The relevance of circulating epithelial tumor cells (CETC) for therapy monitoring during neoadjuvant (primary systemic) chemotherapy in breast cancer

Abstract

Background: Having demonstrated in a previous report that the response of circulating epithelial tumor cells (CETC) during the first cycles of primary (neoadjuvant) chemotherapy perfectly reflects the response of the tumor, in the present study the changes in cell numbers during subsequent cycles and their possible impact on the therapy's outcome were examined. Patients and methods:In 58 breast cancer patients CETC were quantified during therapy with either EC (epirubicin/ cyclophosphamid) or dose intensified E (epirubicin) followed by taxane, with or without trastuzumab, and subsequent CMF (cyclophosphamid/methorexate/ fluorouracil).Results: CETC numbers declined more than 10-fold (good response) in 65% (her2/neu-negative) and 55% (her2/neu-positive) of patients during EC, and in 60% during dose intensified E, respectively, followed by an increase of CETC in all patients. CETC remained increased, decreasing only when adding CMF. A good initial response correlated with estrogen-receptor negativity, a poor response with early distant relapse (P < 0,0001, hazard ratio = 11.91). Conclusion:Response of CETC already during the first cycles of neoadjuvant treatment predicts the final response of the tumor. Hitherto unknown effects of the release of tumor cells during therapy further our understanding of tumor-blood interaction and may improve access of agents like antibodies to cells. The impact on the further course of disease remains to be evaluated.

Prognostic value of circulating tumor cells in advanced gastric cancer patients receiving chemotherapy

“…In 29 patients who were tested for CTCs before and after the first cycle of chemotherapy, multivariate analysis suggested that CTC count increase is an independent poor prognostic marker only for PFS (hazard ratio = 6.58, 95% confidence interval: 1.37-31.6, P=0.019) (Table IV). Our results may be partly consistent with the reports from Matsushita et al and other researchers (5,(27)(28)(29)(30). On the contrary, other studies considered changes in CTC count during the course of chemotherapy to not be predictive of clinical outcome or response to therapy (31,32).…”

Detection of circulating tumor Cells in the context of treatment: Prognostic value in breast cancer patients

“…This seems to be particularly important in neoadjuvant therapy, where CTCs reflects the final response to tumor, already from early cycles. 13 that mutations in the p53 gene in primary breast carcinoma are not essential for hematogenous dissemination of cancer cells. These cells, deficient of p53, are susceptible of accumulating mutations and show a more resistant phenotype.…”

“…11 Furthermore, recent studies have demonstrated the potential of CTCs detection as an indicator of therapeutic success in patients with metastatic breast cancer. [12][13][14] The aim of this study was to assess the role of CTCs in peripheral blood of breast cancer patients as a proxy for tumor recurrence and patient survival. We set out a trial to explore the presence of CTCs during and after chemotherapy.…”

Behavior of circulating epithelial tumor cells (CETC) and FISH (fluorescence &lt;i&gt;in situ&lt;/i&gt; hybridisation) of epidermal growth factor receptor (EGFR)-gene amplification in lung cancer patients during the course of therapy

“…It had been shown already in previous analyses in lung [14] and breast cancer patients [15] that increasing cell numbers after surgery are correlated with a higher risk of relapse, that patients with a good initial response to neoadjuvant treatment have improved relapse free survival [27], as well as that a stable number of CETCs can be detected without disease recurrence even after several years [8].…”