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

IF 7.4 1区医学 Q1 Medicine Breast Cancer Research Pub Date : 2024-10-16 DOI:10.1186/s13058-024-01898-3

Agnes Lindholm, Marie-Louise Abrahamsen, Kristian Buch-Larsen, Djordje Marina, Michael Andersson, Jørn Wulff Helge, Peter Schwarz, Flemming Dela, Linn Gillberg

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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%, Χ² = 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.

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绝经后妇女接受乳腺癌辅助治疗后，促炎细胞因子会暂时增加：一项纵向研究。

背景：乳腺癌患者罹患心脏代谢疾病的风险增加，对许多患者来说，辅助治疗会导致血脂状况改变、胰岛素抵抗和炎症。以往的随访研究对治疗诱发炎症的持续时间没有定论。我们研究了辅助化疗对乳腺癌患者炎症和代谢健康指标的急性和持续性变化：方法：分析了 51 名绝经后早期乳腺癌（EBC）患者以及 41 名年龄和体重指数匹配的健康对照者在辅助化疗前、化疗后不久以及化疗后每六个月至两年的血浆中 IL-6、IL-8、IL-10、IFN-γ、TNF-α、高敏 C 反应蛋白（hsCRP）水平以及代谢健康参数。细胞因子的测定采用了靶标特异性多重分析法：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（17%，Χ2 = 5.15，p = 0.023）相比，患者中 hsCRP 水平超过 2 mg/L 的比例更高（41%）。与辅助化疗前相比，辅助化疗后所有五种细胞因子的血浆水平都显著升高（升高15%-48%；所有P均小于0.05），但hsCRP没有升高。化疗结束六个月后，所有血浆细胞因子水平均明显降低，接近化疗前水平。辅助化疗导致血脂状况恶化（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，且在化疗后的第一年内仍居高不下：结论：绝经后女性 EBC 患者在辅助化疗后，血浆中的促炎细胞因子水平会暂时升高。尽管是一过性的，但治疗引起的血浆细胞因子水平升高，加上血脂异常和胰岛素抵抗，可能会导致接受辅助化疗的乳腺癌患者的心脏代谢风险：该临床试验（注册号 NCT03784651）于 2018 年 12 月 24 日在 www.Clinicaltrials: gov 上注册。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Breast Cancer Research ONCOLOGY-

CiteScore

12.00

自引率

0.00%

发文量

审稿时长

12 weeks

期刊介绍： Breast Cancer Research, an international, peer-reviewed online journal, publishes original research, reviews, editorials, and reports. It features open-access research articles of exceptional interest across all areas of biology and medicine relevant to breast cancer. This includes normal mammary gland biology, with a special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal covers preclinical, translational, and clinical studies with a biological basis, including Phase I and Phase II trials.