Response of circulating tumor cells to systemic therapy in patients with metastatic breast cancer: comparison of quantitative polymerase chain reaction and immunocytochemical techniques.
OBJECTIVE
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 marrow. The aim of this study was to determine the value of this system in monitoring patients with metastatic disease and to compare it with an established immunocytochemical method.


METHODS
Patients with progressive, locally advanced, and metastatic breast cancer (all stage IV) who were due to start systemic treatment were recruited. Blood samples were analyzed for CK-19 transcripts using quantitative PCR (QPCR) and immunocytochemistry (ICC) throughout their course of treatment.


RESULTS
One hundred forty-five blood samples were obtained from 22 patients over 13 months. Seventy-two (49.6%) of these samples were positive by QPCR, 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 71 samples that were positive, 40 (56%) were positive by both methods. The relationship between the number of cells detected and the QPCR values was statistically significant (P <.0001). Of the 25 courses of assessable treatment, 17 (68%) of 25 treatment outcomes (either response or disease progression) were reflected by QPCR measurements, and 12 (57%) of 21 were reflected by ICC. During the course of the study, five patients showed a response, and of these, ICC was in agreement in four cases (80%) and QPCR in three cases (60%). Eighteen courses of treatment resulted in progression of the disease; 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.


CONCLUSIONS
Circulating carcinoma cells are frequently found in patients with metastatic breast cancer. In the majority of patients, cancer cell numbers as evaluated by QPCR or ICC reflected the outcome of systemic treatment.
Smith
B M
BM
Cancer Research Campaign Laboratories, Division of Cancer Cell Biology, and Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, UK.
Slade
M J
MJ
English
J
J
Graham
H
H
Lüchtenborg
M
M
Sinnett
H D
HD
Cross
N C
NC
Coombes
R C
RC
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D009360:Neoplastic Cells, Circulating / Q000276:immunology*; D011237:Predictive Value of Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity