Bazedoxifene + Conjugated Estrogens for Breast Cancer Risk Reduction

Not currently recruiting at 5 trial locations

Overseen By Laura Esserman, MD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: University of Kansas Medical Center

Must not be taking: Anticoagulants, Systemic hormones, Tamoxifen

Disqualifiers: Thromboembolism, BRCA1/2 mutation, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 6

Duration: 6 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a combination of two medications, bazedoxifene and conjugated estrogens, to determine if they can lower the risk of breast cancer in women at moderate risk who experience hot flashes due to menopause. Researchers aim to measure changes in breast tissue using mammograms and a special test that examines cells taken from the breast. Participants will either begin the medication immediately or wait six months before starting, allowing researchers to compare the two groups. This trial may suit women who experience hot flashes at least once a week, have certain menopause conditions, and have a moderate risk of developing breast cancer based on family history or past breast conditions. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group of people.

Will I have to stop taking my current medications?

If you are currently taking oral contraceptives or systemic hormone replacement therapies, you must stop them at least 8 weeks before starting the trial. However, you can continue using low-dose vaginal hormones for vaginal dryness if you've been on them for at least 2 weeks before the trial.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that several clinical trials have tested the safety of bazedoxifene and conjugated estrogens. These trials examined how well people tolerate this treatment over periods ranging from 12 weeks to 24 months. Some users might face a higher risk of developing endometrial cancer (cancer of the uterus lining) and endometrial hyperplasia (thickening of the uterus lining). However, this treatment is associated with a lower risk of breast cancer compared to other hormone therapies.

One study found that using conjugated estrogens alone might reduce the risk of breast cancer. This finding suggests a possible benefit when combined with bazedoxifene, although more specific safety data on the combination is still being gathered.

Overall, evidence indicates that the treatment is generally well-tolerated. However, like any medical treatment, it carries potential risks. Participants should discuss these risks with their healthcare provider when considering joining a trial. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for breast cancer risk reduction?

Unlike the standard breast cancer prevention treatments that often involve surgery or medications like tamoxifen and raloxifene, Bazedoxifene combined with conjugated estrogens offers a potentially safer and more convenient option. This combination not only targets the reduction of breast cancer risk but may also help manage menopausal symptoms, providing dual benefits. Researchers are excited because Bazedoxifene, a selective estrogen receptor modulator, works by blocking estrogen's effects in breast tissue, potentially reducing cancer risk without some of the severe side effects associated with other treatments. Conjugated estrogens complement this by relieving menopausal symptoms, which is not something traditional options address effectively.

What evidence suggests that bazedoxifene plus conjugated estrogens might be an effective treatment for breast cancer risk reduction?

This trial will evaluate the combination of bazedoxifene with conjugated estrogens for reducing breast cancer risk. Research shows that this combination may lower the risk of breast cancer. Previous studies found that using conjugated estrogens alone reduced breast cancer risk by 22%. Adding bazedoxifene helps slow cell growth in breast tissue, an important indicator of cancer development. This combination not only targets breast cancer risk but also alleviates menopause symptoms like hot flashes. The dual benefits of reducing cancer risk and easing menopause symptoms make it a promising option for women at risk. Participants in this trial will receive the combination either immediately or after a 6-month wait period. ^{2 6 7 8 9}

Who Is on the Research Team?

Carol J Fabian, MD

Principal Investigator

University of Kansas Medical Center

Are You a Good Fit for This Trial?

Women aged 45-64 with moderate risk of breast cancer, experiencing menopausal hot flashes at least weekly, and not currently on certain hormone treatments or having specific health conditions. Participants must have a BMI ≤ 38 kg/m2 and at least one breast assessable by Volpara software without prior radiation.

Inclusion Criteria

My kidney and liver tests are within normal ranges.

Must be in one of the four menopausal status categories

I am a woman aged 45-60, or 61-64 with a recent mammogram showing dense breast tissue.

Exclusion Criteria

Sufficiently distressed by vasomotor symptoms that they do not believe they would be able to remain on study for 6 months without additional medications

My breast condition is identified as pleomorphic LCIS.

Any other condition or intercurrent illness that in the opinion of the investigator makes the woman a poor candidate for RPFNA or treatment with BZA+CE

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BZA (20 mg) plus CE (0.45 mg) daily for 6 months

6 months

Baseline and 6-month visits for imaging and biomarker assessments

Waitlist Control

Participants are on a waitlist for 6 months before starting treatment

6 months

Follow-up

Participants are monitored for changes in biomarkers and safety after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bazedoxifene
• Conjugated Estrogens

Trial Overview

The trial is testing if Bazedoxifene plus Conjugated Estrogens can reduce the risk of developing breast cancer in women with vasomotor symptoms. It measures changes in fibroglandular volume and cell proliferation over six months against a control group.

How Is the Trial Designed?

Group I: Bazedoxifene plus conjugated estrogens wait list Experimental Treatment 1 Intervention

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.

Group II: Bazedoxifene plus conjugated estrogens immediately Experimental Treatment 1 Intervention

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

Bazedoxifene is already approved in United States, European Union for the following indications:

Approved in United States as Duavee for:

• Moderate to severe vasomotor symptoms associated with menopause
• Prevention of postmenopausal osteoporosis

Approved in European Union as Duavive for:

• Treatment of estrogen deficiency symptoms in postmenopausal women with an intact uterus
• Prevention of osteoporosis in postmenopausal women at high risk of future fractures

Who Is Running the Clinical Trial?

University of Kansas Medical Center

Lead Sponsor

Trials

527

Recruited

181,000+

National Cancer Institute (NCI)

Collaborator

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Conjugated estrogen/bazedoxifene (CE/BZA) is a new progestin-free therapy for postmenopausal health that effectively manages vasomotor symptoms and helps prevent bone loss, based on results from five Phase III SMART trials.

CE/BZA works by using bazedoxifene to inhibit the proliferative effects of estrogen on the uterus and breast, which reduces side effects like uterine bleeding and breast pain commonly associated with progestin-containing therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Conjugated estrogen/bazedoxifene tablets for the treatment of moderate-to-severe vasomotor symptoms associated with menopause. Mirkin, S., Komm, B., Pickar, JH.[2016]

Duavive, a combination of conjugated oestrogens and bazedoxifene acetate, is effective for treating estrogen deficiency symptoms in postmenopausal women who cannot use progestogen therapy, highlighting its targeted approach for this specific patient group.

Since its approval by the European Medicines Agency in 2014 and launch in the UK in 2016, Duavive has been reviewed for both efficacy and safety, establishing its role in managing menopausal symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bazedoxifene for HRT? [2017]

A pooled analysis of five phase-3 trials involving 4868 healthy, non-hysterectomized postmenopausal women showed that conjugated estrogens/bazedoxifene (CE/BZA) has an acceptable cardiovascular safety profile, with low rates of venous thromboembolic events (VTEs) and comparable rates of stroke and coronary heart disease (CHD) to placebo.

The incidence of VTEs was very low across different doses of CE/BZA, with rates of 0.3 to 0.7 per 1000 woman-years, indicating that CE/BZA is a safe option for managing menopausal symptoms without significantly increasing cardiovascular risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiovascular safety of conjugated estrogens plus bazedoxifene: meta-analysis of the SMART trials. Komm, BS., Thompson, JR., Mirkin, S.[2015]

In a 20-month study involving 95 ovariectomized cynomolgus macaques, the combination of bazedoxifene acetate (BZA) and conjugated equine estrogens (CEE) significantly reduced breast tissue proliferation and density compared to CEE alone, suggesting a potential for lower breast cancer risk.

BZA acted as an estrogen antagonist in the breast, effectively blocking the effects of CEE on estrogen receptor activity and gene expression related to cell proliferation, indicating that BZA could be a safer alternative to traditional estrogen and progestin therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of bazedoxifene acetate with and without conjugated equine estrogens on the breast of postmenopausal monkeys. Ethun, KF., Wood, CE., Register, TC., et al.[2021]

In a 1-year study involving 1061 non-hysterectomized postmenopausal women, Bazedoxifene/conjugated estrogens (BZA/CE) demonstrated no cases of endometrial hyperplasia at the lower dose and only a small incidence at the higher dose, indicating strong endometrial safety.

BZA/CE significantly improved bone mineral density (BMD) in the lumbar spine and total hip compared to placebo, while also showing a favorable safety profile with low rates of bleeding and breast tenderness, making it a promising option for managing menopausal symptoms and preventing osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of bazedoxifene/conjugated estrogens on endometrial safety and bone in postmenopausal women. Mirkin, S., Komm, BS., Pan, K., et al.[2013]

Bazedoxifene acetate is an effective oral treatment for preventing and treating osteoporosis in postmenopausal women, showing positive effects on bone health without stimulating breast or uterine tissue.

In combination with conjugated estrogens, bazedoxifene improves bone mineral density and reduces fracture risk while also alleviating menopausal symptoms, making it a promising option for women at high risk of osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bazedoxifene: a new selective estrogen receptor modulator for the treatment of postmenopausal osteoporosis. Kung, AW., Chu, EY., Xu, L.[2012]

Bazedoxifene acetate is an investigational oral drug that effectively prevents bone loss and reduces vertebral fracture risk in postmenopausal women, without affecting the endometrium or breast tissue.

When combined with conjugated estrogens, bazedoxifene shows promise in improving menopausal symptoms while providing skeletal benefits, making it a potential treatment for postmenopausal osteoporosis and related symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bazedoxifene and bazedoxifene combined with conjugated estrogens for the management of postmenopausal osteoporosis. Lewiecki, EM.[2019]

In a 12-week study involving 664 nonhysterectomized postmenopausal women, conjugated estrogens/bazedoxifene (CE/BZA) significantly improved sexual functioning and lubrication, especially in women who reported pain with intercourse as their most bothersome symptom.

CE/BZA also showed positive effects on vaginal cell counts and overall treatment satisfaction, indicating its efficacy in addressing moderate to severe menopausal symptoms and enhancing quality of life.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Most bothersome symptom in women with genitourinary syndrome of menopause as a moderator of treatment effects. Pinkerton, JV., Bushmakin, AG., Abraham, L., et al.[2018]

Citations

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pubmed.ncbi.nlm.nih.gov

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Bazedoxifene and conjugated estrogens vs waitlist control

Our pilot study suggested it had potential breast cancer risk reduction, and we proposed a multisite Phase IIB primary prevention trial ...

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sciencedirect.com

sciencedirect.com/science/article/pii/S1551714424002805

Bazedoxifene and conjugated estrogens vs waitlist control

Indeed, in the Women's Health Initiative, conjugated estrogens alone, compared to placebo, was associated with a 22 % reduction in risk for breast cancer and 40 ...

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ecancer.org

ecancer.org/en/news/26527-asco-2025-menopause-drug-duavee-may-help-prevent-invasive-breast-cancer

ASCO 2025: Menopause drug duavee may help prevent ...

Kulkarni's team found the drug significantly reduced cell growth in breast tissue, a key marker of cancer progression. Unlike other breast ...

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clinicaltrials.ucsf.edu

clinicaltrials.ucsf.edu/trial/NCT04821141

Phase IIB Trial of Bazedoxifene Plus Conjugated Estrogens

Women at risk for development of breast cancer and experiencing vasomotor menopausal symptoms (hot flashes) will be randomized to bazedoxifene (BZA) plus ...

5.

reporter.nih.gov

reporter.nih.gov/search/FSa0vivtb0uWpsyy7wgS8g/project-details/11145085

Project Details - NIH RePORTER

Duavee® is promising for breast cancer risk reduction given the estrogen antagonist effects in the breast and uterus, and estrogen agonist properties in bone.

6.

pmc.ncbi.nlm.nih.gov

pmc.ncbi.nlm.nih.gov/articles/PMC10389232/

Comparative safety of conjugated estrogens/bazedoxifene ...

CE/BZA users might experience slightly higher rates of endometrial cancer and endometrial hyperplasia, and a lower rate of breast cancer, than EP users in the ...

7.

accessdata.fda.gov

accessdata.fda.gov/drugsatfda_docs/label/2022/022247s007lbl.pdf

This label may not be the latest approved by FDA. For current ...

The safety of conjugated estrogens/bazedoxifene was evaluated in four Phase 3 clinical trials ranging from 12 weeks to 24 months in duration and enrolling ...

8.

duavee.pfizerpro.com

duavee.pfizerpro.com/efficacy

Efficacy & Safety Info

The effect of treatment with Duavee on the risk of breast cancer is unknown. A meta-analysis of 17 prospective and 35 retrospective epidemiology studies ...

9.

insight.jci.org

insight.jci.org/articles/view/182694

Metabolic and transcriptional effects of bazedoxifene ...

These data support the use of BZA/CE to improve metabolic health and reduce breast cancer risk in individuals with obesity.