RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using drugs such as anastrozole and fulvestrant may fight breast cancer by blocking the uptake of estrogen. It is not yet known whether anastrozole is more effective with or without fulvestrant in treating breast cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of anastrozole with or without fulvestrant as first-line therapy in treating postmenopausal women who have metastatic breast cancer.

Condition	Treatment or Intervention	Phase
stage IV breast cancer recurrent breast cancer	Drug: anastrozole  Drug: fulvestrant  Procedure: antiestrogen therapy  Procedure: aromatase inhibition  Procedure: endocrine therapy  Procedure: hormone therapy	Phase III

OBJECTIVES:

• Compare the time to tumor progression in postmenopausal women with metastatic breast cancer treated with anastrozole with or without fulvestrant as first-line therapy.
• Compare the clinical benefit (complete or partial response, confirmed or unconfirmed, or stable disease ≥ 24 weeks) and overall survival of patients treated with these regimens.
• Compare adverse events in patients treated with these regimens.
• Determine the prognostic significance of estrogen receptor positivity and HER2/neu status in patients treated with these regimens.
• Determine parameters of estrogen and clinical pharmacology and estrogen levels in patients treated with these regimens.
• Compare anastrozole plasma levels at 8, 16, and 24 weeks in patients treated with these regimens.
• Compare estradiol serum levels at 8, 16, and 24 weeks in patients treated with these regimens.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to prior adjuvant tamoxifen therapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

• Arm I: Patients receive oral anastrozole once daily on days 1-28.
• Arm II: Patients receive oral anastrozole as in arm I and fulvestrant intramuscularly on day 1. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 6 months for 2 years and then annually for 3 years.

PROJECTED ACCRUAL: A total of 690 patients (345 per treatment arm) will be accrued for this study within 3 years.

Genders Eligible for Study:  Both

Criteria

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer meeting 1 of the following criteria:
• Metastatic disease (M1)
• Multiple sites of new disease that is clinically obvious metastatic disease (e.g., multiple sites of new osseous disease)
• Measurable or nonmeasurable disease
• No known brain or CNS metastases
• Hormone receptor status:
• Estrogen-receptor positive* AND/OR
• Progesterone-receptor positive* NOTE: *Positivity defined as estrogen binding of > 10 fmol/mg cytosol protein by ligand binding assay or positive by immunohistochemistry

PATIENT CHARACTERISTICS: Age

• Not specified

Sex

• Female

Menopausal status

• Postmenopausal, as defined by 1 of the following:
• Prior bilateral oophorectomy
• More than 12 months since last menstrual period with no prior hysterectomy
• At least 55 years of age with prior hysterectomy
• Under 55 years of age with a prior hysterectomy without oophorectomy and with estradiol and follicle-stimulating hormone levels consistent with menopause

Performance status

• Zubrod 0-2

Life expectancy

• Not specified

Hematopoietic

• No bleeding diathesis (e.g., disseminated intravascular coagulation or clotting factor deficiency)

Hepatic

• INR ≤ 1.6

Renal

• Not specified

Other

• HIV negative
• No other malignancy within the past 5 years except adequately treated basal cell or squamous cell skin cancer, carcinoma in situ of the cervix, or adequately treated stage I or II cancer currently in complete remission

PRIOR CONCURRENT THERAPY: Biologic therapy

• No prior immunotherapy for recurrent or metastatic disease
• No concurrent immunotherapy for malignancy

Chemotherapy

• No prior chemotherapy for recurrent or metastatic disease
• More than 12 months since prior adjuvant or neoadjuvant chemotherapy
• No concurrent chemotherapy for malignancy

Endocrine therapy

• No prior hormonal therapy for recurrent or metastatic disease
• Prior adjuvant hormonal therapy allowed
• No prior adjuvant or neoadjuvant (e.g., anastrozole, letrozole, or exemestane) aromatase inhibitors
• No prior fulvestrant
• At least 12 months since prior adjuvant luteinizing hormone-releasing hormone (LHRH) analogues
• Menstrual periods must not have resumed since LHRH therapy
• No other concurrent hormonal therapy for malignancy
• No concurrent hormone replacement therapy

Radiotherapy

• Not specified

Surgery

• Not specified

Other

• No long-term anticoagulant therapy (except antiplatelet therapy)

Alabama
      MBCCOP - Gulf Coast, Mobile,  Alabama,  36607,  United States; Recruiting
Arizona
      Arizona Cancer Center at University of Arizona Health Sciences Center, Tucson,  Arizona,  85724,  United States; Recruiting
      CCOP - Western Regional, Arizona, Phoenix,  Arizona,  85006-2726,  United States; Recruiting
      Veterans Affairs Medical Center - Phoenix (Carl T. Hayden), Phoenix,  Arizona,  85012,  United States; Recruiting
      Veterans Affairs Medical Center - Tucson, Tucson,  Arizona,  85723,  United States; Recruiting
Arkansas
      Arkansas Cancer Research Center at University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States; Recruiting
      Veterans Affairs Medical Center - Little Rock, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States; Recruiting
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States; Recruiting
      Chao Family Comprehensive Cancer Center at University of California Irvine Cancer Center, Orange,  California,  92868,  United States; Recruiting
      City of Hope Comprehensive Cancer Center, Duarte,  California,  91010-3000,  United States; Recruiting
      Jonsson Comprehensive Cancer Center, UCLA, Los Angeles,  California,  90095-1781,  United States; Recruiting
      USC/Norris Comprehensive Cancer Center and Hospital, Los Angeles,  California,  90033,  United States; Recruiting
      Veterans Affairs Medical Center - Loma Linda (Pettis), Loma Linda,  California,  92357,  United States; Recruiting
      Veterans Affairs Outpatient Clinic - Martinez, Martinez,  California,  94553,  United States; Recruiting
Colorado
      University of Colorado Cancer Center at University of Colorado Health Sciences Center, Aurora,  Colorado,  80010,  United States; Recruiting
      Veterans Affairs Medical Center - Denver, Denver,  Colorado,  80220,  United States; Recruiting
District of Columbia
      MBCCOP - Howard University Cancer Center, Washington,  District of Columbia,  20060,  United States; Recruiting
Florida
      Veterans Affairs Medical Center - Tampa (Haley), Tampa,  Florida,  33612,  United States; Recruiting
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States; Recruiting
Hawaii
      MBCCOP - Hawaii, Honolulu,  Hawaii,  96813,  United States; Recruiting
Illinois
      Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood,  Illinois,  60153-5500,  United States; Recruiting
      CCOP - Central Illinois, Decatur,  Illinois,  62526,  United States; Recruiting
      MBCCOP - University of Illinois at Chicago, Chicago,  Illinois,  60612,  United States; Recruiting
      Veterans Affairs Medical Center - Chicago (Westside Hospital), Chicago,  Illinois,  60612,  United States; Recruiting
      Veterans Affairs Medical Center - Hines (Edward Hines, Junior Hospital), Hines,  Illinois,  60141,  United States; Recruiting
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States; Recruiting
      Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City,  Kansas,  66160-7353,  United States; Recruiting
      Veterans Affairs Medical Center - Wichita, Wichita,  Kansas,  67218,  United States; Recruiting
Kentucky
      Markey Cancer Center at University of Kentucky Chandler Medical Center, Lexington,  Kentucky,  40536-0084,  United States; Recruiting
      Veterans Affairs Medical Center - Lexington, Lexington,  Kentucky,  40502-2236,  United States; Recruiting
Louisiana
      Louisiana State University Health Sciences Center - Shreveport, Shreveport,  Louisiana,  71130-3932,  United States; Recruiting
      MBCCOP - LSU Health Sciences Center, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Tulane Cancer Center at Tulane University Hospital and Clinic, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Veterans Affairs Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States; Recruiting
      Veterans Affairs Medical Center - Shreveport, Shreveport,  Louisiana,  71101-4295,  United States; Recruiting
Massachusetts
      Cancer Research Center at Boston Medical Center, Boston,  Massachusetts,  02118,  United States; Recruiting
Michigan
      Barbara Ann Karmanos Cancer Institute, Detroit,  Michigan,  48201-1379,  United States; Recruiting
      CCOP - Beaumont, Royal Oak,  Michigan,  48073-6769,  United States; Recruiting
      CCOP - Grand Rapids, Grand Rapids,  Michigan,  49503,  United States; Recruiting
      CCOP - Michigan Cancer Research Consortium, Ann Arbor,  Michigan,  48106,  United States; Recruiting
      Josephine Ford Cancer Center at Henry Ford Hospital, Detroit,  Michigan,  48202,  United States; Recruiting
      Providence Cancer Institute at Providence Hospital, Southfield,  Michigan,  48075,  United States; Recruiting
      University of Michigan Comprehensive Cancer Center, Ann Arbor,  Michigan,  48109-0912,  United States; Recruiting
      Veterans Affairs Medical Center - Ann Arbor, Ann Arbor,  Michigan,  48105,  United States; Recruiting
      Veterans Affairs Medical Center - Detroit, Detroit,  Michigan,  48201-1932,  United States; Recruiting
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States; Recruiting
      Veterans Affairs Medical Center - Jackson, Jackson,  Mississippi,  39216,  United States; Recruiting
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States; Recruiting
      CCOP - Kansas City, Kansas City,  Missouri,  64131,  United States; Recruiting
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States; Recruiting
      St. Louis University Hospital Cancer Center, Saint Louis,  Missouri,  63110,  United States; Recruiting
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States; Recruiting
New Mexico
      MBCCOP - University of New Mexico HSC, Albuquerque,  New Mexico,  87131,  United States; Recruiting
      Veterans Affairs Medical Center - Albuquerque, Albuquerque,  New Mexico,  87108-5138,  United States; Recruiting
New York
      Herbert Irving Comprehensive Cancer Center at Columbia University, New York,  New York,  10032,  United States; Recruiting
      James P. Wilmot Cancer Center at University of Rochester Medical Center, Rochester,  New York,  14642,  United States; Recruiting
      NYU School of Medicine's Kaplan Comprehensive Cancer Center, New York,  New York,  10016,  United States; Recruiting
North Carolina
      CCOP - Southeast Cancer Control Consortium, Goldsboro,  North Carolina,  27534-9479,  United States; Recruiting
Ohio
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States; Recruiting
      CCOP - Dayton, Dayton,  Ohio,  45429,  United States; Recruiting
      Charles M. Barrett Cancer Center at University Hospital, Cincinnati,  Ohio,  45267-0501,  United States; Recruiting
      Cleveland Clinic Taussig Cancer Center, Cleveland,  Ohio,  44195-9001,  United States; Recruiting
      Veterans Affairs Medical Center - Cincinnati, Cincinnati,  Ohio,  45220-2288,  United States; Recruiting
      Veterans Affairs Medical Center - Dayton, Dayton,  Ohio,  45428-1002,  United States; Recruiting
Oklahoma
      Oklahoma University Medical Center, Oklahoma City,  Oklahoma,  73104,  United States; Recruiting
Oregon
      Cancer Institute at Oregon Health and Science University, Portland,  Oregon,  97201-3098,  United States; Recruiting
      CCOP - Columbia River Oncology Program, Portland,  Oregon,  97225,  United States; Recruiting
      Veterans Affairs Medical Center - Portland, Portland,  Oregon,  97207,  United States; Recruiting
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States; Recruiting
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States; Recruiting
      Hollings Cancer Center at Medical University of South Carolina, Charleston,  South Carolina,  29425,  United States; Recruiting
      Veterans Affairs Medical Center - Charleston, Charleston,  South Carolina,  29401-5799,  United States; Recruiting
Tennessee
      University of Tennessee Cancer Institute, Memphis,  Tennessee,  38104,  United States; Recruiting
      Veterans Affairs Medical Center - Memphis, Memphis,  Tennessee,  38104,  United States; Recruiting
Texas
      Brooke Army Medical Center, Fort Sam Houston,  Texas,  78234-6200,  United States; Recruiting
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States; Recruiting
      Harrington Cancer Center, Amarillo,  Texas,  79106,  United States; Recruiting
      University of Texas - MD Anderson Cancer Center, Houston,  Texas,  77030-4095,  United States; Recruiting
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78229-3900,  United States; Recruiting
      University of Texas Medical Branch, Galveston,  Texas,  77555-0565,  United States; Recruiting
      Veterans Affairs Medical Center - Amarillo, Amarillo,  Texas,  79106,  United States; Recruiting
      Veterans Affairs Medical Center - San Antonio (Murphy), San Antonio,  Texas,  78229,  United States; Recruiting
      Veterans Affairs Medical Center - Temple, Temple,  Texas,  76504,  United States; Recruiting
Utah
      Huntsman Cancer Institute, Salt Lake City,  Utah,  84112-5550,  United States; Recruiting
      Veterans Affairs Medical Center - Salt Lake City, Salt Lake City,  Utah,  84148,  United States; Recruiting
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States; Recruiting
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States; Recruiting
      Puget Sound Oncology Consortium, Seattle,  Washington,  98109,  United States; Recruiting
      Veterans Affairs Medical Center - Seattle, Seattle,  Washington,  98108,  United States; Recruiting
Canada, Ontario
      Cancer Care Ontario-London Regional Cancer Centre, London,  Ontario,  N6A 4L6,  Canada; Recruiting

Study chairs or principal investigators

Rita S. Mehta, MD,  Chao Family Comprehensive Cancer Center   
Theodore A. Vandenberg, MD,  Study Chair,  Cancer Care Ontario-London Regional Cancer Centre   

Study ID Numbers:  CDR0000349337; SWOG-S0226; CAN-NCIC-SWOG-S0226
Record last reviewed:  September 2004
Record first received:  January 9, 2004
ClinicalTrials.gov Identifier:  NCT00075764
Health Authority: Unspecified
ClinicalTrials.gov processed this record on 2004-11-05