Vo Jacqueline B, Ramin Cody, Veiga Lene H S, Brandt Carolyn, Curtis Rochelle E, Bodelon Clara, Barac Ana, Roger Véronique L, Feigelson Heather Spencer, Buist Diana S M, Bowles Erin J Aiello, Gierach Gretchen L, Berrington de González Amy
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Department of Biomedical Sciences, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA.
J Natl Cancer Inst. 2024 Aug 1;116(8):1384-1394. doi: 10.1093/jnci/djae107.
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.
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 years and older, survived ≥1 year). We estimated multivariable adjusted hazard ratios (HRs) for associations between initial chemotherapy regimen type (anthracycline and/or trastuzumab, other chemotherapies, no chemotherapy [referent]) and CVD risk, adjusted for patient characteristics, other treatments, and CVD risk factors. Cumulative incidence was calculated considering competing events.
After 5.79 median years, 14.67% of women developed CVD (cardiomyopathy and/or heart failure [HF], ischemic heart disease, stroke). Women treated with anthracyclines and/or trastuzumab had a higher risk of CVD compared with no chemotherapy (adjusted HR = 1.53, 95% confidence interval [CI] = 1.31 to 1.79), persisting at least 5 years postdiagnosis (adjusted HR5-<10 years = 1.85, 95% CI = 1.44 to 2.39; adjusted HR≥10 years = 1.83, 95% CI = 1.34 to 2.49). Cardiomyopathy and/or HF risks were elevated among women treated with anthracyclines and/or trastuzumab compared with no chemotherapy, especially for those aged younger than 65 years (adjusted HR20-54years = 2.97, 95% CI = 1.72 to 5.12; adjusted HR55-64years = 2.21, 95% CI = 1.52 to 3.21), differing for older women (adjusted HR≥65 years = 1.32, 95% CI = 0.97 to 1.78), and at least 5 years postdiagnosis (adjusted HR5-<10years = 1.89, 95% CI = 1.35 to 2.64; adjusted HR≥10 years = 2.21, 95% CI = 1.52 to 3.20). Anthracyclines and/or trastuzumab receipt was associated with increased ischemic heart disease risks after 5 or more years (adjusted HR5-<10years = 1.51, 95% CI = 1.06 to 2.14; adjusted HR≥10 years = 1.86, 95% CI = 1.18 to 2.93) with no clear age effects, and stroke risk (adjusted HR = 1.33, 95% CI = 1.05 to 1.69), which did not vary by time or age. There was some evidence of long-term cardiomyopathy and/or HF and ischemic heart disease risks with other chemotherapies. Among women aged younger than 65 treated with anthracyclines and/or trastuzumab, up to 16% developed CVD by 10 years (20-54 years = 6.91%; 55-64 years = 16.00%), driven by cardiomyopathy and/or HF (20-54 years = 3.90%; 55-64 years = 9.78%).
We found increased long-term risks of cardiomyopathy and/or HF and ischemic heart disease among breast cancer survivors treated with anthracyclines and/or trastuzumab and increased cardiomyopathy and/or HF risk among women aged younger than 65 years.
尽管乳腺癌幸存者因治疗的晚期效应而有患心血管疾病（CVD）的风险，但缺乏为长期和特定年龄的心血管监测建议提供依据的证据。
我们对华盛顿州和科罗拉多州凯撒医疗集团中10211名被诊断为原发性单侧乳腺癌的女性进行了一项回顾性队列研究（年龄≥20岁，存活≥1年）。我们估计了初始化疗方案类型（蒽环类药物和/或曲妥珠单抗、其他化疗、未化疗[参照组]）与心血管疾病风险之间关联的多变量调整风险比（HR），并对患者特征、其他治疗和心血管疾病风险因素进行了调整。考虑到竞争事件，计算了累积发病率。
中位随访5.79年后，14.67%的女性发生了心血管疾病（心肌病和/或心力衰竭[HF]、缺血性心脏病、中风）。与未接受化疗相比，接受蒽环类药物和/或曲妥珠单抗治疗的女性患心血管疾病的风险更高（调整后HR = 1.53，95%置信区间[CI] = 1.31至1.79），在诊断后至少持续5年（调整后HR5 - <10年 = 1.85，95%CI = 1.44至2.39；调整后HR≥10年 = 1.83，95%CI = 1.34至2.49）。与未接受化疗相比，接受蒽环类药物和/或曲妥珠单抗治疗的女性发生心肌病和/或心力衰竭的风险升高，尤其是年龄小于65岁的女性（调整后HR20 - 54岁 = 2.97，95%CI = 1.72至5.12；调整后HR55 - 64岁 = 2.21，95%CI = 1.52至3.21），老年女性有所不同（调整后HR≥65岁 = 1.32，95%CI = 0.97至1.78），且在诊断后至少5年（调整后HR5 - <10年 = 1.89，95%CI = 1.35至2.64；调整后HR≥10年 = 2.21，95%CI = 1.52至3.20）。接受蒽环类药物和/或曲妥珠单抗治疗5年或更长时间后，缺血性心脏病风险增加（调整后HR5 - <10年 = 1.51，95%CI = 1.06至2.14；调整后HR≥10年 = 1.86，95%CI = 1.18至2.9），无明显年龄效应，中风风险（调整后HR = 1.33，95%CI = 1.05至1.69），且不随时间或年龄变化。有证据表明其他化疗也存在长期心肌病和/或心力衰竭以及缺血性心脏病风险。在接受蒽环类药物和/或曲妥珠单抗治疗的年龄小于65岁的女性中，高达16%在10年内发生了心血管疾病（20 - 54岁 = 6.91%；55 - 64岁 = 16.00%），主要由心肌病和/或心力衰竭导致（20 - 54岁 = 3.90%；55 - 64岁 = 9.78%）。
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患心肌病和/或心力衰竭以及缺血性心脏病的长期风险增加，且年龄小于65岁的女性患心肌病和/或心力衰竭的风险增加。
