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Prognostic and Predictive Significance of MYC and KRAS Alterations in Breast Cancer from Women Treated with Neoadjuvant Chemotherapy

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...

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Autores principales: Pereira, Cynthia Brito Lins, Leal, Mariana Ferreira, de Souza, Carolina Rosal Teixeira, Montenegro, Raquel Carvalho, Rey, Juan Antonio, Carvalho, Antônio Alberto, Assumpção, Paulo Pimentel, Khayat, André Salim, Pinto, Giovanny Rebouças, Demachki, Sâmia, de Arruda Cardoso Smith, Marília, Burbano, Rommel Rodríguez
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608596/
https://www.ncbi.nlm.nih.gov/pubmed/23555992
http://dx.doi.org/10.1371/journal.pone.0060576
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author Pereira, Cynthia Brito Lins
Leal, Mariana Ferreira
de Souza, Carolina Rosal Teixeira
Montenegro, Raquel Carvalho
Rey, Juan Antonio
Carvalho, Antônio Alberto
Assumpção, Paulo Pimentel
Khayat, André Salim
Pinto, Giovanny Rebouças
Demachki, Sâmia
de Arruda Cardoso Smith, Marília
Burbano, Rommel Rodríguez
author_facet Pereira, Cynthia Brito Lins
Leal, Mariana Ferreira
de Souza, Carolina Rosal Teixeira
Montenegro, Raquel Carvalho
Rey, Juan Antonio
Carvalho, Antônio Alberto
Assumpção, Paulo Pimentel
Khayat, André Salim
Pinto, Giovanny Rebouças
Demachki, Sâmia
de Arruda Cardoso Smith, Marília
Burbano, Rommel Rodríguez
author_sort Pereira, Cynthia Brito Lins
collection PubMed
description 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.
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spelling pubmed-36085962013-04-03 Prognostic and Predictive Significance of MYC and KRAS Alterations in Breast Cancer from Women Treated with Neoadjuvant Chemotherapy Pereira, Cynthia Brito Lins Leal, Mariana Ferreira de Souza, Carolina Rosal Teixeira Montenegro, Raquel Carvalho Rey, Juan Antonio Carvalho, Antônio Alberto Assumpção, Paulo Pimentel Khayat, André Salim Pinto, Giovanny Rebouças Demachki, Sâmia de Arruda Cardoso Smith, Marília Burbano, Rommel Rodríguez PLoS One Research Article 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. Public Library of Science 2013-03-26 /pmc/articles/PMC3608596/ /pubmed/23555992 http://dx.doi.org/10.1371/journal.pone.0060576 Text en © 2013 Pereira et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Pereira, Cynthia Brito Lins
Leal, Mariana Ferreira
de Souza, Carolina Rosal Teixeira
Montenegro, Raquel Carvalho
Rey, Juan Antonio
Carvalho, Antônio Alberto
Assumpção, Paulo Pimentel
Khayat, André Salim
Pinto, Giovanny Rebouças
Demachki, Sâmia
de Arruda Cardoso Smith, Marília
Burbano, Rommel Rodríguez
Prognostic and Predictive Significance of MYC and KRAS Alterations in Breast Cancer from Women Treated with Neoadjuvant Chemotherapy
title Prognostic and Predictive Significance of MYC and KRAS Alterations in Breast Cancer from Women Treated with Neoadjuvant Chemotherapy
title_full Prognostic and Predictive Significance of MYC and KRAS Alterations in Breast Cancer from Women Treated with Neoadjuvant Chemotherapy
title_fullStr Prognostic and Predictive Significance of MYC and KRAS Alterations in Breast Cancer from Women Treated with Neoadjuvant Chemotherapy
title_full_unstemmed Prognostic and Predictive Significance of MYC and KRAS Alterations in Breast Cancer from Women Treated with Neoadjuvant Chemotherapy
title_short Prognostic and Predictive Significance of MYC and KRAS Alterations in Breast Cancer from Women Treated with Neoadjuvant Chemotherapy
title_sort prognostic and predictive significance of myc and kras alterations in breast cancer from women treated with neoadjuvant chemotherapy
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3608596/
https://www.ncbi.nlm.nih.gov/pubmed/23555992
http://dx.doi.org/10.1371/journal.pone.0060576
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