Comparisons of patients receiving different cancer treatments reflect the effects of both treatment and patient selection. In breast cancer, however, if radiotherapy decisions are unrelated to laterality, comparisons of left‐sided and right‐sided cancers can demonstrate the causal effects of higher‐versus ‐lower cardiac radiation dose. Cardiac mortality was analysed using individual patient data for 1,934,248 women with breast cancer in 22 countries. The median date of diagnosis was 1996 and the interquartile range was 1987–2002. A total of 1,018,505 women were recorded as irradiated, 223,077 as receiving chemotherapy, 317,619 as receiving endocrine therapy and 55,264 died of cardiac disease. Analyses were stratified by time since breast cancer diagnosis, age at diagnosis, calendar year of diagnosis and country. Patient‐selection effects were evident for all three treatments. For radiotherapy, there was also evidence of selection according to laterality in women irradiated 1990 or later. In patients irradiated before 1990, there was no such selection and cardiac mortality was higher in left‐sided than right‐sided cancer (rate ratio [RR]: 1.13, 95% confidence interval 1.09–1.17). Left‐versus ‐right cardiac mortality RRs were greater among younger women (1.46, 1.19, 1.20, 1.09 and 1.08 after cancer diagnoses at ages <40, 40–49, 50–59, 60–69 and 70+ years, 2p _trend =0.003). Left‐versus ‐right RRs also increased with time since cancer diagnosis (1.03, 1.11, 1.19 and 1.21 during 0–4, 5–14, 15–24 and 25+ years, 2p _trend =0.002) while for women who also received chemotherapy, the left‐versus ‐right RR was 1.42 (95% confidence interval 1.13–1.77), compared to 1.10 (1.05–1.16) for women who did not (2p _difference= 0.03). These results show that the relative increase in cardiac mortality from cardiac exposure during breast cancer radiotherapy given in the past was greater in younger women, lasted into the third decade after exposure and was greater when chemotherapy was also given.

中文翻译：

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乳腺癌放疗、化疗和内分泌治疗后的心脏死亡率：对来自 22 个国家 57 个癌症登记处的 200 万妇女进行的队列研究。


接受不同癌症治疗的患者的比较反映了治疗和患者选择的影响。然而，在乳腺癌中，如果放射治疗决策与偏侧性无关，则左侧和右侧癌症的比较可以证明较高与较低心脏辐射剂量的因果影响。使用 22 个国家 1,934,248 名乳腺癌女性患者的个体数据分析了心脏死亡率。中位诊断日期为 1996 年，四分位数范围为 1987 年至 2002 年。共有 1,018,505 名女性接受过放射治疗，223,077 名女性接受化疗，317,619 名女性接受内分泌治疗，55,264 名女性死于心脏病。分析按乳腺癌诊断后的时间、诊断时的年龄、诊断的日历年份和国家进行分层。所有三种治疗方法的患者选择效应都很明显。对于放射治疗，也有证据表明，根据 1990 年或之后接受放射治疗的女性的偏侧性进行选择。在 1990 年之前接受辐射的患者中，没有这样的选择，左侧癌症的心脏死亡率高于右侧癌症（比率 [RR]：1.13，95% 置信区间 1.09-1.17）。年轻女性的左心脏死亡率 RR与右心脏死亡率 RR 相比更高（<40 岁诊断出癌症后，分别为 1.46、1.19、1.20、1.09 和 1.08，id=11>p_趋势=0.003）。自癌症诊断以来，左相对右 RR 也随着时间的推移而增加（0-4、5-14、15-24 和 25 年以上期间分别为 1.03、1.11、1.19 和 1.21，2 p_趋势=0.002），而对于接受过化疗时，左与右 RR 分别为 1.42（95% 置信区间 1.13-1.77），相比之下 RR 为 1.10（1.05-1.77）。16) 对于没有这样做的女性（2 p_差异= 0.03）。这些结果表明，过去在乳腺癌放射治疗期间，由于心脏暴露导致的心脏死亡率的相对增加在年轻女性中更大，并持续到暴露后的三十岁，并且在同时进行化疗时也更大。