Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials.
Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials.
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DOI：
10.1016/s0140-6736(11)60993-8
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发表时间：
2011-08-27
期刊：
影响因子：
168.9
通讯作者：
Ingle, J.
中科院分区：
文献类型：
--
作者：
Davies, C.;Godwin, J.;Gray, R.;Clarke, M.;Darby, S.;McGale, P.;Wang, Y. C.;Peto, R.;Pan, H. C.;Cutter, D.;Taylor, C.;Ingle, J.
随着他莫昔芬治疗早期乳腺癌5年试验的成熟，激素受体测量（和其他患者特征）与长期结果的相关性可以越来越可靠地评估。我们报告了5年辅助他莫昔芬试验的最新荟萃分析。我们对20项早期乳腺癌试验（n= 21457）的个体患者数据进行了协作荟萃分析，其中他莫昔芬治疗与不辅助他莫昔芬治疗约5年，依从性约为80%。复发率和死亡率（rr）来自分配治疗的对数秩分析。在雌激素受体（ER）阳性疾病（n= 10645）中，分配约5年的他莫昔芬显著降低了前10年的复发率（0 - 4年的RR为0.53 [SE为0.03]，5 - 9年的RR为0.68 [0.06][2p均< 0.00001]；但10 - 14年的RR为0.97[0.10]，表明10年后没有进一步的增加或减少）。即使在边际er阳性疾病（10-19 fmol/mg胞浆蛋白）中，复发率也显著降低（RR = 0.67[0.08]）。在er阳性疾病中，RR大约与孕激素受体状态（或水平）、年龄、淋巴结状态或化疗使用无关。在前15年中，乳腺癌死亡率降低了约三分之一（0 - 4年的RR为0.71[0.05]，5-9年的RR为0.66[0.05]，10-14年的RR为0.68[0.08]；在每个单独的时间段内，死亡率额外降低的p< 0.0001）。总体非乳腺癌死亡率几乎没有受到影响，尽管血栓栓塞性和子宫癌死亡率（均仅在55岁以上的妇女中）的绝对增加很小，因此全因死亡率大大降低。在er阴性疾病中，他莫昔芬对乳腺癌复发或死亡率的影响很小或没有影响。5年辅助性他莫昔芬可安全降低15年乳腺癌复发和死亡风险。内质网状态是唯一重要的预测比例减少的记录因素。因此，他莫昔芬产生的绝对风险降低取决于没有他莫昔芬的绝对乳腺癌风险（在任何化疗后）。英国癌症研究中心，英国心脏基金会和医学研究委员会。
As trials of 5 years of tamoxifen in early breast cancer mature, the relevance of hormone receptor measurements (and other patient characteristics) to long-term outcome can be assessed increasingly reliably. We report updated meta-analyses of the trials of 5 years of adjuvant tamoxifen. We undertook a collaborative meta-analysis of individual patient data from 20 trials (n=21 457) in early breast cancer of about 5 years of tamoxifen versus no adjuvant tamoxifen, with about 80% compliance. Recurrence and death rate ratios (RRs) were from log-rank analyses by allocated treatment. In oestrogen receptor (ER)-positive disease (n=10 645), allocation to about 5 years of tamoxifen substantially reduced recurrence rates throughout the first 10 years (RR 0·53 [SE 0·03] during years 0–4 and RR 0·68 [0·06] during years 5–9 [both 2p<0·00001]; but RR 0·97 [0·10] during years 10–14, suggesting no further gain or loss after year 10). Even in marginally ER-positive disease (10–19 fmol/mg cytosol protein) the recurrence reduction was substantial (RR 0·67 [0·08]). In ER-positive disease, the RR was approximately independent of progesterone receptor status (or level), age, nodal status, or use of chemotherapy. Breast cancer mortality was reduced by about a third throughout the first 15 years (RR 0·71 [0·05] during years 0–4, 0·66 [0·05] during years 5–9, and 0·68 [0·08] during years 10–14; p<0·0001 for extra mortality reduction during each separate time period). Overall non-breast-cancer mortality was little affected, despite small absolute increases in thromboembolic and uterine cancer mortality (both only in women older than 55 years), so all-cause mortality was substantially reduced. In ER-negative disease, tamoxifen had little or no effect on breast cancer recurrence or mortality. 5 years of adjuvant tamoxifen safely reduces 15-year risks of breast cancer recurrence and death. ER status was the only recorded factor importantly predictive of the proportional reductions. Hence, the absolute risk reductions produced by tamoxifen depend on the absolute breast cancer risks (after any chemotherapy) without tamoxifen. Cancer Research UK, British Heart Foundation, and Medical Research Council.