Elevation in inflammatory serum biomarkers predicts response to trastuzumab-containing therapy

Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy. Therefore, there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response. Recently, several lines of evidence have demons...

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Bibliographic Details
Published in:PloS one 2012-12, Vol.7 (12), p.e51379-e51379
Main Authors: Alkhateeb, Ahmed A, Leitzel, Kim, Ali, Suhail M, Campbell-Baird, Cynthia, Evans, Matthew, Fuchs, Eva-Maria, Köstler, Wolfgang J, Lipton, Allan, Connor, James
Format: Article
Language:English
Subjects:
Anti-inflammatory agents
Antibodies, Monoclonal, Humanized - therapeutic use
Antineoplastic Agents - therapeutic use
Biological markers
Biomarkers
Biomarkers - blood
Breast cancer
Breast Neoplasms - blood
Breast Neoplasms - drug therapy
Breast Neoplasms - mortality
C-reactive protein
C-Reactive Protein - metabolism
Cancer
Cancer therapies
Cancer treatment
Chemotherapy
Disease Progression
Disease-Free Survival
Drug dosages
Drugs
Enzyme-Linked Immunosorbent Assay
ErbB-2 protein
Female
Ferritin
Ferritins - blood
Health aspects
Hematology
Humans
Immunotherapy
Inflammation
Inflammation - blood
Inflammation - diagnosis
Inflammation - etiology
Inflammation Mediators - blood
Medicine
Metastasis
Middle Aged
Monoclonal antibodies
Multivariate analysis
Neurosurgery
Oncology
Patients
Proteins
Receptor, ErbB-2 - antagonists & inhibitors
Receptor, ErbB-2 - immunology
Studies
Survival
Survival Rate
Targeted cancer therapy
Therapy
Trastuzumab
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Summary:Approximately half of all HER2/neu-overexpressing breast cancer patients do not respond to trastuzumab-containing therapy. Therefore, there remains an urgent and unmet clinical need for the development of predictive biomarkers for trastuzumab response. Recently, several lines of evidence have demonstrated that the inflammatory tumor microenvironment is a major contributor to therapy resistance in breast cancer. In order to explore the predictive value of inflammation in breast cancer patients, we measured the inflammatory biomarkers serum ferritin and C-reactive protein (CRP) in 66 patients immediately before undergoing trastuzumab-containing therapy and evaluated their progression-free and overall survival. The elevation in pre-treatment serum ferritin (>250 ng/ml) or CRP (>7.25 mg/l) was a significant predictor of reduced progression-free survival and shorter overall survival. When patients were stratified based on their serum ferritin and CRP levels, patients with elevation in both inflammatory biomarkers had a markedly poorer response to trastuzumab-containing therapy. Therefore, the elevation in inflammatory serum biomarkers may reflect a pathological state that decreases the clinical efficacy of this therapy. Anti-inflammatory drugs and life-style changes to decrease inflammation in cancer patients should be explored as possible strategies to sensitize patients to anti-cancer therapeutics.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0051379