drugs may be used as adjuvant treatment with routine antiemetics, pain medicine, and to reduce edema from central nervous system metastasis.

The most common side effects from this class of drugs are hypersensitivity, appearance of Cushing’s syndrome, osteoporosis, diabetes mellitus, and profound immune system suppression. Additional side effects include euphoria, peptic ulcer disease, and steroid psychosis.

ANDROGENS

The generic term for the major sex steroid in males is androgens. The testes produce testosterone, which is the primary male hormone. The main functions of the androgens are male development, spermatogenesis, inhibition of fat deposition, and muscle mass and brain development. The most well-known adrenal androgen is testosterone. Other androgens include the following:

ANTIESTROGENS

It has been apparent to observant clinicians for more than a century that estrogen played an important role in the pathophysiological mechanisms of breast cancer. It became known in the early 1900s that approximately one third of premenopausal women with advanced breast cancer would respond to an oophorectomy (Boyd, 1990; Jordan & Kennedy, 1997). In the same way, some postmenopausal women responded to adrenalectomies and hypophysectomy (Pearson, Ray, & Harold, 1956). With the discovery of the estrogen receptor (Jensen & Jacobson, 1962; Toft & Gorski, 1966) the mechanisms of actions for estrogen on the various target tissues became more apparent. The two most common drug classes used for their antiestrogen-like effects include selective estrogen receptor modulators (SERMs) and estrogen-receptor down-regulators (ERD).

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