RANKL Inhibition and Breast Tissue Biomarkers

RANKL Inhibition and Breast Tissue Biomarkers in Premenopausal Women With Dense Breasts

Status

Completed

Phases

Early Phase 1

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT03629717

Enrollment

Registered

2018-08-14

Start date

2018-06-01

Completion date

2018-12-03

Last updated

2024-10-16

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Breast Cancer Prevention, Mammographic Density

Keywords

Mammographic density, Premenopausal, Breast cancer, Chemoprevention, Denosumab

Brief summary

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.

Interventions

PROCEDUREUltrasound-guided core needle biopsy

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

DRUGDenosumab

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

PROCEDUREBlood draw

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

DRUGCalcium

1200mg daily

DRUGVitamin D

800 IU daily

Study design

Allocation

Intervention model

SINGLE_GROUP

Primary purpose

PREVENTION

Masking

NONE

Eligibility

Sex/Gender

FEMALE

Age

35 Years to No maximum

Healthy volunteers

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.

Design outcomes

Primary

Measure	Time frame	Description
Effect of denosumab on breast tissue gene pathway gene expression	Between baseline and day 60	The investigators will evaluate changes in pathway gene expression between baseline and day 60 using NanoString NCounter platform
Effect of denosumab on pathways that may influence breast cancer development as measured by spatial transcriptomic analysis	Between baseline and day 60	The investigators will evaluate changes in breast tissue spatial transcriptomics.
Effect of denosumab on pathways that may influence breast cancer development as measured by metabolomic analysis	Between baseline and day 60	The investigators will evaluate changes in metabolomics.

Secondary

Measure	Time frame
Correlation of breast tissue gene expression with circulating biomarker levels	60 days

Countries

United States

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026