38P Evolution of Estrogen Receptor (ER) and ErbB2 Expression Between Primary Tumor and Circulating Tumor Cells (CTC) of Metastatic Breast Cancer Patients

Several trials have shown the prognostic relevance of circulating tumor cells (CTC) in early and metastatic breast cancers. CTC, and consequently the metastatic cells, may have a very different receptor status than the related primary tumors. Nonetheless hormone therapy and anti-ErbB2 therapy are prescribed according to the hormone status (ER/PR protein expression) and ErbB2 expression of the initial tumor. Consequently, it is of the highest relevance to analyze ER and ErbB2 expression in the CTC. We tested the CTC presence (CK positivity) and ER and ErbB2 expressions on blood samples (cytospins) collected from 21 metastatic breast cancer patients. A triple fluorescence protocol was used to visualize CK cytokeratin (8/18, 8/19) in green (DyeLight488 conjugate), ER in red (cy3 conjugate) and ErbB2 in blue (AMCA conjugate). We were able to identify more than one third CTC positive patients with the possibility of dramatic changes between primary tumor status and CTC status. One patient which had an ER-positive and erbB2-negative primary tumor exhibited simultaneously the 4 possibilities of receptor expression (ER-pos/erbB2-neg plus ER-pos/erbB2-pos, ER-neg/erbB2-neg and ER-neg/erbB2-pos). The ER-negative and erbB2-negative CTC may direct towards tamoxifen and traztuzumab resistances and have to be identified among other ER-positive and ErbB2 positive cells. We demonstrated that the individual assessment of ER and ErbB2 expression in each CTC outlines the heterogeneity of the CTC and the extreme changes of their receptor status compared to the primary tumor status. Large multicentric cohorts of breast cancer patients treated with adjuvant therapy should now be analyzed for both ER and ErbB2 status of the CTC and of the primary tumors. Such analysis should lead to optimal individualized treatments.