A Randomized Feasibility Study of Letrozole in Postmenopausal Women at Increased Risk for Development of Breast Cancer as Evidenced by High Breast Density
N/A
N/A
Female
Breast Cancer
Trial Information
A Randomized Feasibility Study of Letrozole in Postmenopausal Women at Increased Risk for Development of Breast Cancer as Evidenced by High Breast Density
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.
Inclusion Criteria
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
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Prevention
Outcome Measure:
Percentage change of the BMD parameters from baseline BMD values
Outcome Time Frame:
7 years
Safety Issue:
No
Principal Investigator
Paul E. Goss, MD, PhD
Investigator Role:
Study Chair
Investigator Affiliation:
Massachusetts General Hospital
Authority:
United States: Federal Government
Study ID:
MAP1
NCT ID:
NCT00238316
Start Date:
December 2000
Completion Date:
February 2009
Related Keywords:
- Breast Cancer
- breast cancer
- Breast Neoplasms
Name | Location |
|---|---|
| Massachusetts General Hospital Cancer Center | Boston, Massachusetts 02114 |
| Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute | Boston, Massachusetts 02115 |
