Detection, clinical relevance and specific biological properties of disseminating cancer cells in breast cancer patients.
Authors: Pantel K 
Published: December 2010

Abstract #P2-1

Metastatic relapse of carcinoma patients is mainly due to clinically occult micrometastases present at primary diagnosis, but undetectable even by high-resolution imaging technologies. Frequently, traditional prognostic factors are insufficient to predict metastasis and treatment decisions are mainly based on statistical risk parameters. Highly sensitive and specific cytometric and molecular methods enable now the detection of disseminated tumor cells (DTC) in bone marrow (BM) and circulating tumor cells (CTC) in peripheral blood of breast carcinoma patients. The presence of DTC has prognostic impact for patients with primary breast cancer with regard to metastatic relapse and overall survival (Braun et al, NEJM 2005) and DTC may even contribute to local relapse (Bidard et al., CCR 2008). However, BM analyses are not well accepted by the medical community for the clinical management patients in breast cancer and other solid tumors. Therefore, most current research efforts are directed to evaluate the clinical utility of CTC detection (Pantel & Panabieres, Nat. Clin Pract. Oncol. 2007). Because of the high variability of results obtained by different cytometric and molecular approaches, standardization of current technologies is urgently required (Fehm et al., Cancer 2006; Riethdorf et al., CCR 2008). While the prognostic significance of CTC could be demonstrated for metastatic breast cancer patients (Hayes & Smerage, CCR 2008), studies on the impact of CTC in primary breast cancer patients are still ongoing but the intermediate results are so far promising (Pantel et al., Nat. Clin Pract. Oncol. In press). Moreover, encouraging results on monitoring CTC during primary systemic or adjuvant chemotherapy in breast cancer patients were obtained in recent studies. Now further characterization of CTC is pivotal to understand the biology of tumor cell dissemination (Pantel et al., Nat. Rev. Cancer 2008). The molecular characterization of CTC with special emphasis on potential cancer stem cell features and therapeutically relevant targets such as HER2 (Wülfing et al., CCR 2006) might improve individual risk assessment and stratification of patients for targeted therapies. This characterization will contribute to more “tailored” and personalized anti-metastatic therapies. At present, the success or failure of anti-cancer therapies is only assessed retrospectively by the absence or presence of overt metastases during the post-operative follow up period. Real-time monitoring of peripheral blood (i.e., during and after systemic adjuvant therapy) for CTC might provide unique information for the clinical management of the individual cancer patient and allow an early change in therapy years before the appearance of overt metastases signals incurability (Panabieres et al., CCR 2008). Future clinical trials will show whether the assessment and monitoring of therapeutic targets (e.g., EGF-R, HER2 or VEGF) on CTC (and probably DTC) might become an important diagnostic tool for cancer patients undergoing targeted therapies and may provide new insights into the selection of tumour cells under biological therapies.

Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr P2-1.