Breast cancer prevention with letrozole in postmenopausal women carrying a BRCA1/2 mutation - LIBER

INTERVENTION: Trade Name: FÉMARA® Product Name: FÉMARA® Pharmaceutical Form: Film-coated tablet INN or Proposed INN: letrozole Concentration unit: mg milligram(s) Concentration type: equal Concentration number: 2.5- Pharmaceutical form of the placebo: Film-coated tablet Route of administration of the placebo: Oral use CONDITION: women carrying a mutation in the BRCA1 or 2 genes; MedDRA version: 9.1 Level: LLT Classification code 10006190 Term: Breast cancer invasive NOS PRIMARY OUTCOME: Main Objective: The primary objective of this trial is to evaluate the reduction in the incidence of invasive breast cancer in postmenopausal women carrying a BRCA1/2 mutation. Primary end point(s): - Patients with no prior history of breast cancer:; Five-year invasive breast cancer-free survival, with the diagnosis of breast cancer based on clinical or radiological diagnosis and histological evidence obtained by biopsy or surgical excision. The histological description must include: - the histological type (ductal carcinoma, lobular carcinoma, other histology, carcinoma in situ lesion); - the histological grade; - the expression of estrogen and progesterone receptors. Patients with a history of breast cancer: Five-year contralateral or ipsilateral invasive breast cancer-free survival, subject to review of cases by independent experts to differentiate between new cancers and local recurrences. Secondary Objective: The secondary objectives of this trial are to evaluate: - The reduction in the incidence of breast cancer in situ. - Reduction of the local or metastatic recurrence rate in women who have had breast cancer; - Incidence of non-breast cancers, particularly ovarian, colon and endometrial cancer; - Lipid, cardiovascular and bone tolerance; - Quality of life; INCLUSION CRITERIA: - Breast-free woman or woman with a history of unilateral invasive breast cancer diagnosed more than 5 years prior and no history of recurrence, - Woman carrying a deleterious BRCA1/2 mutation (nonsense or stop mutation), - Age 40 to 70, - WHO ECOG performance status < 2, - Postmenopausal woman with a menopausal status defined by one of the following criteria: - Age > 60 years, - Bilateral oophorectomy, - Age 60, not hysterectomized, and amenorrhea of ​​more than 12 months, - Age 60 with a history of hysterectomy and FSH > 20 IU/L, - No breast cancer on mammography or MRI performed in the previous year, - Normal hematological function (neutrophils > 2 x 10⁹/L, platelets > 100 x 10⁹/L, hemoglobin > 10 g/dL), - Normal liver function (bilirubin < normal, ALT, AST < 2.5 ULN), - Normal kidney function (creatinine clearance = 60 mL/min), - Adequate cardiovascular function, no history of [illness/disease].