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 Cancer Institute (NCI)
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 participant 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 |
|---|---|---|
| Percent Change of Volumetric Percent Density Compared Between Baseline and 12 Months | At baseline and at 12 months | -The investigators used volumetric percent density (VPD) as the primary mammographic breast density measure. The VPD percent change at 12 months from baseline was calculated as volumetric percent density at 12 months divided by baseline volumetric percent density minus 1\*100 (i.e., unit of percentage). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change of Volumetric Percent Density Compared Between Baseline and 24 Months | At baseline and 24 months | The VPD percent change at 12 months from baseline was calculated as volumetric percent density at 24 months divided by baseline volumetric percent density minus 1\*100 (i.e., unit of percentage). |
| Percent Change of Volumetric Percent Density Compared Between Baseline and 36 Months | At baseline and 36 months | The VPD percent change at 12 months from baseline was calculated as volumetric percent density at 36 months divided by baseline volumetric percent density minus 1\*100 (i.e., unit of percentage). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORAdetunji T Toriola, M.D., Ph.D.
Washington University School of Medicine
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 46 years |
| Ethnicity (NIH/OMB) Hispanic or Latino | 4 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 204 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 14 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants |
| Race (NIH/OMB) White | 174 Participants |
| Region of Enrollment United States | 210 participants |
| Sex: Female, Male Female | 210 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 105 | 0 / 105 |
| other Total, other adverse events | 67 / 105 | 64 / 105 |
| serious Total, serious adverse events | 0 / 105 | 0 / 105 |
Outcome results
None listed