Bazedoxifene + Conjugated Estrogens for Breast Cancer Risk

Overseen By Amy L Kreutzjans

Age: 18+

Sex: Female

Trial Phase: Phase < 1

Sponsor: Carol Fabian, MD

Must not be taking: Systemic hormones, Tamoxifen, Raloxifene, others

Disqualifiers: Thromboembolism, Stroke, Renal disease, others

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

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 investigates whether a combination of bazedoxifene and conjugated estrogens (known as Duavee or Duavive) can alter breast MRI results, potentially impacting breast cancer risk. Participants will take these medications for six months, with their breast health closely monitored. Women who have experienced hot flashes or night sweats, have not had a period for at least two months, and possess certain breast cancer risk factors may qualify. The study aims to determine if this treatment is practical and effective for managing breast health in those at moderate risk. As an Early Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking medical insights.

Do I need to stop my current medications to join the trial?

Yes, you will need to stop taking certain medications. You cannot take systemic hormones within two months before the trial starts, and you must not have taken tamoxifen, raloxifene, Duavee®, or similar medications within 12 months before the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that using bazedoxifene with conjugated estrogens is generally safe and might reduce some cancer risks. Studies have found that women using this combination had lower rates of breast cancer compared to those using other hormone treatments. However, there may be a slightly higher chance of developing endometrial cancer and a thickening of the uterine lining.

The FDA has already approved this combination for treating menopause symptoms like hot flashes, indicating it is generally well-tolerated. However, every treatment can have side effects, and individual reactions can differ. Participants should always consult a healthcare provider about potential risks before joining a trial. ^{1 2 3 4 5}

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

Researchers are excited about using bazedoxifene combined with conjugated estrogens for reducing breast cancer risk because this combination offers a unique approach. Unlike the standard hormone therapy options, this treatment combines a selective estrogen receptor modulator (SERM) with estrogen, which might help manage the potential risk of estrogen stimulating breast tissue. Bazedoxifene acts as a shield, potentially blocking the estrogen receptor in breast tissue and reducing the risk of cancer while allowing the positive effects of estrogen on other tissues. This approach could offer a more balanced therapy, minimizing risks traditionally associated with estrogen treatments.

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

Research has shown that the combination of bazedoxifene and conjugated estrogens, known as Duavee®, is approved for managing menopause symptoms and preventing bone loss. Studies have found that using conjugated estrogens alone can lower breast cancer risk by 22%. In this trial, participants will receive bazedoxifene and conjugated estrogens either immediately or after a waiting period. Women using this combination had lower breast cancer rates compared to those using other hormone therapies. The drug significantly slowed cell growth in breast tissue, which is important for reducing cancer progression. These findings suggest that this treatment may help lower the risk of breast cancer. ^{1 3 6 7 8}

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?

This trial is for women aged 45-65 with a BMI under 36, experiencing menopause symptoms, and at moderate risk of breast cancer. They must not have had periods for at least 60 days or have high FSH levels if younger with prior hysterectomy. Participants should be willing to undergo blood tests, mammograms, MRI scans and can't have a history of certain cancers or be on hormone treatments recently.

Inclusion Criteria

Able to understand and sign an informed consent form for screening and for intervention

I am a woman aged 45-49, had a hysterectomy or endometrial ablation, and my FSH level is 25 mIU/ml or higher.

If you want to have the optional RPFNA procedure, you need to meet the criteria for participating in the HSC4601 study about breast tissue risk assessment.

Exclusion Criteria

I started hormone therapy after my initial tests but before being assigned to a treatment group.

I have not received BZA+CE within 3 months before my baseline MRI.

My mammogram or MRI showed possible cancer signs, but any recommended biopsy was not cancerous.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive bazedoxifene plus conjugated estrogens for 6 months

6 months

Baseline and 6-month visits for MRI and mammogram assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Bazedoxifene
• Conjugated Estrogens

Trial Overview The study is testing the combination of bazedoxifene and conjugated estrogens over six months to see how it affects breast MRI parameters in women who are at an increased risk for developing breast cancer but do not currently have it.

How Is the Trial Designed?

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

After a 6-month waiting period, receipt of 6 months of bazedoxifene (20 mg) and conjugated estrogens (0.45 mg) taken together daily.

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

Immediate receipt of 6 months of bazedoxifene (20 mg) and conjugated estrogens (0.45 mg) taken together daily.

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?

Carol Fabian, MD

Lead Sponsor

Trials

16

Recruited

4,100+

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39293780

Bazedoxifene and conjugated estrogens vs waitlist control The combination of bazedoxifene 20 mg (BZA) and conjugated estrogens 0.45 mg (CE) marketed as Duavee® is approved for vasomotor symptom relief and osteoporosis ...

2. 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 ...

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

Comparative safety of conjugated estrogens/bazedoxifene ... Breast cancer rates were lower in women who used CE/BZA than in women who used EP, suggesting that the use of BZA for estrogen opposition does ...

4. news.northwestern.edu news.northwestern.edu/stories/2025/05/menopause-drug-duavee-may-help-prevent-invasive-breast-cancer-clinical-trial-finds

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

5. aacrjournals.org aacrjournals.org/cancerres/article/84/9_Supplement/PS07-08/744703/Abstract-PS07-08-Bazedoxifene-plus-conjugated

Abstract PS07-08: Bazedoxifene plus conjugated estrogen ... In a single arm clinical trial, BZA+CE reduced Ki-67 and mammographic density (PMID: 31420361), and this combination is currently being assessed ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/37449720/

Comparative safety of conjugated estrogens/bazedoxifene ... Conclusions: CE/BZA users might experience slightly higher rates of endometrial cancer and endometrial hyperplasia, and a lower rate of breast ...

7. cancer.gov cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2022-03864

Bazedoxifene and Conjugated Estrogen for the Prevention ... Giving bazedoxifene with conjugated estrogens may reduce the risk of breast cancer in women experiencing menopausal symptoms like hot flashes and are at ...

8. 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 ... A drug already approved by the FDA to treat menopause symptoms may also help prevent invasive breast cancer, according to new findings from a multi-centre ...