title: Evaluation of changes in serum protein profiles during neoadjuvant chemotherapy in HER2-positive breast cancer using an LC-MALDI-TOF/MS procedure.
abstract: Comparison of protein profiles of sera acquired before and after preoperative chemotherapy for breast cancer may reveal tumor markers that could be used to monitor tumor response. In this study, we analyzed pre- and post-chemotherapy protein profiles of sera from 39 HER2-postive breast cancer patients (n=78 samples) who received 6 months of preoperative chemotherapy using LC-MALDI-TOF/MS technology. We detected qualitative and quantitative differences in pair-wise comparison of pre- and post chemotherapy samples that were different in patients who achieved pathological complete response (pCR, n=21) compared with those with residual disease (n=18). We identified 2329 and 3152 peaks as differentially expressed in the pre-chemotherapy samples of the responders and non-responders. Comparison of matching pre- and post-chemotherapy samples identified 34 (32 decreased, two increased) and 304 peaks (157 decreased, 147 increased) that significantly changed (p<0.01, false discovery rate ≤ 20%) after treatment in responders and non-responders, respectively. The top 11 most significantly altered peptide peaks with the greatest change in intensity were positively identified. These corresponded to eight proteins including α-2-macroglobulin, complement 3, hemopexin, and serum amyloid P in the responder group and chains C and A of apolipoprotein A-I, hemopexin precursor, complement C, and amyloid P component in the non-responding groups. All proteins decreased after therapy, except chain C apolipoprotein A and hemopexin precursor that increased. These results suggest that changes in serum protein levels occur in response to chemotherapy and these changes partly appear different in patients who are highly sensitive to chemotherapy compared with those with lesser response.
authors.affiliation: Laboratoire de Transfert Biologique et Oncologique, Marseille University France. chafika.mazouni@igr.fr
authors.forename: Chafika
authors.initials: C
authors.lastname: Mazouni
authors.forename: Keith
authors.initials: K
authors.lastname: Baggerly
authors.forename: David
authors.initials: D
authors.lastname: Hawke
authors.forename: Spyros
authors.initials: S
authors.lastname: Tsavachidis
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.forename: Aman U
authors.initials: AU
authors.lastname: Buzdar
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Martin
authors.forename: Ryuji
authors.initials: R
authors.lastname: Kobayashi
authors.forename: Lajos
authors.initials: L
authors.lastname: Pusztai
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood; D001798:Blood Proteins / Q000378:metabolism*; D001943:Breast Neoplasms / Q000097:blood* / Q000378:metabolism / Q000628:therapy*; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D001798:Blood Proteins; D018719:Erb-b2 Receptor Tyrosine Kinases