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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00673335
Recruitment Status : Active, not recruiting
First Posted : May 7, 2008
Last Update Posted : June 9, 2021
Information provided by (Responsible Party):

Brief Summary:

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 or disease Intervention/treatment Phase
brca1 Mutation Carrier brca2 Mutation Carrier Breast Cancer Hereditary Breast/Ovarian Cancer (brca1, brca2) Drug: letrozole Drug: Placebo Phase 3

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 170 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Prevention of Breast Cancer by Letrozole in Post-menopausal Women Carrying a BRCA1/BRCA2 Mutation
Actual Study Start Date : May 2008
Actual Primary Completion Date : June 2019
Estimated Study Completion Date : August 2023

Arm Intervention/treatment
Experimental: Treatment arm
Letrozole, 1 tablet
Drug: letrozole
Other Name: Femara

Placebo Comparator: Placebo
Comparator, 1 tablet
Drug: Placebo

Primary Outcome Measures :
  1. Survival without contralateral or unilateral invasive breast cancer at 5 years (prior breast cancer) [ Time Frame: 2017 ]
  2. Survival without invasive breast cancer at 5 years [ Time Frame: 2017 ]

Secondary Outcome Measures :
  1. Invasive cancer-free survival at 10 years [ Time Frame: 2022 ]
  2. Breast cancer in situ-free survival at 5 and 10 years [ Time Frame: 2022 ]
  3. Relapse-free (local or metastatic disease) survival in patients with history of breast cancer at 5 and 10 years [ Time Frame: 2017 and 2022 ]
  4. Second cancer-free survival at 5 and 10 years [ Time Frame: 2017 and 2022 ]
  5. Event- free (local relapse or metastatic, contralateral, or second cancer) survival at 5 and 10 years [ Time Frame: 2017 and 2022 ]
  6. Overall survival at 5 and 10 years [ Time Frame: 2017 and 2022 ]
  7. Toxicity according to CTCAE version 3.0 [ Time Frame: 2017 and 2022 ]
  8. Lipid tolerance or cardiovascular or bone event [ Time Frame: 2017 and 2022 ]
  9. Quality of life according to MRS and SF36 questionnaires [ Time Frame: 2017 and 2022 ]

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.

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Ages Eligible for Study:   40 Years to 69 Years   (Adult, Older Adult)
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00673335

Show Show 23 study locations
Sponsors and Collaborators
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Study Chair: Pascal Pujol, MD Hopital Arnaud de Villeneuve
Publications of Results:
Pujol P, Mijonnet S, Karen S, et al.: Breast cancer prevention by letrozole in post menopausal BRCA1/2 mutations carriers: The Onco-03/LIBER trial. [Abstract] 32nd Annual San Antonio Breast Cancer Symposium, December 9-13, 2009, San Antonio, Texas. A-1048, 2009.

Other Publications:
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Responsible Party: UNICANCER Identifier: NCT00673335    
Other Study ID Numbers: UC-0104/0701 - ONCO03
ONCO-03/0701 ( Other Identifier: UNICANCER )
2007-000687-24 ( EudraCT Number )
First Posted: May 7, 2008    Key Record Dates
Last Update Posted: June 9, 2021
Last Verified: June 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Unicancer will share de-identified individual data that underlie the results reported. A decision concerning the sharing of other study documents, including protocol and statistical analysis plan will be examined upon request.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Time Frame: Unicancer will consider access to study data upon written detailed request sent to Unicancer, from 6 months until 5 years after publication of summary data.
Access Criteria: The data shared will be limit to that required for independent mandated verification of the published results, the applicant will need authorization from Unicancer for personal access, and data will only be transferred after signing of a data access agreement.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by UNICANCER:
breast cancer
hereditary breast/ovarian cancer (BRCA1, BRCA2)
BRCA1 mutation carrier
BRCA2 mutation carrier
Additional relevant MeSH terms:
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Breast Neoplasms
Ovarian Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Endocrine Gland Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Antineoplastic Agents
Aromatase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs