High-dose estrogen treatment in postmenopausal breast cancer patients heavily exposed to endocrine therapy

Estrogens administered in high doses were commonly used for therapy of advanced breast cancer before the introduction of contemporary endocrine therapy. While the mechanism of the antitumor effect is unknown, in vitro investigations have shown estrogens in high concentrations to be toxic to cell growth. Further, it has been shown that exposure of MCF-7 cells to estrogens in low concentrations may enhance the sensitivity and also lower the toxicity threshold to estrogens. This study was designed to evaluate treatment with diethylstilbestrol (DES) in postmenopausal women with advanced breast cancer becoming resistant to estrogen deprivation. Thirty-two patients with advanced breast cancer previously exposed to multiple endocrine treatment regimens (median 4, range 2-10) were enrolled. Their tumor should have revealed evidence of endocrine sensitivity (previous partial response or at least stable disease for greater than or equal to 6 months to therapy). Each patient received DES 5 mg t.i.d. Four patients terminated therapy after less than or equal to 2 weeks on therapy due to side effects; another two patients terminated therapy before progression for similar reasons (one patient after SD for 15 weeks and one with a PR after 39 weeks). Four patients obtained CR and six patients PR. In addition, two patients had SD for greater than or equal to 6 months duration. Five patients had an objective response and one patient a SD lasting for greater than or equal to 1 year. Our results reveal estrogens administered in high doses may have antitumor effects in breast cancer patients heavily pretreated with endocrine therapy. Such treatment represents a valuable alternative to chemotherapy in selected patients.