Multiple biomarker expression on circulating tumor cells in comparison to tumor tissues from primary and metastatic sites in patients with locally advanced/inflammatory, and stage IV breast cancer, using a novel detection technology.
Multiple biomarker expression on circulating tumor cells in comparison to tumor tissues from primary and metastatic sites in patients with locally advanced/inflammatory, and stage IV breast cancer, using a novel detection technology.
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DOI：
10.1007/s10549-011-1508-0
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发表时间：
2011-07
影响因子：
3.8
通讯作者：
Bruce, Richard H.
中科院分区：
文献类型：
--
作者：
Somlo, George;Lau, Sean K.;Frankel, Paul;Ben Hsieh, H.;Liu, Xiaohe;Yang, Lixin;Krivacic, Robert;Bruce, Richard H.
局部晚期/炎性乳腺癌 (LABC/IBC) 患者复发的可能性很高，复发或初发 IV 期转移性乳腺癌 (MBC) 的预后仍然较差。原发性乳腺癌或 MBC 上的雌激素 (ER) 和 HER2 受体表达允许进行靶向治疗，但估计 10-18% 的肿瘤不表现出这些生物标志物，这些病例的生存率甚至更差。已经观察到原发性肿瘤和转移性肿瘤之间 ER 和 HER2 受体表达的不一致率存在差异，这种不一致可能导致治疗效果不佳。循环肿瘤细胞（CTC）被认为是残留疾病和远处转移的种子，其特征可以帮助指导治疗选择。为了探索这种可能性，我们使用多种生物标志物评估 CTC 并与原发性和转移性肿瘤部位进行比较。对 36 名 LABC/IBC 或 IV 期 MBC 患者进行了评估。在开始或改变治疗之前采集血样。根据细胞角蛋白和细胞核染色的存在以及 CD45 的不存在来鉴定 CTC。开发了一种多标记测定法来同时定量 HER2、ER 和 ERCC1（一种 DNA 切除修复蛋白）的表达。新型光纤阵列扫描技术（FAST）用于 CTC 的敏感定位。 82% 的 MBC 病例和 62% 的 LABC/IBC 病例中检测到了 CTC。在 18 名 MBC 患者和 8 名含有 CTC 的 LABC/IBC 患者的样本中成功进行了多重标记表达。在 MBC 中，我们检测到 ER 和 HER2 的可操作不一致率分别为 40% 和 23%，其中生物标志物在原发性或转移性肿瘤中呈阴性，而在 CTC 中呈阳性。在 LABC/IBC 中，ER 和 HER2 的可操作不一致分别为 60% 和 20%。根据 CTC 和原发性或转移性肿瘤部位生物标志物表达模式之间可操作的不一致来评估治疗选择有效性的试点试验可能有助于对基于 CTC 的个体化靶向治疗进行前瞻性评估。
Patients with locally advanced/inflammatory breast cancer (LABC/IBC) face a high likelyhood of recurrence and prognosis for relapsed, or de novo stage IV metastatic breast cancer (MBC) remains poor. Estrogen (ER) and HER2 receptor expression on primary or MBC allow targeted therapies, but an estimated 10–18% of tumors do not exhibit these biomarkers and survival in these cases is even poorer. Variations in discordance rates for the expression of ER and HER2 receptors have been observed between primary and metastatic tumors and such discordances may lead to suboptimal treatment. Circulating tumor cells (CTCs) are considered the seeds of residual disease and distant metastases and their characterization could help guide treatment selection. To explore this possibility, we used multiple biomarker assessment of CTCs in comparison to primary and metastatic tumor sites. Thirty-six patients with LABC/IBC, or stage IV MBC were evaluated. Blood samples were procured prior to initiating or changing therapy. CTCs were identified based on presence of cytokeratin and nucleus staining, and the absence of CD45. A multimarker assay was developed to simultaneously quantify expression of HER2, ER, and ERCC1, a DNA excision repair protein. Novel fiber-optic array scanning technology (FAST) was used for sensitive location of CTCs. CTCs were detected in 82% of MBC and 62% LABC/IBC cases. Multiplex marker expression was successfully carried out in samples from18 patients with MBC and in 8 patients with LABC/IBC that contained CTCs. In MBC, we detected actionable discordance rates of 40 and 23%, respectively for ER and HER2 where a biomarker was negative in the primary or metastatic tumor and positive in the CTCs. In LABC/IBC, actionable discordances were 60 and 20% for ER and HER2, respectively. Pilot trials evaluating the effectiveness of treatment selections based on actionable discordances between biomarker expression patterns on CTCs and primary or metastatic tumor sites may allow for a prospective assessment of CTC-based individualized targeted therapies.
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影响因子：
158.5
作者：
Cristofanilli, M;Budd, GT;Hayes, DF
通讯作者：
Hayes, DF
影响因子：
11.5
作者：
Hayes, Daniel F.;Cristofanilli, Massimo;Terstappen, Leon W. W. M.
通讯作者：
Terstappen, Leon W. W. M.
DOI：
10.1186/bcr2131
发表时间：
2008
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Deng G;Herrler M;Burgess D;Manna E;Krag D;Burke JF
通讯作者：
Burke JF
DOI：
10.1073/pnas.0404036101
发表时间：
2004-07-20
影响因子：
11.1
作者：
Krivacic, RT;Ladanyi, A;Bruce, RH
通讯作者：
Bruce, RH
影响因子：
50.5
作者：
Nole, F.;Munzone, E.;Sandri, M. T.
通讯作者：
Sandri, M. T.