Purpose
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.
Patients and Methods
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.
Results
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).
Conclusion
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