Trastuzumab-based chemotherapy modulates systemic redox homeostasis in women with HER2-positive breast cancer

Int Immunopharmacol. 2015 Jul;27(1):8-14. doi: 10.1016/j.intimp.2015.04.037. Epub 2015 Apr 28.

Abstract

Trastuzumab is an immunotargeting therapeutic against breast tumors with amplification of the human epithelial growth factor receptor 2 (HER2). HER2 patients naturally exhibit disruption in the pro-oxidant inflammatory profiling; however, the impact of trastuzumab-based chemotherapy in modulating this process is still unknown. Here we determined the systemic pro-inflammatory profile of women diagnosed with HER2-amplified tumors, undergoing trastuzumab-based chemotherapy (TZ), and compared the results with that of healthy controls (CTR) and untreated patients with HER2-amplified breast cancer (CA). The plasmatic inflammatory profile was assessed by evaluating pro-oxidant parameters such as lipid peroxidation, total antioxidant capacity (TRAP), levels of advanced oxidation protein products (AOPPs), nitric oxide (NO), C-reactive protein (CRP), and total thiol content. Markers of cardiac damage were also assessed. Our findings showed increased NO levels in TZ than that in either CA or CTR groups. Furthermore, TZ augmented TRAP and reduced total thiol than that of the CA group. Our data also revealed that AOPP levels were significantly higher in the TZ than the CA group. AOPP and the MB fraction of creatine-kinase (CKMB) levels were positively correlated in TZ patients. These findings suggest that trastuzumab-associated chemotherapy can modulate the pro-inflammatory markers of HER2-positive breast cancer patients to the levels found in healthy controls.

Keywords: Breast cancer; HER2; Inflammatory status; Oxidative stress; Trastuzumab.

MeSH terms

  • Adult
  • Aged
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / adverse effects
  • Breast Neoplasms / drug therapy*
  • C-Reactive Protein / metabolism
  • Carcinoma, Ductal / drug therapy*
  • Drug Therapy*
  • Female
  • Homeostasis / drug effects
  • Humans
  • Inflammation Mediators / metabolism
  • Lipid Peroxidation / drug effects
  • Middle Aged
  • Molecular Targeted Therapy
  • Neoplasm Staging
  • Nitric Oxide / metabolism
  • Oxidation-Reduction / drug effects
  • Receptor, ErbB-2 / metabolism
  • Sulfhydryl Compounds / metabolism
  • Trastuzumab / administration & dosage*
  • Trastuzumab / adverse effects

Substances

  • Antineoplastic Agents
  • Inflammation Mediators
  • Sulfhydryl Compounds
  • Nitric Oxide
  • C-Reactive Protein
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab