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

• 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
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0051379

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.