RANKL Inhibition and Mammographic Breast Density

• Status: Recruiting
• Trial end date: 2026-08-31
• Target enrollment: 0
• Participant gender: Female

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Washington University School of Medicine
• Collaborator: National Institutes of Health (NIH)
• Treatments: Calcium; Calcium, Dietary; Cholecalciferol; Denosumab; Ergocalciferols; Vitamin D; Vitamins

Criteria

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, i.e. volumetric percent density ≥ 7.5% on Volpara)

• Able to understand and willing to sign an IRB-approved written informed consent document.

Exclusion Criteria:

• History of ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), invasive breast cancer, or other cancer (except non-melanoma skin cancer).

• Known BRCA mutation(s).

• 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 or 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.