Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation (LIBER)

Unicancer

Status and phase

Completed

Phase 3

Conditions

Breast Cancer

brca2 Mutation Carrier

Hereditary Breast/Ovarian Cancer (brca1, brca2)

brca1 Mutation Carrier

Treatments

Drug: letrozole

Drug: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT00673335

EU-20806

2007-000687-24 (EudraCT Number)

NOVARTIS-FNCLCC-ONCO 03/0701

ONCO-03/0701 (Other Identifier)

UC-0104/0701 - ONCO03

Details and patient eligibility

About

RATIONALE: Letrozole may prevent breast cancer in postmenopausal women with a BRCA1 or BRCA2 mutation.

PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with a placebo in preventing breast cancer in postmenopausal women with a BRCA1 or BRCA2 mutation.

Full description

OBJECTIVES:

Primary

Evaluate the reduction of the incidence of invasive breast cancer in postmenopausal women with the BRCA1/BRCA2 mutation treated with letrozole.

Secondary

Determine the reduction of the incidence of in situ breast cancer in these women.
Determine the recurrence rate of local or metastatic disease in women who have had breast cancer.
Determine the incidence of non-breast cancer, especially ovarian, colon, or endometrial cancer.
Assess the tolerance of this drug in terms of lipid, cardiovascular, and bone effects.
Determine the quality of life of women treated with this drug.
Identify serological markers that allow early diagnosis of hereditary predisposition for breast cancer.
Conduct pharmacogenetic analysis.
Identify biomarkers or genes involved in the occurrence of cardiovascular and rheumatologic metabolic aromatase inhibitors.
Study the phenotypic characteristics of cancers that occur during treatment with letrozole, in particular hormonal markers (estrogen and progesterone receptor) and expression profiles of resistance to therapy.

OUTLINE: This is a multicenter study. Patients are stratified according to nature of mutation (BRCA1 vs BRCA2), oophorectomy in premenopausal state (yes vs no), and prior breast cancer (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients receive oral letrozole once daily.
Arm II: Patients receive oral placebo once daily. Treatment in both arms continues for 5 years in the absence of unacceptable toxicity or development of cancer or recurrent disease.

Blood samples are collected periodically for pharmacogenetic studies and analysis of biomarkers or genes associated with hereditary predisposition for breast cancer, toxicities, and resistance to therapy.

After completion of study treatment, patients are followed for 5 years.

Enrollment

170 patients

Sex

Female

Ages

40 to 69 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

DISEASE CHARACTERISTICS:

Must meet the following criteria:
- With or without invasive unilateral breast cancer more than 5 years ago, with no recurrence
  - No evidence of breast cancer by mammography or MRI within the past year
- Carrier of the BRCA1/BRCA2 deleterious mutation (nonsense mutation or stop)
- Refused preventive mastectomy
No prior bilateral breast cancer
No prior bilateral mastectomy
Hormone receptor status not specified

PATIENT CHARACTERISTICS:

Inclusion criteria:

Menopausal status as indicated by 1 of the following criteria:
- Age > 60 years
- Bilateral oophorectomy
- Age ≤ 60 years with no hysterectomy or amenorrhea within the past 12 months
- Age ≤ 60 years with prior hysterectomy or FSH > 20 IU/L
Eastern Cooperative Oncology Group (ECOG) or WHO performance status 0-1
absolute neutrophil count (ANC) > 2,000/mm^3
Platelet count > 100,000/mm^3
Hemoglobin > 10 g/dL
Bilirubin normal
ALT and AST < 2.5 times upper limit of normal
Creatinine clearance ≥ 60 mL/min
Adequate cardiovascular function (e.g., no history of myocardial infarction, angina pectoris, or heart failure)
No osteoporosis by bone density scan (DEXA) within the past 2 years or prior osteoporotic fracture (femur, lumbar spine T score > -2 DS)

Exclusion criteria:

Invasive cancer diagnosed in the past 5 years, except for basal cell or squamous cell skin cancer or carcinoma in situ of the cervix
Prior cerebrovascular accident
Prior cardiac ischemia
Hypersensitivity to letrozole or its excipients, especially titanium oxide
Renal or hepatocellular insufficiency, cholestasis, or cytolysis
Geographical, social, or psychological reasons that preclude medical monitoring in this study
Deprived of liberty or guardianship

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
At least 3 months since prior and no concurrent hormone replacement therapy (e.g., thyroid-stimulating hormone)
No prior hormonal therapy in the past year
No concurrent participation in another therapeutic study with an experimental drug