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

Abstract

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 > or = 6 months to therapy). Each patient received DES 5 mg t.i.d. Four patients terminated therapy after < or = 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 > or = 6 months duration. Five patients had an objective response and one patient a SD lasting for > or = 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.

Estrogen induces apoptosis in estrogen deprivation-resistant breast cancer through stress responses as identified by global gene expression across time

“…A pivotal study of high-dose DES therapy (15 mg daily) in 32 patients with metastatic breast cancer who had been treated exhaustively with antihormonal therapies produced a 30% objective response rate (26). There were 4 of 32 complete responses, and one patient maintained a complete response for an additional 7 y, even after stopping estrogen (27).…”

Development and evolution of therapies targeted to the estrogen receptor for the treatment and prevention of breast cancer

“…There are current proposals to use physiological estrogen to reduce tumor burden in sensitive tumors that have responded and failed two consecutive antihormonal therapies. The clinical basis for estrogen responsiveness has already been demonstrated in this patient group [154] but the use of a twelve week course of low dose estrogen followed by the reintroduction of aromatase inhibition plus fulvestrant would not only incorporate the current laboratory results for the design of a clinical trial but also improve patient disease control prior to chemotherapy [155].…”

Safety of pregnancy following breast cancer diagnosis

“…Breast cancer cells expressing oestrogen or progesterone receptors undergo apoptosis when exposed to high doses of oestrogens [4,5]; which is the case during pregnancy. In this regard it would be interesting to analyse the Danish Breast Cancer Cooperative Group (DBCCG) data for hormone receptor status at diagnosis to see if there is any correlation with improved survival.…”