Randomized, Placebo-Controlled Clinical Trial to Determine the Worth of Tamoxifen for Preventing Breast Cancer
Last Modified: 2/13/2008
Alternate Title Basic Trial Information Objectives Entry Criteria Expected Enrollment Outline Published Results Related Publications Trial Contact Information
Alternate Title
Tamoxifen as a Preventive Agent for Invasive Breast Cancer
Basic Trial Information
Phase | Type | Status | Age | Protocol IDs |
---|
No phase specified | Prevention | Completed | 35 and over | NSABP-P-1 BCPT-1, NSABP P-1, NCI-P91-0022 |
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 ResultsCella 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 Contact Information
Trial Lead Organizations National Surgical Adjuvant Breast and Bowel Project | | | Norman Wolmark, MD, Protocol chair | | Ph: 412-359-3336; 866-680-0004 |
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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. |