Foreword I Bombardieri · Bonadonna · Gianni Breast Cancer Nuclear Medicine in Diagnosis and Therapeutic Options Foreword III E. Bombardieri · G. Bonadonna · L. Gianni (Eds.) Breast Cancer Nuclear Medicine in Diagnosis and Therapeutic Options With Contributions by R. Agresti · A. Alessi · H. Bender · S. Bergomi · T. Beyer · H.-J. Biersack · E. Bombardieri A. K. Buck · E. Brugola · J. R. Buscombe · I. Butti · V. Cappelletti · A. Carbone M. L. Carcangiu · A. Coli · P. F. Conte · F. Crippa · M. G. Daidone · A. Fabbri · F. Fazio L. Florimonte · R. Fonti · O. Gentilini · A. Gerali · L. Gianni · L. Gianolli · M. Gion V. Guarneri · N. Harbeck · K. Hausegger · O. S. Hoekstra · I. Igerc · M. Intra · F. Iommelli N. C. Krak · J. M. H. de Klerk · M. G. E. H. Lam · A. A. Lammertsma · C. Landoni · P. Lind G. Lucignani · G. Madeddu · L. Maffi oli · C. Di Maggio · C. L. Maini · S. Manoukian P. Mariani · N. Mazzuca · C. Messa · A. J. Nordin · H. Palmedo · G. Paganelli · L. Pagani F. Pallotti · A. Paradiso · R. Pasqualoni · F. Piacentini · M. Picchio · P. Reinprecht · S. N. Reske P. P. van Rijk · I. Roca · M. Salvatore · O. Schillaci · M. Schmitt · R. Sciuto · E. Seregni G. Serfi ni · A. Spanu · L. Strigari · F. Sweep · L. Tagliabue · G. Trecate · G. Trifi rò S. Del Vecchio · D. Vernaghi · U. Veronesi · G. Viale · B. Zangheri · A. Zannetti With 72 Figures in 156 Separate Illustrations, 56 in Color and 30 Tables 123 IV Foreword Emilio Bombardieri, MD Division of Nuclear Medicine Department of Diagnostic Imaging and Radiotherapy Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian 1 20133 Milano Italy Luca Gianni, MD Division of Medical Oncology Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian 1 20133 Milano Italy Gianni Bonadonna, MD Chair, Perspective Clinical Trials Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian 1 20133 Milano Italy Library of Congress Control Number: 2007933314 ISBN 978-3-540-36780-2 Springer Berlin Heidelberg New York This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifi cally the rights of translation, reprinting, reuse of illustrations, recitations, broadcasting, reproduction on microfi lm or in any other way, and storage in data banks. Duplication of this publication or parts thereof is permit- ted only under the provisions of the German Copyright Law of September 9, 1965, in its current version, and permis- sion for use must always be obtained from Springer-Verlag. Violations are liable for prosecution under the German Copyright Law. Springer is part of Springer Science+Business Media http//www.springer.com © Springer-Verlag Berlin Heidelberg 2008 Printed in Germany The use of general descriptive names, trademarks, etc. in this publication does not imply, even in the absence of a specifi c statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. Product liability: The publishers cannot guarantee the accuracy of any information about dosage and application contained in this book. In every case the user must check such information by consulting the relevant literature. Medical Editor: Dr. Ute Heilmann, Heidelberg Desk Editor: Ursula N. Davis, Heidelberg Production Editor: Kurt Teichmann, Mauer Typesetting: Verlagsservice Teichmann, Mauer Cover-Design: Frido Steinen-Broo, eStudio Calamar, Spain Printed on acid-free paper – 21/3180xq – 5 4 3 2 1 0 Foreword V Foreword Breast cancer is the most common malignant disease among Western women and rep- resents a major public health problem, with more than 370,000 new cases and 130,000 deaths per year in women aged 35–64 years in Europe alone. It accounts for one third of the cancer-related deaths in women aged 35–55 years. The efforts of modern oncology to deal with this clinical problem are focused on reaching a diagnosis at the earliest stage, when the disease is still limited, the tumour is resectable and it is still possible to treat with curative intent. Another essential goal of modern research is to characterise the tumour cells in order to categorise patients into different risk groups, identify responders versus nonresponders to therapy, and design adequate targeted therapies that are effective also in the adjuvant setting to eradicate breast cancer cells that might have already spread to distant sites at the time of diagnosis. The great impact of nuclear medicine in oncology is due to its important progress in this fi eld in recent years, and the effect of such progress has been particularly noticeable in breast cancer. Research into molecular imaging has led to the development of several radiopharmaceuticals that can explore the cellular metabolism and visualise, at the molecular and subcellular level, pathological processes specifi c to cancer. Advances in diagnostic equipment have made high-technology instruments available such as PET, which is capable of producing high-quality tomographic images. Such imaging has become of major value to physicians because it often reveals alterations and lesions not demonstrated by conventional morphological techniques such as X-rays, US, CT or MRI. Research into image fusion techniques has led to the design of software pro- grammes capable of merging the molecular, functional and metabolic information of nuclear medicine with the morphological information provided by radiology into a single image. Hybrid instruments (PET/CT, SPECT/CT) are now available which allow the fusion of images of a patient in just one diagnostic session. All these impressive achievements are going to produce important results not only for the diagnosis but also the treatment of cancer. Nuclear medicine explores the func- tion and biology of cells and tissues, and can be considered an experimental area of drug development for individual tailored therapies. In fact, radiopharmaceuticals developed specifi cally to target and visualise malignant tumours can also be used, at high doses, for therapeutic purposes. Nuclear medicine therapeutics thus takes advan- tage of selective radiopharmaceuticals that have demonstrated anticancer effi cacy in many types of tumours. VI Foreword This book on the diagnostic and therapeutic applications of nuclear medicine in breast cancer aims to describe the state of the art and the current position of nuclear medicine in the light of these recent developments and in comparison with conven- tional radiological and nonradiological modalities. Some basic concepts regarding breast cancer are treated and discussed with the aim of providing a general overview on a disease that is the subject of continuous stimulating proposals for research and clinical investigation. The text is therefore intended as an update also for non-nuclear- medicine specialists working in senology and oncology. The new defi nition of nuclear medicine is ‘molecular imaging’ and ‘targeted therapy’ and its clinical impact is becoming increasingly important. We have no doubt that the diagnosis and treatment of breast cancer will benefi t from the new horizons opened up by nuclear medicine. Gianni Bonadonna Emilio Bombardieri Luca Gianni Acknowledgements The editors are grateful to Ms Anna Luisa De Simone Sorrentino for her precious help in compiling this manuscript. Preface VII Preface The last three decades have witnessed tremendous advances in the understanding and treatment of breast cancer. As a result, starting shortly before the 1990s, a per- sistent decrease in breast cancer mortality has been documented, primarily in the United States and in several European countries. Breast cancer, however, remains an important health problem. In this book, which is mainly dedicated to nuclear medicine, experts have thoroughly reviewed the achievements made in the diagnosis, monitoring and treatment of this disease. There is no doubt that breast cancer has always been one of the most appealing areas of cancer research; the vast number of new clinical and preclinical studies published every day in the medical literature is an example. More recently, the development of molecular biology techniques has allowed the identifi cation and analysis of molecular factors that play an important role in normal cell growth and differentiation. Such factors have also been shown to infl uence the behavior of tumors in terms of cellular differentiation, growth rate, metastatic pat- tern and response to therapy. Furthermore, they will be instrumental in the develop- ment of new agents for targeted therapies. Using molecular tracers to characterize neoplastic tissues and to select, among the available effective regimens, the one with the highest probability of cure for the individual patient, is an appealing way to con- duct new research. The ability to predict who will need medical therapy and who will or will not respond to a given drug or drug regimen will serve to guide clinical deci- sion-making and treatment recommendations. Although predictive accuracy may not be an all-or-none phenomenon, patients can be spared treatments that are devoid of effi cacy but are associated with toxicity instead. Besides this, delivering treat- ments that have a more pronounced activity against tumors with specifi c molecular features will lead to improved benefi t for the patient, making the difference between cure and palliation. In this area nuclear medicine follows the new developments in oncology: the modern term “molecular imaging” means to visualize a biological phenomenon at the molecular level according to the specifi city and the specifi c