RANKL Inhibition and Breast Tissue Biomarkers

Early Phase 1CompletedNCT03629717

Washington University School of Medicine10 enrolled

Overview

A robust knowledge of how to reduce breast density could play a key role in breast cancer prevention in premenopausal women, but viable preventative targets to reduce breast density-associated breast cancer risk are yet to be developed. The investigators propose to investigate the effect of RANKL inhibition with denosumab on breast tissue markers in high-risk premenopausal women with dense breasts. Study findings could provide robust evidence to move forward with a clinical trial targeting RANKL inhibition in premenopausal breast cancer prevention.

Study Type

INTERVENTIONAL

Allocation

Purpose

PREVENTION

Masking

NONE

Enrollment

Conditions

Breast Cancer Prevention Mammographic Density

Interventions

Ultrasound-guided core needle biopsyPROCEDURE

Tissue collection for this research proposal will be used for research purposes only and will not inform participant care

DenosumabDRUG

Denosumab is a human IgG2 monoclonal antibody with affinity and specificity for human RANKL

Blood drawPROCEDURE

20 mL of fasting whole blood will be collected before denosumab (Day 1) and one month after denosumab administration (day 60 +/- 10 days)

Eligibility

Sex: FEMALEMin age: 35 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Female. * Premenopausal. * At least 35 years of age. * Dense breasts on routine mammogram. * Willing to take calcium (1,200mg) and vitamin D (800 IU) daily. * At increased risk for breast cancer using any of the following: * Positive family history of breast cancer * Breast cancer risk prediction models * Able and willing to return for repeat biopsy. * Able to understand and willing to sign an IRB-approved written informed consent document. Exclusion Criteria: * Current use of tamoxifen, aromatase inhibitors, or bisphosphonates. * Concurrently participating in another cancer chemoprevention trial (unless no longer receiving the intervention). * Pregnant or lactating. * Recent tooth extraction or dental procedure. * Unhealed and/or planned dental/oral surgery. * History of osteonecrosis/osteomyelitis of the jaw. * History of osteoporosis or severe osteopenia. * Unable/unwilling to return for repeat biopsy.

Locations (1)

Washington University School of Medicine

St Louis, Missouri, United States

Outcomes

Primary Outcomes

Effect of denosumab on breast tissue gene pathway gene expression

The investigators will evaluate changes in pathway gene expression between baseline and day 60 using NanoString NCounter platform

Time frame: Between baseline and day 60

Effect of denosumab on pathways that may influence breast cancer development as measured by spatial transcriptomic analysis

The investigators will evaluate changes in breast tissue spatial transcriptomics.

Time frame: Between baseline and day 60

Effect of denosumab on pathways that may influence breast cancer development as measured by metabolomic analysis

The investigators will evaluate changes in metabolomics.

Time frame: Between baseline and day 60

Secondary Outcomes

Correlation of breast tissue gene expression with circulating biomarker levels

Time frame: 60 days

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.