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Study of Breast Cancer Prevention by Letrozole in High Risk Women

This study has been completed.
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Carol Fabian, MD, University of Kansas Medical Center Identifier:
First received: December 18, 2007
Last updated: July 19, 2017
Last verified: July 2017

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.

Condition Intervention Phase
Breast Cancer Drug: Letrozole Drug: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: Study of Breast Cancer Prevention by Letrozole in High Risk Women

Resource links provided by NLM:

Further study details as provided by Carol Fabian, MD, University of Kansas Medical Center:

Primary Outcome Measures:
  • 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 from women at high risk for the development of breast cancer.

Secondary Outcome Measures:
  • 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.

  • 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..

  • Change in Biomarkers Associated With Bone and Cardiovascular Health, Adverse Events, Breast Cancer Prevention Trial (BCPT) Symptom Check List, Hot Flash Score, General Fatigue Inventory, the Fibromyalgia Impact Questionnaire. [ Time Frame: 6 Months, 12 Months ]

Enrollment: 55
Study Start Date: October 2006
Study Completion Date: March 2015
Primary Completion Date: March 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Letrozole
Letrozole, 2.5 mg daily for 6 months
Drug: Letrozole
Letrozole 2.5 mg tablet daily. Then optional open label letrozole for another 6 months.
Other Name: Letrozole(Femara)
Placebo Comparator: Placebo
Placebo, daily for 6 months
Drug: Placebo
Placebo tablet daily for 6 months then optional open label letrozole for 6 months.

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

Ages Eligible for Study:   30 Years to 69 Years   (Adult, Senior)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Post-menopausal women at high risk for development of breast cancer
  • On a 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-OH vitamin 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.
  Contacts and Locations
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Please refer to this study by its identifier: NCT00579826

United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
Sponsors and Collaborators
Carol Fabian, MD
National Cancer Institute (NCI)
Principal Investigator: Carol J Fabian, MD University of Kansas Medical Center
  More Information

Responsible Party: Carol Fabian, MD, Professor, Director Breast Cancer Prevention Unit, University of Kansas Medical Center Identifier: NCT00579826     History of Changes
Other Study ID Numbers: 10587
CFEM345AUS45 ( Other Grant/Funding Number: Novartis )
5R01CA122577-03 ( U.S. NIH Grant/Contract )
Study First Received: December 18, 2007
Results First Received: July 19, 2016
Last Updated: July 19, 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Global results will be published.

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs processed this record on August 22, 2017