Veronesi Umberto, Maisonneuve Patrick, Rotmensz Nicole, Bonanni Bernardo, Boyle Peter, Viale Giuseppe, Costa Alberto, Sacchini Virgilio, Travaglini Roberto, D'Aiuto Giuseppe, Oliviero Pasquale, Lovison Francesco, Gucciardo Giacomo, del Turco Marco Rosselli, Muraca Maria Grazia, Pizzichetta Maria Antonietta, Conforti Serafino, Decensi Andrea
Scientific Directorate, European Institute of Oncology, Milan, Italy.
J Natl Cancer Inst. 2007 May 2;99(9):727-37. doi: 10.1093/jnci/djk154.
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.
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).
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.
Appropriate selection of women at high risk for HR+ disease may improve the risk-benefit ratio of tamoxifen intervention.
意大利随机他莫昔芬预防试验的初步结果显示，使用他莫昔芬并不能降低乳腺癌风险，而美国国家外科辅助乳腺和肠道项目乳腺癌预防试验表明，他莫昔芬治疗可降低雌激素受体阳性乳腺癌的风险。在此，我们展示了意大利试验的延长随访结果。
从1992年10月1日至1997年12月31日，5408名已接受子宫切除术的健康女性被双盲随机分配至他莫昔芬组（每日20毫克）或安慰剂组，为期5年。通过风险比（RRs）和95%置信区间（CIs）比较两组的乳腺癌及其他事件发生率。
经过11年随访，136名女性（74名安慰剂组，62名他莫昔芬组）患乳腺癌（RR = 0.84，95% CI = 0.60至1.17；每年发生率分别为每1000名女性年2.48例和2.07例）。在双侧卵巢切除的女性以及激素受体阳性（HR+）疾病低风险女性中，两个研究组的乳腺癌发生率相似，但在高风险女性中，他莫昔芬组的发生率要低得多（安慰剂组，每1000名女性年6.26例；他莫昔芬组，每1000名女性年1.50例；RR = 0.24，95% CI = 0.10至0.59）。在治疗期间，他莫昔芬组女性报告潮热更多（RR = 1.78，95% CI = 1.57至2.00）、阴道分泌物增多（RR = 3.44，95% CI = 2.90至4.09）、尿路紊乱更多（RR = 1.52，95% CI = 1.23至1.89），但头痛比安慰剂组女性更少（RR = 0.68，95% CI = 0.50至0.94）。他莫昔芬组的高甘油三酯血症（RR = 4.33，95% CI = 1.96至9.53）、血栓栓塞事件（RR = 1.63，95% CI = 1.02至2.62）以及心律失常或心房颤动（RR = 1.73，95% CI = 1.01至2.98）也比安慰剂组更常见。
对HR+疾病高风险女性进行适当选择，可能会改善他莫昔芬干预的风险效益比。
