Fundamental research leading to improved endocrine therapy for breast cancer

Whilst endocrine therapy has a long-established role in the management of patients with advanced breast cancer, current therapies produce remission in, at best, only between 30 and 40% of cases. The most efficient use of hormonal measures therefore requires the accurate identification of individuals with hormone-responsive tumours. Oestrogen receptor measurements are useful but not fully discriminatory and additional predictive factors are required. Markers, such as specific hormonally induced proteins and mRNA, and antagonistic systems, such as epidermal growth factor receptors and cyclic AMP binding proteins are currently being evaluated. In terms of therapy, surgical manoeuvres such as adrenalectomy and hypophysectomy have already been replaced by the medical administration of anti-oestrogens, progestogens and drug regimes such as aminoglutethimide-hydrocortisone. Although castration by surgery or radiation remains the first-line treatment in premenopausal women with advanced disease, the advent of depot preparations of LHRH agonists offers the opportunity of performing medical ovariectomies which have the added advantage of being reversible. As a result of laboratory studies, more potent anti-oestrogens and more specific "suicide" aromatase inhibitors are entering into clinical practice. These can be expected to increase efficacy of treatment whilst reducing its side-effects. Research using cell-lines of human breast cancer also suggests that anti-progestins and agents capable of antagonizing steroid-induced growth factors will inhibit tumour growth. Such novel therapies potentially could make a major impact in the endocrine management of breast cancer. Lastly, although the primary management of early breast cancer predominantly involves non-hormonal modalities, clinical trials are now providing evidence of survival benefit from adjuvant endocrine therapy. The knowledge accrued from the use of newer endocrine agents in advanced cancer could therefore ultimately be relevant to the treatment of earlier stages of the disease.