Study of Breast Cancer Prevention by Letrozole in High Risk Women

May 18, 2023 updated by: Carol Fabian, MD

This is a multi-institution double-blind placebo-controlled trial whose main objective is to determine if 6 months of letrozole (2.5 mg daily) can reduce proliferation as assessed by Ki-67 in high risk postmenopausal women on systemic hormone replacement therapy who have random periareolar fine needle aspiration (RPFNA) evidence of hyperplasia with atypia or borderline atypia, and a minimum Ki-67 of >1.5%.

The primary hypothesis is that proliferation and expression of other estrogen response genes will be favorably modulated by six months of letrozole relative to placebo without substantially increasing hot flashes or worsening overall quality of life.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Subsequent to the 6 month RPFNA for assessment of biomarkers, toxicity and quality of life assessments, all women may receive optional open-label letrozole for an additional 6 months, followed by a third RPFNA and biomarker

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Kansas
      • Kansas City, Kansas, United States, 66160
        • University of Kansas Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

30 years to 69 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Post-menopausal women at high risk for development of breast cancer
  • stable dose of hormone replacement therapy
  • have cytomorphologic evidence of hyperplasia +/- atypia and Ki-67 expression >1.5% in benign breast epithelial cells acquired by RPFNA
  • Serum level of 25-hydroxyvitamin D of at least 30 ng/ml prior to study entry
  • Willing to have a repeat random periareolar fine needle aspiration (RPFNA) and mammogram at 6 months and 12 months (if participating in the open label portion of the study) following initiation of study drug

Exclusion Criteria:

  • Prior history of osteoporosis or osteoporotic fracture.
  • Prior history of invasive breast cancer or other invasive cancer within five years from date of study entry.
  • Current and chronic use of cyclooxygenase-2 (COX-2) specific inhibitors or NSAIDs
  • Receiving treatment for rheumatoid arthritis or fibromyalgia
  • Current history of poorly controlled migraines or perimenopausal symptoms
  • Currently receiving other investigational agents.
  • Receipt of more than 6 months of an aromatase inhibitor (anastrozole, exemestane, letrozole, etc.) at any time in the past.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Letrozole
Letrozole, 2.5 mg daily for 6 months
Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months.
Other Names:
  • Letrozole(Femara)
Placebo Comparator: Placebo
Placebo, daily for 6 months
Placebo tablet daily for 6 months then optional open label letrozole for 6 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Proliferation Rate (Ki-67 by Immunocytochemistry) From Baseline to 6 Months
Time Frame: Baseline to 6 Months
Change in proliferation rate (percent positively stained cells for Ki-67 antigen by immunocytochemistry) in benign breast epithelial cells acquired by random periareolar fine needle aspiration (RPFNA) from women at high risk for the development of breast cancer.
Baseline to 6 Months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Mammographic Density From Baseline to 6 Months..
Time Frame: Baseline to 6 Months
Percent area of the breast considered to be at increased density, as determined by the computer program Cumulus..
Baseline to 6 Months
Assessment of Change in Morphology by the Masood Score.
Time Frame: Baseline to 6 Months

Masood score is a semi-quantitative index of increasing abnormality, thus higher values are worse. Range 6 to 24.

Based on Masood S, Frykberg ER, McLellan GL, Scalapino MC, Mitchum DG, Bullard JB. Prospective evaluation of radiologically directed fine-needle aspiration biopsy of nonpalpable breast lesions. Cancer 1990; 66:1480-7.

Baseline to 6 Months

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Fibromyalgia Impact Questionnaire (FIQ) Score.
Time Frame: Baseline to 6 months
Assessment of impact of fibromyalgia on everyday living activities. Composite score ranges from 0 (best, no interference or impact on activities) to 104 (worst, maximum interference with activities).
Baseline to 6 months
Change in Brief Fatigue Inventory (BFI) Score.
Time Frame: baseline to 6 months
Assessment of the extent to which fatigue interferes in normal everyday living activities. Change over 6 months of treatment is assessed. Range from 0 (best, no fatigue) to 10 (worst). Increase in score indicates greater intensity of fatigue and/or greater interference with activities due to fatigue.
baseline to 6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Carol J Fabian, MD, University of Kansas Medical Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2006

Primary Completion (Actual)

March 1, 2015

Study Completion (Actual)

August 1, 2018

Study Registration Dates

First Submitted

December 18, 2007

First Submitted That Met QC Criteria

December 18, 2007

First Posted (Estimated)

December 24, 2007

Study Record Updates

Last Update Posted (Actual)

June 12, 2023

Last Update Submitted That Met QC Criteria

May 18, 2023

Last Verified

May 1, 2023

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

Global results will be published.

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Breast Cancer

Clinical Trials on Letrozole

3
Subscribe