High dose estrogen as a salvage hormonal strategy for highly refractory metastatic breast cancer (MBC): “back to the future.”.

Abstract

Abstract Abstract #6129 High dose estrogens are an efficacious but widely ignored treatment option for patients with MBC. This is due in part to the introduction of tamoxifen, which was shown to be equivalent in efficacy with fewer side effects in the 1970's. After local Institutional Review Board approval we identified 26 patients with MBC treated in our practice with either diethylstilbestrol (15mg/day) or estradiol, generally, at a dosage of 30mg daily. One patient remains too early to evaluate. The median age at initial diagnosis was 46 and median age for patients at the start of high dose estrogen therapy was 59. All but 2 patients had confirmed hormone receptor positive tumors (one with a very long disease free interval and the other, prior response to hormonal therapy). Two of 26 patients were HER-2neu + by FISH analysis. The median # of sites of disease was 2 (range 1-3) and 50% had dominant visceral disease. Patients had received a median of 3 prior chemotherapy regimens (range 0-7), and 4 prior hormonal regimens (range 1-7), for a median of 7 prior systemic therapies (range 0-12). The median distant disease free interval (DFI) was 62 months (range 0 to 264 months). The median time from recurrence to initiation of estrogen therapy was 57 months (range 1 to 132 months). Six of 25 (24%) currently evaluable patients had objective anti-tumor responses, with one having a complete response in liver of 22 months. In addition, 4 of 25 patients (16%) with less clearly measurable disease had prolonged stable disease for ≥ 6months (7, 9, 13, and 14months, respectively). Clinical benefit (defined as CR, PR, and prolonged SD ≥6months) was 40%, with median duration of 9 months (mean of 12). Two patients are in continuing remission at 7 and 14months, respectively. Toxicities included vaginal bleeding in 7 of 25 (6 grade 1 and 1 grade 2), nausea in 4, and fluid retention in 8 (7 grade 1 and 1 grade 2). The patient with grade 2 fluid retention responded to a dose reduction to 6mg daily. Only 3 of 25 of patients discontinued estrogen therapy due to toxicity (1 vaginal bleeding, 1 refused to continue, and 1 nausea). In addition, one of the 3 patients that discontinued due to toxicity had a prolonged estrogen withdrawal response of 12months duration after 9 months of stable disease. Conclusion: Almost all patients with hormone receptor (+) MBC eventually develop resistance to endocrine agents. These data confirm the efficacy of high dose estrogens as yet another option for heavily-treated patients in whom further endocrine manipulation might still be appropriate. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6129.