Breast Cancer Research and Treatment

, Volume 133, Issue 3, pp 881–888 | Cite as

Differential oxidative status and immune characterization of the early and advanced stages of human breast cancer

  • C. Panis
  • V. J. Victorino
  • A. C. S. A. Herrera
  • L. F. Freitas
  • T. De Rossi
  • F. C. Campos
  • A. N. Colado Simão
  • D. S. Barbosa
  • P. Pinge-Filho
  • R. Cecchini
  • A. L. Cecchini
Preclinical Study


Breast cancer is the malignant neoplasia with the highest incidence in women worldwide. Chronic oxidative stress and inflammation have been indicated as major mediators during carcinogenesis and cancer progression. Human studies have not considered the complexity of tumor biology during the stages of cancer advance, limiting their clinical application. The purpose of this study was to characterize systemic oxidative stress and immune response parameters in early (ED; TNM I and II) and advanced disease (AD; TNM III and IV) of patients diagnosed with infiltrative ductal carcinoma breast cancer. Oxidative stress parameters were evaluated by plasmatic lipoperoxidation, carbonyl content, thiobarbituric reactive substances (TBARS), nitric oxide levels (NO), total radical antioxidant parameter (TRAP), superoxide dismutase, and catalase activities and GSH levels. Immune evaluation was determined by TNF-α, IL-1β, IL-12, and IL-10 levels and leukocytes oxidative burst evaluation by chemiluminescence. Tissue damage analysis included heart (total CK and CKMB), liver (AST, ALT, GGT), and renal (creatinine, urea, and uric acid) plasmatic markers. C-reactive protein (CRP) and iron metabolism were also evaluated. Analysis of the results verified different oxidative stress statuses occur at distinct cancer stages. ED was characterized by reduction in catalase, 8-isoprostanes, and GSH levels, with enhanced lipid peroxidation and TBARS levels. AD exhibited more pronounced oxidative status, with reduction in catalase activity and TRAP, intense lipid peroxidation and high levels of NO, TBARs, and carbonyl content. ED patients presented a Th2 immune pattern, while AD exhibited Th1 status. CRP levels and ferritin were increased in both stages of disease. Leukocytes burst impairment was observed in both the groups. Plasma iron levels were significantly elevated in AD. The data obtained indicated that oxidative stress enhancement and immune response impairment may be necessary to ensure cancer progression to advanced stages and may result from both host and tumor inflammatory mediators.


Breast cancer Immune response status Oxidative stress Inflammation 



Advanced breast cancer patients


Early disease breast cancer patients


Tumor node metastasis classification


Superoxide dismutase


Reduced glutathione


Trichloric acetic acid


Total antioxidant capacity




Relative light unities


Nitric oxide


Thiobarbituric reactive substances






Area under the curve


Low density lipoprotein




Tumor necrosis factor alpha


Estrogen receptors


Progesterone receptors


Human epidermal growth factor receptor




Reduced glutathione


Aspartate aminotransferase


Alanine aminotransferase


Gamma glutamyl transpeptidase


Creatine kinase


Creatine kinase MB fraction


Uric acid levels


Interleukin 1


Interleukin 6


Interleukin 12


Interleukin 10



The authors are grateful to Jesus Vargas for his exceptional technical assistance and the Fundação Araucária, CNPq and CAPES for providing financial support.

Conflict of interest

The authors declare there are no conflicts of interest.


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Copyright information

© Springer Science+Business Media, LLC. 2011

Authors and Affiliations

  • C. Panis
    • 1
  • V. J. Victorino
    • 1
  • A. C. S. A. Herrera
    • 1
  • L. F. Freitas
    • 1
  • T. De Rossi
    • 1
  • F. C. Campos
    • 1
  • A. N. Colado Simão
    • 2
  • D. S. Barbosa
    • 2
  • P. Pinge-Filho
    • 3
  • R. Cecchini
    • 1
  • A. L. Cecchini
    • 1
  1. 1.Laboratório de Patologia e Radicais Livres, Departamento de Patologia Geral—Centro de Ciências BiológicasUniversidade Estadual de LondrinaLondrinaBrazil
  2. 2.Hospital Universitario, Departamento de FarmaciaUniversidade Estadual de LondrinaLondrinaBrazil
  3. 3.Laboratório de Imunopatologia, Departamento de Patologia Geral—Centro de Ciências BiológicasUniversidade Estadual de LondrinaLondrinaBrazil

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