Challenges in Monitoring the Breast Cancer Prevention Trial

  • Carol K. Redmond
  • Joseph P. Costantino
  • Theodore Colton


The Breast Cancer Prevention Trial (BCPT) was a double-masked, placebo-control, randomized clinical trial designed and conducted by the National Surgical Breast and Bowel Project (NSABP), a National Cancer Institute (NCI)-funded cancer cooperative group. The primary hypothesis tested was whether tamoxifen, a drug that is beneficial for treatment of breast cancer, was effective in preventing the occurrence of cancer in women at increased risk. The Endpoint Review, Safety Monitoring, and Advisory Committee (ERSMAC), the independent data monitoring committee for the BCPT, implemented an innovative monitoring strategy that combined traditional monitoring rules for individual diseases with a global monitoring index in order to weigh the beneficial effects of treatment with known and potential detrimental effects. In addition to developing a monitoring plan tailored for a prevention trial with multiple endpoints of interest, other concerns that were addressed included a reassessment of study sample size and power subsequent to a lengthy suspension of accrual during the trial and handling the occurrence of an unexpected ocular toxicity in association with tamoxifen. Although there were numerous issues that arose during its course, the trial progressed to completion of accrual and successful early termination following the fourth interim analysis, when there was reliable evidence that, not only did tamoxifen prevent breast cancer, but that the beneficial effect outweighed adverse effects of taking tamoxifen.


Breast Cancer Endometrial Cancer Invasive Breast Cancer Breast Cancer Incidence Global Index 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Fisher B, Costantino JP. 1997. Highlights of the NSABP breast cancer prevention trial. Cancer Control 4:78–86.Google Scholar
  2. 2.
    Redmond CK, Costantino JP. Design and current status of the NSABP breast cancer prevention trial (BCPT). 1996. In Senn HJ, Gelber RD, Goldhirsch A, Thurlimann B (ed.): Recent Results in Cancer Research. Springer, New York, 140:309–317.Google Scholar
  3. 3.
    Gail MH, Brinton LA, Byar DP, Corle DK, Green SB, Schairer C, Mulvihill JJ. 1989. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst 81:1879–1886.CrossRefGoogle Scholar
  4. 4.
    Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, et al. 1998. Tamoxifen for prevention of breast cancer: Report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst 90:1371–1388CrossRefGoogle Scholar
  5. 5.
    Costantino JP, Gail MH, Pee D, Anderson S, Redmond CK, Benichou J, Wieand HS. 1999. Validation studies for models projecting the risk of invasive and total breast cancer incidence, J Natl Cancer Inst 91:1541–1548.CrossRefGoogle Scholar
  6. 6.
    Gail MH, Costantino JP. Editorial. 2001. Validating and improving models for projecting the absolute risk of breast cancer. J Natl Cancer Inst 93:334–335.Google Scholar
  7. 7.
    Rosner B. 1999. Fundamentals of Biostatistics, ed 4, Boston, 1995, Duxbury Press.Google Scholar
  8. 8.
    Fleming TR, Harrington DP, O’Brien PC. 1984. Designs for group sequential tests. Control Clin Trials 5:348–361.CrossRefGoogle Scholar
  9. 9.
    Freedman L, Anderson G, Kipnis V, Prentice R, Wang CY, Rossouw J, Wittes J, DeMets D. 1996. Approaches to monitoring the results of long-term disease prevention trials: Examples from the Women’s Health Initiative. Control Clin Trials 17:509–525.CrossRefGoogle Scholar
  10. 10.
    Fisher B, Redmond C, Dimitrov NV, Bowman D, Legault-Poisson S, Wickerham DL, Wolmark N, Fisher ER, Margolese R, Sutherland C, et al. 1989. A randomized clinical trial evaluating tamoxifen in the treatment of patients with node-negative breast cancer who have estrogen-receptor positive tumors. N Engl J Med 320:479–484.CrossRefGoogle Scholar
  11. 11.
    Pavlidis N, Petris C, Briassoulis E, Klouvas G, Psilas C, Rempapis J, Petroutsos G. 1992. Clear evidence that long-term, low-dose tamoxifen treatment can induce ocular toxicity. A prospective study of 63 patients. Cancer 69:2961–2964.CrossRefGoogle Scholar
  12. 12.
    Gorin MB, Day R, Costantino JP, Fisher B, Redmond CK, Wickerham L, et al. 1998. Long-term tamoxifen citrate use and potential ocular toxicity Am J Ophthalmol 125:493–501.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Carol K. Redmond
    • 1
  • Joseph P. Costantino
    • 1
  • Theodore Colton
    • 2
  1. 1.Department of Biostatistics, Graduate School of Public HealthUniversity of PittsburghPittsburgh
  2. 2.Department of EpidemiologyBoston University School of Public HealthBoston

Personalised recommendations