Background

Radiotherapy has become much better targeted since the 1980s, improving both safety and efficacy. In breast cancer, radiotherapy to regional lymph nodes aims to reduce risks of recurrence and death. Its effects have been studied in randomised trials, some before the 1980s and some after. We aimed to assess the effects of regional node radiotherapy in these two eras.

Methods

In this meta-analysis of individual patient data, we sought data from all randomised trials of regional lymph node radiotherapy versus no regional lymph node radiotherapy in women with early breast cancer (including one study that irradiated lymph nodes only if the cancer was right-sided). Trials were identified through the EBCTCG's regular systematic searches of databases including MEDLINE, Embase, the Cochrane Library, and meeting abstracts. Trials were eligible if they began before Jan 1, 2009. The only systematic difference between treatment groups was in regional node radiotherapy (to the internal mammary chain, supraclavicular fossa, or axilla, or any combinations of these). Primary outcomes were recurrence at any site, breast cancer mortality, non-breast-cancer mortality, and all-cause mortality. Data were supplied by trialists and standardised into a format suitable for analysis. A summary of the formatted data was returned to trialists for verification. Log-rank analyses yielded first-event rate ratios (RRs) and confidence intervals.

Findings

We found 17 eligible trials, 16 of which had available data (for 14 324 participants), and one of which (henceforth excluded), had unavailable data (for 165 participants). In the eight newer trials (12 167 patients), which started during 1989–2008, regional node radiotherapy significantly reduced recurrence (rate ratio 0·88, 95% CI 0·81–0·95; p=0·0008). The main effect was on distant recurrence as few regional node recurrences were reported. Radiotherapy significantly reduced breast cancer mortality (RR 0·87, 95% CI 0·80–0·94; p=0·0010), with no significant effect on non-breast-cancer mortality (0·97, 0·84–1·11; p=0·63), leading to significantly reduced all-cause mortality (0·90, 0·84–0·96; p=0·0022). In an illustrative calculation, estimated absolute reductions in 15-year breast cancer mortality were 1·6% for women with no positive axillary nodes, 2·7% for those with one to three positive axillary nodes, and 4·5% for those with four or more positive axillary nodes. In the eight older trials (2157 patients), which started during 1961–78, regional node radiotherapy had little effect on breast cancer mortality (RR 1·04, 95% CI 0·91–1·20; p=0·55), but significantly increased non-breast-cancer mortality (1·42, 1·18–1·71; p=0·00023), with risk mainly after year 20, and all-cause mortality (1·17, 1·04–1·31; p=0·0067).

Interpretation

Regional node radiotherapy significantly reduced breast cancer mortality and all-cause mortality in trials done after the 1980s, but not in older trials. These contrasting findings could reflect radiotherapy improvements since the 1980s.

Funding

Cancer Research UK, Medical Research Council.

中文翻译：

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早期乳腺癌局部淋巴结放疗：对 16 项试验中 14 324 名女性进行的个体患者数据荟萃分析

背景

自 20 世纪 80 年代以来，放射治疗的针对性大大提高，安全性和有效性均得到提高。在乳腺癌中，对区域淋巴结进行放射治疗的目的是降低复发和死亡的风险。它的影响已通过随机试验进行了研究，有些是在 20 世纪 80 年代之前，有些是在 20 世纪 80 年代之后。我们的目的是评估这两个时代区域淋巴结放疗的效果。

方法

在这项对个体患者数据的荟萃分析中，我们从早期乳腺癌女性中接受区域淋巴结放疗与不接受区域淋巴结放疗的所有随机试验中寻找数据（包括一项仅在癌症为右侧时才照射淋巴结的研究） ）。试验是通过 EBCTCG 定期系统检索数据库（包括 MEDLINE、Embase、Cochrane 图书馆和会议摘要）来确定的。如果试验在 2009 年 1 月 1 日之前开始，则符合资格。治疗组之间唯一的系统性差异是区域淋巴结放疗（内乳链、锁骨上窝或腋窝，或这些的任意组合）。主要结局是任何部位的复发、乳腺癌死亡率、非乳腺癌死亡率和全因死亡率。数据由试验者提供并标准化为适合分析的格式。格式化数据的摘要已返回给试验者进行验证。对数秩分析得出首次事件发生率 (RR) 和置信区间。

发现

我们发现了 17 项符合条件的试验，其中 16 项有可用数据（14 324 名参与者），其中一项（此后排除）没有可用数据（165 名参与者）。在 1989 年至 2008 年开始的 8 项较新的试验（12 167 名患者）中，区域淋巴结放疗显着降低了复发率（率比 0·88，95% CI 0·81–0·95；p=0·0008）。主要影响是远处复发，因为区域淋巴结复发的报道很少。放疗显着降低乳腺癌死亡率（RR 0·87，95% CI 0·80–0·94；p=0·0010），对非乳腺癌死亡率没有显着影响（0·97，0·84– 1·11；p=0·63），导致全因死亡率显着降低（0·90、0·84–0·96；p=0·0022）。在一项说明性计算中，估计无腋窝淋巴结阳性的女性 15 年乳腺癌死亡率绝对降低了 1·6%，有 1 至 3 个阳性腋窝淋巴结的女性为 2·7%，有腋窝淋巴结阳性的女性为 4·5%。四个或更多阳性腋窝淋巴结。在 1961-78 年开始的八项较早的试验（2157 名患者）中，区域淋巴结放疗对乳腺癌死亡率几乎没有影响（RR 1·04，95% CI 0·91–1·20；p=0·55） ，但显着增加非乳腺癌死亡率 (1·42, 1·18–1·71; p=0·00023)，风险主要在 20 年后，以及全因死亡率 (1·17, 1·04) –1·31；p=0·0067）。

解释

在 20 世纪 80 年代后进行的试验中，区域淋巴结放疗显着降低了乳腺癌死亡率和全因死亡率，但在较早的试验中则不然。这些对比的发现可能反映了 20 世纪 80 年代以来放射治疗的进步。

资金

英国癌症研究中心，医学研究委员会。