© 1998 by Oxford University Press
Initial results of the Breast Cancer Prevention Trial were released last month when women at increased risk of breast cancer who were taking tamoxifen were found to have a 45% reduction in breast cancer incidence compared to women on a placebo. More than 13,000 women had been randomly assigned to either tamoxifen or a placebo; the women on tamoxifen had 85 cases of invasive breast cancer compared to 154 cases in women assigned to placebo.
Bernard Fisher, M.D., scientific director of the National Surgical Adjuvant Breast and Bowel Project, the Pittsburgh-based clinical trials network that ran the study, called the announcement "probably the most emotional of my entire career. . . . This is the first time in history that we have evidence that breast cancer cannot only be treated but also prevented."
Because of the positive outcome of the study, the BCPT results were revealed about 14 months earlier than expected. On average, the participants, women at increased risk of breast cancer who were age 35 and older, had been on the study about 4 years. Tamoxifen is an anti-estrogen that has been used to treat breast cancer for more than 20 years (see previous article).
Tamoxifen did increase the women's chances of three rare but life-threatening health problems. There were 33 cases of endometrial cancer in the tamoxifen group versus 14 in the placebo group, 17 cases of pulmonary embolism in the tamoxifen group versus six in the placebo group, and 30 cases of deep vein thrombosis in the tamoxifen group versus 19 in the placebo group.
"I think it's important to note that none of the risks were unanticipated, and none were greater than we thought they might be going into the trial," said Leslie Ford, M.D., associate director of the National Cancer Institute's Early Detection and Community Oncology Program. Ford coordinated NCI's role in the trial.
Also of note, the adverse effects occurred more often only in women over age 50. Women ages 35 to 49 had no increased risk of the life-threatening problems and had a decrease in breast cancer incidence (see Stat Bite).
Launched in April 1992, the BCPT also looked at whether taking tamoxifen decreases the number of heart attacks and reduces the number of bone fractures in women taking the drug. There was no difference in the number of heart attacks between the tamoxifen and placebo groups, but women taking tamoxifen had fewer bone fractures of the hip, wrist, and spine.
Norman Wolmark, M.D., chairperson of NSABP, said "We do not regard this chemoprevention trial as an isolated study, as an end unto itself, but rather as a continuum of studies that will hopefully lead to improved prevention approaches." The next step for NSABP is a planned trial of tamoxifen versus raloxifene in postmenopausal women at increased risk of breast cancer. Postmenopausal women on the placebo arm of the BCPT are being encouraged to enroll in this study, slated to begin as early as this fall.
Zeneca Pharmaceuticals, Wilmington, Del., provided both the tamoxifen and placebo used in the BCPT without charge. They have committed to providing tamoxifen to both the women who were assigned randomly to tamoxifen (to complete their 5 years of treatment, if they had not already done so) and to women assigned randomly to placebo who would like to take the drug, should they and their physician choose that option.
The estimated 29 million U.S. women who would qualify as at increased risk of breast cancer based on criteria used for the BCPT are being told that tamoxifen is now an option for them. And they are also being told not to rush into the decision without considering their personal risk/benefit ratio.
"We are feverishly working to analyze this data so we can better define what makes a woman at increased risk for breast cancer," said Ford. "But, in addition, there are other things that we'll be looking at to help us better define who is at risk of breast cancer and who is at risk for some of the unwanted side effects that come with tamoxifen therapy. The NCI and the NSABP will be developing tools that can assist women and their healthcare providers in decision making."
The study will be submitted to a peer-reviewed journal in the near future. The data that has been released is available on NCI's Clinical Trials web site at: http://cancertrials.nci.nih.gov.
Scientists running several international trials of tamoxifen in other high-risk populations have said they intend to continue their trials as currently designed.
-- Kara Smigel
Breast Cancer Prevention Trial Shows Major Benefit, Some Risk
Anticipated Risks
New Trial
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  A. K. C. Teo, H. K. Oh, R. B. Ali, and B. F. L. Li The Modified Human DNA Repair Enzyme O6-Methylguanine-DNA Methyltransferase Is a Negative Regulator of Estrogen Receptor-Mediated Transcription upon Alkylation DNA Damage Mol. Cell. Biol., October 15, 2001; 21(20): 7105 - 7114. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. P. Brown, R. L. Morrissey, T. A. Tolhurst, J. A. Crowell, and B. S. Levine Oral Toxicity of 1,2-Dithiole-3-Thione, a Potential Cancer Chemopreventive Agent, in the Rat International Journal of Toxicology, November 1, 2000; 19(6): 375 - 381. [Abstract] [PDF]
|
|
|
|
 |
|
 K. El Abdaimi, N. Dion, V. Papavasiliou, P.-E. Cardinal, L. Binderup, D. Goltzman, L.-G. Ste-Marie, and R. Kremer The Vitamin D Analogue EB 1089 Prevents Skeletal Metastasis and Prolongs Survival Time in Nude Mice Transplanted with Human Breast Cancer Cells Cancer Res., August 1, 2000; 60(16): 4412 - 4418. [Abstract] [Full Text]
|
|
|
|
 |
|
 A. Bollig and R. J. Miksicek An Estrogen Receptor-{alpha} Splicing Variant Mediates Both Positive and Negative Effects on Gene Transcription Mol. Endocrinol., May 1, 2000; 14(5): 634 - 649. [Abstract] [Full Text]
|
|
|
|
|
|
C. M. Cover, S. J. Hsieh, E. J. Cram, C. Hong, J. E. Riby, L. F. Bjeldanes, and G. L. Firestone Indole-3-Carbinol and Tamoxifen Cooperate to Arrest the Cell Cycle of MCF-7 Human Breast Cancer Cells Cancer Res., March 1, 1999; 59(6): 1244 - 1251. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||