Denosumab for Decreasing Breast Density in High Risk Premenopausal Women with Dense Breasts
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.
- Dense breasts on routine mammogram (volumetric percent density >= 7.5% on Volpara, equivalent to Breast Imaging Reporting and Data System [BI-RADS)] category C)
- May be at increased risk for breast cancer using any of the following: * Positive family history of breast cancer in a first-degree relative. * Presence of non-BRCA susceptibility genes (e.g. ATM, BARD1, CDH1, CHEK2, MSH6, PALB2, PTEN, RAD51D, and TP53). * Biopsy confirmed benign breast disease. * Age at first birth > 30 years. * Nulliparity. * Rosner-Colditz risk prediction model.
- Able to understand and willing to sign an Institutional Review Board (IRB)-approved written informed consent document
- 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, 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
Locations & Contacts
Contact: Adetunji T Toriola
Trial Objectives and Outline
I. Quantify the effect of RANKL inhibition with denosumab on mammographic density in high-risk premenopausal women with dense breasts.
I. Determine the effect of RANKL inhibition on expression of RANK pathway genes.
II. Determine the effect of RANKL inhibition on expression of progesterone receptor (PgR) and progesterone-regulated pathway genes.
III. Determine the effect of RANKL inhibition on markers of epithelial proliferation.
IV. Determine the effect of RANKL inhibition on markers of stromal proliferation and growth factors.
V. Determine the effect of RANKL inhibition on gene expression of immune markers.
VI. Determine the effect of RANKL inhibition on gene expression of inflammatory markers.
VII. Evaluate correlations between gene expression within the breast tissues and within the blood.
VIII. Predict response to denosumab using the biomarkers evaluated in the exploratory objectives.
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.
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 are followed up every 2 months for 12 months during the study, and then at 24 and 36 months.
Trial Phase & Type
Siteman Cancer Center at Washington University
Adetunji T Toriola
Secondary IDs NCI-2019-05947
Clinicaltrials.gov ID NCT04067726