Tumour cell detection in the bone marrow of breast cancer patients at primary therapy: results of a 3-year median follow-up

Harbeck, Nadia; Untch, Michael; Pache, L.; Eiermann, W.

doi:10.1038/bjc.1994.103

Cited by 203 publications

(106 citation statements)

References 25 publications

(33 reference statements)

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“…Second, in the setting of autologous bone marrow transplantation (ABMT) or peripheral stem cell reinfusion after high-dose chemotherapy, contamination of the reinfused bone marrow or stem cell population with tumour cells might worsen prognosis (Anderson et al, 1989;Gribben et al, 1991;Brenner et al, 1993;Brugger et al, 1994;Moss et al, 1994). In recent years, especially in breast and colon cancer, it has been shown that occult contamination of the peripheral blood or bone marrow at diagnosis with tumour cells exerts an adverse influence on survival (Berger et al, 1988;Cote et al, 1991;Schlimok et al, 1991;Pantel et al, 1993;Diel et al, 1994;Harbeck et al, 1994;Menard et al, 1994). Often, in these studies, a monoclonal antibody (MAb) or a panel of MAbs directed against tumour cell-surface glycoproteins or cytokeratins was used to detect circulating tumour cells.…”

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confidence: 99%

A quantitative reverse transcriptase polymerase chain reaction-based assay to detect carcinoma cells in peripheral blood

Helfrich¹,

tenPoele²,

Meersma³

et al. 1997

Br J Cancer

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Summary The presence of tumour cells in the circulation may predict disease recurrence and metastasis. To improve on existing methods of cytological or immunocytological detection, we have developed a sensitive and quantitative technique for the detection of carcinoma cells in blood, using the reverse transcriptase polymerase chain reaction (RT-PCR) identifying transcripts of the pancarcinoma-associated tumour marker EGP-2 (KSA or 17-lA antigen). The amount of EGP2 mRNA was quantified using an internal recombinant competitor RNA standard with known concentration and which is both reversely transcribed and co-amplified in the same reaction, allowing for a reliable assessment of the initial amount of EGP2 mRNA in the sample. Calibration studies, seeding blood with MCF-7 breast carcinoma cells, showed that the assay can detect ten tumour cells among 1.0 x 106 leucocytes. The PCR assay revealed that normal bone marrow expresses low levels of EGP2 mRNA, although immunocytochemistry with the anti-EGP2 MAb MOC31 could not identify any positively stained cell. Analyses using this RT-PCR assay may prove to have applications to the assessment of circulating tumour cells in clinical samples.

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confidence: 99%

A quantitative reverse transcriptase polymerase chain reaction-based assay to detect carcinoma cells in peripheral blood

Helfrich¹,

tenPoele²,

Meersma³

et al. 1997

Br J Cancer

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“…[1][2][3][4][5][6][7][8][9][10][11][12][13][14][15] DTCs can be detected in approximately 33% of breast cancer patients without any clinical evidence of metastatic disease (i.e., Stage I-III disease). The presence of DTCs also is described by synonyms, such as bone marrow micrometastasis or minimal residual disease, but the term DTCs is the most precise.…”

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confidence: 99%

A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation

Fehm

Braun

Müller

et al. 2006

Cancer

204

199

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Numerous single-institutional studies and a large pooled analysis have demonstrated that the presence of disseminated tumor cells (DTCs) in the bone marrow (BM) from patients with primary, nonmetastatic breast cancer (Stages I-III) is associated with impaired prognosis. To date, sampling of BM and assessment of DTCs is not considered a routine procedure in the clinical management of breast cancer patients; however, emerging data suggest a future role for risk stratification and monitoring of therapeutic efficacy. Because these clinical options need to be evaluated in trials to verify the principle of this concept in the clinical setting, agreement on the standardized detection of DTCs is necessary. Consequently, the German, Austrian, and Swiss Societies for Senology recently formed a panel 1) to review and discuss the existing methodologies, 2) to find a consen-

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“…Several studies suggest that these objectives can be achieved with the current assays (Cote et al, 1991;Harbeck et al, 1994;Diel et al, 1996;Smith et al, 2000;Terstappen et al, 2000;Gebauer et al, 2001;Jiang et al, 2002;Ozbas et al, 2003;Pantel et al, 2003) and in a few of them the presence of disseminated tumour cells in bone marrow or peripheral blood is recognised as an independent prognostic factor (Diel et al, 1996;Braun et al, 2000;Stathopoulou et al, 2002). However, the literature reports conflicting results and the clinical value of these assays remains to be proven basically because it is uncertain whether the published assays have enough sensitivity, specificity and consistency to be reliably integrated into prospective studies provided with adequate statistical power to answer the most relevant clinical questions (Jiang et al, 2002;Ozbas et al, 2003;Pantel et al, 2003).…”

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confidence: 99%

Effect of different cytokines on mammaglobin and maspin gene expression in normal leukocytes: possible relevance to the assays for the detection of micrometastatic breast cancer

et al. 2005

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In cancer patients, the ability to detect disseminated tumour cells in peripheral blood or bone marrow could improve prognosis and consent both early detection of metastatic disease and monitoring of the efficacy of systemic therapy. These objectives remain elusive mainly due to the lack of specific genetic markers for solid tumours. The use of surrogate tissue-specific markers can reduce the specificity of the assays and give rise to a clinically unacceptable false-positive rate. Mammaglobin (MAM) and maspin are two putative breast tissue-specific markers frequently used for detection of occult tumour cells in the peripheral blood, bone marrow and lymph nodes of breast cancer patients. In this study, it was evaluated whether MAM and maspin gene expression may be induced in the normal blood and bone marrow cells exposed to a panel of cytokines, including chemotactic factors (C5a, interleukin (IL)-8), LPS, proinflammatory cytokines (TNF-a, IL-1b) and growth factors (IL-3, granulocyte-macrophage colony-stimulating factor, granulocyte colony-stimulating factor). The experimental data show that all cytokines included in the panel, except for IL-8, were able to induce maspin expression; on the contrary, MAM gene was never induced. These results suggest that MAM is more specific than maspin and that the possible interference of cytokines should be taken into account in interpreting molecular assays for detection of isolated tumour cells.

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Tumour cell detection in the bone marrow of breast cancer patients at primary therapy: results of a 3-year median follow-up

Cited by 203 publications

References 25 publications

A quantitative reverse transcriptase polymerase chain reaction-based assay to detect carcinoma cells in peripheral blood

A quantitative reverse transcriptase polymerase chain reaction-based assay to detect carcinoma cells in peripheral blood

A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation

Effect of different cytokines on mammaglobin and maspin gene expression in normal leukocytes: possible relevance to the assays for the detection of micrometastatic breast cancer

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