RANKL Inhibition and Breast Tissue Biomarkers

The Washington University

Status and phase: Completed; Early Phase 1

Conditions: Breast Cancer Prevention; Mammographic Density

Treatments: Drug: Denosumab; Procedure: Blood draw; Drug: Vitamin D; Drug: Calcium; Procedure: Ultrasound-guided core needle biopsy

Study type: Interventional

Funder types: Other

Identifiers

NCT03629717

201801105

Details and patient eligibility

About

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.

Enrollment: 10 patients

Sex: Female

Ages: 35+ years old

Volunteers: No 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.

Trial design

Primary purpose: Prevention

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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10 participants in 1 patient group

Denosumab

Experimental group

Description:

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.

Treatment:

Procedure: Ultrasound-guided core needle biopsy

Drug: Calcium

Drug: Vitamin D

Procedure: Blood draw

Drug: Denosumab