Strategies to implement estrogen therapy for advanced estrogen receptor -positive breast cancer are under-developed. Preclinical data suggest that cycling treatment with 17b-estradiol followed by estrogen deprivation can control tumor growth long-term.Post-menopausal women with advanced ER+/HER2- breast cancer with recurrence or progression on ≥1 anti-estrogen- or aromatase inhibitor -based therapy were eligible.
1% and objective response rate was 15.8% . One subject experienced a grade 3 adverse event related to 17b-estradiol. Among patients who received continuous single-agent treatment until a second instance of disease progression, clinical benefit was observed in 5/12 cases. Tumor ER mutations were found by whole-exome profiling in 4/7 vs. 2/9 patients who did vs. did not experience clinical benefit from alternating 17b-estradiol/AI therapy.