AbstractObesity and systemic inflammation are associated with breast cancer (BC) outcomes. Systemic inflammation is increased in obesity. We examined the association between C-reactive protein (CRP) and disease-free survival (DFS) and overall survival (OS) overall, and according to body mass index (BMI).

摘要肥胖和全身炎症与乳腺癌（BC）结局有关。肥胖会增加全身炎症。我们根据体重指数（BMI）检查了C反应蛋白（CRP）与无病生存率（DFS）和总生存率（OS）之间的关系。

We assembled a cohort of women with BC (stage I–III) seen at Aarhus University Hospital between 2010 and 2020 who donated blood at BC diagnosis (N = 2673). CRP levels were measured and divided into quartiles. We followed patients from surgery to recurrence, contralateral BC, other malignancy, death, emigration, or end-of-follow-up.

我们收集了2010年至2020年间在奥胡斯大学医院就诊的BC（I-III期）女性队列，她们在BC诊断时献血（N=2673）。测量CRP水平并将其分为四分位数。我们跟踪患者从手术到复发，对侧BC，其他恶性肿瘤，死亡，移民或随访结束。

We used Cox regression to estimate hazard ratios (HRs) with 95% confidence intervals (95% CIs) to compare outcomes across CRP quartiles, overall and stratified by BMI (normal-weight (18.5 ≤ BMI < 25 kg/m2), overweight (25 ≤ BMI < 30 kg/m2), and obesity (BMI ≥ 30 kg/m2)). During follow-up, 368 events (212 recurrences, 38 contralateral BCs, and 118 deaths) occurred (median follow-up 5.55 years).

我们使用Cox回归来估计95%置信区间（95%CI）的风险比（HR），以比较CRP四分位数的结果，总体和按BMI分层（正常体重（18.5≤≤BMI<25 kg/m2），超重（25≤≤≤BMI<30 kg/m2）和肥胖（BMI≥30 kg/m2））。在随访期间，发生了368例事件（212例复发，38例对侧BC和118例死亡）（中位随访5.55年）。

For DFS, high CRP (CRP ≥ 3.19 mg/L) was associated with an increased risk of events (HRadj:1.62 [95% CI = 1.14–2.28]). In BMI-stratified analyses, high CRP was associated with elevated risk of events in normal-weight and overweight (HRadj:1.70 [95% CI = 1.09–2.66]; HRadj:1.75 [95% CI = 1.08–2.86]), but in obesity, the estimate was less precise (HRadj:1.73 [95% CI = 0.78–3.83]).

对于DFS，高CRP（CRP≥3.19 mg/L）与事件风险增加相关（HRadj:1.62[95%CI=1.14-2.28]）。在BMI分层分析中，高CRP与正常体重和超重事件风险升高相关（HRadj:1.70[95%CI=1.09-2.66]；HRadj:1.75[95%CI:1.08-2.86]），但在肥胖中，估计不太准确（HRadj:1.73[95%CI:0.78-3.83]）。

For OS, high CRP was associated with increased risk of death (HRadj:2.47 [95% CI = 1.62–3.76]). The association was strong in normal-weight and overweight (HRadj:3.66 [95% CI = 1.95–6.87]; HRadj:1.92 [95% CI = 1.06–3.46]), but less clear in obesity (HRadj:1.40 [95% CI = 0.64–3.09]). To sum up, high CRP levels at BC diagnosis were associated with inferior prognosis in early BC irr.

对于OS，高CRP与死亡风险增加有关（HRadj:2.47[95%CI=1.62-3.76]）。；HRadj:1.92[95%CI:1.06-3.46]），但在肥胖方面不太清楚（HRadj:1.40[95%CI:0.64-3.09]）。总之，BC诊断时高CRP水平与BC早期irr预后较差有关。

IntroductionIn 2020, 2.3 million women were diagnosed with breast cancer (BC) globally, making it the most prevalent cancer type (excluding non-melanoma skin cancer) in the world1. Despite 5-year survival rates approaching 90% in North America for patients with BC, nearly 700,000 women died from BC in 2020 worldwide1,2.

引言2020年，全球有230万女性被诊断患有乳腺癌（BC），使其成为世界上最普遍的癌症类型（不包括非黑色素瘤皮肤癌）1。尽管北美BC患者的5年生存率接近90%，但2020年全球有近700000名女性死于BC 1,2。

Alongside, the prevalence of obesity (defined as a body mass index (BMI) ≥ 30 kg/m2) increased excessively worldwide, rising from 7 to 16% among women between 1975 and 20163. Obesity is associated with an increased risk of developing at least 15 types of cancer, including postmenopausal BC4. Also, obesity is a prognostic disadvantage and is associated with shorter disease-free survival (DFS) and overall survival (OS) in BC5,6.Inflammation is a hallmark of cancer7 and systemic inflammation is associated with poor BC prognosis8,9.

此外，肥胖的患病率（定义为体重指数（BMI）≥30 kg/m2）在世界范围内过度增加，在1975年至20163年间，女性从7%上升到16%。肥胖与患至少15种癌症（包括绝经后BC4）的风险增加有关。此外，肥胖是一种预后缺陷，与BC5中较短的无病生存期（DFS）和总生存期（OS）相关[6]。炎症是癌症的标志[7]，全身炎症与BC预后不良有关[8,9]。

Obesity is associated with low-grade inflammation10 and elevated levels of C-reactive protein (CRP)11, also among BC patients12. Thus, both obesity and systemic inflammation are associated with inferior BC outcomes. Yet, it is not clear if BC patients with obesity and high levels of systemic inflammation have a poorer prognosis compared with patients with obesity and lower levels of systemic inflammation.CRP is an acute-phase protein released from the liver upon stimulation from cytokines such as interleukin 613.

。因此，肥胖和全身炎症都与较差的BC结果相关。然而，目前尚不清楚肥胖和全身炎症水平高的BC患者与肥胖和全身炎症水平较低的患者相比，预后是否较差。CRP是在细胞因子如白细胞介素613刺激下从肝脏释放的急性期蛋白。

CRP is part of the inflammatory cascade and a marker of systemic inflammation14,15. CRP levels are increased in people with obesity compared with their normal weight counterparts, and in cancer patients compared with healthy controls or patients with benign diseases16. A systematic review by Savioli et al.

CRP是炎症级联反应的一部分，是全身炎症的标志物14,15。与正常体重人群相比，肥胖人群的CRP水平升高，与健康对照组或良性疾病患者相比，癌症患者的CRP水平升高16。Savioli等人的系统评价。

concluded that high pre-operative CRP levels were associated with an increased risk of BC-specific mortality and all.

得出结论，术前高CRP水平与BC特异性死亡率和all风险增加有关。

Data availability

数据可用性

The datasets generated and/or analyzed are not publicly available due to individual privacy could be compromised, but are available from the corresponding author on reasonable request.

由于个人隐私可能受到损害，生成和/或分析的数据集无法公开获得，但可根据合理要求从通讯作者处获得。

AbbreviationsAUH:

缩写AUH：

Aarhus University Hospital

奥胡斯大学医院

BC:

不列颠哥伦比亚省：

Breast cancer

乳腺癌

BMI:

体重指数：

Body mass index

体重指数

CCI:

CCI公司：

Charlson Comorbidity Index

查尔森合并症指数

CI:

Confidence interval

置信区间

CRP:

CRP：

C-reactive protein

C反应蛋白

DAD :

爸爸：

Danish Anesthesia Database

丹麦麻醉数据库

DBCG:

DBCG：

Danish Breast Cancer Group

丹麦乳腺癌组织

DFS :

DFS：

Disease-free survival

无病生存

DMCG :

DMCG：

Danish Multidisciplinary Cancer Groups

丹麦多学科癌症小组

ER:

急诊室：

Estrogen receptor

雌激素受体

FISH :

鱼：

Fluorescence In Situ Hybridization

荧光原位杂交

HER2:

HER2：

Human Epidermal Growth Factor Receptor 2

人表皮生长因子受体2

HR :

人力资源部：

Hazard ratio

危险比

IQR :

IQR：

Interquartile range

四分位间距

OS :

操作系统：

Overall survival

总体生存率

Q1:

第一季度：

Quartile 1

四分位数1

RBGB:

RBGB：

Regional Bio- and Genome Bank Denmark

丹麦区域生物和基因组银行

RKKP :

RKKP：

The Danish Clinical Quality Program—National Clinical Registries

丹麦临床质量计划国家临床登记处

WHO :

谁：

World Health Organization

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Download referencesAcknowledgementsThis work was supported by the Novo Nordisk Foundation STENO Collaborative Grant (NNF20OC0065928), the NEYE Foundation, the Danish Cancer Society (R288-A16168 & R327-A19070), “Fagerlund Stiftelsen”, and the Department of Oncology Research Foundation.

下载参考文献致谢这项工作得到了诺和诺德基金会STENO合作基金（NNF20OC0065928），NEYE基金会，丹麦癌症协会（R288-A16168＆R327-A19070），“Fagerlund Stiftelsen”和肿瘤研究基金会的支持。

We would like to thank the BC surgery department at AUH for the collection of the blood samples. We would like to thank RBGB for the storage of the blood samples, and the Department of Clinical Biochemistry, AUH, for analyzing CRP levels. And last, but not least, we would like to thank Jan Alsner (PhD) for help with data management and statistical analyses.FundingThis work was supported by the Novo Nordisk Foundation STENO Collaborative Grant (NNF20OC0065928), the NEYE Foundation, the Danish Cancer Society (R288-A16168 & R327-A19070), “Fagerlund Stiftelsen”, and the Department of Oncology Research Foundation.Author informationAuthors and AffiliationsDepartment of Oncology, Aarhus University Hospital, Aarhus, DenmarkJ.

我们要感谢AUH的BC外科收集血液样本。我们要感谢RBGB保存血液样本，感谢AUH临床生物化学系分析CRP水平。最后，但并非最不重要的是，我们要感谢Jan Alsner（博士）在数据管理和统计分析方面的帮助。资助这项工作得到了诺和诺德基金会STENO合作基金（NNF20OC0065928），NEYE基金会，丹麦癌症协会（R288-A16168＆R327-A19070），“Fagerlund Stiftelsen”和肿瘤研究基金会的支持。作者信息作者和附属机构登马克奥胡斯奥胡斯大学医院肿瘤科。

B. Holm & S. BorgquistDepartment of Clinical Medicine, Aarhus University, Aarhus, DenmarkJ. B. Holm, E. Baggesen, D. Cronin-Fenton, J. M. Bruun, P. Christiansen & S. BorgquistDepartment of Clinical Epidemiology, Department of Clinical Medicine, Aarhus University Hospital, Aarhus, DenmarkD. Cronin-FentonDepartment of Endocrinology, Odense University Hospital, Odense, DenmarkJ.

B、 霍尔姆公司。奥尔胡斯大学临床医学系，奥尔胡斯，登马克。B、 霍姆，E。巴格森，D。克罗宁·芬顿，J。M、 布鲁恩，P。。登马克奥胡斯奥胡斯大学医院临床医学系BorgquistDepartment of Clinical Epidemiology，Aurhus University Hospital。克罗宁·芬顿（Cronin Fentondondepartment of Endocrinology，Odense University Hospital，Odense，DenmarkJ）。

FrystykSteno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, DenmarkJ. M. BruunDepartment of Plastic and Breast Surgery, Aarhus University Hospital, Aarhus, DenmarkP. ChristiansenAuthorsJ. B. HolmView author publicationsYou can also search for this author in.

登马克省奥胡斯市奥胡斯大学医院奥胡斯FrystykSteno糖尿病中心。M、 Brundepartment of Plastic and Breast Surgery，奥胡斯大学医院，奥胡斯，登马克，ChristiansenAuthorsJ。B、 HolmView作者出版物您也可以在中搜索此作者。

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PubMed Google ScholarContributionsStudy conception and design: J.B.H., D.C.F., J.M.B., P.C., and S.B. Data collection: J.B.H., E.B., P.C., and S.B. Data analysis: JBH supervised by D.C.F. and S.B. Interpretation of data: J.B.H., E.B., D.C.F., JMB, J.F., P.C., and S.B. (all authors).

PubMed谷歌学术贡献研究概念与设计：J.B.H.，D.C.F.，J.M.B.，P.C。和S.B.数据收集：J.B.H.，E.B.，P.C。和S.B.数据分析：JBH由D.C.F.和S.B.监督。数据解释：J.B.H.，E.B.，D.C.F.，JMB，J.F.，P.C。和S.B.（所有作者）。

Writing—original draft preparation: J.B.H. Writing—review: J.B.H., E.B., D.C.F., J.M.B., J.F., P.C., and S.B. (all authors). Writing—editing: JBH. All authors approved the final manuscript.Corresponding authorCorrespondence to.

写作原稿准备：J.B.H。写作评论：J.B.H.，E.B.，D.C.F.，J.M.B.，J.F.，P.C。和S.B.（所有作者）。写作编辑：JBH。所有作者都批准了最终稿件。对应作者对应。

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Reprints and permissionsAbout this articleCite this articleHolm, J.B., Baggesen, E., Cronin-Fenton, D. et al. Circulating C-reactive protein levels as a prognostic biomarker in breast cancer across body mass index groups.

转载和许可本文引用本文Holm，J.B.，Baggesen，E.，Cronin-Fenton，D。等人循环C反应蛋白水平作为体重指数组乳腺癌的预后生物标志物。

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KeywordsBreast cancerObesityBody mass indexInflammationC-reactive proteinPrognosis

关键词乳腺癌肥胖体质量指数炎症反应蛋白预后

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Breast cancerCancer epidemiologyPrognostic markers

乳腺癌流行病学预测标志物

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