title: Gene expression profile of residual breast cancer after doxorubicin and cyclophosphamide neoadjuvant chemotherapy.
abstract: In breast cancer patients, primary chemotherapy is associated with the same survival benefits as adjuvant chemotherapy. Residual tumors represent a clinical challenge, as they may be resistant to additional cycles of the same drugs. Our aim was to identify differential transcripts expressed in residual tumors, after neoadjuvant chemotherapy, that might be related with tumor resistance. Hence, 16 patients with paired tumor samples, collected before and after treatment (4 cycles doxorubicin/cyclophosphamide, AC) had their gene expression evaluated on cDNA microarray slides containing 4,608 genes. Three hundred and eighty-nine genes were differentially expressed (paired Student's t-test, pFDR<0.01) between pre- and post-chemotherapy samples and among the regulated functions were the JNK cascade and cell death. Unsupervised hierarchical clustering identified one branch comprising exclusively, eight pre-chemotherapy samples and another branch, including the former correspondent eight post-chemotherapy samples and other 16 paired pre/post-chemotherapy samples. No differences in clinical and tumor parameters could explain this clustering. Another group of 11 patients with paired samples had expression of selected genes determined by real-time RT-PCR and CTGF and DUSP1 were confirmed more expressed in post- as compared to pre-chemotherapy samples. After neoadjuvant chemotherapy some residual samples may retain their molecular signature while others present significant changes in their gene expression, probably induced by the treatment. CTGF and DUSP1 overexpression in residual samples may be a reflection of resistance to further administration of AC regimen.
authors.affiliation: Faculdade de Medicina da Universidade de São Paulo, Departamento de Radiologia, Disciplina de Oncologia, São Paulo, SP, Brasil. makoike@lim24.fm.usp.br
authors.forename: Maria Aparecida Azevedo
authors.initials: MA
authors.lastname: Koike Folgueira
authors.forename: Helena
authors.initials: H
authors.lastname: Brentani
authors.forename: Dirce Maria
authors.initials: DM
authors.lastname: Carraro
authors.forename: Mateus
authors.initials: M
authors.lastname: De Camargo Barros Filho
authors.forename: Maria Lucia
authors.initials: ML
authors.lastname: Hirata Katayama
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Santana de Abreu
authors.forename: Edson
authors.initials: E
authors.lastname: Mantovani Barbosa
authors.forename: Célia Tosello
authors.initials: CT
authors.lastname: De Oliveira
authors.forename: Diogo F C
authors.initials: DF
authors.lastname: Patrão
authors.forename: Louise D
authors.initials: LD
authors.lastname: Mota
authors.forename: Mario Mourão
authors.initials: MM
authors.lastname: Netto
authors.forename: José Roberto Figaro
authors.initials: JR
authors.lastname: Caldeira
authors.forename: Maria Mitzi
authors.initials: MM
authors.lastname: Brentani
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D055513:Connective Tissue Growth Factor / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D003520:Cyclophosphamide / Q000008:administration & dosage; D004317:Doxorubicin / Q000008:administration & dosage; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D054638:Dual Specificity Phosphatase 1 / Q000096:biosynthesis / Q000187:drug effects / Q000235:genetics; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D006801:Humans; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D018365:Neoplasm, Residual; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; C526317:CCN2 protein, human; D055513:Connective Tissue Growth Factor; D004317:Doxorubicin; D003520:Cyclophosphamide; D048670:MAP Kinase Kinase 4; C517019:DUSP1 protein, human; D054638:Dual Specificity Phosphatase 1