Response of circulating tumor cells to systemic therapy in patients with metastatic breast cancer: Comparison of quantitative polymerase chain reaction and immunocytochemical techniques

Purpose: We previously developed a quantitative system for the detection of cytokeratin 19 (CK-19) transcripts using reverse transcriptase polymerase chain reaction (PCR) to detect breast carcinoma cells in blood and bone mar row. The aim of this study war to determine the value of this system in mon itoring patients with metastatic disease and to compare it with an establis hed immunocytochemical method, Patients and Methods: Patients with progressive, locally advanced, and meta static breast cancer (all stage IV) who were due to start systemic treatmen t were recruited. Blood samples were analyzed for CK-19 transcripts using q uantitative PCR (QPCR) and immunocytochemistry (ICC) throughout their cours e of treatment. Results: One hundred forty-five blood samples were obtained from 22 patient s over 13 months. Seventy-two (49.6%) of there samples were positive by QPC R, and 56 (42%) of 133 were positive by ICC. Of the 133 specimens analyzed by both techniques, 95 (71.4%) had the same results for each, and of the II samples that were positive, 40 (56%) were positive by both methods. The re lationship between the number of cells detected and the QPCR values was sta tistically significant (P < .0001). Of the 15 courses of assessable treatme nt, 17 (68%) of 15 treatment outcomes (either response or disease progressi on) were reflected by QPCR measurements, and 12 (57%) of 21 were reflected by ICC, During the course of the study, five patients showed ct response, a nd of these, IGC was in agreement in four cases (80%) and QPCR in three car es (60%). Eighteen courses of treatment resulted in progression of the dise ase; however, only 15 of these were assessable by ICC, ICC was in agreement in eight (53%) of 15 of; these cases, and QPCR in 15 (83%) of 18 cases. Conclusion: Circulating carcinoma cells are frequently found in patients wi th metastatic breast cancer. In the majority of patients, cancer cell numbe rs or evaluated by QPCR or ICC reflected the outcome of systemic treatment. (C) 2000 by American Society of Clinical Oncology.