BACKGROUND We aimed to develop dose-response relationships for heart failure (HF) following radiation and anthracyclines in breast cancer treatment, and to assess HF associations with trastuzumab and endocrine therapies. METHODS AND RESULTS A case-control study was performed within a cohort of breast cancer survivors treated during 1980-2009. Cases (n = 102) had HF as first cardiovascular diagnosis and were matched 1:3 on age and date of diagnosis. Individual cardiac radiation doses were estimated, and anthracycline doses and use of trastuzumab and endocrine therapy were abstracted from oncology notes. For HF cases who received radiotherapy, the estimated median mean heart dose (MHD) was 6.8 Gy [interquartile range (IQR) 0.9-13.7]. MHD was not associated with HF risk overall [excess rate ratio (ERR) = 1%/Gy, 95% confidence interval (CI) -2 to 10]. In patients treated with anthracyclines, exposure of ≥20% of the heart to ≥20 Gy was associated with a rate ratio of 5.7 (95% CI 1.7-21.7) compared to <10% exposed to ≥20 Gy. For cases who received radiotherapy, median cumulative anthracycline dose was 247 mg/m2 (IQR 240-319). A dose-dependent increase was observed after anthracycline without trastuzumab (ERR = 1.5% per mg/m2 , 95% CI 0.5-4.1). After anthracycline and trastuzumab, the rate ratio was 34.9 (95% CI 11.1-110.1) compared to no chemotherapy. CONCLUSIONS In absence of anthracyclines, breast cancer radiotherapy was not associated with increased HF risk. Strongly elevated HF risks were observed after treatment with anthracyclines and also after treatment with trastuzumab. The benefits of these systemic treatments usually exceed the risks of HF, but our results emphasize the need to support ongoing efforts to evaluate preventative strategies.

中文翻译：

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乳腺癌治疗后心力衰竭。


背景我们的目的是建立乳腺癌治疗中放射和蒽环类药物治疗后心力衰竭（HF）的剂量-反应关系，并评估心力衰竭与曲妥珠单抗和内分泌治疗的关联。方法和结果 在 1980 年至 2009 年期间接受治疗的乳腺癌幸存者队列中进行了一项病例对照研究。病例 (n = 102) 首次心血管诊断为心力衰竭，并在年龄和诊断日期上进行 1:3 匹配。评估了个体心脏辐射剂量，并从肿瘤学笔记中提取了蒽环类药物剂量以及曲妥珠单抗和内分泌治疗的使用。对于接受放射治疗的心衰病例，估计中位平均心脏剂量 (MHD) 为 6.8 Gy [四分位数范围 (IQR) 0.9-13.7]。 MHD 与总体心衰风险无关[超额发生率 (ERR) = 1%/Gy，95% 置信区间 (CI) -2 至 10]。在接受蒽环类药物治疗的患者中，≥20% 的心脏暴露于 ≥20 Gy 的比率为 5.7 (95% CI 1.7-21.7)，而 <10% 的心脏暴露于 ≥20 Gy 的比率为 5.7 (95% CI 1.7-21.7)。对于接受放射治疗的病例，蒽环类药物累积中位剂量为 247 mg/m2 (IQR 240-319)。在不使用曲妥珠单抗的情况下使用蒽环类药物后观察到剂量依赖性增加（ERR = 1.5%/mg/m2，95% CI 0.5-4.1）。与未接受化疗相比，接受蒽环类药物和曲妥珠单抗治疗后，比率为 34.9 (95% CI 11.1-110.1)。结论 在没有蒽环类药物的情况下，乳腺癌放疗与心力衰竭风险增加无关。在使用蒽环类药物治疗后以及在使用曲妥珠单抗治疗后观察到心力衰竭风险显着升高。这些全身治疗的益处通常超过心力衰竭的风险，但我们的结果强调需要支持持续努力评估预防策略。