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

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

Author Lins Pereira, Cynthia Brito Google Scholar
Leal, Mariana Ferreira Autor UNIFESP Google Scholar
Souza, Carolina Rosal Teixeira de Google Scholar
Montenegro, Raquel Carvalho Google Scholar
Rey, Juan Antonio Google Scholar
Carvalho, Antonio Alberto Google Scholar
Assumpcao, Paulo Pimentel Google Scholar
Khayat, Andre Salim Google Scholar
Pinto, Giovanny Reboucas Google Scholar
Demachki, Samia Google Scholar
Cardoso Smith, Marilia de Arruda Autor UNIFESP Google Scholar
Burbano, Rommel Rodriguez Google Scholar
Institution Ophir Loyola Hosp
Universidade Federal de São Paulo (UNIFESP)
Fed Univ Para
Hosp Univ La Paz
Univ Fed Piaui
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.
Language English
Sponsor Fundacao Amazonia Paraense de Amparo a Pesquisa
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number Fundacao Amazonia Paraense de Amparo a Pesquisa: FAPESPA/PPSUS 247/2009
Fundacao Amazonia Paraense de Amparo a Pesquisa: 300240/2009
Date 2013-03-26
Published in Plos One. San Francisco: Public Library Science, v. 8, n. 3, 9 p., 2013.
ISSN 1932-6203 (Sherpa/Romeo, impact factor)
Publisher Public Library Science
Extent 9
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000317418500140

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