Abstract P2-12-05: Limited Absorption of Low Dose 10µg Intravaginal 17-β Estradiol (Vagifem®) in Postmenopausal Women with Breast Cancer on Aromatase Inhibitors
Authors: Goldfarb SB , Dickler M , Dnistrian A , Patil S , Dunn L , Chang K , Berkowitz A , Tucker N , Carter J , Barakat R , Hudis C , Castiel M 
Published: August 2014

Abstract
Background: Aromatase inhibitors (AIs) are used to treat postmenopausal women with hormone-receptor positive (HR+) breast cancer (BC). AIs block the peripheral conversion of androgens to estrogen (E), resulting in sub-physiologic levels of E that may lead to profound urogenital atrophy. Atrophic vaginitis in BC survivors is prevalent and its management is complex. An observational study (n = 6) demonstrated elevated estradiol levels in 5/6 women on AIs after 2 weeks (wks) of treatment with 25µg 17-β Estradiol (Vagifem ®), which raised questions regarding the safety of intravaginal estradiol in women with HR+ BC. However, the small sample size limited definitive conclusions, yet underscored the need for a clinical trial to evaluate concurrent use of AIs and intravaginal estradiol. In addition, a lower dose 17-β Estradiol (10µg) is now available and effectively treats healthy women with atrophic vaginitis. We hypothesized that the 10µg dose is effective and may have less systemic absorption than the 25µg dose. This is the first study to evaluate the 10µg dose in BC pts on AI therapy.
Methods: A prospective longitudinal IRB-approved study was performed at MSKCC in postmenopausal women with stage I-III HR+ BC on adjuvant letrozole or anastrozole for at least 3 months and had urogenital atrophy. Patients on exemestane were not eligible due to cross-reactivity with the assay. All women were initiated on 10µg intravaginal 17- β estradiol (Vagifem®). Serial estradiol/FSH levels were measured at baseline and wks 2, 7, 12, 18 & 24; we used a highly sensitive estradiol radioimmunoassay, ESTR-US-CT, from Cisbio US, Inc. Estradiol/FSH levels were checked approximately 12 hrs after insertion, chosen to measure peak absorption. The primary endpoint was change in systemic estradiol level from baseline to wk 12. Patients also completed the Female Sexual Function Index (FSFI) and Menopausal Symptom Checklist (MSCL) at baseline and wks 12 & 24.
Results: 26 pts have been treated and 18 are currently evaluable for the primary endpoint at wk 12. Wilcoxon signed rank test showed no statistically significant difference between baseline and wk 12 estradiol levels (p = 0.49) or FSH levels (p = 0.28). The median change in estradiol from baseline to wk 12 was 0.3 with a range from −3 to 14.6 (p = .49). Twelve wk results are anticipated for 6 additional pts on study; however 2 pts withdrew before wk 12. Based on the Wilcoxon signed rank test, estradiol levels were not elevated at wks 2 (n = 17) or 7 (n = 16) when compared to baseline. Graphical analysis showed a relationship with increasing estradiol coinciding with decreasing FSH, as physiologically expected. All patients reported being less bothered by menopausal symptoms on the MSCL from baseline to wk 12. Improvement in sexual function/FSFI scores was noted in all sexually active women.
Conclusion: Treatment with intravaginal 10µg 17- β estradiol (Vagifem ®) did not elevate wks 2, 7 or 12 estradiol. It also provided relief of vaginal and menopausal symptoms and improvement in sexual function in postmenopausal women with HR+ BC on adjuvant AIs. This is consistent with findings in the general population. Updated data from this study will be presented for all patients treated on study.
Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P2-12-05.