National Cancer Institute National Cancer Institute
U.S. National Institutes of Health National Cancer Institute
NCI Home Cancer Topics Clinical Trials Cancer Statistics Research & Funding News About NCI
Clinical Trials (PDQ®)
Patient VersionHealth Professional Version
Last Modified: 7/23/2008     First Published: 9/23/2006  
Page Options
Print This Page  Print This Page
E-Mail This Document  E-Mail This Document
Quick Links
Director's Corner

Dictionary of Cancer Terms

NCI Drug Dictionary

Funding Opportunities

NCI Publications

Advisory Boards and Groups

Science Serving People

Español
NCI Highlights
Colorectal Cancer Drugs Require Careful Patient Selection

Cetuximab for Advanced Lung Cancer

Past Highlights
BreastCancerTrials.org
Phase III Randomized Study of Letrozole in Postmenopausal Women With Hormone Receptor-Positive Breast Cancer Who Have Completed Adjuvant Hormonal Therapy Comprising An Aromatase Inhibitor and/or Tamoxifen Citrate

Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outcomes
Outline
Related Publications
Trial Contact Information
Registry Information

Alternate Title

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

Basic Trial Information

Phase
Type
Status
Age
Sponsor
Protocol IDs

Phase III


Treatment


Active


Any age (postmenopausal)


NCI


NSABP-B-42
NSABP-B-42, NCT00382070

Special Category: CTSU trial

Objectives

Primary

  1. Determine whether or not prolonged adjuvant hormonal therapy comprising letrozole vs placebo will improve disease-free interval 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.
  2. Compare the disease-free survival of patients treated with these regimens.

Secondary

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

Entry Criteria

Disease Characteristics:

  • Histologically confirmed invasive carcinoma of the breast by core needle or open biopsy
    • Clinical stage I, II, or IIIA primary tumor for patients who received neoadjuvant chemotherapy
    • Primary tumor t1-3 on pathologic evaluation and ipsilateral nodes pN0, pN1 (pN1mi, pN1a, pN1b, pN1c), pN2a, pN3a, or pN3b for patients who received adjuvant chemotherapy


  • Received adjuvant hormonal therapy after breast cancer diagnosis for a duration of 57-63 months from the first dose (regardless of the number of missed doses) with 1 of the following:
    • Aromatase inhibitor* (AI)
    • Combination of up to 3 years of tamoxifen citrate followed by an AI for a total of 5 years
      • No tamoxifen citrate during years 4 and 5 of 5-year adjuvant hormonal therapy

     [Note: *Adjuvant AI therapy must be discontinued at the time of randomization]



  • Must have completed adjuvant hormonal therapy within the past 6 months


  • Must have undergone a bilateral mammogram within the past year (unilateral if patient had a mastectomy)
    • Mammogram not required if patient has a prophylactic contralateral mastectomy


  • Must have undergone a bone mineral density test within the past year


  • Must have undergone a lumpectomy with axillary nodal staging followed by breast radiotherapy OR a total mastectomy with axillary nodal staging
    • Nodal staging with sentinel node biopsy alone is allowed provided sentinel nodes were negative on H&E staining


  • No evidence of recurrent breast cancer by history and physical within the past 3 months


  • No diagnosis of bilateral breast cancer, including ductal carcinoma in situ (synchronous or metachronous)


  • Estrogen receptor (ER)-positive and/or progesterone receptor-positive tumor
    • Patients with a tumor considered to be borderline hormone receptor-positive that was treated with tamoxifen citrate and/or AI are allowed


Prior/Concurrent Therapy:

  • See Disease Characteristics
  • No other investigational agent within the past 30 days
  • No other concurrent anticancer therapy
  • No concurrent participation in any other hormonal therapy or placebo-controlled supportive therapy clinical trial
  • No other concurrent hormonal therapy, including any of the following:
    • Hormonal agent for management of osteoporosis (e.g., raloxifene)
    • Selective estrogen receptor modulators (e.g., raloxifene)
    • Sex hormonal therapy (e.g., estrogen- or progesterone-replacement therapy, including low-dose estrogen in the form of vaginal cream) or oral contraceptives
    • Luteinizing hormone-releasing hormone agonists/antagonists (e.g., goserelin)
    • Estradiol acetate
      • Conjugated estrogen ring or estradiol hemihydrate vaginal tab allowed
    • Other aromatase inhibitors
  • Concurrent bisphosphonates allowed provided dose is as recommended for bone protection, not anticancer therapy

Patient Characteristics:

  • Female
  • Postmenopausal as defined by any of the following criteria:
    • Age ≥ 56 years with no spontaneous menses for ≥ 12 months prior to study entry
    • Age ≤ 55 years with no spontaneous menses for ≥ 12 months prior to study entry (e.g., spontaneous or secondary to hysterectomy) AND a documented estradiol level in the postmenopausal range
    • Prior documented bilateral oophorectomy
  • ECOG performance status 0 or 1
  • Cholesterol ≤ grade 1 (with or without cholesterol-lowering therapy) meeting 1 of the following criteria:
    • Criteria must be met within the past year if patient has any of the following:
      • History of hypercholesterolemia controlled with cholesterol-lowering therapy and/or therapeutic lifestyle changes
      • History of ≥ 1 of the following risk factors for cardiovascular events:
        • Diabetes
        • Hypertension
        • Obesity
        • Tobacco use
        • Hypertriglyceridemia
        • Documented coronary artery disease
        • Family history of premature coronary heart disease
    • Criteria must be met within the past 2 years for all other patients
  • Not pregnant or nursing
  • Negative pregnancy test
  • No history of nontraumatic osteoporotic fracture of the wrist, hip, or spine
  • No other malignancies unless disease-free for ≥ 5 years and, in the opinion of the investigator, at low risk for recurrence
  • No other prior malignancy within the past 5 years except for the following:
    • Carcinoma in situ of the cervix
    • Colon carcinoma in situ
    • Melanoma in situ
    • Basal cell or squamous cell carcinoma of the skin

Expected Enrollment

3840

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

Outcomes

Primary Outcome(s)

Disease-free survival

Secondary Outcome(s)

Overall survival
Breast cancer-free interval (time to recurrence or contralateral second primary breast cancer)
Distant recurrence
Incidence of osteoporotic-related fractures (e.g., Colles', hip, and spine)
Incidence of arterial thrombotic events (CTCAE v. 3.0 grades 3, 4, or 5 cardiac ischemia/infarction, CNS cerebrovascular ischemia, peripheral arterial ischemia, and visceral arterial ischemia [nonmyocardial])

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.

  • Arm I: Patients receive oral letrozole once daily.


  • Arm II: Patients receive oral placebo 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.

Related Publications

Mamounas EP, Lembersky B, Jeong JH, et al.: NSABP B-42: a clinical trial to determine the efficacy of five years of letrozole compared with 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. Clin Breast Cancer 7 (5): 416-21, 2006.[PUBMED Abstract]

Trial Contact Information

Trial Lead Organizations

National Surgical Adjuvant Breast and Bowel Project

Terry Mamounas, MD, MPH, FACS, Protocol chair
Ph: 330-438-6281
Email: tmamounas@aultman.com

Trial Sites

U.S.A.
Alabama
  Huntsville
 Clearview Cancer Institute
 Clinical Trials Office - Clearview Cancer Institute
Ph: 256-705-4224
  Mobile
 Providence Cancer Center at Providence Hospital
 Paul Schwarzenberger, MD
Ph: 251-435-5892
Alaska
  Anchorage
 Providence Cancer Center
 Clinical Trials Office - Providence Cancer Center
Ph: 907-261-3109
  Fairbanks
 Fairbanks Cancer Treatment Center at Fairbanks Memorial Hospital
 Jacqueline Vuky
Ph: 907-458-5380
800-678-5458
Arkansas
  Little Rock
 Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
 Clinical Trial Office - Arkansas Cancer Research Center at University of Arkansas for Medical Sciences
Ph: 501-686-8274
California
  Berkeley
 Alta Bates Summit Comprehensive Cancer Center
 Clinical Trials Office - Alta Bates Summit Comprehensive Cancer Center
Ph: 510-204-3428
  Burbank
 Providence Saint Joseph Medical Center - Burbank
 Clinical Trials Office - Providence Saint Joseph Medical Center - Burbank
Ph: 818-847-3220
  Burlingame
 Peninsula Medical Center
 David Irwin, MD
Ph: 510-204-2866
  Castro Valley
 East Bay Radiation Oncology Center
 James Feusner, MD
Ph: 510-428-3689
 Eden Medical Center
 James Feusner, MD
Ph: 510-428-3689
 Valley Medical Oncology Consultants - Castro Valley
 James Feusner, MD
Ph: 510-428-3689
  Duarte
 City of Hope Comprehensive Cancer Center
 Clinical Trials Office - City of Hope Comprehensive Cancer Center
Ph: 800-826-4673
 Email: becomingapatient@coh.org
  Fairfield
 North Bay Cancer Center
 Clinical Trials Office - North Bay Cancer Center
Ph: 707-429-6976
  Fremont
 Kaiser Permanente - Fremont
 Louis Fehrenbacher, MD
Ph: 707-651-2577
 Valley Medical Oncology
 James Feusner, MD
Ph: 510-428-3689
 Washington Township Hospital
 Byron Wilson, MD
Ph: 510-797-1111
  Fresno
 Cancer Care Associates
 Charles Kuzma
Ph: 559-326-1222
877-490-4222
  Glendale
 Glendale Memorial Hospital Comprehensive Cancer Center
 Clinical Trials Office - Glendale Memorial Hospital Comprehensive Cancer Center
Ph: 818-409-7653
  Greenbrae
 California Cancer Care, Incorporated - Greenbrae
 Peter Eisenberg, MD
Ph: 415-925-5000
 Marin Cancer Institute at Marin General Hospital
 David Irwin, MD
Ph: 510-204-2866
 Sutter Health - Western Division Cancer Research Group
 David Irwin, MD
Ph: 510-204-2866
  Hayward
 Kaiser Permanente Medical Center - Hayward
 Louis Fehrenbacher, MD
Ph: 707-651-2577
  La Jolla
 Rebecca and John Moores UCSD Cancer Center
 Clinical Trials Office - Rebecca and John Moores UCSD Cancer Center
Ph: 858-822-5354
 Email: cancercto@ucsd.edu
 Scripps Cancer Center - San Diego
 Joan Kroener, MD
Ph: 858-587-4325
  Loma Linda
 Loma Linda University Cancer Institute at Loma Linda University Medical Center
 Clinical Trials Office - Loma Linda University Cancer Institute
Ph: 909-558-3375
  Long Beach
 Pacific Shores Medical Group - Long Beach
 N. Simon Tchekmedyian, MD, FACP
Ph: 562-590-0345
  Los Angeles
 Jonsson Comprehensive Cancer Center at UCLA
 Clinical Trials Office - Jonsson Comprehensive Cancer Center at UCLA
Ph: 888-798-0719
 USC/Norris Comprehensive Cancer Center and Hospital
 Clinical Trials Office - USC/Norris Comprehensive Cancer Center and Hospital
Ph: 323-865-0451
  Mountain View
 El Camino Hospital Cancer Center
 Clinical Trials Office - El Camino Hospital Cancer Center
Ph: 650-988-7623
  Oakland
 Alta Bates Summit Medical Center - Summit Campus
 Clinical Trials Office - Alta Bates Summit Medical Center - Summit Campus
Ph: 510-204-1414
 Bay Area Breast Surgeons, Incorporated
 James Feusner, MD
Ph: 510-428-3689
 CCOP - Bay Area Tumor Institute
 James Feusner, MD
Ph: 510-428-3689
 Highland General Hospital
 James Feusner, MD
Ph: 510-428-3689
 Kaiser Permanente Medical Center - Oakland
 Louis Fehrenbacher, MD
Ph: 707-651-2577
 Larry G Strieff MD Medical Corporation
 James Feusner, MD
Ph: 510-428-3689
 Tom K Lee, Incorporated
 James Feusner, MD
Ph: 510-428-3689
  Orange
 Chao Family Comprehensive Cancer Center at University of California Irvine Medical Center
 Clinical Trials Office - Chao Family Comprehensive Cancer Center
Ph: 877-UC-STUDY
 Email: ucstudy@uci.edu
 St. Joseph Hospital Regional Cancer Center - Orange
 David Margileth
Ph: 714-771-8999
  Palm Springs
 Desert Regional Medical Center Comprehensive Cancer Center
 Clinical Trials Office - Desert Regional Medical Center Comprehensive Cancer Center
Ph: 760-416-4730
  Pleasanton
 Valley Care Medical Center
 James Feusner, MD
Ph: 510-428-3689
 Valley Medical Oncology Consultants - Pleasanton
 James Feusner, MD
Ph: 510-428-3689
  Pomona
 Robert and Beverly Lewis Family Cancer Care Center at Pomona Valley Hospital Medical Center
 Clinical Trials Office - Robert and Beverly Lewis Family Cancer Care Center
Ph: 909-865-9555
  Rancho Mirage
 Lucy Curci Cancer Center at Eisenhower Memorial Hospital and Medical Center
 Murthy Andavolu
Ph: 760-674-3600
  Redding
 North Valley Breast Clinic
 Lily Lai, MD
Ph: 530-243-5551
  Redwood City
 Kaiser Permanente Medical Center - Redwood City
 Louis Fehrenbacher, MD
Ph: 707-651-2577
  Richmond
 Kaiser Permanente Medical Center - Richmond
 Louis Fehrenbacher, MD
Ph: 707-651-2577
  Roseville
 Kaiser Permanente Medical Center - Roseville
 Louis Fehrenbacher, MD
Ph: 707-651-2577
  Sacramento
 Kaiser Permanente Medical Center - Sacramento
 Louis Fehrenbacher, MD
Ph: 707-651-2577
 South Sacramento Kaiser-Permanente Medical Center
 Louis Fehrenbacher, MD
Ph: 707-651-2577
 Sutter Cancer Center
 Clinical Trial Office - Sutter Cancer Center
Ph: 916-454-6595
  San Diego
 Kaiser Permanente Medical Office -Vandever Medical Office
 Jonathan Polikoff, MD
Ph: 619-528-2596
  San Francisco
 California Pacific Medical Center - California Campus
 David Irwin, MD
Ph: 510-204-2866
 Kaiser Permanente Medical Center - San Francisco Geary Campus
 Louis Fehrenbacher, MD
Ph: 707-651-2577
 San Francisco General Hospital Medical Center
 Judith Luce, MD
Ph: 415-206-8000
  San Jose
 Kaiser Permanente Medical Center - Santa Teresa
 Louis Fehrenbacher, MD
Ph: 707-651-2577
  San Pablo
 Doctors Medical Center - San Pablo Campus
 James Feusner, MD
Ph: 510-428-3689
  San Rafael
 Kaiser Foundation Hospital - San Rafael
 Louis Fehrenbacher, MD
Ph: 707-651-2577
  Sana Rosa
 CCOP - Santa Rosa Memorial Hospital
 Ian Anderson, MD
Ph: 707-521-3830
  Santa Clara
 Kaiser Permanente Medical Center - Santa Clara Kiely Campus
 Louis Fehrenbacher, MD
Ph: 707-651-2577
  Santa Rosa
 Kaiser Permanente Medical Center - Santa Rosa
 Louis Fehrenbacher, MD
Ph: 707-651-2577
  South San Francisco
 Kaiser Permanente Medical Center - South San Francisco
 Louis Fehrenbacher, MD
Ph: 707-651-2577
  Stanford
 Stanford Cancer Center
 Clinical Trials Office - Stanford Cancer Center
Ph: 650-498-7061
 Email: cctoffice@stanford.edu
  Stockton
 Kaiser Permanente Medical Facility - Stockton
 Louis Fehrenbacher, MD
Ph: 707-651-2577
  Vallejo
 Kaiser Permanente Medical Center - Vallejo
 Louis Fehrenbacher, MD
Ph: 707-651-2577
 Sutter Solano Medical Center
 David Irwin, MD
Ph: 510-204-2866
  Walnut Creek
 Kaiser Permanente Medical Center - Walnut Creek
 Louis Fehrenbacher, MD
Ph: 707-651-2577
Colorado
  Aurora
 Aurora Presbyterian Hospital
 Eduardo Pajon, MD
Ph: 303-777-2663
 University of Colorado Cancer Center at UC Health Sciences Center
 Clinical Trials Office - University of Colorado Cancer Center
Ph: 720-848-0650
  Boulder
 Boulder Community Hospital
 Clinical Trials Office - Boulder Community Hospital
Ph: 303-938-5253
  Colorado Springs
 Memorial Hospital Cancer Center - Colorado Springs
 Clinical Trials Office - Memorial Hospital
Ph: 719-365-2406
 Penrose Cancer Center at Penrose Hospital
 Clinical Trials Office - Penrose Cancer Center
Ph: 719-776-5275
  Denver
 CCOP - Colorado Cancer Research Program
 Eduardo Pajon, MD
Ph: 303-777-2663
 Porter Adventist Hospital
 Eduardo Pajon, MD
Ph: 303-777-2663
 Presbyterian - St. Luke's Medical Center
 Clinical Trials Office - Presbyterian - St. Luke's Medical Center
Ph: 303-839-6000
 Rose Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
 St. Anthony Central Hospital
 Eduardo Pajon, MD
Ph: 303-777-2663
 St. Joseph Hospital
 Eduardo Pajon, MD
Ph: 303-777-2663
  Englewood
 Swedish Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Fort Collins
 Front Range Cancer Specialists
 Diana Medgyesy, MD
Ph: 970-212-7600
 Poudre Valley Hospital
 Clinical Trials Office - Poudre Valley Hospital
Ph: 970-495-8226
  Grand Junction
 St. Mary's Regional Cancer Center at St. Mary's Hospital and Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Greeley
 North Colorado Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Lone Tree
 Sky Ridge Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Longmont
 Hope Cancer Care Center at Longmont United Hospital
 Eduardo Pajon, MD
Ph: 303-777-2663
  Loveland
 McKee Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Pueblo
 St. Mary - Corwin Regional Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Thornton
 North Suburban Medical Center
 Eduardo Pajon, MD
Ph: 303-777-2663
  Wheat Ridge