RANKL Inhibition and Breast Tissue Biomarkers

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

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 Overview

• Status: Completed
• Conditions: Breast Cancer Prevention; Mammographic Density
• Intervention / Treatment: Procedure: Ultrasound-guided core needle biopsy; Drug: Denosumab; Procedure: Blood draw; Drug: Calcium; Drug: Vitamin D

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Denosumab; An ultrasound-guided core needle breast biopsy will be performed on day 1 prior to the intervention. A single dose of subcutaneous denosumab 60mg will be administered immediately after the core biopsy on day 1. This will take place on an outpatient basis. Repeat core-needle biopsy will take place on Day 60 (+/-10 days). Blood samples will also be collected at the time of core-needle biopsy to allow for biomarker assay. Gene expression analyses will be done using NanoString nCounter gene expression system.

Procedure: Ultrasound-guided core needle biopsy; Tissue collection for this research proposal will be used for research purposes only and will not inform participant care; Drug: Denosumab; Denosumab is a human IgG2 monoclonal antibody with affinity and specificity for human RANKL; Other Names: Prolia; Xgeva; Procedure: Blood draw; 20 mL of fasting whole blood will be collected before denosumab (Day 1) and one month after denosumab administration (day 60 +/- 10 days); Drug: Calcium; 1200mg daily; Drug: Vitamin D; 800 IU daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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.	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.	Between baseline and day 60

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Washington University School of Medicine
• Investigators: Principal Investigator: Adetunji T Toriola, M.D., Ph.D., MPH, Washington University School of Medicine

Publications and helpful links

Helpful Links

• Alvin J. Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2018
• Primary Completion (Actual): December 3, 2018
• Study Completion (Actual): December 3, 2018

Study Registration Dates

• First Submitted: August 1, 2018
• First Submitted That Met QC Criteria: August 9, 2018
• First Posted (Actual): August 14, 2018

Study Record Updates

• Last Update Posted (Actual): October 16, 2024
• Last Update Submitted That Met QC Criteria: October 11, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Breast cancer; Chemoprevention; Premenopausal; Denosumab; Mammographic density
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Calcium; Denosumab
• Other Study ID Numbers: 201801105

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No