Effect of Trastuzumab and Chemotherapy on Circulating Tumor Cells in Patients with Poor Prognosis Metastatic Breast Cancer.

Abstract

Abstract Background. Trastuzumab has significant activity in HER2 neu amplified metastatic breast cancer (MBC). We hypothesized that it may selectively act against circulating tumor cells (CTC) in HER2-positiveMBC. We assessed the effect of trastuzumab-based regimens on CTC in HER2-positive MBC with poor prognosis (≥ 5 CTC).Patients and Methods. We retrospectively evaluated patients with poor prognosis MBC (baseline ≥ 5 CTC) treated with a first-line regimen consisting of trastuzumab+antimitotic agents in 11 HER2-positive patients not previously pretreated with trastuzumab, chemotherapy with antimitotic agents in 24 HER2-normal patients, and other chemotherapeutic drugs (mainly capecitabine) in other 16 HER2-normal patients. CTC were detected and enumerated using the CellSearch system (Veridex LLC, Warren NJ, USA). We evaluated the effect on CTC counts and on progression-free survival (PFS) and overall survival (OS).Results. At a median follow-up of 16 months (range, 4 to 48), 24 patients (47%) died. All 11 HER2-positive patients treated with trastuzumab+antimitotic agents had <5 CTC during the treatment. Only 16 (67%) with HER2-normal MBC had <5 CTC with antimitotic agents (p = 0.037), and 28 (70%) with other chemotherapeutic regimens (p = 0.048). No statistically significant difference was observed between patients treated with antimitotic agents and those treated with other chemotherapeutic agents (p = 0.73). There was no difference between patients receiving polychemotherapy and monochemotherapy (p = 0.73). The median PFS was 12 months in HER2-positive patients treated with trastuzumab+antimitotic agents compared with 7 months for those with HER2-normal (p = 0.09). The median OS was not reached (>20 months) and 19 months (p = 0.034), respectively. The median PFS was 8 months in HER2-normal patients with ≥5 CTC and 4 months in those with <5 CTC (p = 0.01). The median OS was not reached (>17 months) and 9 months (p = 0.01), respectively.Conclusions. Trastuzumab is highly effective in patients with HER2-positive MBC with poor prognosis (≥ 5 CTC). Antimitotic agents and other chemotherapy agents did not show a similar effect in HER2-normal MBC. CTC might be useful in the monitoring of poor prognosis MBC patients undergoing therapy with trastuzumab. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 3014.