Denosumab for Decreasing Breast Density in High Risk Premenopausal Women with Dense Breasts

Status: closed to accrual

This phase II trial studies how well denosumab works in decreasing breast density in premenopausal women with dense breasts who have a high risk of developing breast cancer. Having dense breasts is associated with an increased risk of developing breast cancer, therefore reducing breast density may decrease this risk. Denosumab is a monoclonal antibody that may reduce breast density by blocking progesterone associated cell growth in breast tissue.

Inclusion Criteria

Female
Premenopausal * When menopausal status is uncertain, we 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 (Breast Imaging Reporting and Data System [BI-RADS] category C and D)
Able to understand and willing to sign an Institutional Review Board (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, 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

PRIMARY OBJECTIVE:

I. Quantify the effect of RANKL inhibition with denosumab on mammographic density in high-risk premenopausal women with dense breasts.

SECONDARY OBJECTIVES:

I. Determine the effect of RANKL inhibition on breast tissue RANK, progesterone, metabolic, immune and inflammatory gene expression.

II. Determine the effect of RANKL inhibition on biomarkers of breast epithelial and stromal proliferation.

III. Determine the effect of RANKL inhibition on breast metabolome.

IV. Evaluate correlations between gene expression within the breast tissues and within the blood.

EXPLORATORY OBJECTIVES:

I. Predict response to denosumab using the biomarkers evaluated in the secondary objectives.

II. Perform pilot spatial analysis in pre-and post-intervention breast tissue samples of women assigned to denosumab who have clinically meaningful decreases in mammographic density

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive denosumab subcutaneously (SC) at baseline and at 6 months. Patients also receive calcium and cholecalciferol orally (PO) once daily (QD) for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo core-needle biopsy and blood sample collection at baseline and 12 months.

ARM II: Patients receive placebo SC at baseline and at 6 months. Patients also receive calcium and cholecalciferol orally PO once daily QD for up to 12 months in the absence of disease progression or unacceptable toxicity. Patients also undergo core-needle biopsy and blood sample collection at baseline and 12 months.

Patients are followed up every month for 12 months during the study, and then at 24 and 36 months.

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Denosumab for Decreasing Breast Density in High Risk Premenopausal Women with Dense Breasts

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