Conjugated Estrogens/Bazedoxifene in Reducing Benign Breast Tissue Proliferation and Menopausal Symptoms in Peri or Post-Menopausal Patients at Moderate Risk for Breast Cancer
This pilot clinical trial studies how well conjugated estrogens/bazedoxifene works in reducing an increase in non-cancerous breast tissue in patients who are experiencing hot flashes due to perimenopause or menopause and who are at a moderate risk for developing breast cancer. Giving conjugated estrogens/bazedoxifene may reduce breast tissue proliferation while also reducing the amount of hot flashes.
Inclusion Criteria
- Inclusion criteria for screening RPFNA
- Women with vasomotor symptoms with a uterus who are postmenopausal (no menstrual period for 12 months) or in late menopause transition (no period for 3 months and elevated follicle stimulating hormone [FSH])
- Body mass index (BMI): < 36 kg/m^2
- Breast imaging: class I-III mammogram within 6 months of RPFNA; if class 0 or 4, must be resolved with additional procedures; if breast imaging pre and post study is performed at Kansas University Medical Center (KUMC), then volumetric assessment by Volpara software will be performed
- If previously on oral contraceptives or hormone replacement, off for 8 weeks or more prior to baseline RPFNA; the exception is low dose vaginal hormones (estring, vagifem, or 0.5 gram or less of conjugated estrogen vaginal cream twice weekly or less often); these vaginal preparations may be continued at the same dose
- Moderate risk of developing breast cancer based on either by having at least one of following: * First or second degree relative with breast cancer age 60 or younger * Prior breast biopsy * Prior RPFNA atypia * Estimated mammographic density of 25% or higher * Gail 5-year risk of > 1.7% (as calculated by the National Cancer Institute [NCI] Breast Cancer Risk Assessment Tool) or a 5 year Gail Risk of 2X that for age group; and/or * International Breast Cancer Intervention Study (IBIS) Breast Cancer Risk Evaluation 10-year relative risk of > 2X that for the population for age group
- Inclusion criteria for intervention phase
- An RPFNA performed less than six months prior to enrollment on study that exhibits at least 500 cells on the cytology or Ki-67 slide, and a Ki-67 positivity measured on at least 500 cells that is less than 4%
- Creatinine < 2.0
- Bilirubin < 2.5
- Albumin > 3.4
- Willingness to comply with study procedures: * Willing to have a blood draw for serum to archive bioavailable estradiol, sex hormone-binding globulin (SHBG), FSH, and bazedoxifene levels as well as a chemistry profile to ensure reasonable normal organ function at baseline and 6 month visits (approximately four tubes of blood collected) * Willing to have a DEXA scan for body composition and waist measurement at baseline and 6-8 months * Willing to have a repeat mammogram and RPFNA at 6-8 months following initiation of study drug * Willing to undergo a history, physical, vitals and breast exam at baseline and 6 month visits * Willing to be contacted by the trial coordinator at months 1 and 3 during the 6 month study period * Willing to complete a 29 item validated menopause quality of life intervention questionnaire and hot flash assessment at baseline and 6 month visits * Willing to sign and able to understand separate consents for the RPFNAs and for study participation
Exclusion Criteria
- Exclusion criteria for RPFNA
- A prior biopsy showing lobular carcinoma in situ (LCIS), ductal carcinoma in situ (DCIS), or invasive breast cancer, or individual with breast cancer 1 or 2, early onset gene (BRCA1/2) deleterious mutation
- Medical conditions: * Have a predisposition to or prior history of thromboembolism, deep venous thrombosis, pulmonary embolism, or stroke * History of renal or liver disease * Prior ovarian or endometrial cancer * Stopped or started hormone replacement within 8 weeks * Any other condition or intercurrent illness that in the opinion of the investigator makes the woman a poor candidate for RPFNA.
- Medications: * Current anticoagulant use (must discontinue for 3 weeks prior to fine needle aspirate [FNA]) * Taking systemic hormones within two months (eight weeks) prior to screening RPFNA * Taken tamoxifen, raloxifene, or an aromatase inhibitor within the past 6 months * Participation on any chemoprevention trial within 6 months
- Exclusion criteria for study intervention
- RPFNA criteria: * Cells suspicious for malignancy
- Intercurrent illness which makes potential participant unsuitable for study or started hormone replacement therapy between RPFNA and enrollment on study
Study sponsor and potential other locations can be found on ClinicalTrials.gov for NCT02729701.
PRIMARY OBJECTIVES:
I. To determine feasibility for a larger clinical trial in women at moderately increased risk.
II. Determine if accrual is brisk as demonstrated by accrual of at least 20 moderate risk women in the initial 6 months (3.5 entrants per month) in a single institution.
III. Determine if there is a 15% or lower dropout rate over the 6 month intervention.
IV. Determine if 20% or fewer women with paired random periareolar fine needle aspiration (RPFNA) specimens exhibit a meaningful increase in benign breast cell proliferation (Ki-67) where meaningful increase is defined as an increase in Ki-67 to 2% or higher in individuals with initial Ki-67< 1% or a doubling of Ki-67 in individuals with initial Ki-67 of 1% or higher.
SECONDARY OBJECTIVES:
I. Assess benign breast tissue for decrease in Ki-67 in women with Ki-67 of 1% or higher.
II. Assess changes in benign breast tissue estrogen responsive genes by real time quantitative polymerase chain reaction (RTqPCR).
III. Assess changes in benign breast tissue peptides and phosphopeptides.
IV. Assess changes in serum bioavailable hormones and cytokines.
V. Assess change in bazedoxifene serum levels as a function of body mass index (BMI), percent body fat, and compliance (by tablet count).
VI. Document change if any in body composition (dual energy x-ray absorptiometry [DEXA]), and waist circumference.
VII. Document change if any in volumetric breast density (Volpara) and compare to % dense area (Cumulus).
OUTLINE:
Patients receive conjugated estrogens/bazedoxifene orally (PO) once daily (QD) for 6-8 months. After 6-8 months, patients undergo a DEXA scan, and repeat mammogram and RPFNA.
After completion of study treatment, patients are followed up at 4 weeks.
Trial PhasePhase II
Trial Typeprevention
Lead OrganizationUniversity of Kansas Cancer Center
Principal InvestigatorCarol J. Fabian
- Primary IDSTUDY00002440
- Secondary IDsNCI-2016-00902
- ClinicalTrials.gov IDNCT02729701