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全身炎症对早期乳腺癌复发的影响。

Effects of systemic inflammation on relapse in early breast cancer.

作者信息

McAndrew Nicholas P, Bottalico Lisa, Mesaros Clementina, Blair Ian A, Tsao Patricia Y, Rosado Jennifer M, Ganguly Tapan, Song Sarah J, Gimotty Phyllis A, Mao Jun J, DeMichele Angela

机构信息

Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, 19104, USA.

Division of Hematology/Oncology, Department of Medicine, University of Pennsylvania, Philadelphia, PA, 19104, USA.

出版信息

NPJ Breast Cancer. 2021 Jan 22;7(1):7. doi: 10.1038/s41523-020-00212-6.

DOI:10.1038/s41523-020-00212-6
PMID:33483516
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7822844/
Abstract

Chronic inflammation has been a proposed mechanism of resistance to aromatase inhibitors in breast cancer. Stratifying by HER2 status, a matched case-control study from the Wellness After Breast Cancer-II cohort was performed to assess whether or not elevated serum inflammatory biomarkers (C-Reactive protein [CRP], interleukin-6 [IL-6], and serum amyloid A [SAA]) and/or the presence of a high-risk IL-6 promoter genotype were associated with recurrence of hormone receptor positive (HR+) early breast cancer. Estrogen levels were also measured and correlated with biomarkers and disease outcomes. CRP and SAA were significantly associated with an increased risk of recurrence in the HR+/HER2- group, but not the HR+/HER2+ group. Mean serum estrogen levels were non-significantly elevated in patients who relapsed vs. non-relapsed patients. Surprisingly, high-risk IL-6 promoter polymorphisms were strongly associated with HER2+ breast cancer relapse, which has potential therapeutic implications, as elevated intracellular IL-6 has been associated with trastuzumab resistance in pre-clinical models.

摘要

慢性炎症被认为是乳腺癌对芳香化酶抑制剂产生耐药性的一种机制。根据HER2状态进行分层，对乳腺癌-II期队列研究中“乳腺癌后健康状况”的一项匹配病例对照研究进行了分析，以评估血清炎症生物标志物（C反应蛋白[CRP]、白细胞介素-6[IL-6]和血清淀粉样蛋白A[SAA]）升高和/或高危IL-6启动子基因型的存在是否与激素受体阳性（HR+）早期乳腺癌的复发相关。还测量了雌激素水平，并将其与生物标志物和疾病结局进行关联分析。CRP和SAA与HR+/HER2-组复发风险增加显著相关，但与HR+/HER2+组无关。复发患者与未复发患者相比，血清雌激素平均水平虽有升高但无统计学意义。令人惊讶的是，高危IL-6启动子多态性与HER2+乳腺癌复发密切相关，这具有潜在的治疗意义，因为在临床前模型中，细胞内IL-6升高与曲妥珠单抗耐药相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b50/7822844/ab9e8c6d6bbb/41523_2020_212_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b50/7822844/3fa72e101489/41523_2020_212_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b50/7822844/4d19613a0c04/41523_2020_212_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b50/7822844/56df2e2589c0/41523_2020_212_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b50/7822844/1977623e71eb/41523_2020_212_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b50/7822844/ab9e8c6d6bbb/41523_2020_212_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b50/7822844/3fa72e101489/41523_2020_212_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b50/7822844/4d19613a0c04/41523_2020_212_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b50/7822844/56df2e2589c0/41523_2020_212_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b50/7822844/1977623e71eb/41523_2020_212_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8b50/7822844/ab9e8c6d6bbb/41523_2020_212_Fig5_HTML.jpg

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