Letrozole in Preventing Breast Cancer in Postmenopausal Women Who Are at Increased Risk for Breast Cancer Due to High Breast Density

March 31, 2020 updated by: NCIC Clinical Trials Group

A Randomized Feasibility Study of Letrozole in Postmenopausal Women at Increased Risk for Development of Breast Cancer as Evidenced by High Breast Density

RATIONALE: Chemoprevention is the use of certain drugs to keep cancer from forming, growing, or coming back. The use of letrozole may stop cancer from forming or coming back in postmenopausal women who are at increased risk for breast cancer due to high breast density.

PURPOSE: This randomized phase II trial is studying how well letrozole works in preventing breast cancer in postmenopausal women who are at increased risk for breast cancer due to high breast density.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

OBJECTIVES:

Primary

  • Determine the proportion of postmenopausal women who are at increased risk for the development or recurrence of breast cancer, based on high breast density (≥ grade 4), who achieve a decrease in breast density of ≥ 1 grade after treatment with letrozole for 1 year.

Secondary

  • Determine whether a decrease in breast density grade is sustained at 1 year in patients treated with this drug.
  • Correlate plasma estrogen profile (E1, E1S, E2) with breast density grade at baseline in these patients.
  • Determine the percentage of patients with breast tissue hyperplasia and atypical hyperplasia, as assessed by histopathological examination of breast tissue biopsies, before and after treatment with this drug.
  • Determine the changes in estrogen profile from baseline, at 1 year, and 1 year after cessation of this drug in these patients.
  • Compare changes in predetermined specific parameters of safety at the end of 1 year of treatment with this drug with baseline evaluations of these patients.
  • Determine whether modifications of these predetermined specific parameters of safety are sustained 1 year after cessation of treatment with this drug in these patients.
  • Determine the general safety of 1 year of treatment with this drug in these patients.
  • Compare the effects of this drug on menopause-specific quality of life of these patients.

OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients are stratified according to breast density grade (4/6 vs 5/6 vs 6/6). Patients are randomized to 1 of 2 treatment arms.

  • Arm I: Patients receive oral letrozole once daily for 1 year in the absence of unacceptable toxicity.
  • Arm II: Patients receive oral placebo once daily for 1 year in the absence of unacceptable toxicity.

Menopause-specific quality of life is assessed at baseline and then at 12 and 24 months.

After completion of study treatment, patients are followed at 6 months and 1 year.

PROJECTED ACCRUAL: A total of 120 patients (80 in arm I and 40 in arm II) will be accrued for this study within 12 months.

Study Type

Interventional

Enrollment (Actual)

68

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

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Tom Baker Cancer Centre - Calgary
    • Nova Scotia
      • Halifax, Nova Scotia, Canada, B3H 1V7
        • Nova Scotia Cancer Centre
    • Ontario
      • Hamilton, Ontario, Canada, L8N 1Y2
        • Hamilton Osteoporosis Diagnostic Services
      • Ottawa, Ontario, Canada, K1H 8L6
        • Ottawa Hospital Regional Cancer Centre - General Campus
      • St. Catharines, Ontario, Canada, L2R 5K3
        • St. Catharines General Hospital at Niagara Health System
      • Toronto, Ontario, Canada, M5G 2M9
        • Princess Margaret Hospital
      • Toronto, Ontario, Canada, M4N 3M5
        • Toronto Sunnybrook Regional Cancer Centre at Sunnybrook Health Sciences Centre
    • Quebec
      • Montreal, Quebec, Canada, H2W 1T8
        • Hotel Dieu de Montreal
  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital Cancer Center
      • Boston, Massachusetts, United States, 02115-6084
        • Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute

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

No older than 120 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

DISEASE CHARACTERISTICS:

  • At increased risk for the development or recurrence of breast cancer, as defined by 1 of the following:

    • Baseline mammogram indicating mammographic density occupying ≥ 25% (grade 4/6, 5/6, or 6/6) of the breast tissue

      • No suspicion of breast cancer, unless subsequently ruled out

    • Prior ductal carcinoma in situ (DCIS)

      • Untreated disease OR > 6 months since completion of adjuvant endocrine therapy
      • Receptor status of lesion is not required

    • Prior invasive breast cancer

      • Breast cancer must have been surgically removed at time of original diagnosis with no evidence of metastases
  • No clinical evidence of breast cancer

  • Acceptable quality dual-energy x-ray absorptiometry (DEXA) of the L2-L4 postero-anterior (PA) spine and hip performed within past 6 months

    • Bone mass density T-score of either PA spine or hip must be ≥ 2.0 SD below the mean peak bone mass in young normal woman
  • Stable chronic leukemia allowed

  • Hormone receptor status:

    • Hormone receptor-negative, -positive, or -equivocal tumor

PATIENT CHARACTERISTICS:

Age

  • Postmenopausal

Sex

  • Female

Menopausal status

  • Postmenopausal, as defined by 1 of the following:

    • Over 55 years of age with spontaneous cessation of menses for ≥ 1 year
    • 55 years of age and under with spontaneous cessation of menses for ≤ 1 year, but amenorrheic (e.g., spontaneous or secondary to hysterectomy) AND follicle-stimulating hormone level > 34.4 IU/L
    • Bilateral oophorectomy

Performance status

  • Not specified

Life expectancy

  • Not specified

Hematopoietic

  • Not specified

Hepatic

  • Not specified

Renal

  • Not specified

Cardiovascular

  • No recent unstable myocardial infarction
  • No prior stroke
  • No high blood pressure
  • No other uncontrolled cardiovascular disease

Other

  • Other prior malignancies without metastatic disease allowed
  • Willing and able to complete quality of life questionnaires in either English or French
  • No uncontrolled metabolic or endocrine disease
  • No malabsorption syndrome

PRIOR CONCURRENT THERAPY:

Biologic therapy

  • No concurrent immunotherapy

Chemotherapy

  • No concurrent chemotherapy

Endocrine therapy

  • See Disease Characteristics
  • At least 3 months since prior and no concurrent hormone replacement therapy or raloxifene
  • At least 6 months since prior tamoxifen
  • No concurrent steroid therapy
  • No concurrent selective estrogen-receptor modulators
  • No other concurrent endocrine or hormonal therapy

Radiotherapy

  • Not specified

Surgery

  • See Disease Characteristics

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: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
Other: Placebo
2.5 mg PO daily for one 1 year
Active Comparator: Letrozole
Drug: letrozole
2.5 mg PO daily for 1 year

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Percentage change of the BMD parameters from baseline BMD values
Time Frame: 7 years
7 years
Percentage change of bone biomarker measurements (serum bone alkaline phosphatase and urine N-telopeptide) from baseline values
Time Frame: 7 years
7 years

Collaborators and Investigators

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

Sponsor

NCIC Clinical Trials Group

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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 (Actual)

December 5, 2000

Primary Completion (Actual)

November 16, 2007

Study Completion (Actual)

February 10, 2009

Study Registration Dates

First Submitted

October 12, 2005

First Submitted That Met QC Criteria

October 12, 2005

First Posted (Estimate)

October 13, 2005

Study Record Updates

Last Update Posted (Actual)

April 2, 2020

Last Update Submitted That Met QC Criteria

March 31, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MAP1
  • CAN-NCIC-MAP1 (Other Identifier: PDQ Identifier)
  • CDR0000445442 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated device product

No

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.

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