Miller W R
University Department of Clinical Surgery, Royal Infirmary, Edinburgh, Scotland.
J Steroid Biochem. 1987;27(1-3):477-85. doi: 10.1016/0022-4731(87)90343-8.
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 In terms of therapy, surgical manoeuvres such as adrenalectomy and hypophysectomy have already been replaced by the medical administration of anti-oestrogens, progestogens and drug regimes such as aminoglutethimide-hydrocortisone.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.
虽然内分泌疗法在晚期乳腺癌患者的治疗中有着长期确立的作用，但目前的疗法最多只能使30%至40%的病例获得缓解。因此，要最有效地利用激素治疗措施，就需要准确识别激素反应性肿瘤患者。雌激素受体检测是有用的，但并不完全具有区分性，还需要其他预测因素。目前正在评估一些标志物，如特定的激素诱导蛋白和mRNA，以及拮抗系统，如表皮生长因子受体和环磷酸腺苷结合蛋白。在治疗方面，诸如肾上腺切除术和垂体切除术等外科手术已被抗雌激素、孕激素以及氨鲁米特 - 氢化可的松等药物治疗方案所取代。虽然手术或放疗去势仍是晚期疾病绝经前女性的一线治疗方法，但长效促性腺激素释放激素激动剂制剂的出现提供了进行药物性卵巢切除的机会，这种方法还有可逆的额外优势。实验室研究的结果是，更强效的抗雌激素和更具特异性的“自杀性”芳香化酶抑制剂正在进入临床实践。这些有望提高治疗效果，同时减少副作用。使用人乳腺癌细胞系的研究还表明，抗孕激素和能够拮抗类固醇诱导生长因子的药物将抑制肿瘤生长。这类新疗法可能会对乳腺癌的内分泌治疗产生重大影响。最后，虽然早期乳腺癌的主要治疗方法主要是非激素疗法，但目前的临床试验正在提供辅助内分泌治疗能带来生存获益的证据。因此，在晚期癌症中使用新型内分泌药物所积累的知识最终可能与该疾病早期阶段的治疗相关。
