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Letrozole in Treating Postmenopausal Women Who Have Received Hormone Therapy for Hormone Receptor-Positive Breast Cancer

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: NCT00382070
Recruitment Status : Active, not recruiting
First Posted : September 28, 2006
Results First Posted : May 20, 2021
Last Update Posted : October 6, 2021
National Cancer Institute (NCI)
Information provided by (Responsible Party):
NSABP Foundation Inc

Tracking Information
First Submitted Date  ICMJE September 26, 2006
First Posted Date  ICMJE September 28, 2006
Results First Submitted Date  ICMJE April 28, 2021
Results First Posted Date  ICMJE May 20, 2021
Last Update Posted Date October 6, 2021
Study Start Date  ICMJE August 2006
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 28, 2021)
Disease-free Survival [ Time Frame: 7 years. ]
Percentage of patients free from DFS events. DFS events include local, regional, or distant recurrence, second primary cancer or death from any cause prior to recurrence or second primary cancer.
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: April 28, 2021)
  • Overall Survival [ Time Frame: 7 years ]
    Percentage of patients alive
  • Breast Cancer-free Interval [ Time Frame: 7 years ]
    Cumulative incidence of breast-cancer-free interval events. BCFI events include local-regional recurrence, distant recurrence or contralateral breast cancer as a first event.
  • Distant Recurrence [ Time Frame: 7 years ]
    Cumulative incidence of distant recurrences.
  • Osteoporotic-related Fractures [ Time Frame: 7 years ]
    Cumulative incidence of osteoporotic-related fractures defined as Colles', hip or spinal fractures
  • Arterial Thrombotic Events [ Time Frame: 7 years ]
    Cumulative incidence of arterial thrombotic events, as defined by CTCAE version 4.0 (grade ≥1 stroke or transient ischaemic attack; grade ≥2 acute coronary syndrome or cerebrovascular ischaemia; grade ≥3 myocardial infarction, peripheral ischaemia, or visceral arterial ischaemia; and grade ≥4 selected thromboembolic events [cerebrovascular event, arterial insufficiency]).
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Letrozole in Treating Postmenopausal Women Who Have Received Hormone Therapy for Hormone Receptor-Positive Breast Cancer
Official Title  ICMJE A Clinical Trial to Determine the Efficacy of Five Years of Letrozole Compared to Placebo in Patients Completing Five Years of Hormonal Therapy Consisting of an Aromatase Inhibitor (AI) or Tamoxifen Followed by an AI in Prolonging Disease-Free Survival in Postmenopausal Women With Hormone Receptor Positive Breast Cancer
Brief Summary

RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether letrozole is more effective than a placebo in treating patients with hormone receptor-positive breast cancer.

PURPOSE: This randomized phase III trial is studying letrozole to see how well it works compared with a placebo in treating postmenopausal women who have received hormone therapy for hormone receptor-positive breast cancer.

Detailed Description



  • Determine whether or not prolonged adjuvant hormonal therapy comprising letrozole vs placebo will improve disease-free survival of postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive breast cancer who have completed 5 years of hormonal therapy with 5 years of an aromatase inhibitor (AI) or 5 years of a combination of up to 3 years of tamoxifen citrate followed by an AI.
  • Compare the disease-free survival of patients treated with these regimens.


  • Compare overall survival of patients treated with these regimens.
  • Compare breast cancer-free interval of patients treated with these regimens.
  • Compare distant recurrence in patients treated with these regimens.
  • Compare the incidence of osteoporotic-related fractures (e.g., Colles', hip, and spine) in these patients treated with these regimens.
  • Compare the incidence of arterial thrombotic events in patients treated with these regimens.

OUTLINE: This is a double-blind, multicenter, placebo-controlled, randomized study. Patients are stratified according to pathologic nodal status (negative vs positive), adjuvant tamoxifen citrate therapy (yes vs no), and lowest bone mineral density T score for lumbosacral spine, total hip, or femoral neck (> -2.0 vs ≤ -2.0 standard deviation). Patients are randomized to 1 of 2 treatment arms.

  • Group I: Patients receive oral placebo once daily.
  • Group II: Patients receive oral letrozole once daily.

In both arms, treatment continues for up to 5 years in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed annually.

PROJECTED ACCRUAL: A total of 3,840 patients will be accrued for this study.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE Breast Cancer
Intervention  ICMJE
  • Drug: Letrozole
    Letrozole 2.5 mg taken orally once daily for 5 years
  • Other: Placebo
    Placebo tablet taken orally once daily for 5 years
Study Arms  ICMJE
  • Experimental: Group 2 Letrozole
    Patients receive oral letrozole once daily for up to 5 years.
    Intervention: Drug: Letrozole
  • Placebo Comparator: Group 1 Placebo
    Patients receive oral placebo once daily for up to 5 years.
    Intervention: Other: Placebo
Publications *

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: April 13, 2010)
Original Enrollment  ICMJE Not Provided
Estimated Study Completion Date  ICMJE December 2022
Actual Primary Completion Date January 2016   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Eligibility Criteria

  • Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (0 = fully active, able to carry on all pre-disease performance without restriction; 1 = restricted in physically strenuous activity but ambulatory).
  • Patients must be postmenopausal at the time of randomization. (Note: Premenopausal or perimenopausal women requiring therapy with luteinizing hormone-releasing hormone [LHRH] analogs to suppress ovarian function are not eligible.) For study purposes, postmenopausal is defined as: age 56 or older with no spontaneous menses for at least 12 months prior to study entry, or age 55 or younger with no spontaneous menses for at least 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) AND with a documented estradiol level in the postmenopausal range according to local institutional/laboratory standards, or a prior documented bilateral oophorectomy.
  • The patient must have remained disease-free from the time of initial breast cancer diagnosis until the time of randomization.
  • The patient must have had histologically-confirmed invasive carcinoma of the breast by diagnostic core needle biopsy or by final pathologic evaluation of the surgical specimen.
  • Patients who received neoadjuvant chemotherapy must have been clinical Stage I, II, or IIIA. For patients who received adjuvant chemotherapy, the primary tumor must have been T1-3 on pathologic evaluation and ipsilateral nodes must have been pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b.
  • The primary tumor must have been estrogen receptor (ER)-positive and/or progesterone receptor (PgR)-positive. (Patients who had a tumor that was considered to be borderline for hormone receptor positivity and who were treated with tamoxifen and/or an aromatases inhibitor (AI) are eligible for this study.)
  • Patients must have undergone either a lumpectomy with axillary nodal staging followed by breast radiotherapy or a total mastectomy with axillary nodal staging. (Acceptable axillary nodal staging procedures include sentinel node biopsy alone, if sentinel nodes were negative on hematoxylin and eosin (H&E) staining.)
  • The duration of the patient's hormonal therapy following breast cancer diagnosis must have been 57-63 months from the first dose regardless of the number of missed doses. Hormonal therapy must have consisted of an AI or a combination of up to 3 years of tamoxifen followed by an AI. Tamoxifen may not have been given during years 4 and 5 of the 5 years of adjuvant hormonal therapy. (Note: Patients must discontinue their adjuvant AI therapy at the time of randomization.)
  • Optional Letrozole Registration Program for patients who have not yet completed 5 years of hormonal therapy. (Note: As of September 5, 2008, the optional NSABP B-42 Registration Program closed to patient enrollment. Accrual and data collection for the NSABP B-42 randomized treatment trial continues as planned.) In order to have a predominantly letrozole-treated population for B-42 study entry, patients who have had a minimum of 2 years of hormonal therapy and who are currently on tamoxifen (for up to 3 years) or an AI may be offered letrozole at no cost until they complete 5 total years of initial adjuvant hormonal therapy.
  • B-42 randomization must be within 6 months following completion of 5 years (57-63 months) of initial adjuvant hormonal therapy.
  • At the time of randomization, the patient must have had the following: history and physical exam within 3 months demonstrating no findings suggestive of recurrent breast cancer; bilateral mammogram within 1 year (unilateral if patient had a mastectomy); mammogram not required if patient had a prophylactic contralateral mastectomy; bone mineral density (BMD) testing within 1 year; and fasting lipid profile (total cholesterol, LDL-C, HDL-C, and triglycerides) with a total cholesterol value less than or equal to grade 1 (according to CTCAE v3.0), with or without cholesterol-lowering therapy.

    • within 1 year if the patient has a history of hypercholesterolemia controlled with cholesterol-lowering therapy and/or therapeutic lifestyle changes or if the patient has a history of one or more of the following risk factors for future cardiovascular events: diabetes, hypertension, obesity, tobacco use, hypertriglyceridemia, documented coronary artery disease, or family history of premature coronary heart disease.
    • within 2 years for all other patients.

Ineligibility Criteria

  • Patients with one or more of the following conditions will be ineligible for this study:
  • History of non-traumatic osteoporotic fracture of wrist, hip, or spine.
  • Diagnosis of bilateral breast cancer including ductal carcinoma in situ (DCIS)[(synchronous or metachronous].
  • Other malignancies unless the patient is considered to be disease-free for 5 or more years prior to randomization, and is deemed by their physician to be at low risk for recurrence. Patients with the following cancers are eligible if diagnosed and treated within the past 5 years: carcinoma in situ of the cervix, colon carcinoma in situ, melanoma in situ, and basal cell and squamous cell carcinoma of the skin.
  • Sex hormonal therapy, e.g., estrogen- or progesterone-replacement therapy or oral contraceptives. These patients are eligible only if this therapy is discontinued prior to randomization.
  • Therapy with any hormonal agent such as raloxifene for management of osteoporosis. Patients are eligible only if these medications are discontinued prior to study entry.
  • Administration of any investigational agent within 30 days before study entry.
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Ages  ICMJE 18 Years to 120 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Canada,   Ireland,   United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00382070
Other Study ID Numbers  ICMJE NSABP B-42
U10CA012027 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party NSABP Foundation Inc
Study Sponsor  ICMJE NSABP Foundation Inc
Collaborators  ICMJE
  • National Cancer Institute (NCI)
  • Novartis
Investigators  ICMJE
Principal Investigator: Norman Wolmark, MD NSABP Foundation Inc
PRS Account NSABP Foundation Inc
Verification Date February 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP