绝经后女性乳腺癌辅助治疗后促炎细胞因子暂时增加：一项纵向研究。

Pro-inflammatory cytokines increase temporarily after adjuvant treatment for breast cancer in postmenopausal women: a longitudinal study.

机构信息

Xlab, Department of Biomedical Sciences, University of Copenhagen, Blegdamsvej 3B, 2200, Copenhagen, Denmark.

Department of Endocrinology, Rigshospitalet, 2100, Copenhagen, Denmark.

出版信息

Breast Cancer Res. 2024 Oct 16;26(1):142. doi: 10.1186/s13058-024-01898-3.

DOI:10.1186/s13058-024-01898-3

PMID:39415181

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11481761/

Abstract

BACKGROUND

Breast cancer patients have an increased risk of cardiometabolic disease and for many patients, adjuvant therapy causes an altered lipid profile, insulin resistance and inflammation. Previous follow-up studies are inconclusive regarding the duration of therapy-induced inflammation. We examined the acute and persistent changes of adjuvant chemotherapy on inflammatory and metabolic health markers in breast cancer patients.

METHODS

Plasma levels of IL-6, IL-8, IL-10, IFN-γ, TNF-α, high-sensitivity C-reactive protein (hsCRP) and metabolic health parameters were analyzed before, shortly after and every six months up to two years after adjuvant chemotherapy treatment in 51 postmenopausal early breast cancer (EBC) patients, as well as in 41 healthy age- and BMI-matched controls. A target-specific multiplex assay was applied for cytokine measurements.

RESULTS

Before initiation of adjuvant therapy, plasma IL-8 levels were higher in EBC patients (31%, p = 0.0001). Also, a larger proportion of the patients had a hsCRP level above 2 mg/L (41%) compared to the controls (17%, Χ = 5.15, p = 0.023). Plasma levels of all five cytokines, but not hsCRP, were significantly increased after compared to before adjuvant chemotherapy (15-48% increase; all p ≤ 0.05). Already six months after ending chemotherapy treatment, all plasma cytokine levels were significantly reduced and close to pre-chemotherapy levels. Adjuvant chemotherapy caused a worsened lipid profile (increased triglycerides, lower HDL levels), insulin resistance and increased plasma insulin levels that remained high during the first year after chemotherapy.

CONCLUSION

Postmenopausal women with EBC have temporarily increased plasma levels of pro-inflammatory cytokines after adjuvant chemotherapy. Although transient, the therapy-induced increase in plasma cytokine levels, together with dyslipidemia and insulin resistance, may contribute to cardiometabolic risk in breast cancer patients treated with adjuvant chemotherapy.

TRIAL REGISTRATION

The clinical trial (registration number NCT03784651) was registered on www.

CLINICALTRIALS

gov on 24 December 2018.

摘要

背景

乳腺癌患者患心脏代谢疾病的风险增加，而且许多患者的辅助治疗会导致血脂谱改变、胰岛素抵抗和炎症。之前的随访研究对于治疗诱导的炎症持续时间没有定论。我们研究了辅助化疗对乳腺癌患者炎症和代谢健康标志物的急性和持续变化。

方法

在 51 名绝经后早期乳腺癌（EBC）患者和 41 名年龄和 BMI 匹配的健康对照者中，在接受辅助化疗前、化疗后不久和每 6 个月直至 2 年，分析白细胞介素 6（IL-6）、白细胞介素 8（IL-8）、白细胞介素 10（IL-10）、干扰素 γ（IFN-γ）、肿瘤坏死因子-α（TNF-α）、高敏 C 反应蛋白（hsCRP）和代谢健康参数的血浆水平。采用靶向特定的多重检测法进行细胞因子检测。

结果

在开始辅助治疗前，EBC 患者的血浆 IL-8 水平较高（31%，p=0.0001）。此外，与对照组相比（17%，Χ=5.15，p=0.023），有更大比例的患者 hsCRP 水平高于 2mg/L（41%）。与辅助化疗前相比，所有五种细胞因子的血浆水平均显著升高（15-48%的升高；所有 p 值均≤0.05）。即使在化疗结束后 6 个月，所有的血浆细胞因子水平仍显著降低且接近化疗前水平。辅助化疗导致脂谱恶化（甘油三酯升高，高密度脂蛋白水平降低）、胰岛素抵抗和血浆胰岛素水平升高，这些在化疗后第一年仍保持较高水平。