title: Prognostic and predictive significance of MYC and KRAS alterations in breast cancer from women treated with neoadjuvant chemotherapy.
abstract: Breast cancer is a complex disease, with heterogeneous clinical evolution. Several analyses have been performed to identify the risk factors for breast cancer progression and the patients who respond best to a specific treatment. We aimed to evaluate whether the hormone receptor expression, HER2 and MYC genes and their protein status, and KRAS codon 12 mutations may be prognostic or predictive biomarkers of breast cancer. Protein, gene and mutation status were concomitantly evaluated in 116 breast tumors from women who underwent neoadjuvant chemotherapy with doxorubicin plus cyclophosphamide. We observed that MYC expression was associated with luminal B and HER2 overexpression phenotypes compared to luminal A (p<0.05). The presence of MYC duplication or polysomy 8, as well as KRAS mutation, were also associated with the HER2 overexpression subtype (p<0.05). MYC expression and MYC gain were more frequently observed in early-onset compared to late-onset tumors (p<0.05). KRAS mutation was a risk factor of grade 3 tumors (p<0.05). A multivariate logistic regression demonstrated that MYC amplification defined as MYC/nucleus ratio of ≥2.5 was a protective factor for chemotherapy resistance. On the other hand, age and grade 2 tumors were a risk factor. Additionally, luminal B, HER2 overexpression, and triple-negative tumors presented increased odds of being resistant to chemotherapy relative to luminal A tumors. Thus, breast tumors with KRAS codon 12 mutations seem to present a worse prognosis. Additionally, MYC amplification may help in the identification of tumors that are sensitive to doxorubicin plus cyclophosphamide treatment. If confirmed in a large set of samples, these markers may be useful for clinical stratification and prognosis.
authors.affiliation: Mastology Unit, Ophir Loyola Hospital, Belém, PA, Brazil.
authors.forename: Cynthia Brito Lins
authors.initials: CB
authors.lastname: Pereira
authors.forename: Mariana Ferreira
authors.initials: MF
authors.lastname: Leal
authors.forename: Carolina Rosal Teixeira
authors.initials: CR
authors.lastname: de Souza
authors.forename: Raquel Carvalho
authors.initials: RC
authors.lastname: Montenegro
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Rey
authors.forename: Antônio Alberto
authors.initials: AA
authors.lastname: Carvalho
authors.forename: Paulo Pimentel
authors.initials: PP
authors.lastname: Assumpção
authors.forename: André Salim
authors.initials: AS
authors.lastname: Khayat
authors.forename: Giovanny Rebouças
authors.initials: GR
authors.lastname: Pinto
authors.forename: Sâmia
authors.initials: S
authors.lastname: Demachki
authors.forename: Marília
authors.initials: M
authors.lastname: de Arruda Cardoso Smith
authors.forename: Rommel Rodríguez
authors.initials: RR
authors.lastname: Burbano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015331:Cohort Studies; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016259:Genes, myc; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D020360:Neoadjuvant Therapy; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D018631:ras Proteins / Q000235:genetics
chemical_list: D011518:Proto-Oncogene Proteins; D016271:Proto-Oncogene Proteins c-myc; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D018631:ras Proteins; C117307:KRAS protein, human
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