Prevention of Breast Cancer by Letrozole in Post-menopausal Women Carrying a BRCA1/BRCA2 Mutation
- 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
- Determine the incidence of non-breast cancer, especially ovarian, colon, or endometrial
- 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
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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer)
Pascal Pujol, MD
Hopital Arnaud de Villeneuve
France: Agence Nationale de Sécurité du Médicament et des produits de santé
UC-0104/0701 - ONCO03