Breast Cancer: Nuclear Medicine in Diagnosis and Therapeutic Options

307 Pages·2008·5.473 MB·English

by  Emilio Bombardieri MD, Luca Gianni MD, Gianni Bonadonna MD (eds.)

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I
Foreword
Bombardieri · Bonadonna · Gianni
Breast Cancer
Nuclear Medicine in Diagnosis and Therapeutic Options
III
Foreword
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
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V
Foreword
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.
VII
Preface
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 biodistribution of a
molecular probe. Cancer can be imaged through metabolic pathways (such as glucose
and amino-acid transport, DNA precursor incorporation, hormone receptors, angio-
genesis, hypoxia, antigen expression) targeted by radioactive tracers. This makes it
possible to supplement the morphological description of a tumor with a considerable
amount of biological information. Nuclear medicine images may provide prognostic
VIII
Preface
indications, predict the response to different treatments, and detect the presence
and activity of viable cancer cells in already treated patients. The same radiophar-
maceuticals that target neoplasia and are used in diagnostic imaging can carry high
amounts of radioactivity to cancer cells and thus selectively deliver a lethal irradia-
tion dose to a tumor. For all these reasons nuclear medicine techniques have acquired
an important role in the study and management of breast cancer, and are becoming
more and more integrated in the new developments of molecular biology, pharmacol-
ogy, diagnostic imaging and therapy.
Gianni Bonadonna
IX
Contents
Contents
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
2 Histological Classifi cation of Breast Cancer
Alessandra Fabbri, Maria Luisa Carcangiu, and Antonino Carbone . . . . . 3

3 Biomarkers for Breast Cancer:
Towards the Proposition of Clinically Relevant Tools
Maria Grazia Daidone, Vera Cappelletti, Angelo Paradiso,
Massimo Gion, Nadia Harbeck, Fred Sweep, and Manfred Schmitt . . . . . . . 15
4 Circulating Tumour Markers in Breast Cancer
Ettore Seregni, Antonio Coli, and Nicola Mazzuca . . . . . . . . . . . . . . . . . . . . . . 33
5 Axillary Lymph Node Status Evaluation in Breast Cancer Patients:
Role of SPECT and Pinhole SPECT with Cationic Lipophilic Radiotracers
Giuseppe Madeddu and Angela Spanu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43

6 Breast Imaging with Scintimammography
Orazio Schillaci and John R. Buscombe . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
7 99mTc-MIBI in the Evaluation of Breast Cancer Biology
Silvana Del Vecchio, Antonella Zannetti, Rosa Fonti,
Francesca Iommelli, and Marco Salvatore . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 71
8 Sentinel Node Detection in Pre-Operative Axillary Staging
Giovanni Paganelli, Giuseppe Trifi rò, Oreste Gentilini, Mattia Intra,
Giuseppe Viale, and Umberto Veronesi . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 83
9 State of the Art of Current Modalities for the Diagnosis of Breast Lesions
Cosimo Di Maggio . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
10 New Trends of MRI in Breast Cancer Diagnosis
Daniele Vergnaghi, Giovanna Trecate, and Siranoush Manoukian . . . . . . . 127
11 PET Imaging of Breast Cancer Molecular Biomarkers
Elisabetta Brugola, Andreas K. Buck, Lucia Tagliabue, Sven N. Reske,
and Giovanni Lucignani . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 145
12 The Role of FDG-PET for Axillary Lymph Node Staging in Primary Breast Cancer
Flavio Crippa, Alberto Gerali, Alessandra Alessi, Roberto Agresti,
and Emilio Bombardieri . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 157
X
Contents
13 Measuring Response to Chemotherapy in Locally Advanced Breast Cancer:
Methodological Considerations
Nanda C. Krak, Otto S. Hoekstra, and Adriaan A. Lammertsma . . . . . . . . . . 169

14 FDG-PET in Monitoring Therapy of Breast Cancer
Hans-Jürgen Biersack, Hans Bender, and Holger Palmedo . . . . . . . . . . . . . . . 181

15 FDG-PET and Tumour Marker Tests for the Diagnosis of Breast Cancer
Emilio Bombardieri, Alessandra Alessi, Federica Pallotti,
Gianluca Serafi ni, Nicola Mazzuca, Ettore Seregni,
and Flavio Crippa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 189

16 Advantages and Limitations of FDG PET in the Follow-Up of Breast Cancer
Peter Lind, Isabel Igerc, Thomas Beyer, Abdul Jalil Nordin,
Peter Reinprecht, and Klaus Hausegger . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 201

17 PET/CT and Breast Cancer
Maria Picchio, Cristina Messa, Barbara Zangheri, Claudio Landoni,
Lugio Gianolli, and Ferruccio Fazio . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 217

18 Current Role of Bone Scan with Phosphonates in the Follow-Up of Breast Cancer
Lorenzo Maffi oli, Luigia Florimonte, Luca Pagani, Ivana Butti,
and Isabel Roca . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227

19 Progress in the Treatment of Early and Advanced Breast Cancer
Valentina Guarneri, Frederico Piacentini, and PierFranco Conte . . . . . . . 239
20 186Re-HEDP for Metastatic Bone Pain in Breast Cancer Patients
Marnix G. E. H. Lam, John M. H. de Klerk, and Peter P. van Rijk . . . . . . . . . . . 257

21 153Sm-EDTM for Bone Pain Treatment in Skeletal Metastases
Carlo Ludovico Maini, Serenella Bergomi, Rosella Pasqualoni,
Lidia Strigari, and Rosa Sciuto . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 271
22 The Choice of the Correct Imaging Modality in Breast Cancer Management
Paola Mariani and Luca Gianni . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 281

Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 293