Hormonal therapies are some of the oldest active systemic anti-cancer therapies in use today. In 1896, Beatson demonstrated that surgical oophorectomy resulted in tumour regression in some premenopausal women with metastatic breast cancer, and, by doing so, he was the first to identify a link between ovarian function and breast cancer (Beatson, 1896).
Substantial evidence now exists that hormones play a key role in both the cause and the outcome of several cancers. Although this is most clearly seen in breast and prostate cancer, other cancers that may exhibit hormone dependence include endometrial, ovarian and testicular cancers.
Hormones are classified into two groups:
• non-steroidal hormones including peptides, polypeptides or derivatives of amino acids, generally acting via cell-membrane-localised receptors which trigger second messengers within the cytoplasm; and
• steroidal hormones, such as oestrogens, androgens and progestins, bind to intracellular receptors to mediate their action.
This chapter will focus primarily on steroidal hormones that are of particular importance in breast and prostate cancer: oestrogens, progestins and androgens. It should be read in conjunction with the relevant site-specific chapters (Chapters 19 and 22). This chapter provides some background knowledge of the production and functioning of hormones and their receptors, which will help in the understanding of commonly used therapies. The aetiology of hormone-related cancers is discussed in the relevant site-specific chapters.
Steroidal hormones have the potential to activate oncogenes or inactivate tumour-suppressor genes, producing a sequence of changes within the cell that ultimately lead to cancer. The continued growth of the cancer often depends on continuing hormone stimulation and so removing the hormonal stimulus causes the cancer to regress. Anti-cancer hormone therapies work in a number of different ways – by affecting hormone synthesis, metabolism or action, or by altering hormone receptor expression within the cell.
A summary of the major historical landmarks in anti-cancer hormonal therapy since Beatson's observation in 1896 is listed here.