Cancer Research UK, Centre for Epidemiology, Mathematics, and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary School of Medicine and Dentistry, University of London, London, UK.
Lancet Oncol. 2011 Jan;12(1):21-9. doi: 10.1016/S1470-2045(10)70266-7. Epub 2010 Dec 7.
Initial results of the UK/ANZ DCIS (UK, Australia, and New Zealand ductal carcinoma in situ) trial suggested that radiotherapy reduced new breast events of ipsilateral invasive and ductal carcinoma in situ (DCIS) compared with no radiotherapy, but no significant effects were noted with tamoxifen. Here, we report long-term results of this trial.
Women with completely locally excised DCIS were recruited into a randomised 2×2 factorial trial of radiotherapy, tamoxifen, or both. Randomisation was independently done for each of the two treatments (radiotherapy and tamoxifen), stratified by screening assessment centre, and blocked in groups of four. The recommended dose for radiation was 50 Gy in 25 fractions over 5 weeks (2 Gy per day on weekdays), and tamoxifen was prescribed at a dose of 20 mg daily for 5 years. Elective decision to withhold or provide one of the treatments was permitted. The endpoints of primary interest were invasive ipsilateral new breast events for the radiotherapy comparison and any new breast event, including contralateral disease and DCIS, for tamoxifen. Analysis of each of the two treatment comparisons was restricted to patients who were randomly assigned to that treatment. Analyses were by intention to treat. All trial drugs have been completed and this study is in long-term follow-up. This study is registered, number ISRCTN99513870.
Between May, 1990, and August, 1998, 1701 women were randomly assigned to radiotherapy and tamoxifen, radiotherapy alone, tamoxifen alone, or to no adjuvant treatment. Seven patients had protocol violations and thus 1694 patients were available for analysis. After a median follow-up of 12·7 years (IQR 10·9-14·7), 376 (163 invasive [122 ipsilateral vs 39 contralateral], 197 DCIS [174 ipsilateral vs 17 contralateral], and 16 of unknown invasiveness or laterality) breast cancers were diagnosed. Radiotherapy reduced the incidence of all new breast events (hazard ratio [HR] 0·41, 95% CI 0·30-0·56; p<0·0001), reducing the incidence of ipsilateral invasive disease (0·32, 0·19-0·56; p<0·0001) as well as ipsilateral DCIS (0·38, 0·22-0·63; p<0·0001), but having no effect on contralateral breast cancer (0·84, 0·45-1·58; p=0·6). Tamoxifen reduced the incidence of all new breast events (HR 0·71, 95% CI 0·58-0·88; p=0·002), reducing recurrent ipsilateral DCIS (0·70, 0·51-0·86; p=0·03) and contralateral tumours (0·44, 0·25-0·77; p=0·005), but having no effect on ipsilateral invasive disease (0·95, 0·66-1·38; p=0·8). No data on adverse events except cause of death were collected for this trial.
This updated analysis confirms the long-term beneficial effect of radiotherapy and reports a benefit for tamoxifen in reducing local and contralateral new breast events for women with DCIS treated by complete local excision.
Cancer Research UK and the Australian National Health and Medical Research Council.
英国/澳新 DCIS（英国、澳大利亚和新西兰导管原位癌）试验的初步结果表明，与不放疗相比，放疗可降低同侧浸润性和导管原位癌（DCIS）的新发乳房事件，但他莫昔芬无显著效果。在此，我们报告该试验的长期结果。
完全局部切除的 DCIS 女性患者被纳入一项放疗、他莫昔芬或两者联合的随机 2×2 析因试验。两种治疗（放疗和他莫昔芬）的随机分配独立进行，按筛查评估中心分层，并按 4 个一组分组。推荐的放射剂量为 50 Gy，共 25 次，每周 5 天（每天 2 Gy），他莫昔芬每日 20 mg 处方，持续 5 年。允许选择保留或不保留其中一种治疗。主要关注的终点是放疗比较的同侧新浸润性乳房事件和任何新发乳房事件，包括对侧疾病和 DCIS。对两种治疗比较的分析均限于随机分配至该治疗的患者。分析采用意向治疗。所有试验药物均已完成，本研究正在进行长期随访。本研究已注册，编号 ISRCTN99513870。
1990 年 5 月至 1998 年 8 月期间，1701 名女性被随机分配至放疗和他莫昔芬、放疗、他莫昔芬或不接受辅助治疗。7 名患者违反了方案，因此有 1694 名患者可进行分析。中位随访 12.7 年后（IQR 10.9-14.7），诊断出 376 例（163 例浸润性[122 例同侧，39 例对侧]、197 例 DCIS[174 例同侧，17 例对侧]和 16 例未知浸润性或侧别）乳腺癌。放疗降低了所有新发乳房事件的发生率（风险比[HR]0.41，95%CI 0.30-0.56；p<0.0001），降低了同侧浸润性疾病的发生率（0.32，0.19-0.56；p<0.0001）和同侧 DCIS（0.38，0.22-0.63；p<0.0001），但对侧乳腺癌无影响（0.84，0.45-1.58；p=0.6）。他莫昔芬降低了所有新发乳房事件的发生率（HR 0.71，95%CI 0.58-0.88；p=0.002），降低了同侧 DCIS 的复发率（0.70，0.51-0.86；p=0.03）和对侧肿瘤的发生率（0.44，0.25-0.77；p=0.005），但对同侧浸润性疾病无影响（0.95，0.66-1.38；p=0.8）。除死因外，本试验未收集不良事件的数据。
本更新分析证实了放疗的长期有益效果，并报告了他莫昔芬在降低完全局部切除的 DCIS 女性局部和对侧新发乳房事件方面的获益。
英国癌症研究协会和澳大利亚国家卫生和医学研究理事会。
