# Biomarker-Based Phase IIB Trial of (Bazedoxifene-Conjugated Estrogen) to Reduce Risk for Breast Cancer

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2021 · $852,459

## Abstract

ABSTRACT
Few risk-eligible women agree to standard endocrine interventions for breast cancer risk reduction due to fear
of side effects combined with incomplete efficacy and lack of a reliable marker of response. Worry about
initiation or worsening vasomotor symptoms is a common barrier. The Tissue Selective Estrogen Complex of
bazedoxifene (BZA) 20 mg and conjugated estrogen (CE) 0.45 mg marketed as Duavee® is FDA-approved for
relief of hot flashes and prevention of osteoporosis. Duavee® is promising for breast cancer risk reduction
given the estrogen antagonist effects in the breast and uterus, and estrogen agonist properties in bone. The
bazedoxifene component does not antagonize CE's favorable effects on vasomotor symptoms despite anti-
tumor efficacy observed for the combination. In our pilot, 6 months of Duavee® given to symptomatic women
at increased risk for breast cancer alleviated hot flashes and favorably modulated risk biomarkers of
mammographic fibroglandular volume (Volpara™ fully automated assessments), benign breast tissue
proliferation (Ki-67), and serum progesterone, IGF-1, and bioavailable testosterone. A phase IIB multi-
institutional trial of 6 months of Duavee® vs placebo is proposed in high-risk women with vasomotor
symptoms. Blood, mammogram, and benign breast tissue, and anthropomorphic and quality of life measures
will be obtained at baseline. Subjects will be stratified by enrollment site, fibroglandular volume, and Ki-67; and
randomized to blinded Duavee® or matched placebo for 6 months, followed by repeat assessments. The
primary endpoint is change in mammographic fibroglandular volume. Secondary endpoints are change in
benign breast tissue Ki-67, estrogen and progesterone receptor protein, ER and PgR target gene expression
(RT-qPCR), serum IGF-1: IGFBP3, bioavailable hormones, the ratio of soluble receptor activator of nuclear
factor kappa-Β ligand (sRANKL) to osteoprotegerin, and patient reported outcome measures related to
vasomotor symptoms, quality of life, and cognition. Reverse phase protein array and RNA-seq are performed
on benign tissue to aid in elucidation of mechanisms of action. The possible influence of BZA levels, body fat,
visceral fat, insulin resistance, and inflammatory cytokines on biomarker modulation will be examined.
Favorable biomarker modulation would provide evidence that Duavee® is likely to reduce risk for breast cancer
and establish potential markers to predict response in a Phase III chemoprevention trial.

## Key facts

- **NIH application ID:** 10122083
- **Project number:** 1R01CA249437-01A1
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** CAROL J. FABIAN
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $852,459
- **Award type:** 1
- **Project period:** 2021-02-26 → 2026-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10122083

## Citation

> US National Institutes of Health, RePORTER application 10122083, Biomarker-Based Phase IIB Trial of (Bazedoxifene-Conjugated Estrogen) to Reduce Risk for Breast Cancer (1R01CA249437-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10122083. Licensed CC0.

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