The role of Circulating Tumor Cells (CTCs) in Predicting the Response of Primary (Neoadjuvant)Chemotherapy and its Impact as a Prognostic Factor in Early Breast Cancer

Background: The enumeration of circulating tumor cells (CTCs) has long been regarded as an attractive diagnostic tool of malignancy, as these cells are thought to reflect aggressiveness of the tumor and may assist in therapeutic decisions in patients with solid malignancies. Primary or neoadjuvant chemotherapy (NACT) which was a standard of care in patients with inoperable locally advanced or inflammatory breast cancer, is now may be considered for patients with early breast cancer. Even though at early stages tumors are clinically restricted to loco- regional tissue, there is often early dissemination of viable tumor cells. One of the purposes of systemic NACT is to attack these circulating tumor cells. This fact has potentiated the interest in the use of NACT
Aim of the study: to detect and measure the count of CTCs in the blood of patients before starting “baseline CTCs count” and after finishing neoadjuvant chemotherapy “post-treatment CTCs count” for early (non- metastatic) breast cancer patients. In addition to determine the correlation between baseline CTCs count with relapse rate, other prognostic factors, disease free survival (DFS) and overall survival (OS).
Patients and methods: Forty patients with confirmed early non-MBC at South Egypt Cancer Institute were recruited to participate in this study with treatment protocols. All patients received three to four cycles of NACT either with AC (adriamycin and cyclophosphamide); FAC (fluorouracil, doxorubicin and cyclophosphamide) or FEC (fluorouracil, epirubicin and cyclophosphamide). CTCs count was measured using flowcytometry in all patients before starting treatment and in only 25 patients after the end of therapy. The study approved by the local ethics committee.
Results: There was statistically significant difference between baseline and post-treatment CTCs counts (P<0.003). Also, there was statistically significant difference between primary tumor size before and after NACT (p=0.001). Pathological complete response (pCR) rate was 55%. The mean baseline and post-treatment CTCs counts were significantly higher in patients who did not achieve pCR than in patients who achieved pCR (P=0.001 and 0.003 respectively). Patients were divided according to baseline CTCs count into 2 prognostic groups: the first group included patients with low CTCs count (Conclusion: CTCs count in breast cancer patients before starting neoadjuvant chemotherapy could predict response to neoadjuvant chemotherapy. High CTCs count is associated with an increased risk of disease recurrence or relapse and shortened DFS and OS. We should consider detection on a large scale and more standardization of the methodology.