Sunderland M C, Osborne C K
Department of Medicine, University of Texas Health Science Center, San Antonio 78284-7884.
J Clin Oncol. 1991 Jul;9(7):1283-97. doi: 10.1200/JCO.1991.9.7.1283.
The antiestrogen tamoxifen is the most widely used hormonal therapy for breast cancer. The drug exerts its antiproliferative effects primarily through estrogen receptor (ER)-mediated mechanisms, although other cellular actions may augment tumor inhibition. Clinically, tamoxifen has been less well studied in premenopausal than in postmenopausal patients. The drug has complex endocrine effects that are dependent on the treatment duration and dose, menopausal status, and target organ. In postmenopausal women receiving tamoxifen, serum estrogen levels remain low, and the normally elevated gonadotropin levels decrease. In contrast, serum estrogen levels are strikingly elevated in many premenopausal women, and gonadotropin concentrations are either unchanged or slightly increased. Large systematic trials in metastatic breast cancer have established tamoxifen as the recommended hormonal therapy for postmenopausal women with ER-positive tumors. Tamoxifen is also an active agent for premenopausal metastatic disease, and response rates are comparable to those reported for oophorectomy. Clinical experience with tamoxifen in this younger age group, however, is more limited. Few premenopausal women (less than 400) have been included in phase II and phase III trials. Two randomized trials (total of 160 patients) comparing oophorectomy with tamoxifen do not definitively establish therapeutic equivalence, and a survival advantage for either treatment cannot be excluded. Many questions remain concerning the appropriate role for tamoxifen in premenopausal patients. Still, tamoxifen has an attractive toxicity profile, and it offers a favorable therapeutic alternative for premenopausal women with ER-positive metastatic breast cancer who wish to avoid surgical or radiation castration.
抗雌激素药物他莫昔芬是乳腺癌最常用的激素疗法。该药物主要通过雌激素受体（ER）介导的机制发挥其抗增殖作用，尽管其他细胞作用可能增强肿瘤抑制效果。临床上，他莫昔芬在绝经前患者中的研究不如绝经后患者充分。该药物具有复杂的内分泌效应，这取决于治疗持续时间和剂量、绝经状态以及靶器官。在接受他莫昔芬治疗的绝经后女性中，血清雌激素水平保持较低，而通常升高的促性腺激素水平会降低。相比之下，许多绝经前女性的血清雌激素水平显著升高，促性腺激素浓度要么不变，要么略有升高。转移性乳腺癌的大型系统试验已将他莫昔芬确立为ER阳性肿瘤绝经后女性的推荐激素疗法。他莫昔芬也是绝经前转移性疾病的有效药物，缓解率与卵巢切除术报告的缓解率相当。然而，他莫昔芬在这个较年轻年龄组的临床经验更为有限。很少有绝经前女性（不到400名）被纳入II期和III期试验。两项比较卵巢切除术与他莫昔芬的随机试验（共160名患者）并未明确确立治疗等效性，也不能排除任何一种治疗方法的生存优势。关于他莫昔芬在绝经前患者中的适当作用仍有许多问题。尽管如此，他莫昔芬具有吸引人的毒性特征，对于希望避免手术或放射去势的ER阳性转移性乳腺癌绝经前女性来说，它提供了一种有利的治疗选择。
