Detection of Micrometastases in Patients With Primary Breast Cancer

Redding, W H; Monaghan, Paul; Imrie, S F; Ormerod, M.G.; Gazet, J.‐C.; Coombes, R. Charles; Clink, H.M.; Dearnaley, D.; Sloane, J P; Powles, Trevor J.; Neville, A. Munro

doi:10.1016/s0140-6736(83)91150-9

Cited by 230 publications

(9 citation statements)

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“…Most breast cancer deaths are due to metastatic relapse after treatment of apparently localized disease, and occult dissemination of tumour cells occurs at this early phase [1,2]. Post-operative systemic therapies (chemotherapy, endocrine therapy and more recently passive immunotherapy/targeted therapy with anti-HER2 monoclonal antibody) have been shown to improve recurrence-free and overall survival in patients with early breast cancer [3,4].…”

Section: Introductionmentioning

confidence: 99%

Prognostic value of the expression of C-Chemokine Receptor 6 and 7 and their ligands in non-metastatic breast cancer

et al. 2011

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BackgroundChemokines and chemokine receptors are major actors of leukocytes trafficking and some have been shown to play an important role in cancer metastasis. Chemokines CCL19, CCL20 and CCL21 and their receptors CCR6 and CCR7, were assessed as potential biomarkers of metastatic dissemination in primary breast cancer.MethodsBiomarker expression levels were evaluated using immunohistochemistry on paraffin-embedded tissue sections of breast cancer (n = 207).ResultsCCR6 was expressed by tumor cells in 35% of cases. CCR7 was expressed by spindle shaped stromal cells in 43% of cases but not by tumor cells in this series. CCL19 was the only chemokine found expressed in a significant number of breast cancers and was expressed by both tumor cells and dendritic cells (DC). CCR6, CCL19 and CCR7 expression correlated with histologic features of aggressive disease. CCR6 expression was associated with shorter relapse-free survival (RFS) in univariate and but not in multivariate analysis (p = 0.0316 and 0.055 respectively), and was not associated with shorter overall survival (OS). Expression of CCR7 was not significantly associated with shorter RFS or OS. The presence of CCL19-expressing DC was associated with shorter RFS in univariate and multivariate analysis (p = 0.042 and 0.020 respectively) but not with shorter OS.ConclusionThese results suggest a contribution of CCR6 expression on tumor cells and CCL19-expressing DC in breast cancer dissemination. In our series, unlike what was previously published, CCR7 was exclusively expressed on stromal cells and was not associated with survival.

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Section: Introductionmentioning

confidence: 99%

Prognostic value of the expression of C-Chemokine Receptor 6 and 7 and their ligands in non-metastatic breast cancer

et al. 2011

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“…It is generally believed that distant metastases spread from the primary tumor through invasion into circulation and finally distant sites, where they may reinitiate growth, depending on the microenvironment. One of the surrogates of hematological spread are disseminated tumor cells (DTC) as detected in bone marrow aspirations by Redding et al in one of the first studies of its kind, using epithelial membrane antigen to identify DTC in bone marrow at the time of primary surgery in women with no overt metastases [1], and later by our group using a combination of epithelial cell surface antigens and cytokeratins to identify DTC in early stage breast carcinoma [2,3]. The prognostic significance of the presence of DTC in bone marrow aspirates has been established for several cancers, with most evidence related to breast cancer [4].…”

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confidence: 99%

Progress in circulating tumor cell capture and analysis: implications for cancer management

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Lin

Williams

et al. 2012

Expert Review of Molecular Diagnostics

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The hematogenous dissemination of cancer and development of distant metastases is the cause of nearly all cancer deaths. Detection of circulating tumor cells (CTCs) as a surrogate biomarker of metastases has gained increasing interest. There is accumulating evidence on development of novel technologies for CTC detection, their prognostic relevance and their use in therapeutic response monitoring. Many clinical trials in the early and metastatic cancer setting, particularly in breast cancer, are including CTCs in their translational research programs and as secondary end points. We summarize the progress of detection methods in the context of their clinical importance and speculate on the possibilities of wider implementation of CTCs as a diagnostic oncology tool, the likelihood that CTCs will be used as a useful biomarker, especially to monitor therapeutic response, and what may be expected from the future improvements in technologies.

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“…Most early studies focused on the detection of DTCs. Initially, antibodies to epithelial cell surface antigens such as epithelial membrane antigen were used to identify DTCs by immunostaining of the bone marrow at the time of primary surgery in women diagnosed with breast cancer with no overt metastases (4). Later on, antibodies to cytokeratins were increasingly used immunohistochemically to identify DTCs in early-stage breast carcinoma (5, 6).…”

Section: Clinical Significance Of Metastasismentioning

confidence: 99%

Circulating Tumor Cells: From Bench to Bedside

et al. 2013

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Circulating tumor cells (CTCs) represent a surrogate biomarker of hematogenous metastases. In recent years, their detection has gained increasing interest. There is ample evidence regarding the ability to detect CTCs and their prognostic relevance, but their demonstrated predictive value in therapeutic response monitoring is clinically even more meaningful. Many clinical trials in the early and metastatic cancer setting now include CTCs as a monitoring parameter, and numerous translational studies attempting their molecular characterization are under way. There has been great progress in defining the clinical importance of CTCs, and it now seems likely that we may expect wider implementation of CTCs as a diagnostic oncology tool to monitor therapeutic response in real time. Novel technologies may further facilitate molecular characterization of CTCs and development of novel therapeutic targets, possibly leading to more powerful treatment strategies for cancer patients. As the detection and evaluation of CTCs are becoming an increasingly important diagnostic and prognostic tool, the goal of this review is to communicate the knowledge obtained through analysis of primary tumors and CTCs to oncologists and medical specialists in managing patients with cancer.

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Detection of Micrometastases in Patients With Primary Breast Cancer

Cited by 230 publications

References 10 publications

Prognostic value of the expression of C-Chemokine Receptor 6 and 7 and their ligands in non-metastatic breast cancer

Prognostic value of the expression of C-Chemokine Receptor 6 and 7 and their ligands in non-metastatic breast cancer

Progress in circulating tumor cell capture and analysis: implications for cancer management

Circulating Tumor Cells: From Bench to Bedside

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