brca1 Mutation Carrier, brca2 Mutation Carrier, Breast Cancer, Hereditary Breast/Ovarian Cancer (brca1, brca2)
Conditions
Keywords
breast cancer, hereditary breast/ovarian cancer (BRCA1, BRCA2), BRCA1 mutation carrier, BRCA2 mutation carrier
Brief summary
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.
Detailed 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.
Interventions
DRUGletrozole
DRUGPlacebo
Sponsors
UNICANCER
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
40 Years to 69 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer) | 2017 |
| Survival without invasive breast cancer at 5 years | 2017 |
Secondary
| Measure | Time frame |
|---|---|
| Relapse-free (local or metastatic disease) survival in patients with history of breast cancer at 5 and 10 years | 2017 and 2022 |
| Second cancer-free survival at 5 and 10 years | 2017 and 2022 |
| Event- free (local relapse or metastatic, contralateral, or second cancer) survival at 5 and 10 years | 2017 and 2022 |
| Invasive cancer-free survival at 10 years | 2022 |
| Toxicity according to CTCAE version 3.0 | 2017 and 2022 |
| Lipid tolerance or cardiovascular or bone event | 2017 and 2022 |
| Quality of life according to MRS and SF36 questionnaires | 2017 and 2022 |
| Overall survival at 5 and 10 years | 2017 and 2022 |
| Breast cancer in situ-free survival at 5 and 10 years | 2022 |
Countries
France
Outcome results
None listed