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Prevention of Breast Cancer by Letrozole in Post-menopausal Women Carrying a BRCA1/BRCA2 Mutation

Phase 3
40 Years
69 Years
Open (Enrolling)
brca1 Mutation Carrier, brca2 Mutation Carrier, Breast Cancer, Hereditary Breast/Ovarian Cancer (brca1, brca2)

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Trial Information

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
breast cancer.

- 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.

Inclusion Criteria


- Must meet the following criteria:

- With or without invasive unilateral breast cancer more than 5 years ago, with no

- 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


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 (including curatorship)


- 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

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Outcome Measure:

Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer)

Outcome Time Frame:


Safety Issue:


Principal Investigator

Pascal Pujol, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Hopital Arnaud de Villeneuve


France: Agence Nationale de Sécurité du Médicament et des produits de santé

Study ID:

UC-0104/0701 - ONCO03



Start Date:

May 2008

Completion Date:

February 2022

Related Keywords:

  • brca1 Mutation Carrier
  • brca2 Mutation Carrier
  • Breast Cancer
  • Hereditary Breast/Ovarian Cancer (brca1, brca2)
  • breast cancer
  • hereditary breast/ovarian cancer (BRCA1, BRCA2)
  • BRCA1 mutation carrier
  • BRCA2 mutation carrier
  • Breast Neoplasms
  • Ovarian Neoplasms