Try our beta test site

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 Research Institute Identifier:
First received: December 18, 2007
Last updated: May 11, 2016
Last verified: May 2016

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 Blind (Subject, 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 University of Kansas Medical Center:

Primary Outcome Measures:
  • Assessment of proliferation rate (Ki-67 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. [ Time Frame: 6 Month ]

Secondary Outcome Measures:
  • Assessment of change in morphology by nuclear morphometry and the semi-quantitative Masood score index and change in qRT-PCR assessed estrogen response genes. [ Time Frame: 6 Months, 12 Months ]
  • Mammographic density and bioavialable estradiol and testosterone will be assessed as well. [ Time Frame: 6 Months, 12 Months ]
  • Change in biomarkers associated with bone and cardiovascular health, adverse events, BCPT Symptom Check List, hot flash score, general fatigue inventory, the Fibromyalgia Impact Questionnaire. [ Time Frame: 6 Months, 12 Months ]
  • 25-OH vitamin D levels will be assessed. [ Time Frame: Baseline and 6 month 2 ]

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: 1
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: 2
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 cytomophologic 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 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 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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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 Research Institute Identifier: NCT00579826     History of Changes
Other Study ID Numbers: 10587  CFEM345AUS45  5R01CA122577-03 
Study First Received: December 18, 2007
Last Updated: May 11, 2016
Individual Participant Data  
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 February 20, 2017