RATIONALE: Hormone therapy using exemestane may fight breast cancer by reducing the
production of estrogen and progesterone.
PURPOSE: This randomized phase III trial is studying exemestane to see how well it works in
preventing cancer in postmenopausal women who are at increased risk of developing breast
cancer.
- Compare the incidence of invasive breast cancer in postmenopausal women at increased
risk of developing breast cancer when treated with exemestane vs placebo.
- Compare reduction in total incidence of invasive and non-invasive (ductal carcinoma in
- Compare reduction in total incidence of receptor-negative invasive breast cancer in
- Compare the incidence of lobular cancer in situ and atypical ductal hyperplasia in
- Compare the number of clinical breast biopsies in patients treated with these regimens.
- Compare the incidence of all clinical fractures, and specifically hip and vertebral
- Compare the incidence of clinically relevant cardiac events (i. e., significant coronary
- Compare the impact of these regimens on menopausal symptoms and quality of life of
- Compare adverse effects of these regimens in these patients.
- Compare the incidence of other malignancies in patients treated with these regimens.
OUTLINE: This is a randomized, double-blind, placebo-controlled, multicenter study. Patients
are stratified according to concurrent low dose (≤ 100 mg/day) aspirin use (yes vs no) and
Gail score (≤ 2 vs > 2). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral exemestane once daily for 5 years.
- Arm II: Patients receive oral placebo once daily for 5 years. In both arms, treatment
continues in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed at baseline, every 6 months for 1 year, and then annually for 4
years.
Patients are followed every 6 months for 1 year and then annually thereafter.
PROJECTED ACCRUAL: A total of 4,560 patients (2,280 per treatment arm) will be accrued for
this study within 3 years.
DISEASE CHARACTERISTICS:
- At increased risk of developing breast cancer, due to at least one of the following
risk factors:
- Gail score > 1. 66
- Age ≥ 60 years
- Prior atypical ductal hyperplasia or lobular carcinoma in situ on breast biopsy
- Prior ductal carcinoma in situ (DCIS) treated with mastectomy
- No prior DCIS treated with adjuvant tamoxifen
- No prior invasive breast cancer
- Hormone receptor status:
- Not specified
PATIENT CHARACTERISTICS:
Age
- 35 and over
Sex
- Female
Menopausal status
- Postmenopausal, defined as one of the following:
- > 50 years of age with no spontaneous menses for at least 12 months before study
entry
- ≤ 50 years of age with no menses (spontaneous or secondary to hysterectomy) for
at least 12 months before study entry AND with follicle-stimulating hormone
level within postmenopausal range
- Bilateral oophorectomy
Performance status
- Not specified
Life expectancy
- Not specified
Hematopoietic
- Not specified
Hepatic
- Not specified
Renal
- Not specified
Other
- No other malignancies within the past 5 years except adequately treated nonmelanoma
skin cancer, curatively treated carcinoma in situ of the cervix, or other curatively
treated solid tumors with no evidence of disease for ≥ 5 years
- No uncontrolled hypothyroidism or hyperthyroidism
- No major medical or psychiatric illness (including substance and alcohol abuse within
the past 2 years) that would preclude study participation or compliance
- Willing to complete quality of life questionnaires in either English or French
PRIOR CONCURRENT THERAPY:
Biologic therapy
- Not specified
Chemotherapy
- Not specified
Endocrine therapy
- See Disease Characteristics
- More than 3 months since prior and no concurrent hormone replacement therapies
- More than 3 months since systemic estrogenic, androgenic, or progestational agents
- More than 3 months since prior and no concurrent hormonal therapies, including, but
not limited to the following:
- Luteinizing-hormone releasing-hormone analogs (e. g., goserelin or leuprolide)
- Progestogens (e. g., megestrol)
- Prolactin inhibitors (e. g., bromocriptine)
- Antiandrogens (e. g., cyproterone acetate)
- Selective estrogen-receptor modulators (e. g., tamoxifen, toremifene, or
raloxifene)
- No concurrent endocrine therapy
- No concurrent estrogens, androgens, or progesterones
Radiotherapy
- Not specified
Surgery
- See Disease Characteristics
- See Menopausal status
Other
- More than 30 days or 5 half-lives since prior investigational drugs
- Concurrent low dose (≤ 100 mg/day) prophylactic aspirin allowed
- Concurrent bisphosphonates for prevention or treatment of osteoporosis allowed
- No other concurrent medications that may have an effect on study endpoints
Altamira Family and Prevention Clinic, San Juan 00920, Puerto Rico; Recruiting
Jamie Claudio, Phone: 787-792-9026
Orocovis Medical Center, Orocovis 00720, Puerto Rico; Recruiting
Jose Sabino Aponte Pagan, Phone: 787-867-0272
Jefferson Clinic, PC, Birmingham, Alabama 35233, United States; Recruiting
Rowell S. Ashford II, Phone: 205-279-2867
UAB Comprehensive Cancer Center, Birmingham, Alabama 35294, United States; Recruiting
Clinical Trials Office - UAB Comprehensive Cancer Center, Phone: 205-934-0309
Providence Cancer Center, Anchorage, Alaska 99508, United States; Recruiting
Clinical Trials Office - Providence Cancer Center, Phone: 907-261-3109
British Columbia Cancer Agency - Centre for the Southern Interior, Kelowna, British Columbia V1Y 5L3, Canada; Recruiting
Susan Ellard, Phone: 250-712-3922
British Columbia Cancer Agency - Vancouver Cancer Centre, Vancouver, British Columbia V5Z 4E6, Canada; Recruiting
Karen Gelmon, Phone: 604-877-6000
Los Angeles Biomedical Research Institute, Torrance, California 90502, United States; Recruiting
Rowan Chlebowski, Phone: 310-222-2217
UCSF Helen Diller Family Comprehensive Cancer Center, San Francisco, California 94115, United States; Recruiting
Clinical Trials Office - UCSF Helen Diller Family Comprehensi, Phone: 877-827-3222
University of California Davis Cancer Center, Sacramento, California 95817, United States; Recruiting
Clinical Trials Office - University of California Davis Cancer, Phone: 916-734-3089
University of Colorado Cancer Center at UC Health Sciences Center, Aurora, Colorado 80045, United States; Recruiting
Clinical Trials Office - University of Colorado Cancer Center, Phone: 720-848-0650
Carole and Ray Neag Comprehensive Cancer Center at the University of Connecticut Health Center, Farmington, Connecticut 06360-2875, United States; Recruiting
Clinical Trials Office - Carole and Ray Neag Comprehensive Can, Phone: 800-579-7822
Norwalk Hospital, Norwalk, Connecticut 06856, United States; Recruiting
Richard C. Frank, Phone: 203-845-2132
George Washington University Medical Center, Washington, District of Columbia 20037, United States; Recruiting
Clinical Trials Office - George Washington University Medical, Phone: 202-741-2981
MedStar Research Institute, Washington, District of Columbia 20003, United States; Recruiting
Clinical Trials Office - MedStar Research Institute, Phone: 202-787-5710
Mayo Clinic - Jacksonville, Jacksonville, Florida 32224, United States; Recruiting
Clinical Trials Office - All Mayo Clinic Locations, Phone: 507-538-7623
University of Miami Sylvester Comprehensive Cancer Center - Miami, Miami, Florida 33136, United States; Recruiting
University of Miami Sylvester Comprehensive Cancer Center Clin, Phone: 866-574-5124, Email: Sylvester@emergingmed.com
Georgia Cancer Specialists - Tucker, Tucker, Georgia 30084, United States; Recruiting
Mansoor Saleh, Phone: 404-256-4777
Cardinal Bernardin Cancer Center at Loyola University Medical Center, Maywood, Illinois 60153, United States; Recruiting
Clinical Trials Office - Cardinal Bernardin Cancer Center, Phone: 708-226-4357
CCOP - Carle Cancer Center, Urbana, Illinois 61801, United States; Recruiting
Clinical Trials Office - CCOP - Carle Cancer Center, Phone: 800-446-5532
John H. Stroger, Jr. Hospital of Cook County, Chicago, Illinois 60612, United States; Recruiting
Pamela S. Ganschow, Phone: 312-864-4436
Mercy Hospital and Medical Center, Chicago, Illinois 60616, United States; Recruiting
Alejandra Perez-Tamayo, Phone: 312-567-5469
Mid-Illinois Hematology-Oncology Associates at Community Cancer Center, Normal, Illinois 61761, United States; Recruiting
John Migas, Phone: 309-452-9701
Trinity Cancer Center at Trinity Medical Center - 7th Street Campus, Moline, Illinois 61265, United States; Recruiting
Costas L. Constantinou, Phone: 563-779-5059
University of Chicago Cancer Research Center, Chicago, Illinois 60637-1470, United States; Recruiting
Clinical Trials Office - University of Chicago Cancer Research, Phone: 773-834-7424
Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, Indiana 46202-5289, United States; Recruiting
Clinical Trials Office - Indiana University Cancer Center, Phone: 317-274-2552
Kansas Masonic Cancer Research Institute at the University of Kansas Medical Center, Kansas City, Kansas 66160-7357, United States; Recruiting
Clinical Trials Office - Kansas Masonic Cancer Research Instit, Phone: 913-588-4709
Maine Center for Cancer Medicine and Blood Disorders - Scarborough, Scarborough, Maine 04074-9308, United States; Recruiting
Tracey F. Weisberg, Phone: 207-885-7600
CancerCare Manitoba, Winnipeg, Manitoba R3E 0V9, Canada; Recruiting
Andrew L. Cooke, Phone: 204-787-1458
Suburban Hospital Cancer Program, Bethesda, Maryland 20817, United States; Recruiting
Carolyn Hendricks, Phone: 301-897-1503
Dana-Farber/Harvard Cancer Center at Dana Farber Cancer Institute, Boston, Massachusetts 02115, United States; Recruiting
Judy E. Garber, Phone: 617-632-3800
Massachusetts General Hospital, Boston, Massachusetts 02114, United States; Recruiting
Clinical Trials Office - Massachusetts General Hospital, Phone: 877-726-5130
Hutzel Hospital, Detroit, Michigan 48201, United States; Recruiting
Susan Hendrix, Phone: 313-745-0499
William Beaumont Hospital - Royal Oak Campus, Royal Oak, Michigan 48073, United States; Recruiting
Clinical Trials Office - William Beaumont Hospital - Royal Oak, Phone: 248-551-7695
Mayo Clinic Cancer Center, Rochester, Minnesota 55905, United States; Recruiting
Clinical Trials Office - All Mayo Clinic Locations, Phone: 507-538-7623
Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis, St. Louis, Missouri 63110, United States; Recruiting
Antonella Rastelli, Phone: 314-454-8017
Saint John Regional Hospital, Saint John, New Brunswick E2L 4L2, Canada; Recruiting
Hugh M.C. Scarth, Phone: 506-648-7921
Cancer Institute of New Jersey at UMDNJ - Robert Wood Johnson Medical School, New Brunswick, New Jersey 08903, United States; Recruiting
Clinical Trials Office - Cancer Institute of New Jersey, Phone: 732-235-8675
Albert Einstein Cancer Center at Albert Einstein College of Medicine, Bronx, New York 10461, United States; Recruiting
Clinical Trials Office - Albert Einstein Cancer Center at Albe, Phone: 718-904-2730, Email: aecc@aecom.yu.edu
Roswell Park Cancer Institute, Buffalo, New York 14263-0001, United States; Recruiting
Clinical Trials Office - Roswell Park Cancer Institute, Phone: 877-275-7724
Kinston Medical Specialists, Kinston, North Carolina 28501, United States; Recruiting
Misbah U. Qadir, Phone: 252-559-2201
Charles M. Barrett Cancer Center at University Hospital, Cincinnati, Ohio 45219, United States; Recruiting
Kathleen A. Havlin, Phone: 514-584-6178
Oklahoma University Cancer Institute, Oklahoma City, Oklahoma 73104, United States; Recruiting
William C. Dooley, Phone: 405-271-7867
Algoma District Cancer Program at Sault Area Hospital, Sault Ste. Marie, Ontario P6A 2C4, Canada; Recruiting
Silvana Spadafora, Phone: 705-759-3434
Cancer Centre of Southeastern Ontario at Kingston General Hospital, Kingston, Ontario K7L 5P9, Canada; Recruiting
Conrad Falkson, Phone: 613-544-2631
Edmond Odette Cancer Centre at Sunnybrook, Toronto, Ontario M4N 3M5, Canada; Recruiting
Kathleen I. Pritchard, Phone: 416-480-4616
London Regional Cancer Program at London Health Sciences Centre, London, Ontario N6A 4L6, Canada; Recruiting
Eric W. Winquist, Phone: 519-685-8640
Margaret and Charles Juravinski Cancer Centre, Hamilton, Ontario L8V 5C2, Canada; Recruiting
James R. Wright, Phone: 905-387-9495
Meadowlands Family Health Center, Ottawa, Ontario K2C 3R2, Canada; Recruiting
Barry Dworkin, Phone: 613-228-2882
Mount Sinai Hospital - Toronto, Toronto, Ontario M5G 1X5, Canada; Recruiting
Angela M. Cheung, Phone: 416-340-4301
New Women's College Hospital, Toronto, Ontario M5S 1B2, Canada; Recruiting
Lavina Lickley, Phone: 416-323-6120
Northeastern Ontario Regional Cancer Centre, Sudbury, Ontario P3E 5J1, Canada; Recruiting
Amanda Hey, Phone: 705-522-6237
Ottawa Hospital Regional Cancer Centre - General Campus, Ottawa, Ontario K1H 8L6, Canada; Recruiting
Shailendra Verma, Phone: 613-737-7700
Princess Margaret Hospital, Toronto, Ontario M5G 2M9, Canada; Recruiting
Angela M. Cheung, Phone: 416-340-4301
Toronto East General Hospital, Toronto, Ontario M4C 3E7, Canada; Recruiting
Yasmin H. Rahim, Phone: 416-469-3325
Abramson Cancer Center of the University of Pennsylvania, Philadelphia, Pennsylvania 19104-4283, United States; Recruiting
Clinical Trials Office - Abramson Cancer Center of the Univers, Phone: 800-474-9892
CHUM - Hopital Saint-Luc, Montreal, Quebec H3X 3J4, Canada; Recruiting
Marie-Helen Mayrand, Phone: 514-890-8000
Hopital du Saint-Sacrement - Quebec, Quebec City, Quebec G1S 4L8, Canada; Recruiting
Louise Provencher, Phone: 418-682-7511
Hopital Notre-Dame du CHUM, Montreal, Quebec H2L 4M1, Canada; Recruiting
Edgard Nassif, Phone: 514-890-8000
Maisonneuve-Rosemont Hospital, Montreal, Quebec H1T 2M4, Canada; Recruiting
Pierre Dube, Phone: 514-252-3822
Memorial Hospital of Rhode Island, Pawtucket, Rhode Island 02860, United States; Recruiting
Michele Cyr, Phone: 401-444-8537
University of Tennessee College of Medicine, Memphis, Tennessee 38163, United States; Recruiting
Clinical Trials Office - University of Tennessee College of Me, Phone: 901-516-2212
Fletcher Allen Health Care - University Health Center Campus, Burlington, Vermont 05401, United States; Recruiting
Clinical Trials Office - Fletcher Allen Health Care, Phone: 802-656-8990
Fred Hutchinson Cancer Research Center, Seattle, Washington 98109-1024, United States; Recruiting
Anne McTiernan, Phone: 206-667-6196
Medical College of Wisconsin Cancer Center, Milwaukee, Wisconsin 53226, United States; Recruiting
Clinical Trials Office - Medical College of Wisconsin Cancer C, Phone: 414-805-4380
University of Wisconsin Center for Women's Health Research, Madison, Wisconsin 53715, United States; Recruiting
Gloria E. Sarto, Phone: 608-267-5572
Richardson H, Johnston D, Pater J, Goss P. The National Cancer Institute of Canada Clinical Trials Group MAP.3 trial: an international breast cancer prevention trial. Curr Oncol. 2007 Jun;14(3):89-96.
