Tamoxifen therapy in premenopausal patients with metastatic breast cancer

Tamoxifen was evaluated in a phase II trial as initial hormonal therapy in premenopausal patients with metastatic breast cancer. The study design was such that responders remained on tamoxifen therapy; those who initially or subsequently progressed went on to ovarian ablation either by surgery or irradiation. Of 42 evaluable patients treated with tamoxifen, three had complete responses (CR), ten had partial responses (PR), and four remained stable (ST), giving total response rates of 32% (CR + PR) or 41% (CR + PR + ST). Among the 18 patients with positive estrogen (ER) or progesterone (PgR) receptors, there were eight responders, but only one responder (ST) in the nine patients with negative ER or PgR. Of the 25 patients who failed to respond to tamoxifen, 13 underwent ovarian ablation; all failed to respond. These 13 included four patients who were ER positive or equivocal and PgR positive or unknown. Nine tamoxifen responders (CR + PR + ST) have subsequently progressed; of these, eight have gone on to ovarian ablation. Six of these eight have responded (five PR and one ST) to ovarian ablation, and one has failed to respond. Thus, steroid receptors generally predicted a patient's response to tamoxifen therapy, but response to tamoxifen also strongly predicted a patient's subsequent response to ovarian ablation.