Abstract PD6-3: Comparison of the HER2, estrogen and progesterone receptor expression profile of primary tumor, metastases and circulating tumor cells in metastatic breast cancer patients

Background: Several breast cancer studies have indicated that the expression of predictive markers including HER2, estrogen (ER) and progesterone (PR) receptor can change during the course of disease. Therefore, reassessment of these markers at the time of disease progression might help to optimize treatment decisions. In this context, characterization of circulating tumor cells (CTCs) could be of relevance in the future, since metastatic tissue may be difficult to obtain for repeated analysis. Therefore, the present study compared the HER2/ER/PR expression profile of primary tumor and metastases, primary tumor and CTCs as well as metastases and CTCs. Patients and Methods: A total of 84 patients with metastatic breast cancer from eight German University Breast Cancer Centers were enrolled in this study. Blood was obtained at the time of first diagnosis of metastatic disease or disease progression and analyzed for CTCs (EpCAM, MUC1 and HER2 transcripts) using the AdnaTest BreastCancer (AdnaGen AG, Germany). Expression of the ER and PR receptor was assessed in an additional RT-PCR. The analysis of PCR products was performed by capillary electrophoresis on the Agilent Bioanalyzer 2100. Results for HER2 status on CTCs was additionally assessed using the FDA-approved CellSearch® assay. Results: Applying the AdnaTest, the overall detection rate for CTCs was 43% (36/84 patients) with the expression rates of 50% for HER2 (18/36 patients), 14% for ER (5/36 patients) and 8% for PR (3/36 patients), respectively. Comparisons of expression profiles on CTCs with those on tissue samples were only performed in CTC-positive patients. Primary tumors and CTCs displayed a concordant HER2, ER and PR status in 59% (p = 0.262), 39% (p = 0,51) and 44% (p = 0,62) of cases, respectively. For metastases and CTCs, the concordance values were 67% for HER2 (p = 0.04), 43% for ER (p = 0.16) and 46% for PR (p = 0.6), respectively. Interestingly, in 26/36 patients with ER/PR-positive metastases, CTCs were positive in 27% of cases and in the other 10 ER/PR-negative patients, the concordance was 100% (p = 0.066). Applying the CellSearch® assay as a gold standard for CTC detection, the CTC-positivity rate was 53% (42/79 patients) with the expression rate of 29% for HER2 (12/42 patients). No significant concordance was found when HER2 status on CTCs was compared with HER2 expression on primary tumors (p = 0,28) and on metastases (p = 0,44). In addition, primary tumor and metastases displayed a concordant HER2, ER and PR status in 80% (p = 0.0013), 91% (p = 0.000002) and 89% (p = 0.000006) of cases, respectively. Conclusion: Although we could show that primary tumors and their metastases showed a highly significant concordance of the expression of predictive markers, characterization of CTCs could be of relevance in case metastatic tissue may be difficult to obtain. Here we demonstrate that the molecular detection of a HER2 overexpression in CTC using the AdnaTest is able to significantly predict the HER2 status on metastases. More detailed analysis of ER/PR expression rates in tissue samples might help in addition to decide whether CTCs might be a useful tool for treatment decisions based on each expression profile. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr PD6-3.