Different Prognostic Value of Cytokeratin-19 mRNA–Positive Circulating Tumor Cells According to Estrogen Receptor and HER2 Status in Early-Stage Breast Cancer

• Published in: Journal of clinical oncology Vol. 25; no. 33; pp. 5194 - 5202
• Main Authors: IGNATIADIS, Michail, XENIDIS, Nikos, SOTIRIOU, Christos, GEORGOULIAS, Vassilis, MAVROUDIS, Dimitris, PERRAKI, Maria, APOSTOLAKI, Stella, POLITAKI, Eleni, KAFOUSI, Maria, STATHOPOULOS, Efstathios N, STATHOPOULOU, Aliki, LIANIDOU, Evi, CHLOUVERAKIS, Grigorios
• Format: Journal Article
• Language: English
• Published: Baltimore, MD American Society of Clinical Oncology 20.11.2007; Lippincott Williams & Wilkins
• Subjects: Adult; Aged; Biological and medical sciences; Breast Neoplasms - chemistry; Breast Neoplasms - metabolism; Breast Neoplasms - mortality; Breast Neoplasms - pathology; Female; Gynecology. Andrology. Obstetrics; Humans; Keratin-19 - genetics; Mammary gland diseases; Medical sciences; Middle Aged; Multivariate Analysis; Neoplasm Staging; Neoplastic Cells, Circulating - metabolism; Prognosis; Receptor, ErbB-2 - analysis; Receptors, Estrogen - analysis; RNA, Messenger - analysis; Tumors; Estrogen receptor; Prognosis; erbB2 Gene; Early stage; Breast cancer; Cytokeratin 19; Tumoral marker; Malignant tumor; Human Epidermal growth factor Receptor 2; Mammary gland diseases; Cancerology; Messenger RNA; C-Onc gene; Tumor cell; Protooncogene; Cancer; Hormonal receptor
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2007.11.7762

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. 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. 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). 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.