Letrozole in Treating Breast Cancer in Postmenopausal Women With Stage I, Stage II, or Stage III Breast Cancer Previously Treated With Tamoxifen

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 2010 by National Cancer Institute (NCI)
Information provided by:
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
First received: February 5, 2010
Last updated: August 23, 2013
Last verified: February 2010

RATIONALE: Estrogen can cause the growth of breast cancer cells. Letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known which regimen of letrozole is most effective in treating breast cancer in postmenopausal women who have received tamoxifen.

PURPOSE: This randomized phase III trial is comparing different regimens of letrozole to see how well they work in treating postmenopausal women with stage I, stage II, or stage III breast cancer previously treated with tamoxifen.

Condition Intervention Phase
Breast Cancer
Drug: letrozole
Procedure: adjuvant therapy
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Masking: Open Label
Primary Purpose: Treatment
Official Title: Letrozole Adjuvant Therapy Duration (LEAD) Study: Standard Versus Long Treatment. A Phase III Trial in Post-Menopausal Women With Early Breast Cancer.

Resource links provided by NLM:

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Disease-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Overall survival [ Designated as safety issue: No ]
  • Safety [ Designated as safety issue: Yes ]

Estimated Enrollment: 4050
Study Start Date: August 2005
Estimated Primary Completion Date: August 2015 (Final data collection date for primary outcome measure)
Detailed Description:



  • To compare the disease-free survival of previously treated, post-menopausal women with early-stage breast cancer treated with standard- (2-3 years of tamoxifen followed by 2-3 years of letrozole) versus long-treatment (2-3 years of tamoxifen followed by 5 years of letrozole) adjuvant letrozole.


  • To compare the overall survival of these patients.
  • To compare the safety of these patients.

OUTLINE: Patients are randomized to 1 or 2 treatment arms.

  • Arm I (standard treatment): Patients previously treated with tamoxifen for 2 years receive letrozole for an additional 3 years; patients previously treated with tamoxifen for 3 years receive letrozole for an additional 2 years; and patients previously treated with tamoxifen for 2-3 years receive letrozole , so the total duration of the endocrine treatment (i.e., tamoxifen followed by letrozole) is 5 years.
  • Arm II (long treatment): Patients receive letrozole for an additional 5 years regardless of the duration of the previous tamoxifen treatment.

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No


  • Histologically confirmed breast cancer at first diagnosis

    • Stage I, II, or III disease
    • Documented (microscopic) infiltration of the skin (pT4) allowed
  • Nx, pNo, pN1, pN2, PN3 axillary nodal status allowed
  • Received adjuvant tamoxifen for at least 2 years but no more than 3 years and 3 months

    • Patients treated with adjuvant chemotherapy must have begun receiving tamoxifen within 3 months after the completion of chemotherapy
  • Definitive surgical treatment must be either mastectomy or breast-conserving surgery with axillary lymph node dissection OR sentinel node biopsy for operable breast cancer
  • Hormone receptor status not specified


  • ECOG or WHO performance status 0-1
  • Post-menopausal status meeting 1 of the following criteria:

    • Age > 55 years with cessation of menses
    • Age < 55 years but no spontaneous menses for at least 1 year
    • Age < 55 years and spontaneous menses within the past 1 year, but currently amenorrheic (e.g., spontaneous or secondary to hysterectomy), AND with postmenopausal gonadotropin levels (luteinizing hormone and follicle-stimulating hormone levels > 40 IU/L) or postmenopausal estradiol levels (< 5 ng/dL) or according to the definition of "postmenopausal range" for the laboratory involved
    • Underwent a bilateral oophorectomy
  • Must be accessible for treatment and follow-up


  • See Disease Characteristics
  • Prior aromatase inhibitors allowed
  • Concurrent bisphosphonates allowed
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01064635

Istituto Nazionale per la Ricerca sul Cancro Recruiting
Genoa, Italy, 16132
Contact: Contact Person    39-010-560-0387      
Sponsors and Collaborators
Gruppo Italiano Mammella (GIM)
Principal Investigator: Lucia Del Mastro, MD National Institute for Cancer Research, Italy
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT01064635     History of Changes
Other Study ID Numbers: CDR0000665188, GIM-4-LEAD, EUDRACT-2005-001212-44, EU-21003
Study First Received: February 5, 2010
Last Updated: August 23, 2013
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
stage IA breast cancer
stage IB breast cancer
stage II breast cancer
stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer

Additional relevant MeSH terms:
Breast Neoplasms
Breast Diseases
Neoplasms by Site
Skin Diseases
Antineoplastic Agents
Aromatase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on May 21, 2015