Pilot Study of the Effect of Duavee® on Benign Breast Tissue Proliferation

Phase 2

Completed

Brief Summary: The purpose of this study is to learn whether daily use of Duavee® is accepted and tolerated by peri- and post-menopausal women at moderate risk for development of breast cancer.

Detailed Description: Duavee® is tissue specific estrogen complex of bazedoxifene plus conjugated estrogen which is FDA approved for relief of menopausal symptoms and prevention of osteoporosis in women with a uterus who have not been diagnosed with estrogen dependent neoplasia. The overall purpose of this research is to demonstrate in a preliminary fashion that despite reduction in menopausal symptoms, (Duavee®) does not increase and may decrease proliferation in benign breast tissue in a cohort of peri- or post-menopausal women at moderately increased risk for breast cancer. If this pilot shows rapid accrual, good retention, and lack of significant increase in the risk biomarker Ki-67 in benign breast tissue, a larger prevention trial is envisioned

Recruitment & Eligibility

Inclusion Criteria

Women with vasomotor symptoms with a uterus who are postmenopausal or in late menopause transition
Body Mass Index (BMI) <36 kg/m2
Class I-III mammogram within 6 months of Random Periareolar Fine Needle Aspiration (RPFNA); If Class 0 or 4, must be resolved with additional procedures
If previously on oral contraceptives or hormone replacement, off for 8 weeks or more prior to baseline RPFNA; the exception is low dose vaginal hormones
Confirmed moderate risk of developing breast cancer
RPFNA results within study defined range
Kidney and liver function within study defined range
Willing and able to comply with study related procedures

Exclusion Criteria

Previous biopsy showing evidence of breast cancer
Have a predisposition to or prior history of thromboembolism, deep venous thrombosis, pulmonary embolism, or stroke
History of renal or liver disease
Prior ovarian or endometrial cancer
Stopped or started hormone replacement within 8 weeks
Any other condition or intercurrent illness that in the opinion of the investigator makes the woman a poor candidate for RPFNA
Currently taking or have taken specific medications in the past 6 months
Participation on any chemoprevention trial within 6 months
Current illness which would make potential participant unsuitable for enrollment

Arm && Interventions

Group	Intervention	Description
Duavee	Duavee	Participants will be asked to take Duavee for 6 months while on the study.

Primary Outcome Measures

Name	Time	Method
Feasibility for a Larger Trial	6 Months	Outcome will be based on three separate factors used collectively to determine feasibility of the study and consideration of a subsequent larger trial. These are accrual rate (ability to accrue target number of subjects in a timely manner), dropout rate (frequency of subjects who are compliant and complete the intervention) and change in Ki-67 (increase vs decrease in percent of cells stained positive in the majority of subjects). Should accrual be inadequate or too slow; or if retention is too low; then a decision would be made not to proceed to a larger trial. Also, if there is evidence of an increase in proliferation (Ki-67) then no further studies would be planned.

Secondary Outcome Measures

Name	Time	Method
Levels of Bazedoxifene in the Blood	Month 6	Assessment of concentration of bazedoxifene in plasma by High-performance liquid chromatography (HPLC)
Change in Ki-67	Change from Baseline to Month 6	Assessment by immunocytochemistry of the percent of breast epithelial cells staining positive. Per protocol, restricted to those subjects with baseline Ki-67 positivity \>1.0% but \< 4%
Change in Fibroglandular Volume (FGV)	Change from Baseline to Month 6	Assessment of mammograms for percent of breast defined as FGV by Volpara automated assessment.
Change in Body Composition (Total Mass)	Change from Baseline to Month 6	Assessment by Dual Energy X-ray Absorptivity (DEXA)

Locations (2): University of Kansas Medical Center Breast Cancer Prevention Center
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Westwood, Kansas, United States
University of Kansas Medical Center
🇺🇸
Kansas City, Kansas, United States