Principles of endocrine therapy

It has long been known that oestrogen is capable of stimulating the growth of breast cancer and androgens the growth of prostate cancer. Manipulation of the hormonal environment may result in regression of a number of tumours particularly breast cancer, endometrial cancer and prostate cancer. Hormonal therapy is in general not curative. It may, however, provide control of a tumour for a period of time often with few side-effects. The presence of cell surface receptors for the hormone in question is a prerequisite for the therapy to be effective. The binding of hormone to receptor and translocation of the hormone- receptor complex into the nucleus, where it reacts with the DNA, is shown diagrammatically.
Patients with breast cancer frequently have receptors for oestrogens and progesterones. Hormonal manipulation includes the use of the anti-oestrogen tamoxifen, the reduction of endogenous oestrogen by oophorectomy or ‘medical oophorectomy’ via pituitary down-regulation using a luteinizing hormone releasing hormone (LHRH) analogue. Progestogens and aromatase inhibitors also have antitumour activity.

Mechanism of the cell receptor system.
Mechanism of the cell receptor system.

Endometrial tumours also have receptors for both oestrogens and progesterones. These tumours frequently respond to the administration of progesterone and also to the anti-oestrogen tamoxifen. In prostate cancer the commonest hormonal manipulation used to be the administration of oestrogen. By a negative feedback on the pituitary this resulted in anorchid levels of testosterone and was associated with a response of the tumour in the majority of patients. Unfortunately the severe side-effects with oestrogens, including increased mortality from cardiovascular and cerebrovascular disease, significantly reduced the overall benefit. Another alternative was to carry out an orchidectomy, which reduced circulating testosterone but without the oestrogenic side-effects. More recently the use of an LHRH analogue to create a ‘medical’ orchidectomy and the availability of antiandrogenic drugs have revolutionized the medical treatment of prostate cancer, achieving a response in most patients with few sideeffects.

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