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根据雌激素受体和HER2状态，细胞角蛋白-19 mRNA阳性循环肿瘤细胞在早期乳腺癌中的不同预后价值。

Different prognostic value of cytokeratin-19 mRNA positive circulating tumor cells according to estrogen receptor and HER2 status in early-stage breast cancer.

作者信息

Ignatiadis Michail, Xenidis Nikos, Perraki Maria, Apostolaki Stella, Politaki Eleni, Kafousi Maria, Stathopoulos Efstathios N, Stathopoulou Aliki, Lianidou Evi, Chlouverakis Grigorios, Sotiriou Christos, Georgoulias Vassilis, Mavroudis Dimitris

机构信息

Department of Medical Oncology, University General Hospital of Heraklion, PO Box 1352, Heraklion 711 10, Crete, Greece.

出版信息

J Clin Oncol. 2007 Nov 20;25(33):5194-202. doi: 10.1200/JCO.2007.11.7762. Epub 2007 Oct 22.

DOI:10.1200/JCO.2007.11.7762

PMID:17954712

Abstract

PURPOSE

To examine the prognostic value of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in early-stage breast cancer patients focusing on clinically relevant subgroups based on estrogen receptor (ER) and HER2 expression.

PATIENTS AND METHODS

CK-19 mRNA-positive CTCs were detected by real-time reverse transcriptase polymerase chain reaction in the blood of 444 consecutive, stage I-III, breast cancer patients before initiation of adjuvant chemotherapy. The association between detection of CK-19 mRNA-positive CTCs and clinical outcome was analyzed for patients with ER-positive, ER-negative, triple-negative, HER2-positive, and ER-positive/HER2-negative tumors.

RESULTS

CK-19 mRNA-positive CTCs were detected in 181 (40.8%) of 444 patients; 109 (41.9%) of 260 patients with ER-positive tumors; 71 (40.6%) of 175 patients with ER-negative tumors; 27 (35%) of 77 patients with triple-negative tumors; 35 (39.8%) of 88 patients with HER2-positive tumors; and 82 (44.1%) of 186 patients with ER-positive/HER2-negative tumors. After a median follow-up of 53.5 months, patients with CK-19 mRNA-positive CTCs experienced reduced disease-free survival (DFS; P < .001) and overall survival (OS; P < .001); this was mainly observed in patients with ER-negative (P < .001 and P < .001, respectively) but not ER-positive tumors (P = .172 and P = .425, respectively) and in patients with triple-negative (P = .008 and P = .001, respectively) and HER2-positive (P = .023 and P = .040, respectively) but not ER-positive/HER2-negative tumors (P = .210 and P = .578, respectively). In multivariate analysis, the interaction between CK-19 mRNA-positive CTCs and ER status was the strongest independent prognostic factor for reduced DFS (hazard ratio [HR], 3.808; 95% CI, 2.415 to 6.003; P < .001) and OS (HR, 4.172; 95% CI, 2.477 to 9.161; P < .001).

CONCLUSION

Detection of CK-19 mRNA-positive CTCs before adjuvant chemotherapy predicts poor clinical outcome mainly in patients with ER-negative, triple-negative, and HER2-positive early-stage breast cancer.

摘要

目的

基于雌激素受体（ER）和HER2表达，研究细胞角蛋白19（CK-19）mRNA阳性循环肿瘤细胞（CTC）在早期乳腺癌患者中的预后价值，重点关注临床相关亚组。

患者与方法

采用实时逆转录聚合酶链反应检测444例连续的Ⅰ-Ⅲ期乳腺癌患者在辅助化疗开始前血液中的CK-19 mRNA阳性CTC。分析ER阳性、ER阴性、三阴性、HER2阳性以及ER阳性/HER2阴性肿瘤患者中CK-19 mRNA阳性CTC检测与临床结局之间的关联。

结果

444例患者中有181例（40.8%）检测到CK-19 mRNA阳性CTC；260例ER阳性肿瘤患者中有109例（41.9%）；175例ER阴性肿瘤患者中有71例（40.6%）；77例三阴性肿瘤患者中有27例（35%）；88例HER2阳性肿瘤患者中有35例（39.8%）；186例ER阳性/HER2阴性肿瘤患者中有82例（44.1%）。中位随访53.5个月后，CK-19 mRNA阳性CTC患者的无病生存期（DFS；P <.001）和总生存期（OS；P <.001）缩短；这主要在ER阴性患者中观察到（分别为P <.001和P <.001），而在ER阳性肿瘤患者中未观察到（分别为P =.172和P =.425），在三阴性患者中（分别为P =.008和P =.001）以及HER2阳性患者中（分别为P =.023和P =.040）观察到，而在ER阳性/HER2阴性肿瘤患者中未观察到（分别为P =.210和P =.578）。多因素分析中，CK-19 mRNA阳性CTC与ER状态之间的相互作用是DFS降低（风险比[HR]，3.808；95%可信区间[CI]，2.415至6.003；P <.001）和OS降低（HR，4.172；95%CI，2.477至9.161；P <.001）的最强独立预后因素。