Klaus Pantel

Discordance in Human Epidermal Growth Factor Receptor 2 (HER2) Phenotype Between Primary Tumor and Circulating Tumor Cells in Women With HER2-Negative Metastatic Breast Cancer

PurposeDiscordance in human epidermal growth factor receptor 2 (HER2) status between primary tumor and metastases might have important implications for treatment response and therapy decisions. Here, we evaluate both the frequency of circulating tumor cells (CTCs) and the factors predicting HER2 discordance between primary tumor and CTCs as a potential surrogate for tumor biology and tumor heterogeneity in patients with metastatic breast cancer.Patients and MethodsThe number of CTCs in 7.5 mL of peripheral blood and HER2 status were evaluated in 1,123 women with HER2-negative metastatic breast cancer. HER2 discordance was defined as the presence of at least one CTC with a strong immunocytochemical HER2 staining intensity. Factors predicting discordance in HER2 phenotype were assessed using multivariable logistic regression.ResultsOverall, 711 (63.3%) of 1,123 screened patients were positive for CTCs (≥ one CTC). Discordance in HER2 phenotype between primary tumor and CTCs was observed in 134 patients (18....

Circulating and Disseminated Tumor Cells from Solid Tumors—Research and Clinical Aspects

Increasing evidence indicates that tumor cell dissemination starts already early during tumor development and progression. Sensitive immunocytochemical and molecular assays allow now the detection of single circulating tumor cells (CTC) in the peripheral blood and disseminated tumor cells (DTC) in the bone marrow (BM) as a common and easily accessible homing organ for cells released by epithelial tumors of various origins. Tumor cells are frequently detected in the blood and BM of cancer patients without clinical or even histopathologic signs of metastasis. The detection of DTC and CTC may yield important prognostic information and might help to tailor systemic therapies to the individual needs of a cancer patient. A single DTC or CTC can express properties distinct from that of the primary tumor (e.g., increased rate of HER2/neu expression/amplification), and characterization of DTC/CTC could, therefore, help to identify therapeutic targets and select patients whose tumors are most likely to respond to targeted agents. Moreover, CTC measurements could be used for monitoring the efficacy of systemic therapies. Ongoing clinical trials will reveal whether changes in CTC status will be linked to clinical outcome. Here, we review the data on (i) BM as common homing organ for disseminating tumor cells and (ii) clinical studies on disseminating tumor cells that help to establish CTC/DTC measurements in clinical practice, and outline the (iii) biological characteristics of DTC and CTC.

Detection and Characterisation of Occult Metastatic Cells in Bone Marrow of Breast Cancer Patients: Implications for Adjuvant Therapy

The early and clinically occult spread of viable tumour cells to the organism is becoming acknowledged as a hallmark in cancer progression, since abundant clinical and experimental data suggest that these cells are precursors of subsequent distant relapse. Prospective clinical studies have shown that the presence of such immunostained cells in bone marrow is prognostically relevant with regard to relapse-free and overall survival of breast cancer patients. As current treatment strategies have not resulted in a substantial improvement of breast cancer mortality rates so far, it is noteworthy to consider the intriguing options of immunocytochemical screening of bone marrow aspirates for occult metastatic cells. Besides improved tumour staging, such screening offers opportunities for guiding patient stratification for adjuvant therapy trials, monitoring response to adjuvant therapies, which, at present, can only be assessed retrospectively after an extended period of clinical follow-up, or for specifically targeting tumour-biological therapies against disseminated tumour cells.