Circulating Tumor Cells in Breast Cancer Metastatic Disease

This book is aimed to summarise the key aspects of the role of circulating tumour cells (CTCs) in breast cancer, with special attention to their contribution to tumour progression and establishment of metastatic disease. We aim to give a clear overview of the knowledge about CTCs, framed in the context of breast cancer, by analysing basic and clinical research carried out so far. In a broader sense, we will address what are the main clinical needs of this disease based on its molecular heterogeneity (subtypes) and lay out the knowledge and understanding that CTCs are giving about it and how they are contributing and can still improve the better monitoring and management of breast cancer patients. We will discuss the evidences of the use of CTCs as a tool to monitor cancer progression and therapy response, based on the prognostic and predictive value they have, as well as a tool to unravel mechanisms of resistance to therapy and to identify new biomarkers allowing to predict therapy success. Moreover, we will analyse the main aspects of ongoing clinical trials and how they can contribute to determine the clinical utility of CTCs as a breast cancer biomarker. We will also touch upon general knowledge or basic notions of the biology of the metastatic process in epithelial cancers, in order to understand the origin and biology of CTCs. In this sense, we will pay special attention to EMT (epithelial to mesenchymal transition), dormancy and minimal residual disease, three key aspects that determine the outcome of the disease. We will also cover general aspects on the isolation and characterization techniques applies to the study of CTCs, and also the possibilities that the study of CTCs, as a biomarker with biological function, is opening in terms of understanding the biology of metastatic cells and the identification of therapeutic targets based on the functional and molecular characterization of CTCs. Lastly, we will try to foresee the future of CTCs in terms of clinical application and implementation in the clinical routine.

Preface Chapter 1.

Introduction – Biology of Breast Cancer Metastasis and Importance of the Analysis of CTCs

Chapter 2.

Epithelial-Mesenchymal Plasticity in Circulating Tumor Cells, the Precursors of Metastasis

Chapter 3.

Disseminated Tumor Cells and Dormancy in Breast Cancer Progression

Chapter 4.

Methodology for the Isolation and Analysis of CTCs

Chapter 5. Advances in the Characterization of Circulating Tumor Cells in Metastatic Breast Cancer: Single Cell Analyses and Interactions, and Patient-derived Models for Drug Testing

Chapter 6. Circulating Tumor Cells (CTCs) Heterogeneity in Metastatic Breast Cancer: Different Approaches for Different Needs

Chapter 7.

Relevance of CTC Clusters in Breast Cancer Metastasis

Chapter 8.

Epigenetics of Circulating Tumor Cells in Breast Cancer

Chapter 9.

Circulating Tumor Cells: Applications for Early Breast Cancer

Chapter 10.

Clinical Relevance and Therapeutic Application of CTCs in Advanced Breast Cancer

Roberto Piñeiro completed his doctoral studies on the biology and metabolism of cardiomyocytes in 2005, in the Department of Medicine at the University of Santiago de Compostela. In 2007 he joined the Phosphoinositide group for his post-doctoral in the Blizard Institute, Queen Mary University of London, where he studied the role of the GPR55 receptor and its ligand, lysophosphatidyl inositol (LPI) on cell proliferation in prostate and ovarian cancer.

Then in 2011 he was incorporated into the Cell Signalling group of Barts Cancer Institute, Queen Mary University of London, currently located at the UCL Cancer Institute, University College London. In this laboratory, Roberto worked studying the role of Class I PI3K in cell signalling in cancer and the tumour micro environment using “knock-in” mice and cellular models.

He is currently Head of the Cancer Modelling Line of the Roche-Chus Joint Unit