Letrozole in Preventing Breast Cancer in Postmenopausal Women With a BRCA1 or BRCA2 Mutation (LIBER)

This study is ongoing, but not recruiting participants.
Information provided by (Responsible Party):
ClinicalTrials.gov Identifier:
First received: May 6, 2008
Last updated: August 5, 2014
Last verified: August 2014

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.

Condition Intervention Phase
brca1 Mutation Carrier
brca2 Mutation Carrier
Breast Cancer
Hereditary Breast/Ovarian Cancer (brca1, brca2)
Drug: letrozole
Phase 3

Study Type: Interventional
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

Resource links provided by NLM:

Further study details as provided by UNICANCER:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 386
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)
Arms Assigned Interventions
Experimental: Treatment arm
Letrozole, 1 tablet
Drug: letrozole
Other Name: Femara
Placebo Comparator: Placebo
Comparator, 1 tablet

Detailed Description:



  • 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.


Ages Eligible for Study:   40 Years to 69 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • 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


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


  • 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
  Contacts and Locations
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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
CHU Poitiers
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
Sponsors and Collaborators
Study Chair: Pascal Pujol, MD Hopital Arnaud de Villeneuve
  More Information

Responsible Party: UNICANCER
ClinicalTrials.gov Identifier: NCT00673335     History of Changes
Other Study ID Numbers: UC-0104/0701 - ONCO03  ONCO-03/0701  EU-20806  NOVARTIS-FNCLCC-ONCO 03/0701  2007-000687-24 
Study First Received: May 6, 2008
Last Updated: August 5, 2014
Health Authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé

Keywords provided by UNICANCER:
breast cancer
hereditary breast/ovarian cancer (BRCA1, BRCA2)
BRCA1 mutation carrier
BRCA2 mutation carrier

Additional relevant MeSH terms:
Breast Neoplasms
Ovarian Neoplasms
Adnexal Diseases
Breast Diseases
Endocrine Gland Neoplasms
Endocrine System Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Gonadal Disorders
Neoplasms by Site
Ovarian Diseases
Skin Diseases
Urogenital Neoplasms
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Steroid Synthesis Inhibitors

ClinicalTrials.gov processed this record on May 26, 2016