RANKL Inhibition and Mammographic Breast Density

Phase 2Active Not RecruitingNCT04067726

Washington University School of Medicine210 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

TRIPLE

Enrollment

210

Conditions

Dense Breasts

Interventions

Eligibility

Sex: FEMALEMin age: 40 Years

Medical Language ↔ Plain English

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.

Outcomes

Primary Outcomes

Change in mammographic breast density between the two arms as measured by volumetric percent density

-The investigators will use volumetric percent density (VPD) as the primary mammographic breast density measure.

Time frame: From baseline to 12 months

Secondary Outcomes

Change in mammographic breast density between the two arms as measured by volumetric percent density

Time frame: From baseline to 24 months

Change in mammographic breast density between the two arms as measured by volumetric percent density

Time frame: From 12 months to 24 months

Change in expression gene related to RANK in breast tissue compared between the two arms