Cynthia Brito Lins Pereira1, Mariana Ferreira Leal2, Eliana Saul Furquim Werneck Abdelhay3, Sâmia Demachki4, Paulo Pimentel Assumpção4, Mirian Carvalho de Souza3, Caroline Aquino Moreira-Nunes5, Adriana Michiko da Silva Tanaka6, Marília Cardoso Smith7, Rommel Rodríguez Burbano8. 1. 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. 2. 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. 3. Divisão de Epidemiologia, Instituto Nacional de Câncer, Rio de Janeiro, Brazil. 4. Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil. 5. Departamento de Fisiologia e Farmacologia, Universidade Federal do Ceará, Fortaleza, Brazil. 6. Clínica de Radiologia Lobo, Belém, Brazil. 7. Disciplina de Genética, Departamento de Morfologia e Genética, Universidade Federal de São Paulo, São Paulo, Brazil. 8. Núcleo de Pesquisas em Oncologia, Universidade Federal do Pará, Belém, Brazil; Laboratório de Biologia Molecular, Hospital Ophir Loyola, Belém, Brazil.
Abstract
BACKGROUND: 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. MATERIAL AND METHODS: 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. RESULTS: 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. CONCLUSION: The analysis of MYC amplification may help in the identification of patients that may have a better response to AC+T treatment.
BACKGROUND: 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. MATERIAL AND METHODS: 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 taxanedocetaxel (T) neoadjuvant chemotherapy (AC+T regimen) in 51 patients with invasive ductal breast cancer. RESULTS: 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. CONCLUSION: The analysis of MYC amplification may help in the identification of patients that may have a better response to AC+T treatment.
Authors: Julia Rohrberg; Daniel Van de Mark; Meelad Amouzgar; Joyce V Lee; Moufida Taileb; Alexandra Corella; Seda Kilinc; Jeremy Williams; Marie-Lena Jokisch; Roman Camarda; Sanjeev Balakrishnan; Rama Shankar; Alicia Zhou; Aaron N Chang; Bin Chen; Hope S Rugo; Sophie Dumont; Andrei Goga Journal: Cell Rep Date: 2020-03-10 Impact factor: 9.423
Authors: Edina Wang; Anabel Sorolla; Paula T Cunningham; Heique M Bogdawa; Samuel Beck; Emily Golden; Robert E Dewhurst; Laura Florez; Mark N Cruickshank; Katrin Hoffmann; Richard M Hopkins; Jonghwan Kim; Andrew J Woo; Paul M Watt; Pilar Blancafort Journal: Oncogene Date: 2018-08-03 Impact factor: 9.867
Authors: Francianne Silva Rocha; Jersey Heitor da Silva Maués; Cynthia Mara Brito Lins Pereira; Caroline Aquino Moreira-Nunes; Rommel Mário Rodriguez Burbano Journal: Breast Cancer (Dove Med Press) Date: 2021-05-21