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 Sponsor Protocol IDs No phase specified Prevention Completed 35 and over NCI 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.

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.

Cuzick 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