Study of Breast Cancer Prevention by Letrozole in High Risk Women

• ClinicalTrials.gov Identifier: NCT00579826
• Recruitment Status: Completed
• First Posted: December 24, 2007
• Results First Posted: February 23, 2017
• Last Update Posted: January 19, 2022
• Sponsor: Carol Fabian, MD
• Collaborators: Novartis; National Cancer Institute (NCI)
• Information provided by (Responsible Party): Carol Fabian, MD, University of Kansas Medical Center

Study Description

Brief Summary:

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 or disease	Intervention/treatment	Phase
Breast Cancer	Drug: Letrozole; Drug: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 55 participants
• 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
• Study Start Date: October 2006
• Actual Primary Completion Date: March 2015
• Actual Study Completion Date: August 2018

Arms and Interventions

Arm	Intervention/treatment
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.

Outcome Measures

Primary Outcome Measures :

1. 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 :

1. 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.
2. 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..
3. 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 ]

Eligibility Criteria

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

Criteria

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

Locations

United States, Kansas

University of Kansas Medical Center

Kansas City, Kansas, United States, 66160

Sponsors and Collaborators

Carol Fabian, MD

Novartis

National Cancer Institute (NCI)

Investigators

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

  Study Documents (Full-Text)

Documents provided by Carol Fabian, MD, University of Kansas Medical Center:

Study Protocol and Statistical Analysis Plan  [PDF] July 5, 2012

More Information

• Responsible Party: Carol Fabian, MD, Professor, Director Breast Cancer Prevention Unit, University of Kansas Medical Center
• ClinicalTrials.gov Identifier: NCT00579826
• Other Study ID Numbers: 10587; CFEM345AUS45 ( Other Grant/Funding Number: Novartis ); 5R01CA122577-03 ( U.S. NIH Grant/Contract )
• First Posted: December 24, 2007
• Results First Posted: February 23, 2017
• Last Update Posted: January 19, 2022
• Last Verified: January 2022

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; Neoplasms; Breast Diseases; Skin Diseases; Letrozole; 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