Background Although breast cancer survivors are at risk for cardiovascular disease (CVD) from treatment late effects, evidence to inform long-term and age-specific cardiovascular surveillance recommendations is lacking. Methods We conducted a retrospective cohort study of 10,211 women diagnosed with first primary unilateral breast cancer in Kaiser Permanente Washington or Colorado (aged 20+, survived ≥1 year). We estimated multivariable adjusted hazard ratios (aHR) for associations between initial chemotherapy regimen type (anthracycline and/or trastuzumab, other chemotherapies, no chemotherapy [reference]) and CVD risk, adjusted for patient characteristics, other treatments, and CVD risk factors. Cumulative incidence was calculated considering competing events. Results After 5.79 median years, 14.67% of women developed CVD (cardiomyopathy/heart failure (CM/HF), ischemic heart disease (IHD), stroke). Women treated with anthracyclines and/or trastuzumab had a higher risk of CVD compared with no chemotherapy (aHR=1.53,95%CI=1.31-1.79), persisting 5+years post-diagnosis (aHR5-<10 years=1.85,95%CI=1.44-2.39;aHR10+ years=1.83,95%CI=1.34-2.49). CM/HF risks were elevated among women treated with anthracyclines and/or trastuzumab compared with no chemotherapy, especially for ages<65 (aHR20-54years=2.97,95%CI=1.72-5.12;aHR55-64years=2.21,95%CI=1.52-3.21), differing for older women (aHR65+years=1.32,95%CI=0.97-1.78), and 5+years post-diagnosis (aHR5-<10years=1.89,95%CI=1.35-2.64;aHR10+years=2.21,95%CI=1.52-3.20). Anthracyclines and/or trastuzumab receipt was associated with increased IHD risks after 5+years (aHR5-<10years=1.51,95%CI=1.06-2.14;aHR10+years=1.86,95%CI=1.18-2.93) with no clear age effects, and stroke risk (aHR=1.33,95%CI=1.05-1.69) which did not vary by time or age. There was some evidence of long-term CM/HF and IHD risks with other chemotherapies. Among women aged<65 treated with anthracyclines and/or trastuzumab, up to 16% developed CVD by 10-years (20-54=6.91%;55-64=16.00%), driven by CM/HF (20-54=3.90%;55-64=9.78%). Conclusions We found increased long-term risks of CM/HF and IHD among breast cancer survivors treated with anthracyclines and/or trastuzumab, and increased CM/HF risk among women aged<65.

中文翻译：

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美国乳腺癌幸存者接受蒽环类药物和曲妥珠单抗治疗后的长期心血管疾病风险

背景 尽管乳腺癌幸存者因治疗后期影响而面临心血管疾病 (CVD) 的风险，但缺乏长期和特定年龄心血管监测建议的证据。方法 我们对华盛顿州或科罗拉多州 Kaiser Permanente 诊断患有首发原发性单侧乳腺癌的 10,211 名女性（年龄 20 岁以上，生存≥1 年）进行了一项回顾性队列研究。我们评估了初始化疗方案类型（蒽环类和/或曲妥珠单抗、其他化疗、无化疗[参考]）与 CVD 风险之间关联的多变量调整风险比 (aHR)，并根据患者特征、其他治疗和 CVD 风险因素进行了调整。计算累积发生率时考虑了竞争事件。结果 中位年数 5.79 年后，14.67% 的女性出现 CVD（心肌病/心力衰竭 (CM/HF)、缺血性心脏病 (IHD)、中风）。与未接受化疗的女性相比，接受蒽环类药物和/或曲妥珠单抗治疗的女性患 CVD 的风险更高 (aHR=1.53,95%CI=1.31-1.79)，并且在诊断后持续 5 年以上 (aHR5-<10 年=1.85,95) %CI=1.44-2.39；aHR10+岁=1.83，95%CI=1.34-2.49）。与未接受化疗的女性相比，接受蒽环类药物和/或曲妥珠单抗治疗的女性的 CM/HF 风险升高，尤其是年龄 <65 岁的女性 (aHR20-54years=2.97,95%CI=1.72-5.12;aHR55-64years=2.21,95%CI= 1.52-3.21），对于老年女性（aHR65+岁=1.32，95%CI=0.97-1.78）和诊断后5年以上（aHR5-<10年=1.89，95%CI=1.35-2.64；aHR10）有所不同+年=2.21,95%CI=1.52-3.20）。接受蒽环类药物和/或曲妥珠单抗与 5 年以上 IHD 风险增加相关（aHR5-＜10 年=1.51,95%CI=1.06-2.14；aHR10+年=1.86,95%CI=1.18-2.93），但尚无明确证据年龄影响和中风风险（aHR=1.33，95%CI=1.05-1.69），不随时间或年龄而变化。有一些证据表明其他化疗存在长期 CM/HF 和 IHD 风险。在接受蒽环类药物和/或曲妥珠单抗治疗的 65 岁以下女性中，在 CM/HF (20-54=3.90) 的推动下，高达 16% 的女性在 10 年内出现 CVD (20-54=6.91%;55-64=16.00%) %;55-64=9.78%)。结论 我们发现接受蒽环类药物和/或曲妥珠单抗治疗的乳腺癌幸存者中 CM/HF 和 IHD 的长期风险增加，并且 65 岁以下女性的 CM/HF 风险增加。