Bone marrow micrometastases in primary breast cancer: Prognostic significance after 6 years' follow-up

Mansi, Janine; Easton, Douglas F.; Berger, U.; Gazet, J.‐C.; Ford, H. T.; Dearnaley, D.; Coombes, R. Charles

doi:10.1016/0277-5379(91)90413-8

Cited by 188 publications

(88 citation statements)

References 11 publications

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“…Several studies have shown that the detection of bone marrow (DTCs) [2][3][4] or peripheral blood [CTCs; [5][6] tumor cells is associated with an increased risk of relapse and reduced survival in patients with stage I/III breast cancer. In most of the studies, the detection of CTCs was performed using CK19 as a marker of epithelial cells.…”

Section: Discussionmentioning

confidence: 99%

“…The detection of occult tumor cells either in the bone marrow or the peripheral blood has been demonstrated to represent an independent prognostic factor for disease relapse and reduced survival [2][3][4][5][6]. Indeed, a meta-analysis involving 4,703 patients with stage I-III breast cancer confirmed the independent prognostic value of DTCs [7].…”

Section: Introductionmentioning

confidence: 98%

“…Among these markers are cytokeratin-19 (CK19), mammaglobin, maspin, and carcinoembryonic antigen (CEA) [2][3][4][5][8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Apostolaki

Perraki

Kallergi

et al. 2008

Breast Cancer Res Treat

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

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Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Apostolaki

Perraki

Kallergi

et al. 2008

Breast Cancer Res Treat

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“…28 In patients with primary breast cancer, the presence of BM micrometastases is significantly associated with shorter survival but is not an independent prognostic factor, as shown by short-term as well as long-term follow-up studies. 29,30 Hence, it might be specific cellular properties, rather than the mere presence of disseminated carcinoma cells in BM, that determine the clinical outcome.…”

Section: Resultsmentioning

confidence: 99%

Differential display analysis of breast carcinoma cells enriched by immunomagnetic target cell selection: Gene expression profiles in bone marrow target cells

Ree

Engebraaten

Hovig

et al. 2001

Intl Journal of Cancer

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The red bone marrow (BM) is an important indicator organ of hematogenous micrometastatic spread of carcinomas. Characterization of biological properties specific for BM micrometastatic cells, however, is technically challenging due to the limited number of target cells usually available for the purpose. This report provides referrals to qualitative gene expression profiling of BM micrometastatic cells enriched by immunomagnetic selection. First, an experimental strategy was used to study regulatory mechanisms involved when BM micrometastatic cells colonize distant organs. The MA-11 cells, originating from BM micrometastases in a breast cancer patient clinically devoid of overt metastatic disease, were injected into immunodeficient rats. Metastatic MA-11 cells were subsequently immunoselected from the resulting in vivo lesions. The selected cell populations were compared to the injected cells by differential display analysis, and several genes possibly involved in tumor cell invasion and proliferation were confirmed as differentially expressed among the various MA-11 cell populations. A direct approach to qualitative gene expression profiling of BM micrometastatic cells was also explored. Carcinoma cells were immunoselected from BM and axillary lymph nodes obtained from breast cancer patients, and the isolated cell populations were compared by differential display analysis. Two candidate genes, identified as factors involved in cellular growth control, appeared as differentially expressed by the target cells from BM. Our study provides detailed information on how to combine an immunomagnetic selection procedure and differential display analysis to reveal gene expression profiles that may characterize BM micrometastatic cells. © 2002 Wiley-Liss, Inc. Key words: bone marrow; micrometastasis; breast cancer; immunomagnetic cell preparation; differential cloningClinical and experimental evidence suggests that epithelial tumor cells are able to disseminate to secondary organs at an early stage of primary tumor development. The red bone marrow (BM) compartment represents an important indicator organ of hematogenous micrometastatic spread of carcinomas. According to current concepts, however, disseminated tumor cells detected in the BM are not able to grow as distant metastatic lesions unless they possess certain biological characteristics, among which the ability of invasion into and proliferation within the target organ is considered highly significant. [1][2][3] The classical, experimental works on mechanisms of tumor metastasis demonstrated that only a small subset of cells within the parental population is capable of metastasizing 4 and that the cellular composition of secondary tumors differs from that of the primaries. 5 Subsequent reports introduced the concept of dynamic heterogeneity, which argues that although the metastatic phenotype is a genetically controlled trait, it is inherently unstable. 6 Indeed, cellular properties that are crucial for initiation of distant tumor growth may be obscured by the heterog...

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“…This increases the chance of detecting tumour cells if these are relatively few (Trojani et al, 1987;Neville et al, 1990;Mansi et al, 1991).…”

Section: Discussionmentioning

confidence: 99%

Keratin 19 mRNA measurement to detect micrometastases in lymph nodes in breast cancer patients

Schoenfeld

Luqmani²,

Sinnett³

et al. 1996

Br J Cancer

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Bone marrow micrometastases in primary breast cancer: Prognostic significance after 6 years' follow-up

Cited by 188 publications

References 11 publications

Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Detection of occult HER2 mRNA-positive tumor cells in the peripheral blood of patients with operable breast cancer: evaluation of their prognostic relevance

Differential display analysis of breast carcinoma cells enriched by immunomagnetic target cell selection: Gene expression profiles in bone marrow target cells

Keratin 19 mRNA measurement to detect micrometastases in lymph nodes in breast cancer patients

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