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 adva nced breast cancer before the introduction of contemporary endocrine therap y. While the mechanism of the antitumor effect is unknown, in vitro investi gations have shown estrogens in high concentrations to be toxic to cell gro wth. Further, it has been shown that exposure of MCF-7 cells to estrogens i n low concentrations may enhance the sensitivity and also lower the toxicit y threshold to estrogens. This study was designed to evaluate treatment wit h diethylstilbestrol (DES) in postmenopausal women with advanced breast can cer becoming resistant to estrogen deprivation. Thirty-two patients with ad vanced breast cancer previously exposed to multiple endocrine treatment reg imens (median 4, range 2-10) were enrolled. Their tumor should have reveale d evidence of endocrine sensitivity (previous partial response or at least stable disease for greater than or equal to 6 months to therapy). Each pati ent received DES 5 mg t.i.d. Four patients terminated therapy after less th an or equal to 2 weeks on therapy due to side effects; another two patients terminated therapy before progression for similar reasons (one patient aft er SD for 15 weeks and one with a PR after 39 weeks). Four patients obtaine d 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 b reast cancer patients heavily pretreated with endocrine therapy. Such treat ment represents a valuable alternative to chemotherapy in selected patients .