Jordan V C, Fritz N F, Gottardis M M
Department of Human Oncology, University of Wisconsin Clinical Cancer Center, Madison 53792.
J Steroid Biochem. 1987;27(1-3):493-8. doi: 10.1016/0022-4731(87)90345-1.
Current clinical research is focused upon the application of adjuvant therapy for the treatment of breast cancer. Combination chemotherapy is the most successful adjuvant therapy for premenopausal patients whereas the antiestrogen tamoxifen (1 or 2 yr) is successful in postmenopausal disease. We have developed a unifying strategy for the treatment of breast cancer. The thesis is based upon the application of continuous adjuvant therapy with tamoxifen in a low estrogen environment. Chemotherapy causes a chemical castration in premenopausal patients. In contrast, tamoxifen causes an increase in steroidogenesis. A combination of both approaches will work against each other until ovarian failure occurs. Patients should be checked for castration to provide a low estrogen environment in which tamoxifen, a competitive antagonist of estrogen action, can effectively work. Laboratory evidence using carcinogen-induced rat mammary tumor models demonstrates the efficacy of long-term therapy. Studies with the human breast cell line MCF-7 grown in athymic mice show that tamoxifen is a tumoristatic agent so that once the therapy is stopped, tumors can be regrown by estrogen administration. Patients should receive continuous tamoxifen therapy to prevent the growth-stimulating effects of adrenal steroids, environmental and phyto-estrogens.
当前的临床研究主要集中在辅助治疗在乳腺癌治疗中的应用。联合化疗是绝经前患者最成功的辅助治疗方法，而抗雌激素药物他莫昔芬（服用1或2年）对绝经后疾病治疗有效。我们已经开发出一种统一的乳腺癌治疗策略。该策略基于在低雌激素环境中应用他莫昔芬进行持续辅助治疗。化疗会导致绝经前患者化学性去势。相比之下，他莫昔芬会导致类固醇生成增加。在卵巢功能衰竭发生之前，这两种方法的联合使用会相互抵消作用。应检查患者是否处于去势状态，以提供一个低雌激素环境，使作为雌激素作用竞争性拮抗剂的他莫昔芬能够有效发挥作用。使用致癌物诱导的大鼠乳腺肿瘤模型的实验室证据证明了长期治疗的有效性。对在无胸腺小鼠体内生长的人乳腺癌细胞系MCF-7进行的研究表明，他莫昔芬是一种肿瘤生长抑制剂，因此一旦停止治疗，通过给予雌激素肿瘤就会重新生长。患者应接受持续的他莫昔芬治疗，以防止肾上腺类固醇、环境雌激素和植物雌激素的促生长作用。
