Comparative evaluation of cell-free tumor DNA in blood and disseminated tumor cells in bone marrow of patients with primary breast cancer.

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Comparative evaluation of cell-free tumor DNA in blood and disseminated tumor cells in bone marrow of patients with primary breast cancer. / Schwarzenbach, Heidi; Pantel, Klaus; Kemper, Birthe; Beeger, Cord; Otterbach, Friedrich; Kimmig, Rainer; Kasimir-Bauer, Sabine.

in: BREAST CANCER RES, Jahrgang 11, Nr. 5, 5, 2009, S. 71.

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@article{c01f60aefc1b4ff7b64269aa86a6b7b6,
title = "Comparative evaluation of cell-free tumor DNA in blood and disseminated tumor cells in bone marrow of patients with primary breast cancer.",
abstract = "INTRODUCTION: The origin and clinical relevance of circulating cell-free tumor DNA in the blood of cancer patients is still unclear. Here we investigated whether the detection of this DNA is related to bone marrow (BM) micrometastasis and tumor recurrence in breast cancer patients. METHODS: BM aspirates of 81 primary breast cancer patients were analyzed for the presence of disseminated tumor cells (DTC) by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. PCR-based fluorescence microsatellite analysis was performed for detection of loss of heterozygosity (LOH) at 6 polymorphic markers using cell-free serum DNA. The data were correlated with established risk factors, and patients were followed-up over 6-10 years. RESULTS: LOH was detected in 33.5% of blood samples. The occurrence of LOH at the entire microsatellite marker set correlated with histopathology (P = 0.05) and grading (P = 0.006) of the primary tumor. The genomic region characterized by marker D9S171 was only affected by LOH in patients with increased tumor stages (pT2-4, P <0.05) and older age (> or = 55 years, P = 0.05). Kaplan-Meier analysis showed that LOH at D3S1255 (P = 0.009) and D9S171 (P = 0.001) were significantly associated with tumor relapse. In BM, DTC were detected in 39.5% of the patients, and this finding correlated with distant metastases (P <0.05). Patients with DTC-positive BM had higher DNA yields in their blood than patients with DTC-negative BM (P <0.05). However, no significant correlations were found between the presence of DTC in BM and the detection of marker-specific LOH on blood DNA. CONCLUSIONS: The detection of LOH on cell-free tumor DNA in blood is unrelated to BM micrometastasis and provides independent information on breast cancer progression.",
author = "Heidi Schwarzenbach and Klaus Pantel and Birthe Kemper and Cord Beeger and Friedrich Otterbach and Rainer Kimmig and Sabine Kasimir-Bauer",
year = "2009",
doi = "10.1186/bcr2404",
language = "Deutsch",
volume = "11",
pages = "71",
journal = "BREAST CANCER RES",
issn = "1465-5411",
publisher = "BioMed Central Ltd.",
number = "5",

}

RIS

TY - JOUR

T1 - Comparative evaluation of cell-free tumor DNA in blood and disseminated tumor cells in bone marrow of patients with primary breast cancer.

AU - Schwarzenbach, Heidi

AU - Pantel, Klaus

AU - Kemper, Birthe

AU - Beeger, Cord

AU - Otterbach, Friedrich

AU - Kimmig, Rainer

AU - Kasimir-Bauer, Sabine

PY - 2009

Y1 - 2009

N2 - INTRODUCTION: The origin and clinical relevance of circulating cell-free tumor DNA in the blood of cancer patients is still unclear. Here we investigated whether the detection of this DNA is related to bone marrow (BM) micrometastasis and tumor recurrence in breast cancer patients. METHODS: BM aspirates of 81 primary breast cancer patients were analyzed for the presence of disseminated tumor cells (DTC) by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. PCR-based fluorescence microsatellite analysis was performed for detection of loss of heterozygosity (LOH) at 6 polymorphic markers using cell-free serum DNA. The data were correlated with established risk factors, and patients were followed-up over 6-10 years. RESULTS: LOH was detected in 33.5% of blood samples. The occurrence of LOH at the entire microsatellite marker set correlated with histopathology (P = 0.05) and grading (P = 0.006) of the primary tumor. The genomic region characterized by marker D9S171 was only affected by LOH in patients with increased tumor stages (pT2-4, P <0.05) and older age (> or = 55 years, P = 0.05). Kaplan-Meier analysis showed that LOH at D3S1255 (P = 0.009) and D9S171 (P = 0.001) were significantly associated with tumor relapse. In BM, DTC were detected in 39.5% of the patients, and this finding correlated with distant metastases (P <0.05). Patients with DTC-positive BM had higher DNA yields in their blood than patients with DTC-negative BM (P <0.05). However, no significant correlations were found between the presence of DTC in BM and the detection of marker-specific LOH on blood DNA. CONCLUSIONS: The detection of LOH on cell-free tumor DNA in blood is unrelated to BM micrometastasis and provides independent information on breast cancer progression.

AB - INTRODUCTION: The origin and clinical relevance of circulating cell-free tumor DNA in the blood of cancer patients is still unclear. Here we investigated whether the detection of this DNA is related to bone marrow (BM) micrometastasis and tumor recurrence in breast cancer patients. METHODS: BM aspirates of 81 primary breast cancer patients were analyzed for the presence of disseminated tumor cells (DTC) by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. PCR-based fluorescence microsatellite analysis was performed for detection of loss of heterozygosity (LOH) at 6 polymorphic markers using cell-free serum DNA. The data were correlated with established risk factors, and patients were followed-up over 6-10 years. RESULTS: LOH was detected in 33.5% of blood samples. The occurrence of LOH at the entire microsatellite marker set correlated with histopathology (P = 0.05) and grading (P = 0.006) of the primary tumor. The genomic region characterized by marker D9S171 was only affected by LOH in patients with increased tumor stages (pT2-4, P <0.05) and older age (> or = 55 years, P = 0.05). Kaplan-Meier analysis showed that LOH at D3S1255 (P = 0.009) and D9S171 (P = 0.001) were significantly associated with tumor relapse. In BM, DTC were detected in 39.5% of the patients, and this finding correlated with distant metastases (P <0.05). Patients with DTC-positive BM had higher DNA yields in their blood than patients with DTC-negative BM (P <0.05). However, no significant correlations were found between the presence of DTC in BM and the detection of marker-specific LOH on blood DNA. CONCLUSIONS: The detection of LOH on cell-free tumor DNA in blood is unrelated to BM micrometastasis and provides independent information on breast cancer progression.

U2 - 10.1186/bcr2404

DO - 10.1186/bcr2404

M3 - SCORING: Zeitschriftenaufsatz

VL - 11

SP - 71

JO - BREAST CANCER RES

JF - BREAST CANCER RES

SN - 1465-5411

IS - 5

M1 - 5

ER -