Dynamics of circulating tumor cells in early breast cancer under neoadjuvant therapy

Abstract

At present, the majority of patients with breast cancer are diagnosed at early stages of disease development. However, a considerable number of such cases develop secondary malignancies after a relatively short period of time. The presence of circulating tumor cells (CTCs) has been proposed as a strong biomarker to predict disease recurrence in metastatic breast cancer. However, the prognostic significance is not clear in early breast cancer. We present results on CTC determination in peripheral blood in non-metastatic breast cancer patients in the context of neoadjuvant treatment. Twenty-six breast cancer patients, scheduled for neoadjuvant therapy, were enrolled in a prospective study, of which 24 were able to complete therapy. CTC assessment was performed by sorting out cytokeratin-positive cells from 10 ml of peripheral blood using immunomagnetic separation, followed by immunocytochemical characterization of cells. Seventeen blood samples out of 24 patients were CTC-positive when collected prior to neoadjuvant chemotherapy. No significant correlations were found between the presence of CTCs and lymph node status (p=0.1), histological type (p=0.802), stage (p=0.43) or overall survival (OS) (p=0.599). Thirteen CTC-positive samples were observed in blood samples collected after treatment. Univariate analyses revealed that the presence of CTCs was related to OS when the detection was positive both before and after treatment (p=0.023). CTCs can be a strong prognostic marker in early breast cancer. The persistence of CTCs before and after treatment can identify a subpopulation of patients with an increased risk of recurrence.

Figure 1.

Circulating tumor cell detected in a breast cancer patient after neoadjuvant therapy.

Figure 2.

Association between persistence of circulating tumor cells (CTCs) and mortality in breast cancer patients with neoadjuvant therapy. Grey, number of patients that are alive and exhibiting CTCs; Black, number of patients deceased and exhibiting CTCs. (A) No. of patients in basal status with CTCs. (B) No. of patients after treatment with CTCs. (C) No. of patients with CTCs prior to and after treatment.

Figure 3.

Kaplan-Meier analysis of the overall survival in connection with the detection of CK⁺ cells showing that only patients with the persistence of CK⁺ cells in peripheral blood were associated with short survival.