RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. It is not yet known if chemotherapy given before surgery is more effective with or without docetaxel given before or after surgery for breast cancer. PURPOSE: Randomized phase III trial to compare the effectiveness of chemotherapy using doxorubicin and cyclophosphamide with or without docetaxel in treating women who have stage II or stage III breast cancer .

Condition	Treatment or Intervention	Phase
stage I breast cancer stage II breast cancer stage IIIA breast cancer	Drug: cyclophosphamide  Drug: docetaxel  Drug: doxorubicin  Drug: tamoxifen	Phase III

Further Study Details: 

OBJECTIVES: I. Compare overall and disease-free survival in patients with operable adenocarcinoma of the breast treated with 4 courses of preoperative doxorubicin and cyclophosphamide (AC) alone vs 4 courses of preoperative or postoperative docetaxel (TXT) following 4 courses of preoperative AC. II. Evaluate whether the addition of preoperative TXT to preoperative AC results in improved rates of clinical and pathologic locoregional tumor response. III. Assess whether the addition of preoperative TXT to preoperative AC results in improved rates of breast conservation. IV. Assess whether postoperative TXT improves disease-free and overall survival in patients who receive preoperative AC, especially in certain subgroups of patients (e.g., those with pathologically positive nodes).

PROTOCOL OUTLINE: This is a randomized, multicenter study. Patients are stratified according to age (under 50 vs 50 and over), clinical tumor size (less than 2.1 cm vs 2.1-4.0 cm vs greater than 4.0 cm), clinical nodal status (negative vs positive), and participating center. Patients are randomized to one of three treatment arms. Arm I: Patients receive doxorubicin IV followed by cyclophosphamide IV over 30 minutes to 2 hours on day 1. Patients receive oral tamoxifen daily for 5 years, starting on day 1. Following completion of chemotherapy, patients are offered surgery (e.g., lumpectomy with axillary node dissection, or modified radical mastectomy). Post operative radiotherapy is given post lumpectomy. Arm II: Patients receive doxorubicin IV followed by cyclophosphamide IV over 30 minutes to 2 hours followed by docetaxel IV over 1 hour on day 1. Patients receive oral tamoxifen daily for 5 years, starting on day 1. Surgery is offered (as in arm I) following chemotherapy. Radiotherapy follows surgery in post lumpectomy patients. Arm III: Patients receive doxorubicin IV followed by cyclophosphamide IV over 30 minutes to 2 hours on day 1. Patients receive oral tamoxifen daily for 5 years, starting on day 1. After completion of chemotherapy, surgery is offered (as in arm I). Following surgical recovery, docetaxel IV is given over 1 hour. Radiotherapy follows docetaxel in post lumpectomy patients. Chemotherapy is repeated every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity. Patients are followed every 6 months for 2.5 years, then annually thereafter.

PROJECTED ACCRUAL: Approximately 2,400 patients will be accrued for this study over 5 years.

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Histologically or cytologically proven invasive adenocarcinoma of the breast; Fine-needle aspiration is acceptable; Core or Tru-cut biopsies are preferable; No more than 63 days between initial diagnosis and randomization
• Tumor palpable on clinical exam and confined to the breast and ipsilateral axilla
• If clinically negative axillary nodes (N0): primary tumor greater than 1 cm (T1c-T3)
• If clinically positive axillary nodes (N1): any size primary tumor (T1-3)
• No N2 disease, i.e., ipsilateral nodes clinically fixed to one another or to other structures
• No skeletal pain unless: Bone scan and/or roentgenologic exam negative for metastatic disease; Suspicious findings confirmed as benign by x-ray, MRI, or biopsy
• No ulceration, erythema, skin infiltration (complete fixation), or peau d'orange, or skin edema of any magnitude; Tethering or dimpling of skin or nipple inversion allowed
• No bilateral malignancy; Suspicious contralateral mass proven benign on biopsy allowed
• None of the following unless proven benign on biopsy: Suspicious palpable nodes in contralateral axilla; Palpable supraclavicular or infraclavicular nodes
• Hormone receptor status: Any status

--Prior/Concurrent Therapy--

• No prior therapy for breast cancer
• No prior anthracyclines for any malignancy
• No concurrent sex hormones (e.g., birth control pills or ovarian replacement therapy)

--Patient Characteristics--

• Age: Any age
• Sex: Female
• Menopausal status: Not specified
• Performance status: Not specified
• Life expectancy: At least 10 years (exclusive of cancer diagnosis)
• Hematopoietic: WBC at least 4,000/mm3; Platelet count at least 100,000/mm3
• Hepatic: Bilirubin normal; AST/ALT normal; Alkaline phosphatase normal
• Renal: Creatinine normal
• Cardiovascular: No active cardiac disease that precludes doxorubicin, e.g.: Documented myocardial infarction; History of congestive heart failure; Angina pectoris requiring medication; Valvular disease with documented cardiac function compromise; Arrhythmia associated with heart failure or cardiac dysfunction; Poorly controlled hypertension, i.e., diastolic blood pressure greater than 100 mm Hg; Cardiomegaly on chest x-ray or ventricular hypertrophy on EKG unless left ventricular ejection fraction at least 45% by MUGA
• Other: No second malignancy within 10 years except: Segmentally resected lobular carcinoma in situ of the ipsilateral or contralateral breast; Effectively treated nonmelanomatous skin cancer; Surgically treated carcinoma in situ of the cervix; No systemic disease that precludes therapy; No psychiatric or addictive disorder that precludes informed consent; Geographically accessible for follow-up; Not pregnant

Alabama
      Huntsville Hospital System, Huntsville,  Alabama,  35801,  United States
Arizona
      CCOP - Greater Phoenix, Phoenix,  Arizona,  85006-2726,  United States
California
      Beckman Research Institute, City of Hope, Los Angeles,  California,  91010,  United States
      Catholic Healthcare West - Westbay Region, San Francisco,  California,  94107-1728,  United States
      CCOP - Bay Area Tumor Institute, Oakland,  California,  94609-3305,  United States
      CCOP - Santa Rosa Memorial Hospital, Santa Rosa,  California,  95403,  United States
      Chao Family Comprehensive Cancer Center, Orange,  California,  92868,  United States
      Comprehensive Cancer Centers of the Desert, Palm Springs,  California,  92262,  United States
      Kaiser Permanente Medical Center - Vallejo, Vallejo,  California,  94589,  United States
      Kaiser Permanente-Southern California Permanente Medical Group, San Diego,  California,  92120,  United States
      Loma Linda University Medical Center, Loma Linda,  California,  92354,  United States
      Saint Mary Medical Center - Long Beach, Long Beach,  California,  90813-0887,  United States
      Sutter Health Western Division Cancer Research Group, Greenbrae,  California,  94904,  United States
Colorado
      CCOP - Colorado Cancer Research Program, Inc., Denver,  Colorado,  80209-5031,  United States
      University of Colorado Cancer Center, Denver,  Colorado,  80262,  United States
Connecticut
      Hartford Hospital, Hartford,  Connecticut,  06102-5037,  United States
      University of Connecticut Health Center, Farmington,  Connecticut,  06360-7106,  United States
Delaware
      CCOP - Christiana Care Health Services, Wilmington,  Delaware,  19899,  United States
District of Columbia
      George Washington University Cancer Center, Washington,  District of Columbia,  20037,  United States
Florida
      Baptist Regional Cancer Institute - Jacksonville, Jacksonville,  Florida,  32207,  United States
      CCOP - Mount Sinai Medical Center, Miami Beach,  Florida,  33140,  United States
      Good Samaritan Medical Center, West Palm Beach,  Florida,  33401,  United States
      Halifax Medical Center, Daytona Beach,  Florida,  32114,  United States
      Sylvester Cancer Center, University of Miami, Miami,  Florida,  33136,  United States
Georgia
      CCOP - Atlanta Regional, Atlanta,  Georgia,  30342-1701,  United States
      Dwight David Eisenhower Army Medical Center, Fort Gordon,  Georgia,  30905-5650,  United States
      Medical College of Georgia Comprehensive Cancer Center, Augusta,  Georgia,  30912-4000,  United States
      Winship Cancer Institute, Atlanta,  Georgia,  30322,  United States
Hawaii
      Cancer Research Center of Hawaii, Honolulu,  Hawaii,  96813,  United States
Idaho
      North Idaho Cancer Center, Coeur D Alene,  Idaho,  83814,  United States
Illinois
      CCOP - Carle Cancer Center, Urbana,  Illinois,  61801,  United States
      CCOP - Evanston, Evanston,  Illinois,  60201,  United States
      CCOP - Illinois Oncology Research Association, Peoria,  Illinois,  61602,  United States
      Illinois Masonic Medical Center, Chicago,  Illinois,  60657,  United States
      Rockford Clinic, Rockford,  Illinois,  61103,  United States
Indiana
      Memorial Hospital of South Bend, South Bend,  Indiana,  46601,  United States
      St. Vincent Hospital and Health Care Center, Indianapolis,  Indiana,  46260,  United States
Iowa
      CCOP - Iowa Oncology Research Association, Des Moines,  Iowa,  50309-1016,  United States
      University of Iowa Hospitals and Clinics, Iowa City,  Iowa,  52242,  United States
Kansas
      CCOP - Wichita, Wichita,  Kansas,  67214-3882,  United States
Kentucky
      Lucille Parker Markey Cancer Center, University of Kentucky, Lexington,  Kentucky,  40536-0093,  United States
      Norton Healthcare System, Louisville,  Kentucky,  40202-5070,  United States
Louisiana
      CCOP - Ochsner, New Orleans,  Louisiana,  70121,  United States
      Louisiana State University Medical Center - New Orleans, New Orleans,  Louisiana,  70112,  United States
      Tulane University School of Medicine, New Orleans,  Louisiana,  70112,  United States
Maine
      Eastern Maine Medical Center, Bangor,  Maine,  04401,  United States
Maryland
      Franklin Square Hospital Center, Baltimore,  Maryland,  21237,  United States
      National Naval Medical Center, Bethesda,  Maryland,  20889-5000,  United States
      Regional Cancer Therapy Center - Frederick, Frederick,  Maryland,  21701,  United States
Massachusetts
      Baystate Medical Center, Springfield,  Massachusetts,  01199,  United States
      Berkshire Medical Center, Pittsfield,  Massachusetts,  01201,  United States
      Boston Medical Center, Boston,  Massachusetts,  02118,  United States
      Lahey Clinic - Burlington, Burlington,  Massachusetts,  01805,  United States
Michigan
      CCOP - Ann Arbor Regional, Ann Arbor,  Michigan,  48106,  United States
      CCOP - Grand Rapids Clinical Oncology Program, Grand Rapids,  Michigan,  49503,  United States
      CCOP - Kalamazoo, Kalamazoo,  Michigan,  49007-3731,  United States
      Henry Ford Hospital, Detroit,  Michigan,  48202,  United States
      Michigan State University, East Lansing,  Michigan,  48824,  United States
      Providence Hospital - Southfield, Southfield,  Michigan,  48075-9975,  United States
Minnesota
      CCOP - Duluth, Duluth,  Minnesota,  55805,  United States
      Hennepin County Medical Center - Minneapolis, Minneapolis,  Minnesota,  55415,  United States
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
Missouri
      CCOP - Cancer Research for the Ozarks, Springfield,  Missouri,  65807,  United States
      CCOP - St. Louis-Cape Girardeau, Saint Louis,  Missouri,  63141,  United States
      Ellis Fischel Cancer Center - Columbia, Columbia,  Missouri,  65203,  United States
      St. Louis University School of Medicine, Saint Louis,  Missouri,  63104,  United States
Montana
      CCOP - Montana Cancer Consortium, Billings,  Montana,  59101,  United States
Nebraska
      CCOP - Missouri Valley Cancer Consortium, Omaha,  Nebraska,  68131,  United States
      Methodist Cancer Center - Omaha, Omaha,  Nebraska,  68114,  United States
Nevada
      CCOP - Southern Nevada Cancer Research Foundation, Las Vegas,  Nevada,  89106,  United States
New Jersey
      Cancer Institute of New Jersey, New Brunswick,  New Jersey,  08901,  United States
      Cancer Institute of New Jersey at Hamilton, Hamilton,  New Jersey,  08690,  United States
      CCOP - Northern New Jersey, Hackensack,  New Jersey,  07601,  United States
      Cooper Cancer Institute, Camden,  New Jersey,  08103,  United States
      Hackensack University Medical Center, Hackensack,  New Jersey,  07601,  United States
      Newark Beth Israel Medical Center, Newark,  New Jersey,  07112,  United States
      Overlook Hospital, Summit,  New Jersey,  07902-0220,  United States
      Trinitas Hospital - Jersey Street Campus, Elizabeth,  New Jersey,  07201,  United States
      University of Medicine and Dentistry of New Jersey, Newark,  New Jersey,  07103-2425,  United States
New Mexico
      University of New Mexico Cancer Research & Treatment Center, Albuquerque,  New Mexico,  87131,  United States
New York
      CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., Syracuse,  New York,  13210,  United States
North Carolina
      CCOP - Southeast Cancer Control Consortium, Winston Salem,  North Carolina,  27104-4241,  United States
      Comprehensive Cancer Center of Wake Forest University Baptist Medical Center, Winston Salem,  North Carolina,  27157-1082,  United States
      East Carolina University School of Medicine, Greenville,  North Carolina,  27858-4354,  United States
      Lineberger Comprehensive Cancer Center, UNC, Chapel Hill,  North Carolina,  27599-7295,  United States
North Dakota
      CCOP - Merit Care Hospital, Fargo,  North Dakota,  58122,  United States
Ohio
      Akron City Hospital, Akron,  Ohio,  44309,  United States
      Arthur G. James Cancer Hospital - Ohio State University, Columbus,  Ohio,  43210,  United States
      Aultman Cancer Center, Canton,  Ohio,  44710,  United States
      Barrett Cancer Center, The University Hospital, Cincinnati,  Ohio,  45219,  United States
      CCOP - Columbus, Columbus,  Ohio,  43206,  United States
      CCOP - Dayton, Kettering,  Ohio,  45429,  United States
      Jewish Hospital of Cincinnati, Inc., Cincinnati,  Ohio,  45236,  United States
      South Pointe Hospital, Cleveland,  Ohio,  44122,  United States
Oklahoma
      CCOP - Sooner State, Tulsa,  Oklahoma,  74136,  United States
Oregon
      CCOP - Columbia River Program, Portland,  Oregon,  97213,  United States
      Oregon Cancer Center at Oregon Health Sciences University, Portland,  Oregon,  97201-3098,  United States
Pennsylvania
      Allegheny General Hospital, Pittsburgh,  Pennsylvania,  15212-4772,  United States
      CCOP - MainLine Health, Wynnewood,  Pennsylvania,  19096,  United States
      Geisinger Medical Center, Danville,  Pennsylvania,  17822-2001,  United States
      Lehigh Valley Hospital, Allentown,  Pennsylvania,  18105-1556,  United States
      Mercy Hospital Cancer Center - Scranton, Scranton,  Pennsylvania,  18501,  United States
      St. Luke's Network - Bethlehem, Bethlehem,  Pennsylvania,  18015,  United States
      University of Pittsburgh Cancer Institute, Pittsburgh,  Pennsylvania,  15213,  United States
      York Hospital, York,  Pennsylvania,  17315,  United States
Rhode Island
      Kent County Memorial Hospital - Rhode Island, Warwick,  Rhode Island,  02886,  United States
South Carolina
      CCOP - Greenville, Greenville,  South Carolina,  29615,  United States
      CCOP - Upstate Carolina, Spartanburg,  South Carolina,  29303,  United States
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States
South Dakota
      CCOP - Sioux Community Cancer Consortium, Sioux Falls,  South Dakota,  57105-1080,  United States
Tennessee
      CCOP - Baptist Cancer Institute, Memphis,  Tennessee,  38117,  United States
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States
      CCOP - Scott and White Hospital, Temple,  Texas,  76508,  United States
      Joe Arrington Cancer Research and Treatment Center, Lubbock,  Texas,  79410-1894,  United States
      Medical Group of Texas, Dallas,  Texas,  75243,  United States
      Simmons Cancer Center - Dallas, Dallas,  Texas,  75235-9154,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78284-7811,  United States
      University of Texas Medical Branch, Galveston,  Texas,  77555-1329,  United States
Utah
      Utah Valley Regional Medical Center - Provo, Provo,  Utah,  84604,  United States
Vermont
      CCOP - Southwestern Vermont Regional Cancer Center, Bennington,  Vermont,  05201,  United States
      Vermont Cancer Center, Burlington,  Vermont,  05401-3498,  United States
Virginia
      Eastern Virginia Medical School, Norfolk,  Virginia,  23507,  United States
      MBCCOP - Massey Cancer Center, Richmond,  Virginia,  23298-0037,  United States
      Virginia Oncology Associates, Newport News,  Virginia,  23606,  United States
Washington
      CCOP - Northwest, Tacoma,  Washington,  98405-0986,  United States
      CCOP - Virginia Mason Research Center, Seattle,  Washington,  98101,  United States
      Puget Sound Oncology Consortium, Seattle,  Washington,  98109,  United States
West Virginia
      Camden-Clark Memorial Hospital, Parkersburg,  West Virginia,  26102,  United States
      David Lee Cancer Center, Charleston,  West Virginia,  25304,  United States
      West Virginia University Hospitals, Morgantown,  West Virginia,  26506-9162,  United States
Wisconsin
      CCOP - Marshfield Medical Research and Education Foundation, Marshfield,  Wisconsin,  54449,  United States
      Medical College of Wisconsin, Milwaukee,  Wisconsin,  53226,  United States
      St. Luke's Medical Center, Milwaukee,  Wisconsin,  53215,  United States
      St. Vincent Hospital, Green Bay,  Wisconsin,  54307-3508,  United States
Canada, Alberta
      Cross Cancer Institute, Edmonton,  Alberta,  T6G 1Z2,  Canada
      Tom Baker Cancer Center - Calgary, Calgary,  Alberta,  T2N 4N2,  Canada
Canada, Manitoba
      CancerCare Manitoba, Winnipeg,  Manitoba,  R3E 0V9,  Canada
Canada, Ontario
      Credit Valley Hospital, Mississauga,  Ontario,  L5M 2N1,  Canada
Canada, Quebec
      Centre Hospitalier de l'Universite de Montreal, Montreal,  Quebec,  H2L-4M1,  Canada
      Hopital du Saint-Sacrament, Quebec, Quebec City,  Quebec,  G1S 4L8,  Canada
      Jewish General Hospital - Montreal, Montreal,  Quebec,  H3T 1E2,  Canada
      L'Hopital Laval, Ste Foy,  Quebec,  G1V 4G5,  Canada
      Montreal General Hospital, Montreal,  Quebec,  H3G 1A4,  Canada
      Royal Victoria Hospital - Montreal, Montreal,  Quebec,  H3A 1A1,  Canada
      St. Mary's Hospital Center, Montreal,  Quebec,  H3T 1M5,  Canada

Study chairs or principal investigators

Harry D. Bear,  Study Chair,  National Surgical Adjuvant Breast and Bowel Project (NSABP)   

Study ID Numbers:  CDR0000064521; NSABP-B-27
Record last reviewed:  May 2004
Last Updated:  October 13, 2004
Record first received:  November 1, 1999
ClinicalTrials.gov Identifier:  NCT00002707
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08