Dense Breasts
Conditions
Keywords
Mammographic density, Breast cancer, RANKL, Denosumab, Prevention, Premenopausal
Brief summary
Data supporting a role for RANKL signaling in mammographic density and breast cancer development has begun to emerge, but clinical trial data providing definitive evidence that would allow the adoption of RANKL inhibition in primary breast cancer prevention are not yet available. The hypothesis is that RANKL inhibition with denosumab will decrease mammographic density in high-risk premenopausal women with dense breasts. To address this, the investigators have developed this clinical trial to quantify the impact of RANKL inhibition on mammographic density in high-risk premenopausal women with dense breasts and to determine the effect of RANKL inhibition on markers of proliferation and biomarkers of breast cancer risk. Successful demonstration that RANKL inhibition reduces mammographic density could open up additional approaches to primary breast cancer prevention in high-risk premenopausal women, who do not have dominant genetic predisposition.
Interventions
DRUGDenosumab
Denosumab is commercially available and will be provided at no cost to participants.
DRUGPlacebo
Placebo will be made available as 1 mL sterile, non-pyrogenic water solution in a single-use prefilled syringe.
DRUGCalcium
-Participants will be instructed to take calcium (at least 500 mg) daily for 12 months between baseline examination and 12- month mammographic breast density examination.
DRUGVitamin D3
Participants will be instructed to take vitamin D3 (at least 400 IU) supplements daily for 12 months between baseline examination and 12- month mammographic breast density examination.
PROCEDURECore needle biopsy
Baseline and 12 months
PROCEDUREBlood draw
Baseline and 12 months
Sponsors
Washington University School of Medicine
National Institutes of Health (NIH)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Stratified permuted block randomized design will be used to generate the randomization table where permuted block randomization will be used for each stratum by age, with a varying block size of 4 and 6.
Eligibility
Sex/Gender
FEMALE
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Female. * Premenopausal (when menopausal status is uncertain, the investigators will measure follicle-stimulating hormone and estradiol to ascertain that a partcipant is premenopausal) * At least 40 years of age. * Dense breasts on routine mammogram (BI-RADS Category C and D) * Able to understand and willing to sign an IRB-approved written informed consent document.
Exclusion criteria
* History of breast or any other invasive cancer except for DCIS (ductal carcinoma in situ) who received only lumpectomy, LCIS (lobular carcinoma in situ), atypical hyperplasia, non-melanoma skin cancer, carcinoma in situ of the cervix. * Current use of tamoxifen, aromatase inhibitors, or bisphosphonates, or RANKL inhibitors * Concurrent participation in another cancer chemoprevention trial (unless no longer receiving the intervention). * Pregnant, lactating, or planning to get pregnant while the trial is ongoing. * Recent history of invasive dental procedure (e.g. tooth extraction, dental implant, oral surgery). * Unhealed and/or planned dental/oral surgery. * History of osteonecrosis/osteomyelitis of the jaw. * History of osteoporosis or severe osteopenia.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in mammographic breast density between the two arms as measured by volumetric percent density | From baseline to 12 months | -The investigators will use volumetric percent density (VPD) as the primary mammographic breast density measure. |
Secondary
| Measure | Time frame |
|---|---|
| Change in mammographic breast density between the two arms as measured by volumetric percent density | From baseline to 24 months |
| Change in expression gene related to RANK in breast tissue compared between the two arms | Baseline and 12 months |
| Change in expression gene related to progesterone in breast tissue compared between the two arms | Baseline and 12 months |
| Change in expression gene related to metabolics in breast tissue compared between the two arms | Baseline and 12 months |
| Change in expression gene related to immune in breast tissue compared between the two arms | Baseline and 12 months |
| Change in expression gene related to inflammatory in breast tissue compared between the two arms | Baseline and 12 months |
| Change in expression of markers of breast epithelial and stromal proliferation compared between the two arms | Baseline and 12 months |
| Change in breast metabolome compared between the two arms | Baseline and 12 months |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAdetunji T Toriola, M.D., Ph.D.
Washington University School of Medicine
Outcome results
None listed