Cytokeratin-19 mRNA-Positive Circulating Tumor Cells After Adjuvant Chemotherapy in Patients With Early Breast Cancer

• Published in: Journal of clinical oncology Vol. 27; no. 13; pp. 2177 - 2184
• Main Authors: XENIDIS, Nikolaos, IGNATIADIS, Michail, GEORGOULIAS, Vassilis, MAVROUDIS, Dimitris, APOSTOLAKI, Stella, PERRAKI, Maria, KALBAKIS, Kostas, AGELAKI, Sofia, STATHOPOULOS, Efstathios N, CHLOUVERAKIS, Grigorios, LIANIDOU, Evi, KAKOLYRIS, Stylianos
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 01-05-2009
• Subjects: Adult; Aged; Biological and medical sciences; Breast Neoplasms - drug therapy; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Chemotherapy, Adjuvant; Disease-Free Survival; Female; Gynecology. Andrology. Obstetrics; Humans; Keratin-19 - genetics; Mammary gland diseases; Medical sciences; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Neoplastic Cells, Circulating - metabolism; RNA, Messenger - analysis; Tumors; Human; Breast disease; Adjuvant treatment; Breast cancer; Cytokeratin 19; Tumoral marker; Malignant tumor; Mammary gland diseases; Chemotherapy; Treatment; Cancerology; Messenger RNA; Early; Tumor cell; Cancer
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2008.18.0497

To evaluate the prognostic significance of cytokeratin-19 (CK-19) mRNA-positive circulating tumor cells (CTCs) in peripheral blood of women with early-stage breast cancer after the completion of adjuvant chemotherapy.
Blood was obtained from 437 patients with early breast cancer before the start and after the completion of adjuvant chemotherapy, and the presence of CK-19 mRNA-positive CTCs was assessed by real-time reverse transcriptase polymerase chain reaction. Interaction with known prognostic factors and association of CTCs with clinical outcome were investigated.
CK-19 mRNA-positive CTCs were detected before chemotherapy in 179 patients (41.0%). After adjuvant chemotherapy, a significant change in CK-19 status was observed, as status for 51% of patients with initially CK-19 mRNA-positive disease turned negative, and status for 22% of patients with initially CK-19 mRNA-negative disease became positive (McNemar test P = .004). The detection of CK-19 mRNA-positive CTCs postchemotherapy was associated with involvement of more than three axillary lymph nodes (P = .026). Clinical relapses and disease-related deaths were significantly increased in patients with detectable postchemotherapy CK-19 mRNA-positive CTCs (both P < .001, respectively). Disease-free and overall survival were significantly reduced in patients with detectable CK-19 mRNA-positive CTCs postchemotherapy (P < .001 and P = .001, respectively). In multivariate analysis, the detection of CK-19 mRNA-positive CTCs before and after adjuvant chemotherapy was an independent factor associated with reduced disease-free survival (P < .001) and overall survival (P = .003).
The detection of CK-19 mRNA-positive CTCs in the blood after adjuvant chemotherapy is an independent risk factor indicating the presence of chemotherapy-resistant residual disease.