Tamoxifen in premenopausal patients with metastatic breast cancer: a review.

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.