Abstract 3261: Pilot study of the combination of bazedoxifene and conjugated estrogen to modulate risk biomarkers in women with hot flashes at increased risk for breast cancer
Authors: Fabian Carol J. , Powers Kandy R. , Nydegger Jennifer L. , Kreutzjans Amy L. , Metheny Trina , Phillips Teresa A. , Nye Lauren , Zalles Carola M. , Kimler Bruce F. 
Published: August 2018

Abstract
Uptake of anti-hormonal agents for primary prevention of breast cancer is poor due to concern about side effects, especially induction of menopausal symptoms. A combination of 20 mg bazedoxifene plus 0.045 mg conjugated estrogen is FDA approved (as Duavee®) for treatment of hot flashes and prevention of osteoporosis in postmenopausal women with a uterus. We undertook a pilot study to assess the feasibility of using this formulation as a breast cancer prevention agent in women at increased risk for development of breast cancer. Feasibility was to be assessed by accrual, retention, and documentation of a lack of enhanced proliferation in benign breast tissue acquired by random periareolar fine needle aspiration (RPFNA). Eligibility criteria included risk &gt;2X that of average risk woman for age group, postmenopausal having hot flashes or night sweats and not on systemic hormone replacement, and at least 500 cells on a baseline RPFNA. Women were ineligible if they had LCIS or DCIS, a BRCA1/2 germline mutation, had had a hysterectomy, or had &gt;4% Ki-67 positive cells by immunocytochemistry. Fasting blood draw, digital mammography with Volpara software, and DXA scan for body composition was performed at baseline along with QOL questionnaires. Women then received Duavee® daily for 6 months, followed by repeat of baseline tests. We accrued the first 20 subjects in 14 months. Many of the women followed in our cohort and interested in the trial were not eligible due to prior hysterectomy, prior LCIS or a high penetrance gene mutation. Thus accrual was slower than anticipated. All women have reported improvement in hot flash frequency and intensity. None have discontinued prematurely or had a study related serious adverse event. Fourteen women have completed the 6-month intervention and are evaluable for modulation of biomarkers. There have been no protocol-defined increases in proliferation (to &gt;2% Ki-67 for baseline Ki-67 &lt;1% or doubling if baseline Ki-67 ≥1%), with 10 of 14 paired specimens exhibiting a decrease. Ten women had Volpara fibroglandular assessments pre- and post-study with a median relative decrease of 11% (8 decreased and 2 increased). For the first ten subjects where serum hormones and growth factors were assessed in paired assays, favorable modulation was observed for estradiol, testosterone, SHBG, bioavailable testosterone, IGF-1, and the molar ratio of IGF1:IGFBP3. A primary prevention trial in symptomatic women appears feasible given the favorable initial results. The current pilot will continue to accrue so as to inform the design of a randomized, placebo-controlled Phase II trial of Duavee® in women at risk for breast cancer. Financial support provided by grants from the Breast Cancer Research Foundation (BCRF-16-049, BCRF-17-049). Duavee® provided by Pfizer, Inc. which was not involved in design, conduct, or analysis of the study.
Citation Format: Carol J. Fabian, Kandy R. Powers, Jennifer L. Nydegger, Amy L. Kreutzjans, Trina Metheny, Teresa A. Phillips, Lauren Nye, Carola M. Zalles, Bruce F. Kimler. Pilot study of the combination of bazedoxifene and conjugated estrogen to modulate risk biomarkers in women with hot flashes at increased risk for breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3261.