RANKL Inhibition and Breast Tissue Biomarkers

Sponsor

Washington University School of Medicine (Other)

Overall Status

Completed

CT.gov ID

NCT03629717

Collaborator

(none)

Enrollment

Location

Arm

6.1

Actual Duration (Months)

1.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Prevention Mammographic Density	Procedure: Ultrasound-guided core needle biopsy Drug: Denosumab Procedure: Blood draw Drug: Calcium Drug: Vitamin D	Early Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

10 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

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

Actual Study Start Date :

Jun 1, 2018

Actual Primary Completion Date :

Dec 3, 2018

Actual Study Completion Date :

Dec 3, 2018

Arms and Interventions

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: Xgeva Prolia 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

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:

Xgeva

Prolia

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

Outcome Measures

Primary Outcome Measures

Effect of denosumab on breast tissue gene RANK pathway gene expression [Between baseline and day 60]
-The investigators will evaluate changes in RANK pathway gene expression between baseline and day 60 using NanoString NCounter platform
Effect of denosumab on breast tissue gene expression in progesterone-regulated pathways [Between baseline and day 60]
The investigators will evaluate changes in progesterone-regulated pathways gene expression between baseline and day 60 using NanoString NCounter platform.
Effect of denosumab on breast tissue breast tissue ki-67 proliferation [Between baseline and day 60]
The investigators will evaluate changes in ki-67 proliferation between baseline and day 60 using immunohistochemistry
Effect of denosumab on breast stromal proliferation [Between baseline and day 60]
The investigators will evaluate changes in gene expression of markers of stromal proliferation between baseline and day 60 using NanoString NCounter platform.

Secondary Outcome Measures

Correlation of breast tissue RANK pathway gene expression with circulating biomarker levels [60 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years and Older

Sexes Eligible for Study:

Female

Accepts 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.