Study of Oral Drug Bazedoxifene Plus Conjugated Estrogens for Treating Hot Flashes in Women at High Risk for Breast Cancer

About the Study

Bazedoxifene is a type of drug known as a selective estrogen receptor modulator (SERM) that is similar to the drug tamoxifen. A combination of bazedoxifene and estrogen taken orally has been used to control hot flashes. This study will look at hot flashes, quality of life and breast changes in high-risk women taking the combination of drugs compared with women not taking the combination of drugs. The study will involve breast imaging, blood tests and small sampling of breast tissue at the beginning and end of the study. 

What the Study Involves

Participants will be selected at random and assigned to one of two groups. 

• Group 1 will receive the drugs bazedoxifene and estrogen taken together orally once daily for 6 months. 
• Group 2 will not receive the drug combination for 6 months. After 6 months, participants in this group will have the option to begin taking the medications. 

Participants will be asked to undergo the following tests at baseline and 6 months: 

• fine needle aspiration of breast tissue to measure biomarkers
• breast imaging
• blood tests for biomarkers

Study Sites

California

• Duarte
  City of Hope Medical Center
  Lead researchers: Victoria Seewaldt, MD; Lisa Yee, MD
• San Francisco
  University of California San Francisco
  Lead researcher: Laura Esserman, MD

Illinois

• Chicago
  Northwestern Medical Center
  Lead Researcher: Sema Khan, MD    

Kansas

• Kansas City
  University of Kansas Medical Center
  Lead researchers: Carol J Fabian, MD; [email protected]
  Contact: Amy L Kreutzjans, [email protected]

Massachusetts

• Boston
  Dana-Farber Cancer Institute
  Lead researcher: Judy Garber, MD

Women, ages 45-60, who meet the following may be eligible:

• Current symptoms of hot flashes, night sweats, or both. These do not need to be frequent or severe but should occur at least once a week.
• Must be in one of the four menopausal status categories (below):
  • age 45-60 with an intact uterus and no periods in the past 12 months. 
  • age 45-60 with an intact uterus and no periods in the past 2 months prior to eligibility testing for this study. 
  • age 50-60 and prior hysterectomy, prior endometrial ablation with subsequent lack of periods, or menses suppression due to Mirena IUD or other contraceptives. 
  • age 45-59 and prior hysterectomy, prior endometrial ablation with subsequent lack of periods, or menses suppression due to Mirena IUD or other contraceptives.  A pre-study follicle-stimulating hormone (FSH) test must be in postmenopausal range.
• must have at least one ovary.
• BMI: ≤ 35 kg/m2.
• must have at least one breast which hasn't received radiation treatment.
• Moderate risk of developing breast cancer based on having at least one of the following:
  • women with known gene mutations associated with an increased risk for breast cancer such as ATM, CDH1, CHEK2, NBN, NF1, PALB2, PTEN, STK11, P53 (Note: BRCA1/2 are excluded as women 45 and over should have undergone risk-reducing bilateral salpingo-oophorectomy).
  • first or second degree relative with breast cancer age 60 or younger.
  • a prior breast biopsy showing proliferative breast disease, or 2 or more prior biopsies regardless of benign histology.
  • 10-year relative risk of ≥2X that for the average population for age group as calculated by a risk-assessment tool. 
• vaginal hormones: low dose vaginal hormones, such as Estring(®, Vagifem®, Imvexy®, or 0.5 gram or less of conjugated estrogen vaginal cream twice weekly or less often may be continued at the same dose.
• systemic hormones: if previously on oral contraceptives or systemic hormone replacement, must be off for 8 weeks or more.

Contact study team for full eligibility and ineligibility.

People with the following may not participate: 

• increased risk or previous history of blood clots.
• have had both ovaries removed. 
• have a BRCA1 or BRCA2 inherited mutation.
• have been diagnosed with LCIS, DCIS, or invasive breast cancer, uterine cancer or ovarian cancer.
• abnormal liver and kidney function tests.

Medications

• must discontinue anticoagulant use (must have discontinued for 3 weeks before breast fine needle aspirate. 
• taking tamoxifen, raloxifene, or an aromatase inhibitor within 6 months of baseline blood imaging or needle aspirate.

Willing to comply with study procedures.

• fasting blood drawn at baseline and 6 months.
• dual energy x-ray absorptiometry (iDXA) at baseline and 6 months (at KUMC only).
• repeat mammogram and RPFNA at 6 months following initiation of study drug. (12-month mammogram for waitlist control only is optional)
• must be willing to use non-hormonal contraceptive precautions.

Contact study team for full eligibility and ineligibility.