Pereira Cynthia Brito Lins, Leal Mariana Ferreira, Abdelhay Eliana Saul Furquim Werneck, Demachki Sâmia, Assumpção Paulo Pimentel, de Souza Mirian Carvalho, Moreira-Nunes Caroline Aquino, Tanaka Adriana Michiko da Silva, Smith Marília Cardoso, Burbano Rommel Rodríguez
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.
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.
Clin Breast Cancer. 2017 Jun;17(3):188-194. doi: 10.1016/j.clbc.2016.12.005. Epub 2016 Dec 24.
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.
新辅助化疗是II期和III期乳腺癌的标准治疗方法。确定可能有助于预测新辅助治疗反应的生物标志物，对于更精确地定义能诱导更好反应的最佳药物或药物组合至关重要。
我们评估了51例浸润性导管癌患者中，Ki67、激素受体表达、HER2、MYC基因及其蛋白状态，以及KRAS密码子12突变作为蒽环类药物-环磷酰胺（AC）序贯紫杉类多西他赛（T）新辅助化疗（AC+T方案）病理反应预测因素的作用。
新辅助化疗后，82.4%的患者显示病理部分缓解，仅9.8%的患者显示病理完全缓解。在多变量分析中，MYC免疫反应性和定义为MYC/细胞核≥5的高MYC扩增是病理部分缓解的显著预测因素。通过受试者工作特征曲线分析，确定2.5 MYC/CEP8比值（敏感性80%，特异性89.1%）或7个MYC/细胞核拷贝数（敏感性80%，特异性73.9%）作为预测病理完全缓解的最佳临界值。因此，MYC可能在对AC和/或多西他赛药物的化疗敏感性中发挥作用。此外，MYC扩增可能是乳腺癌患者对AC+T方案病理反应的预测因素。而且，MYC拷贝数增加的患者对这种新辅助治疗更频繁地显示病理完全缓解。
MYC扩增分析可能有助于识别对AC+T治疗反应较好的患者。
