运动不耐受贯穿乳腺癌全程的机制：个体患者数据的汇总分析。
Mechanisms of Exercise Intolerance Across the Breast Cancer Continuum: A Pooled Analysis of Individual Patient Data.
机构信息
Memorial Sloan Kettering Cancer Center, New York, NY.
Queen's University, Kingston, ON, CANADA.
出版信息
Med Sci Sports Exerc. 2024 Apr 1;56(4):590-599. doi: 10.1249/MSS.0000000000003348. Epub 2023 Nov 27.
PURPOSE
The purpose of this study is to evaluate the prevalence of abnormal cardiopulmonary responses to exercise and pathophysiological mechanism(s) underpinning exercise intolerance across the continuum of breast cancer (BC) care from diagnosis to metastatic disease.
METHODS
Individual participant data from four randomized trials spanning the BC continuum ([1] prechemotherapy [n = 146], [2] immediately postchemotherapy [n = 48], [3] survivorship [n = 138], and [4] metastatic [n = 47]) were pooled and compared with women at high-risk of BC (BC risk; n = 64). Identical treadmill-based peak cardiopulmonary exercise testing protocols evaluated exercise intolerance (peak oxygen consumption; V̇O2peak) and other resting, submaximal, and peak cardiopulmonary responses. The prevalence of 12 abnormal exercise responses was evaluated. Graphical plots of exercise responses were used to identify oxygen delivery and/or uptake mechanisms contributing to exercise intolerance. Unsupervised, hierarchical cluster analysis was conducted to explore exercise response phenogroups.
RESULTS
Mean V̇O2peak was 2.78 ml O2.kg-1·min-1 (95% confidence interval [CI], -3.94, -1.62 mL O2.kg-1·min-1; P < 0.001) lower in the pooled BC cohort (52 ± 11 yr) than BC risk (55 ± 10 yr). Compared with BC risk, the pooled BC cohort had a 2.5-fold increased risk of any abnormal cardiopulmonary response (odds ratio, 2.5; 95% confidence interval, 1.2, 5.3; P = 0.014). Distinct exercise responses in BC reflected impaired oxygen delivery and uptake relative to control, although considerable inter-individual heterogeneity within cohorts was observed. In unsupervised, hierarchical cluster analysis, six phenogroups were identified with marked differences in cardiopulmonary response patterns and unique clinical characteristics.
CONCLUSIONS
Abnormal cardiopulmonary response to exercise is common in BC and is related to impairments in oxygen delivery and uptake. The identification of exercise response phenogroups could help improve cardiovascular risk stratification and guide investigation of targeted exercise interventions.
目的
本研究旨在评估乳腺癌（BC）诊治全过程（从诊断到转移性疾病）中异常心肺运动反应的流行率和运动不耐受的病理生理机制。
方法
跨越 BC 诊治全过程（[1]化疗前[n=146]、[2]化疗后即刻[n=48]、[3]生存[n=138]和[4]转移性[n=47]）的四项随机试验的个体参与者数据被汇总并与 BC 高危人群（BC 风险；n=64）进行比较。采用相同的跑步机峰值心肺运动测试方案评估运动不耐受（峰值摄氧量；V̇O2peak）和其他静息、亚极量和峰值心肺反应。评估了 12 种异常运动反应的流行率。使用运动反应的图形图来确定导致运动不耐受的氧输送和/或摄取机制。进行无监督的层次聚类分析以探索运动反应表型组。
结果
汇总的 BC 队列（52±11 岁）的平均 V̇O2peak 比 BC 风险（55±10 岁）低 2.78 ml O2.kg-1·min-1（95%置信区间[CI]，-3.94，-1.62 ml O2.kg-1·min-1；P<0.001）。与 BC 风险相比，汇总的 BC 队列发生任何异常心肺反应的风险增加了 2.5 倍（优势比，2.5；95%CI，1.2，5.3；P=0.014）。BC 中的异常运动反应反映了与对照相比氧输送和摄取受损，尽管在各队列中观察到相当大的个体间异质性。在无监督的层次聚类分析中，确定了六个表型组，这些组在心肺反应模式和独特的临床特征方面存在明显差异。
结论
BC 中异常的心肺运动反应很常见，与氧输送和摄取受损有关。识别运动反应表型组有助于改善心血管风险分层，并指导针对特定运动干预的研究。
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