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Randomized, Placebo-Controlled Clinical Trial to Determine the Worth of Tamoxifen for Preventing Breast Cancer
Alternate Title Tamoxifen as a Preventive Agent for Invasive Breast Cancer
Objectives I. Determine whether long-term tamoxifen therapy is effective in preventing the occurrence of invasive breast cancer and in reducing mortality attributed to breast cancer. II. Determine whether the administration of tamoxifen reduces mortality from cardiovascular disease. III. Evaluate the effect of tamoxifen on the incidence of bone fractures. IV. Evaluate the toxicity and side effects of tamoxifen therapy in order to assess benefit vs. risk resulting from the use of tamoxifen in women at increased risk of developing breast cancer. Entry Criteria Disease Characteristics: See General Eligibility Criteria Prior/Concurrent Therapy: Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for breast cancer No concurrent chemotherapy for benign disease (e.g., methotrexate for arthritis) Endocrine therapy: No concurrent or recent (within 3 months) estrogen or progesterone replacement therapy, oral contraceptives, or androgens (e.g., danazol) Radiotherapy: No prior radiotherapy for breast cancer Surgery: Prior hysterectomy or surgical oophorectomy allowed if not performed for malignancy or, if for malignancy, performed more than 10 years prior to entry Other: Nonhormonal medications (e.g., vitamin D, fluoride, calcitonin, bisphosphonates) for bone mineral density augmentation allowed Thyroid replacement therapy allowed provided hormone levels are routinely followed No current coumadin therapy Other anticoagulant therapy (e.g., aspirin, persantin) allowed Patient Characteristics: Age: 35 and over (see Population) Performance status: Ambulatory and capable of reasonably normal activity Life expectancy: At least 10 years Hematopoietic: WBC at least 4,000 Platelets at least 100,000 Hepatic: Bilirubin within normal limits AST or ALT within normal limits Renal: Creatinine within normal limits Cardiovascular: Prior cardiovascular events (e.g., myocardial infarction, stroke) allowed No history of deep vein thrombosis or pulmonary embolus Other: Concurrent low-fat diet and lipid-lowering medications allowed No history of macular degeneration of the retina No other nonmalignant disease that would preclude administration of tamoxifen No second malignancy within 10 years except: Nonmelanomatous skin cancer In situ cervical cancer No psychiatric condition (including history of clinical depression) or addictive disorder that would preclude informed consent or interfere with protocol compliance No pregnant women Adequate contraception required of fertile women Geographically accessible for follow-up Additional referral information for this trial is available in the PDQ News, from CancerFax (dial 301-402-5874 from the telephone on your fax machine), from the Cancer Information Service (1-800-4-CANCER; 1-800-422-6237), and from the American Cancer Society's Cancer Response System at 1-800-ACS-2345. In Canada, centers participating in the study can be located through several organizations based on location: in British Columbia and the Yukon, call 1-604-879-2323; in Ontario, call 1-800-263-6750; in Quebec, call 1-800-361-4212; and in remaining regions, call 1-416-387-1153. General Eligibility Criteria: See the PDQ News for additional information about the status of this study --Population-- Women with an increased risk for developing breast cancer in the following categories: Age at least 35 with histologic diagnosis of lobular carcinoma in situ treated by local excision only Age 35-59 with a minimum projected 5-year probability of invasive breast cancer at least equivalent to that of women 60 years of age as determined by the Breast Cancer Assessment Profile generated by the NSABP Biostatistical Center Composite risk is based on the number of first-degree relatives with breast cancer, one or more prior benign breast biopsies, previous diagnosis of atypical hyperplasia of the breast, age at first live birth, nulliparity, and age at onset of menarche Age 60 and over, regardless of other breast cancer risk factors No clinical evidence of malignancy on breast exam No evidence of invasive breast cancer on mammogram performed within 180 days prior to entry No prior invasive breast cancer of any type; no prior intraductal carcinoma in situ; and no prior lobular carcinoma in situ treated by mastectomy, radiotherapy, or systemic adjuvant therapy No participation in another cancer prevention study involving pharmacologic intervention Normal pelvic exam within 180 days prior to entry Successful endometrial sampling or successful D&C prior to randomization required in patients randomized after 7/8/94 who have not had a hysterectomy (optional for patients randomized prior to 7/8/94) --Prior/Concurrent Therapy-- Biologic therapy: Not specified Chemotherapy: No prior chemotherapy for breast cancer No concurrent chemotherapy for benign disease (e.g., methotrexate for arthritis) Endocrine therapy: No concurrent or recent (within 3 months) estrogen or progesterone replacement therapy, oral contraceptives, or androgens (e.g., danazol) Radiotherapy: No prior radiotherapy for breast cancer Surgery: Prior hysterectomy or surgical oophorectomy allowed if not performed for malignancy or, if for malignancy, performed more than 10 years prior to entry Other: Nonhormonal medications (e.g., vitamin D, fluoride, calcitonin, bisphosphonates) for bone mineral density augmentation allowed Thyroid replacement therapy allowed provided hormone levels are routinely followed No current coumadin therapy Other anticoagulant therapy (e.g., aspirin, persantin) allowed --Patient Characteristics-- Age: 35 and over (see Population) Performance status: Ambulatory and capable of reasonably normal activity Life expectancy: At least 10 years Hematopoietic: WBC at least 4,000 Platelets at least 100,000 Hepatic: Bilirubin within normal limits AST or ALT within normal limits Renal: Creatinine within normal limits Cardiovascular: Prior cardiovascular events (e.g., myocardial infarction, stroke) allowed No history of deep vein thrombosis or pulmonary embolus Other: Concurrent low-fat diet and lipid-lowering medications allowed No history of macular degeneration of the retina No other nonmalignant disease that would preclude administration of tamoxifen No second malignancy within 10 years except: Nonmelanomatous skin cancer In situ cervical cancer No psychiatric condition (including history of clinical depression) or addictive disorder that would preclude informed consent or interfere with protocol compliance No pregnant women Adequate contraception required of fertile women Geographically accessible for follow-up Additional referral information for this trial is available in the PDQ News, from CancerFax (dial 301-402-5874 from the telephone on your fax machine), from the Cancer Information Service (1-800-4-CANCER; 1-800-422-6237), and from the American Cancer Society's Cancer Response System at 1-800-ACS-2345. In Canada, centers participating in the study can be located through several organizations based on location: in British Columbia and the Yukon, call 1-604-879-2323; in Ontario, call 1-800-263-6750; in Quebec, call 1-800-361-4212; and in remaining regions, call 1-416-387-1153. Expected Enrollment A total of 13,000 subjects will be randomized. Outline This is a randomized, placebo-controlled study. Patients are stratified by participating institution, age, race, and relative breast cancer risk (based on risk-factor analysis). Patients are randomly assigned to receive oral tamoxifen or oral placebo daily for 5 years. Patients are followed at 3 and 6 months and every 6 months thereafter.Published Results Cella D, Land SR, Chang CH, et al.: Symptom measurement in the Breast Cancer Prevention Trial (BCPT) (P-1): psychometric properties of a new measure of symptoms for midlife women. Breast Cancer Res Treat 109 (3): 515-26, 2008.[PUBMED Abstract] Abramson N, Costantino JP, Garber JE, et al.: Effect of Factor V Leiden and prothrombin G20210-->A mutations on thromboembolic risk in the national surgical adjuvant breast and bowel project breast cancer prevention trial. J Natl Cancer Inst 98 (13): 904-10, 2006.[PUBMED Abstract] Beattie MS, Costantino JP, Cummings SR, et al.: Endogenous sex hormones, breast cancer risk, and tamoxifen response: an ancillary study in the NSABP Breast Cancer Prevention Trial (P-1). J Natl Cancer Inst 98 (2): 110-5, 2006.[PUBMED Abstract] Chalas E, Costantino JP, Wickerham DL, et al.: Benign gynecologic conditions among participants in the Breast Cancer Prevention Trial. Am J Obstet Gynecol 192 (4): 1230-7; discussion 1237-9, 2005.[PUBMED Abstract] Fisher B, Costantino JP, Wickerham DL, et al.: Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 97 (22): 1652-62, 2005.[PUBMED Abstract] Cushman M, Costantino JP, Bovill EG, et al.: Effect of tamoxifen on venous thrombosis risk factors in women without cancer: the Breast Cancer Prevention Trial. Br J Haematol 120 (1): 109-16, 2003.[PUBMED Abstract] Tan-Chiu E, Wang J, Costantino JP, et al.: Effects of tamoxifen on benign breast disease in women at high risk for breast cancer. J Natl Cancer Inst 95 (4): 302-7, 2003.[PUBMED Abstract] Garber JE, Costantino JP, Wickerham DL, et al.: Factor V Leiden (FVL) and prothrombin G20210A (PTG) mutations and risk of thromboembolic events (TE) in NSABP P-1, the breast cancer prevention trial (BCPT). [Abstract] Breast Cancer Res Treat 76 (Suppl 1): A-413, 2002. Day R, Ganz PA, Costantino JP: Tamoxifen and depression: more evidence from the National Surgical Adjuvant Breast and Bowel Project's Breast Cancer Prevention (P-1) Randomized Study. J Natl Cancer Inst 93 (21): 1615-23, 2001.[PUBMED Abstract] Day R; National Surgical Adjuvant Breast and Bowel Projet P-1 study (NSABP-1).: Quality of life and tamoxifen in a breast cancer prevention trial: a summary of findings from the NSABP P-1 study. National Surgical Adjuvant Breast and Bowel Project. Ann N Y Acad Sci 949: 143-50, 2001.[PUBMED Abstract] King MC, Wieand S, Hale K, et al.: Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2: National Surgical Adjuvant Breast and Bowel Project (NSABP-P1) Breast Cancer Prevention Trial. JAMA 286 (18): 2251-6, 2001.[PUBMED Abstract] Reis SE, Costantino JP, Wickerham DL, et al.: Cardiovascular effects of tamoxifen in women with and without heart disease: breast cancer prevention trial. National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial Investigators. J Natl Cancer Inst 93 (1): 16-21, 2001.[PUBMED Abstract] Wolmark N, Dunn BK: The role of tamoxifen in breast cancer prevention: issues sparked by the NSABP Breast Cancer Prevention Trial (P-1). Ann N Y Acad Sci 949: 99-108, 2001.[PUBMED Abstract] Costantino JP, Gail MH, Pee D, et al.: Validation studies for models projecting the risk of invasive and total breast cancer incidence. J Natl Cancer Inst 91 (18): 1541-8, 1999.[PUBMED Abstract] Day R, Ganz PA, Costantino JP, et al.: Health-related quality of life and tamoxifen in breast cancer prevention: a report from the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Clin Oncol 17 (9): 2659-69, 1999.[PUBMED Abstract] Fisher B, Costantino JP, Wickerham DL, et al.: Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90 (18): 1371-88, 1998.[PUBMED Abstract] Ganz PA, Day R, Ware JE Jr, et al.: Base-line quality-of-life assessment in the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial. J Natl Cancer Inst 87 (18): 1372-82, 1995.[PUBMED Abstract] Redmond CK, Wickerham DL, Cronin W, et al.: The NSABP breast cancer prevention trial (BCPT): a progress report. [Abstract] Proceedings of the American Society of Clinical Oncology 12: A-78, 69, 1993. Related PublicationsCuzick J, Forbes JF, Howell A: Re: Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 98 (9): 643; author reply 643-4, 2006.[PUBMED Abstract] Dunn BK, Wickerham DL, Ford LG: Prevention of hormone-related cancers: breast cancer. J Clin Oncol 23 (2): 357-67, 2005.[PUBMED Abstract] Tchou J, Hou N, Rademaker A, et al.: Acceptance of tamoxifen chemoprevention by physicians and women at risk. Cancer 100 (9): 1800-6, 2004.[PUBMED Abstract] Vogel VG, Costantino JP, Wickerham DL, et al.: National surgical adjuvant breast and bowel project update: prevention trials and endocrine therapy of ductal carcinoma in situ. Clin Cancer Res 9 (1 Pt 2): 495S-501S, 2003.[PUBMED Abstract] Vogel VG, Costantino JP, Wickerham DL, et al.: The study of tamoxifen and raloxifene: preliminary enrollment data from a randomized breast cancer risk reduction trial. Clin Breast Cancer 3 (2): 153-9, 2002.[PUBMED Abstract] Wickerham L: Tamoxifen--an update on current data and where it can now be used. Breast Cancer Res Treat 75 (Suppl 1): S7-12; discussion S33-5, 2002.[PUBMED Abstract] Fallowfield L, Fleissig A, Edwards R, et al.: Tamoxifen for the prevention of breast cancer: psychosocial impact on women participating in two randomized controlled trials. J Clin Oncol 19 (7): 1885-92, 2001.[PUBMED Abstract] Fisher B, Land S, Mamounas E, et al.: Prevention of invasive breast cancer in women with ductal carcinoma in situ: an update of the national surgical adjuvant breast and bowel project experience. Semin Oncol 28 (4): 400-18, 2001.[PUBMED Abstract] Gail MH, Costantino JP, Bryant J, et al.: Weighing the risks and benefits of tamoxifen treatment for preventing breast cancer. J Natl Cancer Inst 91 (21): 1829-46, 1999.[PUBMED Abstract] Trial Lead Organizations National Surgical Adjuvant Breast and Bowel Project
Note: The purpose of most clinical trials listed in this database is to test new cancer treatments, or new methods of diagnosing, screening, or preventing cancer. Because all potentially harmful side effects are not known before a trial is conducted, dose and schedule modifications may be required for participants if they develop side effects from the treatment or test. The therapy or test described in this clinical trial is intended for use by clinical oncologists in carefully structured settings, and may not prove to be more effective than standard treatment. A responsible investigator associated with this clinical trial should be consulted before using this protocol. |
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