Comparison between circulating and disseminated tumor cells in breast cancer.
Authors: T Fehm, EF Solomayer, O Hoffmann, S Becker, D Wallwiener, R Kimmig, S Kasimir-Bauer
Journal: Cancer Research (2009)

Abstract Abstract #301 Background: The presence of disseminated tumor cells (DTC) in the bone marrow (BM) of breast cancer patients is an independent prognostic factor. The role of circulating tumor cells (CTC) in blood is not yet defined. Since BM aspiration is less accepted by patients compared to blood drawing, it would be highly desirable to replace BM aspiration by blood analysis. Therefore, the purpose of the present study was: (1) to examine the presence of CTC in peripheral blood (2) to assess the correlation between CTC in blood and DTC in BM and (3) since adjuvant therapy targets minimal residual disease (MRD), to compare the expression profile of therapeutic relevant markers between CTC (a potential surrogate marker for MRD) and the primary tumor.&amp;#x2028; Materials and Methods: 282 blood samples from primary breast cancer patients were collected. All samples underwent immunomagnetic enrichment using the AdnaTest BreastCancerSelect (AdnaGen AG, Germany) within 4 hours after blood withdrawal followed by RNA isolation and subsequent gene expression analysis by reverse transcription and Multiplex-PCR in separated tumor cells using the AdnaTest BreastCancerDetect. CTC were analyzed for the three breast cancer associated markers: GA733-2, Muc-1, Her-2 and β–actin as an internal PCR control. Expression of the estrogen (ER) and progesterone (PR) receptor was assessed in an additional RT-PCR. The analysis of PCR products was performed by capillary electrophoresis on the Agilent Bioanalyzer 2100. Furthermore, two BM aspirates from each of these patients were analyzed by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Evaluation of DTC was performed with the ACIS system (Chromavision) and the ARIOL system (Applied Imaging) according to the ISHAGE evaluation criteria.&amp;#x2028; Results: 282 patients could be included into this study. 44/282 (16%) of these patients had detectable CTC in the bloodstream. BM samples could be analyzed in 267/282 patients. DTC were found in 64/267 patients, resulting in a positivity rate for DTC in the BM of 23%. BM status did not correlate with the presence of CTC (p=0.112) supporting the theory of different clinical relevance. MUC-1 and GA 73.3 were expressed by 57% and 61% of the CTC, respectively. CTC were HER2 positive in 39% of patients whereas only 11% of the corresponding primary tumor overexpressed HER2. Most of the patients had ER und PR positive tumors (84% and 73%, respectively). However, the majority of the CTC were ER and PR negative (75% and 98%, respectively).&amp;#x2028; Conclusions: (1) These data indicate that due to the discordance between CTC and DTC the clinical relevance may be different. (2) The expression profile between CTC (a possible surrogate marker for MRD) and the primary tumor (the current gold standard for selecting targeted therapy against MRD) differs. Thus, the consequence for selecting HER2 targeted or anti - endocrine therapy has to be evaluated. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 301.