title: MYC Amplification as a Predictive Factor of Complete Pathologic Response to Docetaxel-based Neoadjuvant Chemotherapy for Breast Cancer.
abstract: Neoadjuvant chemotherapy is a standard treatment for stage II and III breast cancer. The identification of biomarkers that may help in the prediction of response to neoadjuvant therapies is necessary for a more precise definition of the best drug or drug combination to induce a better response.
  
  
  
  We assessed the role of Ki67, hormone receptors expression, HER2, MYC genes and their protein status, and KRAS codon 12 mutations as predictor factors of pathologic response to anthracycline-cyclophosphamide (AC) followed by taxane docetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer.
  
  
  
  After neoadjuvant chemotherapy, 82.4% of patients showed pathologic partial response, with only 9.8% showing pathologic complete response. In multivariate analysis, MYC immunoreactivity and high MYC gain defined as MYC/nucleus ≥ 5 were significant predictor factors for pathologic partial response. Using the receiver operating characteristic curve analysis, the ratio of 2.5 MYC/CEP8 (sensitivity of 80% and specificity of 89.1%) or 7 MYC/nuclei copies (sensitivity of 80% and specificity of 73.9%) as the best cutoff in predicting a pathologic complete response was identified. Thus, MYC may have a role in chemosensitivity to AC and/or docetaxel drugs. Additionally, MYC amplification may be a predictor factor of pathologic response to the AC+T regimen in patients with breast cancer. Moreover, patients with an increased number of MYC copies showed pathologic complete response to this neoadjuvant treatment more frequently.
  
  
  
  The analysis of MYC amplification may help in the identification of patients that may have a better response to AC+T treatment.
authors.affiliation: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil; Divisão de Epidemiologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil; Laboratório de Biologia Molecular, Hospital Ophir Loyola, Belém, Brazil.
authors.forename: Cynthia Brito Lins
authors.initials: CBL
authors.lastname: Pereira
authors.affiliation: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil; Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, Brazil; Departamento de Ortopedia e Traumatologia, Universidade Federal de São Paulo, São Paulo, Brazil. Electronic address: mariana.morf@epm.br.
authors.forename: Mariana Ferreira
authors.initials: MF
authors.lastname: Leal
authors.affiliation: Divisão de Epidemiologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Eliana Saul Furquim Werneck
authors.initials: ESFW
authors.lastname: Abdelhay
authors.affiliation: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil.
authors.forename: Sâmia
authors.initials: S
authors.lastname: Demachki
authors.affiliation: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil.
authors.forename: Paulo Pimentel
authors.initials: PP
authors.lastname: Assumpção
authors.affiliation: Divisão de Epidemiologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil.
authors.forename: Mirian Carvalho
authors.initials: MC
authors.lastname: de Souza
authors.affiliation: Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, Brazil.
authors.forename: Caroline Aquino
authors.initials: CA
authors.lastname: Moreira-Nunes
authors.affiliation: Clínica de Radiologia Lobo, Belém, Brazil.
authors.forename: Adriana Michiko da Silva
authors.initials: AMDS
authors.lastname: Tanaka
authors.affiliation: Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, Brazil.
authors.forename: Marília Cardoso
authors.initials: MC
authors.lastname: Smith
authors.affiliation: Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil; Laboratório de Biologia Molecular, Hospital Ophir Loyola, Belém, Brazil.
authors.forename: Rommel Rodríguez
authors.initials: RR
authors.lastname: Burbano
mesh_terms: D000328:Adult; D018943:Anthracyclines / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D003520:Cyclophosphamide / Q000008:administration & dosage; D000077143:Docetaxel; D005260:Female; D005500:Follow-Up Studies; D005784:Gene Amplification; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D011379:Prognosis; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D015996:Survival Rate; D043823:Taxoids / Q000008:administration & dosage
chemical_list: D018943:Anthracyclines; D014408:Biomarkers, Tumor; D003520:Cyclophosphamide; D000077143:Docetaxel; D016271:Proto-Oncogene Proteins c-myc; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D043823:Taxoids; C489427:MYC protein, human; C508053:ERBB2 protein, human
keywords: Breast cancer; Chemotherapy; Gene amplification; MYC; Pathologic response