Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Breast Neoplasms

Hot Flashes

Breast Diseases

Skin Diseases

Menopause

All Drugs and Chemicals

Bone Density Conservation Agents

Estrogens, Conjugated (USP)

Estrogens

Bazedoxifene

Hormones

Hormone Antagonists

Selective Estrogen Receptor Modulators

Estrogen Receptor Modulators

BZA (20 mg) plus CE (0.45 mg) taken together once daily for 6 months, commencing immediately.

No intervention for initial 6 months (wait list), then BZA (20 mg) plus CE (0.45 mg) taken together once daily for 6 months, commencing 6 months after enrollment. Optional on the part of subject.

BZA (20 mg) plus CE (0.45 mg) taken together once daily

Bazedoxifene and Conjugated Estrogens

Carol J Fabian, MD

Bruce Kimler, PhD

Lisa D Yee, MD

Victoria L Seewaldt, MD

Rachel Woody

Molly Baxter

Laura Esserman, MD

Sarah DeHorn

Sema Khan, MD

Amy L Kreutzjans

Hadley Barr

Alexander Husband

Judy Garber, MD

Women at risk for development of breast cancer and experiencing vasomotor menopausal symptoms (hot flashes) will be randomized to bazedoxifene (BZA) plus conjugated estrogens (CE) for 6 months versus a wait list control. Two risk factors for development of breast cancer will be studied pre-study and after 6 months: fibroglandular volume (FGV) on mammogram as assessed by Volpara software and proliferation by Ki-67 immunocytochemistry in benign breast tissue acquired by random periareolar fine needle aspiration (RPFNA). Change in biomarkers will be compared between groups.

Phase IIB trial of 6 months of BZA 20 mg +CE 0.45 mg (subsequently designated as BZA+CE) vs a waitlist control. Trial is informed by prior results of a single arm trial that used Duavee® (combination of BZA+CE that is FDA-approved for relief of hot flashes). Since Duavee® is currently not available commercially, the two separate components are used instead. Breast imaging, benign breast tissue by RPFNA, and blood for biomarkers will be obtained at baseline and at 6 months using similar assessment techniques. The primary endpoint is the difference between the BZA+CE and control groups for absolute change from baseline to 6 months in the risk biomarker fibroglandular volume (FGV). Volpara® fully automated assessments overcome the interpretive variance inherent in subjective assessments. Additional endpoints include changes in benign breast epithelial immunolabeling for Ki-67, estrogen receptor alpha (ERα), progesterone receptor (PR), and anterior gradient-2 protein (AGR2); and systemic levels of bioavailable hormones, IGF-1, IGFBP3, and measures of insulin sensitivity. The modifying effects of baseline BMI, visceral adipose, and plasma BZA concentrations on markers will be studied.

Randomization to immediate 6 months of BZA+CE versus wait list for 6 months followed by option to receive 6 months of BZA+CE.

Only designated biostatistician is aware of randomization assignment until after a subject is enrolled and assigned, Then assignment is unblinded and agents are open-label.

Phase IIB Trial of Bazedoxifene Plus Conjugated Estrogens

Randomized IIB Study of the Effect of Bazedoxifene Plus Conjugated Estrogens on Breast Imaging and Tissue Biomarkers in Peri or Post-Menopausal Women at Increased Risk for Development of Breast Cancer

Exploratory analysis of change in levels of hormones (estradiol, progesterone, testosterone, sex hormone binding globulin, etc.) assessed by ELISA or RIA methods at baseline and at 6 months.

Exploratory analysis of changes and patterns of change in levels of mRNA assessed by qRT-PCR

Change in fibroglandular volume assessed on 3-D digital mammogram by Volpara software.

change in percent of breast epithelial cells staining positive for Ki-67 by immunocytochemistry

Spots Global Cancer Trial Database for bazedoxifene and conjugated estrogens