Trastuzumab-based chemotherapy modulates systemic redox homeostasis in women with HER2-positive breast cancer.
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.
Bone Marrow Transplantation Center, National Cancer Institute, INCA, Rio de Janeiro, Brazil.
L G T
LG
Lemos
Faculty of Medicine, University of São Paulo, USP, São Paulo, Brazil.
V J
VJ
Victorino
Bone Marrow Transplantation Center, National Cancer Institute, INCA, Rio de Janeiro, Brazil.
A C S A
AC
Herrera
Laboratory of Physiopathology and Free Radicals, Londrina State University, UEL, Londrina, Paraná, Brazil.
A M F
AM
Aranome
Laboratory of Physiopathology and Free Radicals, Londrina State University, UEL, Londrina, Paraná, Brazil.
A L
AL
Cecchini
Universitary Hospital, Department of Pharmacy, State University of Londrina, Londrina, Paraná, Brazil.
A N C
AN
Simão
Laboratory of Inflammatory Mediators, State University of West Paraná, UNIOESTE, Francisco Beltrão, Paraná, Brazil. Electronic address: carolpanis@sercomtel.com.br.
C
C
Panis
Laboratory of Physiopathology and Free Radicals, Londrina State University, UEL, Londrina, Paraná, Brazil.
R
R
Cecchini
D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001943:Breast Neoplasms / Q000188:drug therapy*; D002097:C-Reactive Protein / Q000378:metabolism; D044584:Carcinoma, Ductal / Q000188:drug therapy*; D004358:Drug Therapy; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008875:Middle Aged; D058990:Molecular Targeted Therapy; D009367:Neoplasm Staging; D009569:Nitric Oxide / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism; D000068878:Trastuzumab / Q000008:administration & dosage* / Q000009:adverse effects
D000970:Antineoplastic Agents; D002097:C-Reactive Protein; D018836:Inflammation Mediators; D009569:Nitric Oxide; D018719:Erb-b2 Receptor Tyrosine Kinases; D013438:Sulfhydryl Compounds; D000068878:Trastuzumab; C508053:ERBB2 protein, human
Breast cancer; HER2; Inflammatory status; Oxidative stress; Trastuzumab