Purpose:

Exercise has been shown to improve physical and psychological conditions during cancer therapy, but mechanisms remain poorly understood. The purpose of the present study was to report the results of cancer-related biomarkers and metabolomics outcomes from the PASAPAS feasibility study.

Methods:

In the PASAPAS randomized controlled trial, 61 women beginning adjuvant chemotherapy for localized breast cancer were randomized in a 6-month program of weekly aerobic exercises associated with nutritional counseling versus usual care with nutritional counseling. In the present analysis of 58 women for whom blood samples were available, first, circulating levels of biomarkers (ie, insulin, insulin-like growth factor 1, estradiol, adiponectin, leptin, interleukin-6, and tumor necrosis factor α) were measured at baseline and 6-month follow-up. Changes in biomarkers were compared between exercisers (n = 40) and controls (n = 18) using mixed-effect models. Second, serum metabolites were studied using an untargeted ¹H nuclear magnetic resonance spectroscopy, and orthogonal partial least squares analyses were performed to discriminate exercisers and controls at baseline and at 6 months.

Results:

Over the 6-month intervention, no statistically significant differences were observed between exercisers and controls regarding changes in biomarkers and metabolomic profiles.

Conclusion:

The present analysis of the PASAPAS feasibility trial did not reveal any improvement in circulating biomarkers nor identified metabolic signatures in exercisers versus controls during adjuvant breast cancer treatment. Larger studies preferably in women with poor physical activity level to avoid ceiling effect, testing different doses and types of exercise on additional biological pathways, could allow to clarify the mechanisms mediating beneficial effects of physical exercise during cancer treatment.

Trial registration:

ClinicalTrials.gov Identifier: NCT01331772. Registered 8 April 2011, https://clinicaltrials.gov/ct2/show/NCT01331772?term=pasapas&rank=1

中文翻译：

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运动和营养干预对局部乳腺癌辅助治疗期间循环生物标志物和代谢组学分析的影响：PASAPAS 可行性随机对照试验的结果

目的：

运动已被证明可以改善癌症治疗期间的身体和心理状况，但其机制仍知之甚少。本研究的目的是报告来自 PASAPAS 可行性研究的癌症相关生物标志物和代谢组学结果。

方法：

在 PASAPAS 随机对照试验中，61 名开始接受局部乳腺癌辅助化疗的女性被随机分配到为期 6 个月的每周有氧运动与营养咨询相关的计划与营养咨询的常规护理相比。在对 58 名可获得血液样本的女性进行的分析中，首先，测量了生物标志物（即胰岛素、胰岛素样生长因子 1、雌二醇、脂联素、瘦素、白细胞介素 6 和肿瘤坏死因子 α）的循环水平在基线和 6 个月的随访中。使用混合效应模型比较锻炼者 (n = 40) 和对照组 (n = 18) 之间生物标志物的变化。其次，使用非靶向¹在基线和 6 个月时，进行 H 核磁共振波谱和正交偏最小二乘分析以区分锻炼者和对照组。

结果：

在 6 个月的干预中，在生物标志物和代谢组学特征的变化方面，锻炼者和对照组之间没有观察到统计学上的显着差异。

结论：

目前对 PASAPAS 可行性试验的分析没有揭示循环生物标志物的任何改善，也没有发现在辅助乳腺癌治疗期间锻炼者与对照组的代谢特征。更大规模的研究最好是针对身体活动水平较差的女性以避免天花板效应，在其他生物途径上测试不同剂量和类型的运动，可以阐明在癌症治疗期间调节身体锻炼有益效果的机制。

试用注册：

ClinicalTrials.gov 标识符：NCT01331772。2011 年 4 月 8 日注册，https://clinicaltrials.gov/ct2/show/NCT01331772?term=pasapas&rank=1