Pearson O H, Manni A, Arafah B M
Cancer Res. 1982 Aug;42(8 Suppl):3424s-3429s.
The nonsteroidal antiestrogen tamoxifen has emerged as a highly effective, nontoxic endocrine therapy for women with Stage IV and II estrogen receptor-positive breast cancer. Tamoxifen appears to act by blocking endogenous estrogen action at the target tissue level rather than by suppression of circulating estrogen levels. In a series of 113 consecutive, selected patients with Stage IV breast cancer, tamoxifen induced objective remissions in 50% lasting an average period of 21 + months and a median period of 16 months. These results are comparable to previous results with surgical hypophysectomy. Recent randomized studies comparing pharmacological doses of estrogen versus tamoxifen in postmenopausal women with Stage IV breast cancer have shown comparable results with these two treatment modalities. Antiestrogen therapy has been shown to be effective in some patients after prior endocrine additive therapy and, in particularly, after ablative procedures, such as ovariectomy, adrenalectomy, and hypophysectomy. It has been shown that circulating estrogens are not completely eliminated following ablation of these endocrine glands, which may account for the effectiveness of antiestrogen in this setting. Other endocrine therapies have been shown to be effective after prior treatment with antiestrogen. Hypophysectomy can induced remissions in 60% of patients who initially responded to tamoxifen and in 25% of patients who failed to benefit from tamoxifen. Recent studies have shown that aminoglutethimide plus hydrocortisone may also induce remissions in some patients after prior treatment with tamoxifen. This latter finding is of particular interest since aminoglutethimide is thought to work by blocking estrogen production, and the finding suggests that tamoxifen does not completely block all endogenous estrogen activity. Fluoxymesterone has been shown to induce remissions after tamoxifen or after tamoxifen plus hypophysectomy, and there was no correlation between the response to antiestrogen abd subsequent response to androgen. Because of its effectiveness and minimal side effects, tamoxifen is considered to be an initial endocrine therapy of choice in women with breast cancer. However, it has its limitations, as demonstrated by the results of secondary endocrine therapies such as hypophysectomy, medical adrenalectomy, and androgen therapy.
非甾体类抗雌激素药物他莫昔芬已成为治疗IV期和II期雌激素受体阳性乳腺癌女性患者的一种高效、无毒的内分泌疗法。他莫昔芬似乎是通过在靶组织水平阻断内源性雌激素的作用，而非通过抑制循环雌激素水平来发挥作用。在一系列连续入选的113例IV期乳腺癌患者中，他莫昔芬使50%的患者出现客观缓解，缓解平均持续21 +个月，中位持续时间为16个月。这些结果与先前垂体切除手术的结果相当。近期的随机研究比较了绝经后IV期乳腺癌女性患者使用药理剂量雌激素与他莫昔芬的疗效，结果显示这两种治疗方式效果相当。抗雌激素疗法已被证明在一些先前接受过内分泌辅助治疗的患者中有效，尤其是在进行了诸如卵巢切除术、肾上腺切除术和垂体切除术等去除内分泌腺的手术后。研究表明，切除这些内分泌腺后，循环雌激素并未完全消除，这可能是抗雌激素在这种情况下有效的原因。其他内分泌疗法在先前接受抗雌激素治疗后也被证明有效。垂体切除术可使60%最初对他莫昔芬有反应的患者以及25%未从他莫昔芬治疗中获益的患者出现缓解。近期研究表明，氨鲁米特加氢化可的松在先前接受他莫昔芬治疗后的一些患者中也可能诱导缓解。后一发现尤其令人关注，因为氨鲁米特被认为是通过阻断雌激素生成起作用的，这一发现表明他莫昔芬并未完全阻断所有内源性雌激素活性。氟甲睾酮已被证明在他莫昔芬治疗后或他莫昔芬加垂体切除术后可诱导缓解，且对抗雌激素的反应与随后对雄激素的反应之间无相关性。由于其有效性和极小的副作用，他莫昔芬被认为是乳腺癌女性患者首选的初始内分泌疗法。然而，正如垂体切除术、药物性肾上腺切除术和雄激素疗法等二线内分泌疗法的结果所示，它也有其局限性。
