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.
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DOI：
10.1371/journal.pone.0060576
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Burbano RR
中科院分区：
文献类型：
--
作者：
Pereira CB;Leal MF;de Souza CR;Montenegro RC;Rey JA;Carvalho AA;Assumpção PP;Khayat AS;Pinto GR;Demachki S;de Arruda Cardoso Smith M;Burbano RR
乳腺癌是一种复杂的疾病，具有异质性的临床演变。已经进行了几项分析，以确定乳腺癌进展的危险因素，以及对特定治疗反应最好的患者。我们的目的是评估激素受体表达、HER2和MYC基因及其蛋白状态，以及KRAS密码子12突变是否可能是乳腺癌的预后或预测生物标志物。对接受阿霉素加环磷酰胺新辅助化疗的116例乳腺肿瘤患者的蛋白质、基因和突变情况进行了分析。我们观察到，与腔A相比，MYC的表达与腔B和HER2的过度表达表型相关(p<；0.05)。MYC重复或8多倍体的存在以及KRAS突变也与HER2过表达亚型相关(p<；0.05)。与晚发肿瘤相比，早发肿瘤的MYC表达和MYC增加更常见(p<；0.05)。KRAS突变是3级肿瘤的危险因素(p<；0.05)。多因素Logistic回归分析显示，以≥2.5的MYC/核比例定义的MYC扩增是化疗耐药的保护性因素。另一方面，年龄和2级肿瘤是一个危险因素。此外，与腔A肿瘤相比，腔B、HER2过表达和三阴性肿瘤表现出更高的化疗耐药几率。因此，具有KRAS密码子12突变的乳腺肿瘤似乎呈现出更差的预后。此外，MYC扩增可能有助于识别对阿霉素加环磷酰胺治疗敏感的肿瘤。如果在大量样本中得到证实，这些标记物可能对临床分层和预后有用。
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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影响因子：
3.3
作者：
Park, K;Kwak, K;Han, S
通讯作者：
Han, S
影响因子：
8
作者：
Neve, RM;Sutterlüty, H;Hynes, NE
通讯作者：
Hynes, NE
影响因子：
8.8
作者：
Deming SL;Nass SJ;Dickson RB;Trock BJ
通讯作者：
Trock BJ
影响因子：
9
作者：
Moon, Hyeong-Gon;Han, Wonshik;Noh, Dong-Young
通讯作者：
Noh, Dong-Young
影响因子：
1.9
作者：
Dechaphunkul A;Phukaoloun M;Kanjanapradit K;Graham K;Ghosh S;Santos C;Mackey JR
通讯作者：
Mackey JR