RATIONALE: Estrogen can stimulate the growth of breast cancer cells. Hormone therapy using
exemestane may fight breast cancer by reducing the production of estrogen by the tumor
cells. It is not yet known whether exemestane is effective in preventing the recurrence of
breast cancer.
PURPOSE: Randomized phase III trial to study the effectiveness of exemestane in preventing
cancer recurrence in postmenopausal women who have resected stage I, stage II, or stage IIIA
breast cancer and have completed 5 years of tamoxifen.
- Determine whether the administration of 5 years of exemestane after 5 years of
tamoxifen therapy is more effective than 5 years of prior tamoxifen therapy alone in
prolonging disease-free survival, overall survival, and time to treatment failure in
postmenopausal women with resected stage I, II, or IIIA breast cancer.
- Determine the effect of tamoxifen withdrawal on bone, in terms of height, fractures,
and total alkaline phosphatase in these patients and on bone mineral density and bone
biochemical markers in a subset of patients.
- Determine the effect of exemestane on bone loss after tamoxifen withdrawal in these
OUTLINE: This is a randomized study. Patients are randomized to 1 of 2 treatment arms.
- Arm II (closed as of 10/15/03): Patients receive an oral placebo daily for 5 years.
Quality of life is assessed at baseline and then every 6 months for 5. 5 years.
Patients are followed every 6 months for 6 years and then annually thereafter.
PROJECTED ACCRUAL: A total of 3,000 patients will be accrued for this study within 3 years
and 4 months.
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
DISEASE CHARACTERISTICS:
- Histologically confirmed invasive adenocarcinoma of the breast at time of original
diagnosis
- Tumor confined to the breast and ipsilateral axilla on clinical exam (T1-3,
N0-1, M0) (stage I-IIIA)
- No ipsilateral lymph nodes clinically fixed to one another or to other
structures (N2 disease) at time of original diagnosis
- Prior surgical resection, including 1 of the following:
- Total mastectomy and axillary dissection (modified radical mastectomy) OR
- Lumpectomy and axillary dissection
- Prior post-lumpectomy breast radiotherapy required
- Prior sentinel node biopsy allowed with the exception of the following:
- If any sentinel node is histologically positive by hematoxylin and eosin (H
& E) OR histologically suspicious on H & E and confirmed positive by
immunohistochemistry then the patient must have a complete axillary
dissection
- Previously resected margins must be clear of invasive tumor and ductal carcinoma
in situ
- Currently disease free
- Previously treated with tamoxifen for 57-66 months
- Completed tamoxifen within the past 180 days
- No bilateral malignancy or mass in the opposite breast suspicious for malignancy
unless biopsy proven negative
- No local, regional, or distant recurrence of disease or second primary breast
malignancy (including contralateral breast cancer)
- No advanced disease at time of original diagnosis (e. g., ulceration, erythema,
infiltration of the skin or underlying chest wall [complete fixation], peau d'orange,
or skin edema of any magnitude)
- Tethering or dimpling of the skin or nipple inversion allowed
- Current skeletal pain allowed if a bone scan and/or radiologic exam is negative for
metastatic disease
- Hormone receptor status:
- Primary tumor estrogen receptor (ER) positive AND/OR
- Progesterone receptor positive
- Borderline ER positive tumors allowed if previously treated with tamoxifen
PATIENT CHARACTERISTICS:
Age:
- Postmenopausal
Sex:
- Female
Menopausal status:
- Postmenopausal, defined as 1 of the following:
- Prior bilateral oophorectomy
- Absence of spontaneous menstrual cycle for more than 1 year
- Follicle-stimulating hormone within the postmenopausal range if under 55 and had
a prior hysterectomy without a bilateral oophorectomy
Performance status:
- Not specified
Life expectancy:
- At least 10 years
Hematopoietic:
- Absolute granulocyte count at least 1,500/mm^3
- Platelet count at least 100,000/mm^3
- Hemoglobin normal
Hepatic:
- Bilirubin less than 2 times upper limit of normal (ULN)
- SGOT or SGPT no greater than 2. 5 times ULN
- Alkaline phosphatase less than 2 times ULN
- No systemic hepatic disease that would preclude study participation
Renal:
- Creatinine no greater than 1. 5 times ULN
- No systemic renal disease that would preclude study participation
Cardiovascular:
- No systemic cardiovascular disease that would preclude study participation
Other:
- No other malignancy within the past 5 years except effectively treated squamous cell
or basal cell skin cancer, surgically treated carcinoma in situ of the cervix, or
surgically treated lobular carcinoma in situ of the ipsilateral or contralateral
breast
- No nonmalignant systemic disease that would preclude study participation
- No psychiatric or addictive disorder that would preclude informed consent
- Not pregnant
PRIOR CONCURRENT THERAPY:
Biologic therapy:
- Not specified
Chemotherapy:
- Prior adjuvant chemotherapy allowed if administered concurrently with or prior to
tamoxifen
Endocrine therapy:
- See Disease Characteristics
- No concurrent estrogen, progesterone, clomiphene, testosterone,
gonadotropin-releasing hormone, oral contraceptives, selective estrogen-receptor
modulators, or dehydroepiandrosterone (DHEA)
- Estring or estrogen vaginal cream at 0. 3 mg or 1/8 of an applicator applied
vaginally 3 times a week allowed
- No other concurrent systemic hormonal therapy (e. g., tamoxifen or raloxifene)
Radiotherapy:
- See Disease Characteristics
- Prior post-mastectomy loco-regional radiotherapy or post-lumpectomy regional
radiotherapy allowed
Surgery:
- See Disease Characteristics
Other:
- Prior participation in other adjuvant NSABP study allowed if study was reported in
peer-review publication or tamoxifen was not a study drug
- Concurrent bisphosphonates or calcitonin for prevention or treatment of osteoporosis
allowed
- Concurrent statins (simvastatin, pravastatin, fluvastatin, atorvastatin, or
lovastatin) or other drugs to control lipid levels allowed
MBCCOP - San Juan, San Juan 00927-5800, Puerto Rico
Comprehensive Cancer Institute of Huntsville, Huntsville, Alabama 35801, United States
Tom Baker Cancer Center - Calgary, Calgary, Alberta T2N 4N2, Canada
Cross Cancer Institute, Edmonton, Alberta T6G 1Z2, Canada
CCOP - Greater Phoenix, Phoenix, Arizona 85006-2726, United States
University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States
British Columbia Cancer Agency, Vancouver, British Columbia V5Z 4E6, Canada
City of Hope Comprehensive Cancer Center, Duarte, California 91010-3000, United States
California Cancer Center, Fresno, California 93720, United States
Sutter Health Western Division Cancer Research Group, Greenbrae, California 94904, United States
Rebecca and John Moores UCSD Cancer Center, La Jolla, California 92093-0658, United States
Scripps Cancer Center, La Jolla, California 92037, United States
Loma Linda University Cancer Institute, Loma Linda, California 92354, United States
Pacific Shores Medical Group, Long Beach, California 90813, United States
Jonsson Comprehensive Cancer Center, UCLA, Los Angeles, California 90095-1781, United States
Chao Family Comprehensive Cancer Center, Orange, California 92868, United States
Comprehensive Cancer Centers of the Desert, Palm Springs, California 92262, United States
Sutter Cancer Center, Sacramento, California 95816, United States
Kaiser Permanente Medical Center/Kaiser Foundation Hospital - San Diego, San Diego, California 92120, United States
CCOP - Santa Rosa Memorial Hospital, Santa Rosa, California 95403, United States
Stanford University Medical Center, Stanford, California 94305-5408, United States
Kaiser Permanente Medical Center - Vallejo, Vallejo, California 94589, United States
CCOP - Colorado Cancer Research Program, Incorporated, Denver, Colorado 80224, United States
University of Colorado Cancer Center, Denver, Colorado 80010, United States
University of Connecticut, Farmington, Connecticut 06032, United States
Hartford Hospital, Hartford, Connecticut 06102-5037, United States
CCOP - Christiana Care Health Services, Newark, Delaware 19899, United States
George Washington University Medical Center, Washington, District of Columbia 20037, United States
Morton Plant Hospital, Clearwater, Florida 33756, United States
Halifax Medical Center, Daytona Beach, Florida 32114, United States
Baptist Regional Cancer Institute - Jacksonville, Jacksonville, Florida 32207, United States
CCOP - Mount Sinai Medical Center, Miami Beach, Florida 33140, United States
Sylvester Cancer Center, University of Miami, Miami, Florida 33136, United States
MD Anderson Cancer Center Orlando, Orlando, Florida 32806, United States
Cancer Research Network Inc., Plantation, Florida 33324, United States
Oncology Hematology Consultants, Sarasota, Florida 34239, United States
Emory University School of Medicine, Atlanta, Georgia 30322, United States
Medical College of Georgia, Augusta, Georgia 30912, United States
Dwight David Eisenhower Army Medical Center, Fort Gordon, Georgia 30905-5650, United States
Cancer Center of Hawaii, Honolulu, Hawaii 96826, United States
North Idaho Cancer Center, Coeur d'Alene, Idaho 83814, United States
Illinois Oncology, Ltd., Belleville, Illinois 62221, United States
Illinois Masonic Medical Center, Chicago, Illinois 60657, United States
Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, United States
CCOP - Central Illinois, Decatur, Illinois 62526, United States
Alexian Brothers Medical Center, Elk Grove Village, Illinois 60007, United States
CCOP - Evanston, Evanston, Illinois 60201, United States
West Suburban Hospital Medical Center, Oak Park, Illinois 60302, United States
CCOP - Illinois Oncology Research Association, Peoria, Illinois 61602, United States
CCOP - Carle Cancer Center, Urbana, Illinois 61801, United States
Clarian Health Partners Inc., Indianapolis, Indiana 46206-1367, United States
St. Vincent Hospital and Health Care Center, Indianapolis, Indiana 46260, United States
CCOP - Northern Indiana CR Consortium, South Bend, Indiana 46601, United States
Genesis Medical Center, Davenport, Iowa 52803, United States
CCOP - Iowa Oncology Research Association, Des Moines, Iowa 50309-1016, United States
Holden Comprehensive Cancer Center, Iowa City, Iowa 52242-1009, United States
CCOP - Wichita, Wichita, Kansas 67214-3882, United States
Lucille Parker Markey Cancer Center, University of Kentucky, Lexington, Kentucky 43213, United States
Consultants in Blood Disorders and Cancer, Louisville, Kentucky 40207, United States
Norton Healthcare System, Louisville, Kentucky 40202-5070, United States
CCOP - Ochsner, New Orleans, Louisiana 70121, United States
Louisiana State University Medical Center - New Orleans, New Orleans, Louisiana 70112, United States
Tulane University Medical Center, New Orleans, Louisiana 70112, United States
Eastern Maine Medical Center, Bangor, Maine 04401, United States
Franklin Square Hospital Center, Baltimore, Maryland 21237, United States
National Naval Medical Center, Bethesda, Maryland 20889-5000, United States
Boston Medical Center, Boston, Massachusetts 02118, United States
Lahey Clinic - Burlington, Burlington, Massachusetts 01805, United States
Berkshire Medical Center, Pittsfield, Massachusetts 01201, United States
Baystate Medical Center, Springfield, Massachusetts 01199, United States
CCOP - Michigan Cancer Research Consortium, Ann Arbor, Michigan 48106, United States
Henry Ford Health System, Detroit, Michigan 48202, United States
Michigan State University, East Lansing, Michigan 48824, United States
CCOP - Grand Rapids, Grand Rapids, Michigan 49503, United States
CCOP - Kalamazoo, Kalamazoo, Michigan 49007-3731, United States
William Beaumont Hospital, Royal Oak, Michigan 48073, United States
Providence Hospital - Southfield, Southfield, Michigan 48075-9975, United States
CCOP - Duluth, Duluth, Minnesota 55805, United States
Abbott-Northwestern Hospital, Minneapolis, Minnesota 55415, United States
CCOP - Metro-Minnesota, Saint Louis Park, Minnesota 55416, United States
Ellis Fischel Cancer Center - Columbia, Columbia, Missouri 65203, United States
CCOP - Kansas City, Kansas City, Missouri 64131, United States
CCOP - St. Louis-Cape Girardeau, Saint Louis, Missouri 63141, United States
St. Louis University Health Sciences Center, Saint Louis, Missouri 63110-0250, United States
CCOP - Cancer Research for the Ozarks, Springfield, Missouri 65807, United States
CCOP - Montana Cancer Consortium, Billings, Montana 59101, United States
CCOP - Missouri Valley Cancer Consortium, Omaha, Nebraska 68106, United States
Methodist Hospital Cancer Center - Omaha, Omaha, Nebraska 68114, United States
CCOP - Southern Nevada Cancer Research Foundation, Las Vegas, Nevada 89106, United States
CCOP - Northern New Jersey, Hackensack, New Jersey 07601, United States
Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, United States
Newark Beth Israel Medical Center, Newark, New Jersey 07112, United States
MBCCOP - University of New Mexico HSC, Albuquerque, New Mexico 87131, United States
New York Oncology Hematology, P.C., Albany, New York 12208, United States
Lincoln Medical and Mental Health Center, Bronx, New York 10451, United States
MBCCOP-Our Lady of Mercy Cancer Center, Bronx, New York 10466, United States
Glens Falls Hospital, Glens Falls, New York 12801, United States
Staten Island University Hospital, Staten Island, New York 10305, United States
CCOP - Syracuse Hematology-Oncology Associates of Central New York, P.C., Syracuse, New York 13217, United States
Alamance Cancer Center, Burlington, North Carolina 27216, United States
Lineberger Comprehensive Cancer Center, UNC, Chapel Hill, North Carolina 27599-7295, United States
East Carolina University School of Medicine, Greenville, North Carolina 27858-4354, United States
CCOP - Southeast Cancer Control Consortium, Winston-Salem, North Carolina 27104-4241, United States
Comprehensive Cancer Center at Wake Forest University, Winston-Salem, North Carolina 27157-1082, United States
CCOP - Merit Care Hospital, Fargo, North Dakota 58122, United States
Akron City Hospital, Akron, Ohio 44309, United States
Aultman Cancer Center, Canton, Ohio 44710, United States
Barrett Cancer Center, Cincinnati, Ohio 45267-0502, United States
Jewish Hospital of Cincinnati, Inc., Cincinnati, Ohio 45236, United States
Ireland Cancer Center, Cleveland, Ohio 44106-5065, United States
Arthur G. James Cancer Hospital - Ohio State University, Columbus, Ohio 43210-1240, United States
CCOP - Columbus, Columbus, Ohio 43206, United States
CCOP - Dayton, Kettering, Ohio 45429, United States
CCOP - Toledo Community Hospital, Toledo, Ohio 43623-3456, United States
South Pointe Hospital - Cancer Care Center, Warrensville Heights, Ohio 44122, United States
CCOP - Oklahoma, Tulsa, Oklahoma 74136, United States
Credit Valley Hospital, Mississauga, Ontario L5M 2N1, Canada
Toronto Sunnybrook Regional Cancer Centre, Toronto, Ontario, Canada
CCOP - Columbia River Oncology Program, Portland, Oregon 97213, United States
Lehigh Valley Hospital, Allentown, Pennsylvania 18103, United States
Geisinger Medical Center, Danville, Pennsylvania 17822-2001, United States
Albert Einstein Cancer Center, Philadelphia, Pennsylvania 19141, United States
Kimmel Cancer Center of Thomas Jefferson University - Philadelphia, Philadelphia, Pennsylvania 19107-5541, United States
Allegheny General Hospital, Pittsburgh, Pennsylvania 15212-4772, United States
University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania 15213-3489, United States
Reading Hospital and Medical Center, Reading, Pennsylvania 19612-6052, United States
Mercy Hospital Cancer Center - Scranton, Scranton, Pennsylvania 18501, United States
CCOP - MainLine Health, Wynnewood, Pennsylvania 19096, United States
York Cancer Center, York, Pennsylvania 17315, United States
Centre Hospitalier de l'Universite de Montreal, Montreal, Quebec H2L-4M1, Canada
Jewish General Hospital - Montreal, Montreal, Quebec H3T 1E2, 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
Hopital du Saint-Sacrement, Quebec, Quebec City, Quebec G1S 4L8, Canada
CCOP - Greenville, Greenville, South Carolina 29615, United States
CCOP - Upstate Carolina, Spartanburg, South Carolina 29303, United States
CCOP - Sioux Community Cancer Consortium, Sioux Falls, South Dakota 57104, United States
Thompson Cancer Survival Center, Knoxville, Tennessee 37916, United States
Center for Oncology Research and Treatment, Medical City Hospital, Dallas, Texas 75230, United States
Simmons Cancer Center - Dallas, Dallas, Texas 75235-9154, United States
Baylor College of Medicine, Houston, Texas 77030, United States
Joe Arrington Cancer Research and Treatment Center, Lubbock, Texas 79410-1894, United States
University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7811, United States
CCOP - Scott and White Hospital, Temple, Texas 76508, United States
Utah Valley Regional Medical Center - Provo, Provo, Utah 84604, United States
Huntsman Cancer Institute, Salt Lake City, Utah 84112, United States
Green Mountain Oncology Group, Bennington, Vermont 05201, United States
Vermont Cancer Center, Burlington, Vermont 05405-0075, United States
Virginia Oncology Associates - Newport News, Newport News, Virginia 23606, United States
Eastern Virginia Medical School, Norfolk, Virginia 23507, United States
Massey Cancer Center, Richmond, Virginia 23298-0037, United States
Oncology and Hematology Associates of Southwest Virginia, Inc., Roanoke, Virginia 24014, United States
CCOP - Virginia Mason Research Center, Seattle, Washington 98101, United States
Puget Sound Oncology Consortium, Seattle, Washington 98109, United States
CCOP - Northwest, Tacoma, Washington 98405-0986, United States
Camcare Health, Charleston, West Virginia 25304, United States
Camden-Clark Memorial Hospital, Parkersburg, West Virginia 26102, United States
St. Vincent Hospital, Green Bay, Wisconsin 54307-3508, United States
CCOP - Marshfield Medical Research and Education Foundation, Marshfield, Wisconsin 54449, United States
Medical College of Wisconsin Cancer Center, Milwaukee, Wisconsin 53226, United States
St. Luke's Medical Center, Milwaukee, Wisconsin 53215, United States