© The Author 2007. Published by Oxford University Press.
ARTICLES |
Tamoxifen for the Prevention of Breast Cancer: Late Results of the Italian Randomized Tamoxifen Prevention Trial Among Women With Hysterectomy
For the Italian Tamoxifen Study Group
Affiliations of authors: Scientific Directorate (UV), Division of Epidemiology and Biostatistics (PM, NR), Division of Cancer Prevention and Genetics (BB, AD), Division of Pathology (GV), and Division of Senology (VS), European Institute of Oncology, Milan, Italy; School of Medicine, University of Milan, Milan, Italy (GV); International Agency for Research on Cancer, Lyon, France (PB); Fondazione Maugeri, Pavia, Italy (AC); Memorial Sloan-Kettering Cancer Center, New York, NY (VS); Comitato Prevenzione Tumori al seno, Milan, Italy (RT); Department of Senology, Istituto per lo Studio e la Cura dei Tumori "Fondazione Pascale," Naples, Italy (GDA, PO); Lega Italiana per la lotta contro i tumori, Vicenza, Italy (FL); Ospedale San Camillo-Forlanini, Rome, Italy (GG); General Surgery Division, Centro per lo Studio e la Prevenzione Oncologica, Florence, Italy (MRDT, MGM); Centro Regionale di Riferimento Oncologico, Aviano, Italy (MAP); Ospedale di Cosenza, Cosenza, Italy (SC); Ospedali Galliera, Genova, Italy (AD)
Correspondence to: Umberto Veronesi, MD, Istituto Europeo di Oncologia, Via G. Ripamonti 435, 20141 Milano, Italy (e-mail: umberto.veronesi{at}ieo.it).
Background: Initial findings of the Italian Randomized Tamoxifen Prevention Trial found no reduction in risk of breast cancer with tamoxifen use, whereas the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial showed that tamoxifen treatment reduces risk of estrogen receptor–positive breast cancer. Here we present an extended follow-up of the Italian trial.
Methods: From October 1, 1992, to December 31, 1997, 5408 otherwise healthy women who had undergone hysterectomy were randomly assigned in a double-blind manner to tamoxifen (20 mg daily) or placebo for 5 years. Rates of breast cancer and other events in the two groups were compared by the use of risk ratios (RRs) and 95% confidence intervals (CIs).
Results: After 11 years of follow-up, 136 women (74 placebo, 62 tamoxifen) developed breast cancer (RR = 0.84, 95% CI = 0.60 to 1.17; annual rates were 2.48 and 2.07 per 1000 women-years, respectively). The rates of breast cancer in the two study groups were similar among women who had had bilateral oophorectomy and among women at low risk for hormone receptor–positive (HR+) disease but were much lower in the tamoxifen group among women at high risk (placebo, 6.26 per 1000 women-years, tamoxifen, 1.50 per 1000 women-years; RR = 0.24, 95% CI = 0.10 to 0.59). During the treatment period, women in the tamoxifen group reported more hot flashes (RR = 1.78, 95% CI = 1.57 to 2.00), vaginal discharge (RR = 3.44, 95% CI = 2.90 to 4.09), and urinary disturbances (RR = 1.52, 95% CI = 1.23 to 1.89) but fewer headaches (RR = 0.68, 95% CI = 0.50 to 0.94) than women in the placebo group. Hypertriglyceridemia (RR = 4.33, 95% CI = 1.96 to 9.53), thromboembolic events (RR = 1.63, 95% CI = 1.02 to 2.62), and cardiac arrhythmia or atrial fibrillation (RR = 1.73, 95% CI = 1.01 to 2.98) were also more frequent in the tamoxifen group than in the placebo group.
Conclusions: Appropriate selection of women at high risk for HR+ disease may improve the risk–benefit ratio of tamoxifen intervention.
| CONTEXT AND CAVEATS Prior knowledge The initial results from the Italian Tamoxifen Trial showed no reduction in risk of breast cancer with tamoxifen treatment compared with placebo, which was in contrast to the National Surgical Adjuvant Breast and Bowel Project Breast Cancer Prevention Trial. Study design Randomized double-blind phase III trial of tamoxifen treatment among healthy women who had undergone hysterectomy. Data were also analyzed based on the woman's baseline risk, low or high, for hormone receptor–positive (HR+) breast cancer. Contributions Rates of breast cancer were similar in both groups among women at low risk but were lower in the tamoxifen group than in the placebo group among women at high risk. More women in the tamoxifen group than in the placebo group reported side effects, including hot flashes and cardiovascular events. Implications Women who are at high risk for breast cancer and not for cardiovascular disease may benefit from tamoxifen treatment as a prevention strategy for HR+ breast cancer. Limitations Most women were not at high risk for breast disease.
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Manuscript received October 23, 2006; revised March 20, 2007; accepted March 23, 2007.
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J Natl Cancer Inst 2007 99: 657.
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