Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma
Divergent effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple negative invasive ductal breast carcinoma
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DOI：
10.1007/s10549-010-1256-6
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发表时间：
2011-10-01
影响因子：
3.8
通讯作者：
Wesseling, Jelle
中科院分区：
文献类型：
--
作者：
Hartog, Hermien;Horlings, Hugo M.;Wesseling, Jelle
胰岛素样生长因子1型受体（IGF 1 R）参与乳腺癌的进展和对全身治疗的抵抗。因此，靶向IGF 1 R信号传导可能有益于全身治疗。我们报告了IGF 1 R表达对浸润性导管乳腺癌（IDC）预后的影响，浸润性导管乳腺癌是最常见的乳腺癌类型。对429例接受可手术原发性IDC治疗的女性患者的肿瘤组织进行免疫组化。IGF 1 R表达与临床病理参数、无病生存期（DFS）和乳腺癌特异性生存期（BCSS）之间的关系通过关注ER阳性和三阴性IDC（TN-IDC）的多变量分析进行评估。为了扩大TN-IDC队列，我们分析了来自我们的系列的51个TN-IDC肿瘤与64个具有相似临床病理参数的TN-IDC的组合数据集。肿瘤表达胞浆IGF 1 R的患者的DFS和BCSS较长（DFS：HR 0.46，95% CI 0.27-0.49，P = 0.005; BCSS：HR 0.38，95% CI 0.19-0.74，P = 0.005）。这种效应在ER阳性肿瘤中最为突出。然而，在105例TN-IDC的联合系列中，细胞质IGF 1 R表达与较短的DFS相关（HR = 2.29，95% CI 1.08-4.84，P = 0.03），在多变量模型中也是如此，包括众所周知的预后因素（HR 2.06; 95% CI 0.95-4.47; P = 0.07）。ER阳性IDC中IGF 1 R表达与良好的DFS和BCSS密切相关，但与TN-IDC肿瘤中较短的DFS密切相关。IDC亚组中IGF 1 R表达的这种差异效应可能会影响IGF 1 R靶向治疗患者的选择。
The insulin-like growth factor type 1 receptor (IGF1R) is involved in progression of breast cancer and resistance to systemic treatment. Targeting IGF1R signaling may, therefore, be beneficial in systemic treatment. We report the effect of IGF1R expression on prognosis in invasive ductal breast carcinoma (IDC), the most common type of breast cancer. Immunohistochemistry was performed on tumor tissue of a consecutive cohort of 429 female patients treated for operable primary IDC. Associations between IGF1R expression with clinicopathological parameters, disease free survival (DFS) and breast cancer specific survival (BCSS) were evaluated by multivariate analyses focusing on ER-positive and triple negative IDC (TN-IDC). To enlarge the TN-IDCs cohort, we analyzed a combined dataset of 51 TN-IDC tumors from our series with 64 TN-IDCs with similar clinicopathological parameters. Patients with tumors expressing cytoplasmic IGF1R have a longer DFS and BCSS (DFS: HR 0.46, 95% CI 0.27-0.49, P = 0.005, BCSS: HR 0.38, 95% CI 0.19-0.74, P = 0.005). This effect was most prominent in ER-positive tumors. However, in a combined series of 105 TN-IDCs cytoplasmic IGF1R expression was associated with a shorter DFS (HR = 2.29, 95% CI 1.08-4.84, P = 0.03), also when combined in a multivariate model, including well-known prognostic factors (HR 2.06; 95% CI 0.95-4.47; P = 0.07). IGF1R expression in ER-positive IDC is strongly related to a favorable DFS and BCSS, but to a shorter DFS in TN-IDC tumors. This divergent effect of IGF1R expression in subgroups of IDC may affect selection of patients for IGF1R targeted therapy.