Abstract

Within the field of cancer research, focus on the study of minimal residual disease (MRD) in the context of carcinoma has grown exponentially over the past several years. MRD encompasses circulating tumour cells (CTCs)—cancer cells on the move via the circulatory or lymphatic system, disseminated tumour cells (DTCs)—cancer cells which have escaped into a distant site (most studies have focused on bone marrow), and resistant cancer cells surviving therapy—be they local or distant, all of which may ultimately give rise to local relapse or overt metastasis. Initial studies simply recorded the presence and number of CTCs and DTCs; however recent advances are allowing assessment of the relationship between their persistence, patient prognosis and the biological properties of MRD, leading to a better understanding of the metastatic process. Technological developments for the isolation and analysis of circulating and disseminated tumour cells continue to emerge, creating new opportunities to monitor disease progression and perhaps alter disease outcome. This review outlines our knowledge to date on both measurement and categorisation of MRD in the form of CTCs and DTCs with respect to how this relates to cancer outcomes, and the hurdles and future of research into both CTCs and DTCs.

Highlights

  • Breast cancer is the most commonly diagnosed female cancer with the exclusion of skin cancers

  • minimal residual disease (MRD) encompasses circulating tumour cells (CTCs)—cancer cells on the move via the circulatory or lymphatic system, disseminated tumour cells (DTCs)— cancer cells which have escaped into a distant site, and resistant cancer cells surviving therapy—be they local or distant, all of which may give rise to local relapse or overt metastasis

  • Malignant cells must intravasate into blood or lymphatic vessels, penetrate basement membranes and endothelial walls, survive whilst in the circulation, evade immune defences and other cell death mechanisms such as apoptosis, and travel to a secondary site [27,28,29]. At this point they must extravasate into the distant tissue and regain or enhance cellular characteristics that allow for anchorage, communication, survival and adaptation into the new microenvironment, in turn promoting mechanisms that enable the proliferation of a cohesive mass of tumour cells which will become an overt macrometastasis [29]

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Summary

REVIEW ARTICLE

Minimal residual disease in breast cancer: an overview of circulating and disseminated tumour cells. This article is published with open access at Springerlink.com

Introduction
Understanding the metastatic cascade
Local mechanisms of disease relapse
Therapy resistant cells
Mechanisms of therapy resistance
Evidence that CTCs are malignant cells
Cancer dissemination and dormancy
MRD and the CSC phenotype
Oestrogen and progesterone receptor status in MRD
Platelet clumping
Findings
Circulating tumour microemboli
Full Text
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