In 1977 tamoxifen was approved by the Food and Drug Administration (FDA) for use in the treatment of breast cancer, initially only in postmenopausal women with metastatic breast cancer. Of this population approximately one-third responded to tamoxifen treatment. When used in addition to chemotherapy for patients with metastatic disease, a higher response rate, a longer time to treatment failure, and improved survival were reported. In postmenopausal patients tamoxifen appeared to be effective at virtually all stages of disease, with its major contribution in patients who had exhausted most other forms of hormonal therapy.

SHOULD CHEMOTHERAPY BE GIVEN AT THE SAME TIME AS TAMOXIFEN?

Since most tumors are a mixture of estrogen-receptor-positive and estrogen-receptor-negative cells, and tamoxifen specifically inhibits cells with estrogen receptors, combination therapy using both cytotoxic drugs and tamoxifen has been suggested to prevent the recurrence of the estrogen-receptor-negative cells. Clinical trials examining the simultaneous use of chemotherapy and tamoxifen suggest that the drugs probably should not be given at the same time. Although higher response rates were achieved in some studies when the drugs were given together, most analyses have shown that the overall survival of patients is not prolonged by simultaneous administration.

WHAT ABOUT SEQUENTIAL CHEMOTHERAPY AND TAMOXIFEN?

The administration of cytotoxic chemotherapy followed by tamoxifen has been examined in several programs. Sequential administration appears to avoid the problems noted when the drugs are administered simultaneously. Patients treated sequentially seem to have fewer residual side effects from chemotherapy during tamoxifen treatment, which may ultimately improve their quality of life. Sequential use has also been demonstrated to be very effective in the treatment of metastatic breast cancer. In advanced disease the sequential addition of tamoxifen to chemotherapy results in some patients having a higher response rate, a longer time until treatment failure, and improved overall survival.

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