RANKL Inhibition and Breast Tissue Biomarkers

Early Phase 1

Completed

• Conditions: Breast Cancer Prevention; Mammographic Density
• Interventions: Procedure: Ultrasound-guided core needle biopsy; Drug: Denosumab; Procedure: Blood draw; Drug: Calcium; Drug: Vitamin D

• Registration Number: NCT03629717
• Lead Sponsor: Washington University School of Medicine

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2018-06-01
• Study First Submitted: 2018-08-01
• Study First Submitted QC: 2018-08-09
• Study First Posted: 2018-08-14
• Primary Completion: 2018-12-03
• Study Completion: 2018-12-03
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-11
• Last Update Posted: 2024-10-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 10

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Denosumab	Ultrasound-guided core needle biopsy	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.
Denosumab	Blood draw	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.
Denosumab	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.
Denosumab	Vitamin D	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.
Denosumab	Calcium	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.

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Correlation of breast tissue gene expression with circulating biomarker levels	60 days

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States