Chronic Inflammation and Breast Cancer Recurrence

Division of Hematology-Oncology, Department of Medicine
Journal of Clinical Oncology (Impact Factor: 18.43). 06/2009; 27(21):3418-9. DOI: 10.1200/JCO.2009.21.9782
Source: PubMed
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    • "Previous evidence has indicated that inflammation within the tumor microenvironment may play an important role in breast cancer progression [15]. Most previous studies have reported an association of high levels of circulating proinflammatory cytokines with poor prognosis in breast cancer [1,3]. "
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    ABSTRACT: Inflammation within the tumor microenvironment has been reported to show an association with poor prognosis in breast cancer. However, the associations may differ according to breast cancer subtype. In this study, we investigated the association between inflammation-related markers and breast cancer recurrence according to patients' tumor subtypes. This prospective study included 240 patients who underwent surgery for management of newly diagnosed breast cancer. Levels of inflammation-related markers (interleukin [IL]-1β, IL-6, IL-8, monocyte chemoattractant protein-1 [MCP-1], leptin, and adiponectin) were measured at diagnosis, and the associations between these markers and breast cancer recurrence during a six-year follow-up period were examined using the Kaplan-Meier statistical method. Overall, inflammation-related markers showed no association with breast cancer recurrence. However, when data were stratified by tumor subtype, higher levels of some mediators showed an association with poor prognosis among patients with particular subtypes. Compared to patients without recurrence, patients with recurrence had higher levels of circulating IL-6 (p=0.024) and IL-8 (p=0.016) only among those with HER2(-) tumors and had higher levels of leptin (p=0.034) only among those with estrogen receptor (ER)(+)/progesterone receptor (PR)(+) tumors. Results of survival analyses revealed an association of high levels of IL-6 (p=0.016) and IL-8 (p=0.022) with poor recurrence-free survival in patients with HER2(-) tumors. In addition, higher leptin levels indicated shorter recurrence-free survival time only among patients with ER(+)/PR(+) tumors (p=0.022). We found that certain cytokines could have a differential prognostic impact on breast cancer recurrence according to breast cancer subtype. Conduct of additional large studies will be required in order to elucidate the precise roles of these cytokines in breast cancer progression.
    Cancer Research and Treatment 09/2013; 45(3):210-9. DOI:10.4143/crt.2013.45.3.210 · 3.32 Impact Factor
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    • "An inflammatory tumor microenvironment consists of infiltrating immune cells and activated fibroblasts, both of which can secrete cytokines, chemokines, and growth factors, as well as DNA-damaging agents 11. Some studies show evidence that chronic inflammation is linked to breast cancer recurrence and that elevated biomarkers of inflammation are associated with reduced survival among breast cancer patients 12, 13. In addition, experimental studies clearly indicate that inflammatory mediators promote tumor development in cancer prone animal strains 14. "
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    ABSTRACT: Tumor necrosis factor-alpha (TNF-α) is a proinflammatory cytokine that has been linked to breast cancer development. Estrogen metabolic pathway is also involved in breast carcinogenesis and DNA adducts formation. In this study we investigated the effect of TNF-α on the estrogen metabolic pathway in MCF-7, a breast cancer cell line. Capillary liquid chromatography/mass spectrometry (LC/MS) and High performance liquid chromatography (HPLC) were used for analysis of estrogen metabolites and estrogen-DNA adducts levels respectively. Reporter gene assay, Real time reverse transcription polymerase chain reaction (real time RT-PCR) and Western blot were used to assess the expression of estrogen metabolizing genes and enzymes. TNF-α significantly increased the total EM and decreased the estrone (E1) / 17-β estradiol (E2) ratio. Moreover, it altered the expression of genes and enzymes involved in E2 activation and deactivation pathways e.g. Cytochrome P-450 1A1 (CYP1A1), Cytochrome P-450 1B1 (CYP1B1), Catechol-O-methyl transferase (COMT) and Nicotinamide adenine dinucleotide phosphate-quinone oxidoreductase 1 (NQO1). In addition, there were increased levels of some catechol estrogens e.g. 4-hydroxy-estrone (4-OHE1) and 2-hydroxyestradiol (2-OHE2) with decreased levels of methylated catechols e.g. 2-methoxy estradiol (2-MeOE2). DNA adducts especially 4-OHE1-[2]-1-N3 Adenine was significantly increased. TNF-α directs the estrogen metabolism into more hormonally active and carcinogenic products in MCF-7. This may implicate a new possible explanation for inflammation associated breast cancer.
    Journal of Cancer 07/2012; 3(1):310-21. DOI:10.7150/jca.4584 · 3.27 Impact Factor
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    • "Indeed, epidemiological studies have shown that chronic inflammation predisposes individuals to various types of cancer including breast cancer, and underlying inflammatory responses are linked to 15–20% of all deaths from cancer worldwide (Mantovani et al., 2008). In addition, chronic inflammation is reported to be associated with recurrence of breast cancer (Cole, 2009). Moreover, cancer treatments are potential inducers of inflammation. "
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    ABSTRACT: Over two-thirds of the 11.4 million cancer survivors in the United States can expect long-term survival, with many others living with cancer as a chronic disease controlled by ongoing therapy. However, behavioral co-morbidities often arise during treatment and persist long-term to complicate survival and reduce quality of life. In this review, the inter-relationships between cancer, depression, and sleep disturbance are described, with a focus on the role of sleep disturbance as a risk factor for depression. Increasing evidence also links alterations in inflammatory biology dynamics to these long-term effects of cancer diagnosis and treatment, and the hypothesis that sleep disturbance drives inflammation, which together contribute to depression, is discussed. Better understanding of the associations between inflammation and behavioral co-morbidities has the potential to refine prediction of risk and development of strategies for the prevention and treatment of sleep disturbance and depression in cancer survivors.
    Brain Behavior and Immunity 05/2012; 30. DOI:10.1016/j.bbi.2012.05.002 · 5.89 Impact Factor
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