Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation (LIBER)
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.
brca1 Mutation Carrier
brca2 Mutation Carrier
Hereditary Breast/Ovarian Cancer (brca1, brca2)
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Prevention of Breast Cancer by Letrozole in Post-menopausal Women Carrying a BRCA1/BRCA2 Mutation|
- Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer) [ Time Frame: 2017 ] [ Designated as safety issue: No ]
- Survival without invasive breast cancer at 5 years [ Time Frame: 2017 ] [ Designated as safety issue: No ]
- Invasive cancer-free survival at 10 years [ Time Frame: 2022 ] [ Designated as safety issue: No ]
- Breast cancer in situ-free survival at 5 and 10 years [ Time Frame: 2022 ] [ Designated as safety issue: No ]
- Relapse-free (local or metastatic disease) survival in patients with history of breast cancer at 5 and 10 years [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: No ]
- Second cancer-free survival at 5 and 10 years [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: No ]
- Event- free (local relapse or metastatic, contralateral, or second cancer) survival at 5 and 10 years [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: No ]
- Overall survival at 5 and 10 years [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: No ]
- Toxicity according to CTCAE version 3.0 [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: Yes ]
- Lipid tolerance or cardiovascular or bone event [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: Yes ]
- Quality of life according to MRS and SF36 questionnaires [ Time Frame: 2017 and 2022 ] [ Designated as safety issue: No ]
|Study Start Date:||May 2008|
|Estimated Study Completion Date:||February 2022|
|Estimated Primary Completion Date:||February 2017 (Final data collection date for primary outcome measure)|
Experimental: Treatment arm
Letrozole, 1 tablet
Other Name: Femara
Placebo Comparator: Placebo
Comparator, 1 tablet
- Evaluate the reduction of the incidence of invasive breast cancer in postmenopausal women with the BRCA1/BRCA2 mutation treated with letrozole.
- 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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00673335
|Institut Sainte Catherine|
|Avignon, France, 84082|
|Centre Regional Francois Baclesse|
|Caen, France, 14076|
|Centre Jean Perrin|
|Clermont-Ferrand, France, 63011|
|Centre Oscar Lambret|
|Lille, France, 59020|
|Centre Leon Berard|
|Lyon, France, 69373|
|Marseille Institute of Cancer - Institut J. Paoli and I. Calmettes|
|Marseille, France, 13273|
|Hopital Arnaud de Villeneuve|
|Montpellier, France, 34295|
|Centre Catherine de Sienne|
|Nantes, France, 02|
|Centre Antoine Lacassagne|
|Nice, France, 06189|
|Centre Hospitalier General de Niort|
|Niort, France, 79021|
|Institut Curie Hopital|
|Paris, France, 75248|
|Hotel Dieu de Paris|
|Paris, France, 75181|
|Hopital Saint Michel|
|Paris, France, 75015|
|Poitiers, France, 86021|
|Polyclinique De Courlancy|
|Reims, France, F-51100|
|Centre Eugene Marquis|
|Rennes, France, 35042|
|Centre Henri Becquerel|
|Rouen, France, 76038|
|Centre Rene Huguenin|
|Saint Cloud, France, 92211|
|CHU Sainte-Etienne - Hopital Nord|
|Sainte-Etienne, France, 42055|
|Centre Paul Strauss|
|Strasbourg, France, 67065|
|Institut Claudius Regaud|
|Toulouse, France, 31052|
|Centre Alexis Vautrin|
|Vandoeuvre-les-Nancy, France, 54511|
|Institut Gustave Roussy|
|Villejuif, France, F-94805|
|Study Chair:||Pascal Pujol, MD||Hopital Arnaud de Villeneuve|