title: Elevation in inflammatory serum biomarkers predicts response to trastuzumab-containing therapy.
abstract: 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.
authors.affiliation: Department of Neurosurgery, The Pennsylvania State University Hershey Medical Center, Hershey, PA, USA.
authors.forename: Ahmed A
authors.initials: AA
authors.lastname: Alkhateeb
authors.forename: Kim
authors.initials: K
authors.lastname: Leitzel
authors.forename: Suhail M
authors.initials: SM
authors.lastname: Ali
authors.forename: Cynthia
authors.initials: C
authors.lastname: Campbell-Baird
authors.forename: Matthew
authors.initials: M
authors.lastname: Evans
authors.forename: Eva-Maria
authors.initials: EM
authors.lastname: Fuchs
authors.forename: Wolfgang J
authors.initials: WJ
authors.lastname: Köstler
authors.forename: Allan
authors.initials: A
authors.lastname: Lipton
authors.forename: James
authors.initials: J
authors.lastname: Connor
mesh_terms: D061067:Antibodies, Monoclonal, Humanized / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood*; D001943:Breast Neoplasms / Q000097:blood / Q000188:drug therapy / Q000401:mortality*; D002097:C-Reactive Protein / Q000378:metabolism; D018450:Disease Progression; D018572:Disease-Free Survival; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005293:Ferritins / Q000097:blood*; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000175:diagnosis / Q000209:etiology; D018836:Inflammation Mediators / Q000097:blood*; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000276:immunology; D015996:Survival Rate; D000068878:Trastuzumab
chemical_list: D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D015415:Biomarkers; D002097:C-Reactive Protein; D005293:Ferritins; D018836:Inflammation Mediators; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab