Diethylstilbestrol revisited in advanced breast cancer management

Abstract

Prior to the introduction of tamoxifen, diethylstilbestrol (DES) was widely used as the first-line endocrine therapy in postmenopausal women with advanced breast cancer. Since randomized trials reported that tamoxifen has a similar response rate but fewer side effects than DES, its use has declined markedly. We administered DES in a dose of 10-20 mg daily to 11 postmenopausal women with advanced breast cancer, all of whom had received previous endocrine and some cytotoxic therapy also. Four women showed tumour responses to DES (1 complete and 3 partial), 5 had stable disease, and 2 progressive disease. Amongst the patients who responded, 2 had previously been unresponsive to other endocrine treatments. Of the women with stable disease, 3 had prolonged relief of symptoms. No withdrawal responses were noted. The major side effects were nausea (severe in 2 patients, mild in 1) and cardiac failure (2 patients). We conclude that DES remains a useful, active agent in the management of advanced breast cancer in postmenopausal women, even in patients with tumours unresponsive to other endocrine therapy.

The use of high-dose estrogens for the treatment of breast cancer

“…As of the 1990s, the use of estrogens for the treatment of advanced breast cancer was revisited as HDEs showed efficacy in patients who were exposed to multiple prior hormone therapies. In 1990, Boyer and Tattersall [28] treated 11 postmenopausal patients with disseminated breast cancer with DES after they had observed an impressive response to DES in a breast cancer patient with pulmonary metastasis resistant to several other hormone therapies. The dose of DES ranged between 10 and 20 mg per day.…”

“…Objective response and clinical benefit rates of estrogens versus AIs/FUL in heavily pre-treated patients. Figure created based on data from Boyer and Tattersall [28] and Lonning et al [12] for DES; Ellis et al [18] (two dose levels), Chalasani et al [16] and Zucchini et al [17] for E2; Agrawal et al [13] and Iwase et al [15] for EE; Ingle et al [29] (two dose levels), Jones et al [30], Lonning et al [31], Gennatas et al [34] for AIs; Franco et al [32] and Ingle et al [33] for FULV; Massarweh et al [35] for FULV with everolimus. The number of studies included in this figure for each compound is given between brackets.…”

Estrogen as therapy for breast cancer

“…It has become the present author's experience that a step-wise escalation of the estrogen dose over 1–2 weeks, and in some cases longer, will ameliorate the toxicity and make the treatment tolerable. A previous report also identified efficacy for DES in a smaller group of 11 patients, in whom all but one had received at least two prior therapies and four achieved a complete response or a partial response [6]. …”

The Two Faces of Janus: Sex Steroids as Mediators of Both Cell Proliferation and Cell Death

“…Tamoxifen treatment superseded the use of DES because the former was better tolerated than the latter (31). However, tumors that ceased to respond to tamoxifen underwent clinical regression after DES treatment (32), suggesting different underlying mechanisms. As Song et al (1) mentioned, a recent update of the original trial comparing DES with tamoxifen demonstrated that patients treated with DES survived longer than patients receiving tamoxifen.…”