Monitoring cytokeratin19 (KRT19) levels as response of circulating tumor cells (CTC) to neoadjuvant chemotherapy (NAC) in breast cancer (BC).

Abstract

Abstract Abstract #5022 Background: KRT19 mRNA+ cells before the initiation of adjuvant chemotherapy has been shown as an independent prognostic factor for disease recurrence in patients with early BC. Its usefulness for monitoring response to NAC it is not clear. We have studied changes in KRT19 levels during NAC and correlated it with response. Material and Methods: We analyzed a prospective series of 70 BC patients treated with NAQ. Stage II (45%), Stage III (55%), HR negative (43%), HER-2 positive (42%). Treatment was based on sequential anthracyclines and taxanes. Trastuzumab was given concomitant in HER2 disease. KRT19 level expression was measured from lymphocytes of peripheral blood using a quantitative RT-PCR. The analysis was performed at diagnosis (baseline), before taxane administration, at the end of NAC, and after surgery. On the other hand, 27 healthy donors and 18 metastasic BC patients were also analyzed in order to determine a cut-off value for CTC positivity according to receiver operating characteristics [ROC] analysis. Association between variables was performed by Pearson's Chi-squared and Fisher's tests. Results: We observed a differential rate in KRT19 expression, between the control and the metastasic series being higher in the last group (U-Mann-Withney test, p=0.010). According to the selected cut-off value (AUC 0.272; p=0.010), we detected CTC in 46/70 (65.7%) patients at baseline, 22/40 (55%) prior to taxane administration, 36/50 (72%) at the end of NAC and 13/17 (76.5%) after surgery.Forty out of 57 patients (70.2%) responded to NAC(15 CR and 25 PR). Decreased in CTCs levels during treatment wasn't associated with response, on the contrary, residual CTCs were detected after surgery in all those cases that responded (p=0.005). The presence of CTCs after completion of chemotherapy, previous to surgery, was inversely related to tumor stage (p=0.012). Negative tumors for HER2 and tumors with high levels of ER expression maintain the CTC levels detected at diagnosis (p=0.044 and p=0.057 respectively). DISCUSSION: We weren't able to find a correlation between response and decrease in CTCs levels. The presence of residual CTCs in responding cases could suggest a release of tumor cells into blood by NAQ and surgery The prognostic factor of residual CTCs needs to be addressed with longer follow up, and taking into account the effect of others therapies. This study is financed by the grant GVA07/130. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 5022.