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Abstract：
BACKGROUND: Physical activity (PA) reduces the risk of developing breast cancer (BC) and mortality rate in BC patients starting PA after diagnosis. Immunomodulation is considered responsible for these effects. However, limited data exist on the immunomodulation induced by moderate PA (mPA) during neoadjuvant chemotherapy (NACT). We have investigated the longitudinal change of cytokines during NACT alone or combined with mPA.
METHODS: Twenty-three cytokines were analyzed in BC patients at consecutive timepoints: at baseline (T0), before starting mPA (T1), before surgery (T2), and after surgery (T3). mPA consisted of 3-weekly brisk-walking sessions for 9-10 consecutive weeks.
RESULTS: Ninety-two patients were assessed: 21 patients refused mPA (untrained) and 71 agreed (trained). At T1, NACT induced significant up-regulation of interleukin (IL)-5, IL-6, IL-15, chemokine ligand (CCL)-2, interferon-γ, and C-X-C motif ligand (CXCL)-10 and reduction of expression of IL-13 and CCL-22. At T2, NACT and mPA induced up-regulation of IL-21, CCL-2, and tumor necrosis factor-α and reduction of expression of IL-8, IL-15, vascular endothelial growth factor, and soluble interleukin 6 receptor. Only CXCL-10 increased in untrained patients. A cytokine score (CS) was created to analyze, all together, the changes between T1 and T2. At T2 the CS decreased in trained and increased in untrained patients. We clustered the patients using cytokines and predictive factors and identified two clusters. The cluster A, encompassing 90% of trained patients, showed more pathological complete response (pCR) compared to the cluster B: 78% versus 22%, respectively.
CONCLUSIONS: mPA interacts with NACT inducing CS reduction in trained patients not observed in untrained patients, suggesting a reduction of inflammation, notwithstanding chemotherapy. This effect may contribute to the higher rate of pCR observed in the cluster A, including most trained patients.
METHODS: Twenty-three cytokines were analyzed in BC patients at consecutive timepoints: at baseline (T0), before starting mPA (T1), before surgery (T2), and after surgery (T3). mPA consisted of 3-weekly brisk-walking sessions for 9-10 consecutive weeks.
RESULTS: Ninety-two patients were assessed: 21 patients refused mPA (untrained) and 71 agreed (trained). At T1, NACT induced significant up-regulation of interleukin (IL)-5, IL-6, IL-15, chemokine ligand (CCL)-2, interferon-γ, and C-X-C motif ligand (CXCL)-10 and reduction of expression of IL-13 and CCL-22. At T2, NACT and mPA induced up-regulation of IL-21, CCL-2, and tumor necrosis factor-α and reduction of expression of IL-8, IL-15, vascular endothelial growth factor, and soluble interleukin 6 receptor. Only CXCL-10 increased in untrained patients. A cytokine score (CS) was created to analyze, all together, the changes between T1 and T2. At T2 the CS decreased in trained and increased in untrained patients. We clustered the patients using cytokines and predictive factors and identified two clusters. The cluster A, encompassing 90% of trained patients, showed more pathological complete response (pCR) compared to the cluster B: 78% versus 22%, respectively.
CONCLUSIONS: mPA interacts with NACT inducing CS reduction in trained patients not observed in untrained patients, suggesting a reduction of inflammation, notwithstanding chemotherapy. This effect may contribute to the higher rate of pCR observed in the cluster A, including most trained patients.
摘要：
背景：体力活动（PA）可降低诊断后开始使用PA的BC患者患乳腺癌（BC）的风险和死亡率。免疫调节被认为是这些作用的原因。然而,关于新辅助化疗(NACT)期间中度PA(mPA)诱导的免疫调节的数据有限.我们研究了NACT单独或与mPA联合使用时细胞因子的纵向变化。
方法：在连续时间点分析了BC患者的23种细胞因子：在基线（T0），在启动mPA(T1)之前，手术前（T2），和手术后（T3）。mPA包括连续9-10周每周3次的快走训练。
结果：对92例患者进行了评估：21例患者拒绝mPA（未经训练），71例患者同意（经训练）。T1时,NACT显著上调白细胞介素(IL)-5、IL-6、IL-15、趋化因子配体(CCL)-2、干扰素-γ、和C-X-C基序配体(CXCL)-10以及IL-13和CCL-22的表达减少。在T2，NACT和mPA诱导IL-21，CCL-2和肿瘤坏死因子-α的上调和IL-8，IL-15，血管内皮生长因子的表达减少，和可溶性白细胞介素6受体。只有CXCL-10在未经训练的患者中增加。创建细胞因子评分（CS）进行分析，一起,T1和T2之间的变化。在T2时，经过训练的患者CS降低，未经训练的患者CS升高。我们使用细胞因子和预测因子对患者进行聚类，并确定了两个聚类。集群A,包括90%受过训练的病人，与B组相比，显示出更多的病理完全缓解（pCR）：78％对22％，分别。
结论：mPA与NACT相互作用，在未经训练的患者中未观察到的训练患者中诱导CS降低，表明炎症的减少，尽管化疗。这种效应可能有助于在簇A中观察到更高的pCR率，包括大多数受过训练的病人。
方法：在连续时间点分析了BC患者的23种细胞因子：在基线（T0），在启动mPA(T1)之前，手术前（T2），和手术后（T3）。mPA包括连续9-10周每周3次的快走训练。
结果：对92例患者进行了评估：21例患者拒绝mPA（未经训练），71例患者同意（经训练）。T1时,NACT显著上调白细胞介素(IL)-5、IL-6、IL-15、趋化因子配体(CCL)-2、干扰素-γ、和C-X-C基序配体(CXCL)-10以及IL-13和CCL-22的表达减少。在T2，NACT和mPA诱导IL-21，CCL-2和肿瘤坏死因子-α的上调和IL-8，IL-15，血管内皮生长因子的表达减少，和可溶性白细胞介素6受体。只有CXCL-10在未经训练的患者中增加。创建细胞因子评分（CS）进行分析，一起,T1和T2之间的变化。在T2时，经过训练的患者CS降低，未经训练的患者CS升高。我们使用细胞因子和预测因子对患者进行聚类，并确定了两个聚类。集群A,包括90%受过训练的病人，与B组相比，显示出更多的病理完全缓解（pCR）：78％对22％，分别。
结论：mPA与NACT相互作用，在未经训练的患者中未观察到的训练患者中诱导CS降低，表明炎症的减少，尽管化疗。这种效应可能有助于在簇A中观察到更高的pCR率，包括大多数受过训练的病人。
