Antiestrogen treatment of breast cancer: An overview

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 particular, 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 induce 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 remission after tamoxifen or after tamoxifen plus hypophysectomy, and there was no correlation between the response to antiestrogen and 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.