Endocrinology of Breast Cancer

387 Pages·1999·13.507 MB·English

by  Richard E. Blackwell PhD,MD, Karen R. Hammond MSN,CRNP (auth.), Andrea Manni MD (eds.)

ENDOCRINOLOGY
OF BREAST CANCER
CONTEMPORARY ENDOCRINOLOGY
P. Michael Conn, EonoR
SERIEs
19. Human Growth Hormone: Research and Clinical Practice, edited by RoY G. SMITH
AND MICHAEL 0. THORNER, 1999
18. Menopause: Endocrinology and Management, edited by DAVID B. SEIFER AND
ELIZABETH A. KENNARD, 1999
17. The IGF System: Molecular Biology, Physiology, and Clinical Applications,
edited by RON G. ROSENFELD AND CHARLES ROBERTS, 1999
16. Neurosteroids: A New Regulatory Function in the Nervous System, edited by
ETIENNE-EMILE BAULIEU, MICHAEL SCHUMACHER, AND PAUL ROBEL, 1999
15. Autoimmune Endocrinopathies, edited by ROBERT VOLPE, 1999
14. Hormone Resistance Syndromes, edited by J LARRY JAMESON, 1999
13. Hormone Replacement Therapy, edited by A. WAYNE MEIKLE, 1999
12. Insulin Resistance: Epidemiology, Pathophysiology, and Nondiabetic Clinical
Syndromes, edited by GERALD M. REAVEN AND AMI LAWS, 1999
11. Endocrinology ofB reast Cancer, edited by ANDREA MANNI, 1999
10. Molecular and Cellular Pediatric Endocrinology, edited by
STUART HANDWERGER, 1999
9. The Endocrinology ofP regnancy, edited by FuLLER W. BAZER, 1998
8. Gastrointestinal Endocrinology, edited by GEORGE H. GREELEY, JR., 1999
7. Clinical Management ofD iabetic Neuropathy, edited by ARISTIDIS VEVES, 1998
6. G Proteins, Receptors, and Disease, edited by ALLEN M. SPIEGEL, 1998
5. Natriuretic Peptides in Health and Disease, edited by Wnus K. SAMSON
AND ELLIS R. LEVIN, 1997
4. Endocrinology ofC ritical Diseases, edited by K. PATRICK 0BER, 1997
3. Diseases oft he Pituitary: Diagnosis and Treatment, edited by
MARGARET E. WiERMAN, 1997
2. Diseases oft he Thyroid, edited by LEWIS E. BRAVERMAN, 1997
1. Endocrinology oft he Vasculature, edited by JAMES R. SowERS, 1996
ENDOCRINOWGY
oF CANcER
BREAST
Edited by
ANDREA MANNI, MD
The Pennsylvania State University
College ofM edicine, Hershey, PA
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Originally published by Humana Press Inc. in 1999
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Library of Congress Cataloging-in-Publication Data
Endocrinology of breast cancer I edited by Andrea Manni
p. em. --(Contemporary endocrinology; II)
Includes index.
ISBN 978-1-4757-5139-0 ISBN 978-1-59259-699-7 (eBook)
DOI 10.1007/978-1-59259-699-7
I. Breast-Cancer-Endocrine aspects. I. Manni, Andrea. II. Series:
Contemporary endocrinology (Totwa, N. J.); II.
[DNLM: I. Breast Neoplasms-physiopathology. 2. Breast Neoplasms-etiology.
3. Breast Neoplasms-therapy. 4. Hormones. WP 870E565 1999]
RC280.B8E54 19999
6 16.99'449---<lc21
DNLM/DLC 98-33989
for Library of Congress CIP
PREFACE
Breast cancer is the most common malignancy affecting women in developed coun~
tries. It is estimated that one in eight women will develop this disease in her lifetime.
Close to 200,000 new cases are diagnosed each year in the United States alone. Breast
cancer frequently affects women during the most productive and interactive years oft heir
lives, thus having major financial, social, and psychological consequences. The impor
tance of hormones in the development and growth of human breast cancer has been
recognized for over a century, when Beatson in 1897 reported the therapeutic efficacy of
ovariectomy in women with advanced disease. More recently, over the last couple of
decades, considerable evidence has indicated that estrogens are the predominant hor
mones involved in the biology ofhuman breast cancer. With the advent of molecular
biology techniques, an enormous wealth of new information has been generated on a
variety ofc ellular mechanisms by which hormones influence breast cancer development
and proliferation. Concomitantly, on the clinical side, improved antihormonal agents
have been and are being developed with the goal of introducing them not only in the
treatment, but also in the prevention ofbreast cancer. This explosion ofn ew information
covers a wide spectrum of basic and clinical disciplines ranging from endocrinology to
tumor biology, genetics, medical oncology, surgery, and pathology. The major object of
Endocrinology ofB reast Cancer is to integrate this wealth ofm ultidisciplinary informa
tion into a single volume that will constitute a highly useful reference for all those basic
scientists and clinicians from diverse backgrounds who share an interest in breast cancer.
Section 1 focuses primarily on the hormonal mechanisms controlling normal breast
development and growth. Special emphasis is placed on reviewing the roles ofe strogens,
progesterone, insulin-like growth factors, and their binding proteins.
Section 2 addresses possible derangements in the hormonal milieu oft he host that can
lead to mammary carcinogenesis. The likely importance of local estrogen production,
mediated by overexpression of the aromatase enzyme, is emphasized. This section also
contains an updated review of the genetic changes implicated in breast cancer develop
ment. This is a topic of major importance, since growth factor signaling activated by
various oncogenes is likely to interact with the "classic" estrogen receptor pathway in
inducing the transformed phenotype. Although estrogens are likely to be involved in the
genesis of virtually every breast cancer, transition to hormone independence and to a
more aggressive phenotype inevitably occurs in every case, leading to the patient's de
mise. Considerable research efforts are being devoted to elucidating the steps involved
in such tumor progression, since they can be targeted for therapy. Updated information
on this important area of breast cancer biology is summarized in Section 3. The roles of
oncogenes and tumor suppressor genes, stromal-epithelial interactions, angiogenesis,
the IGF system, and polyamines are reviewed. An updated summary of the prognostic
value of expression of related factors in clinical breast cancer is also provided.
Although estrogens are the predominant hormones affecting human breast cancer
biology, other hormones may be exerting an important influence. Section 4 summarizes
the roles of progesterone, prolactin, and their receptors. In parallel with the increased
awareness oft he importance ofe strogens in human breast cancer, major efforts have been
v
vi Preface
made to introduce methods for the inhibition of estrogen biosynthesis and action into
clinical practice. This important area is covered in Section 5, which provides an updated
review of the clinical use ofLHRH superagonist/antagonists, aromatase inhibitors, and
antiestrogens. Finally, Section 6 covers important aspects of benign breast disease with
emphasis on their treatment and potential for malignant transformation.
By providing an integrated overview of the most significant basic and clinical devel
opments related to the hormonal aspects ofbreast cancer, Endocrinology ofB reast Can
cer will constitute an invaluable broad-ranging resource for all basic scientists, clinicians,
students, and fellows-in-training. Our thanks go to the many contributors to this volume
who are leading experts in their fields and without whose major efforts this book would
not be possible.
Andrea Manni, MD
CONTENTS
Preface ........................................................................................................ v
Contributors .............................................................................................. ix
Part I Hormonal Control of Mammary Development
and Growth
1 Honnonal Control ofNonnal Breast Morphology and Function .... 3
Richard E. Blackwell and Karen R. Hammond
2 Interactions Between Estradiol and Progesterone in
Nonnal Breast: Implications for Mammary Carcinogenesis .... 21
Genevieve Plu-Bureau, Philippe Touraine,
and Pierre Mauvais-Jarvis
3 Expression and Regulation of Insulin-like Growth Factors and
Their Binding Proteins in the Nonnal Breast ............................ 39
Monica M. Richert and Teresa L. Wood
Part II Carcinogenesis
4 Estrogens and Breast Cancer: An Epidemiologic Perspective ....... SS
Heather Spencer Feigelson and Brian E. Henderson
S Androgens, Estrogens, and Breast Cancer Risk ............................. 69
V. H. T James
6 Local Estrogen Production: Is Aromatase An Oncogene? ............. 79
Rajeshwar Rao Tekmal and Richard J. Santen
7 Oncogenes and Mammary Carcinogenesis .................................... 93
Maria Luisa Veronese, Florencia Bullrich,
and Carlo M Croce
8 Categorization of Breast Cyst Fluid and Breast Cancer Risk ...... 109
Luigi Dog/iotti and Pasquale Caraci
Part III Tumor Progression
9 The Role of Tumor Suppressor Genes in
Breast Cancer Progression ....................................................... 119
Robert Callahan
10 Oncogene Activation and Breast Cancer Progression ................. 133
Richard J. Pietras and Mark D. Pegram
11 Interactions Between Stroma and Epithelium
in Breast Cancer: Implications for Tumor Genesis,
Growth, and Progression ......................................................... 1SS
Kevin J Cullen, Sahana S. Kaup, and Audrey A. Rasmussen
VII
viii Contents
12 The Role of Angiogenesis in the Transition to Hormone
Independence and Acquisition of the
Metastatic Phenotype ................................................................ 169
Francis G. Kern
13 Role of the IGF System in Breast Cancer Proliferation
and Progression ......................................................................... 187
A. V. Lee and D. Yee
14 Prognostic and Predictive Factors in Breast Cancer .................... 205
Jan G. M. Klijn, Els M. J. J. Berns, and John A. Foekens
15 Role of the Polyamine Pathway in the Natural History
of Breast Cancer ....................................................................... 221
Andrea Manni
Part IV Estrogen, Progestins, and Prolactin in Breast
Cancer Biology: Targets for Treatment
16 Aromatase Inhibitors in Breast Carcinoma .................................. 233
Harold A. Harvey
17 Role of Progestins and Progesterone Receptors
in Breast Cancer Biology ......................................................... 245
Anne Guiochon-Mantel and Edwin Milgram
18 Prolactin and its Receptors in Human Breast Cancer .................. 261
Barbara K. Vonderhaar
PartY Endocrine Therapy of Breast Cancer
19 Pharmacology and Use of Antiestrogens in Treatment and
Chemoprevention of Breast Cancer ......................................... 283
William J. Gradishar and V. Craig Jordan
20 LHRH Superagonists and Antagonists in the Treatment
of Breast Cancer ....................................................................... 313
P. N. Mainwaring and M. Dowsett
Part VI Benign Breast Disease
21 Benign Breast Lesions: Pathologic Classification
and Risk Potential ..................................................................... 331
Roy A. Jensen
22 Hormonal Treatment of Fibrocystic Disease ............................... 347
Luigi Dogliotti and Pasquale Caraci
23 Gynecomastia and Galactorrhea ................................................... 359
David L. Kleinberg
Index ....................................................................................................... 383
CONTRIBUTORS
ELs M. J. J. BERNS, Dr. Daniel den Hoed Cancer Center, Rotterdam Cancer Institute,
Rotterdam, The Netherlands
RICHARD E. BLACKWELL, Department of Obstetrics and Gynecology, Reproductive
Biology and Endocrinology, The University ofA labama at Birmingham School of
Medicine, Birmingham, AL
FLORENCIA BuLLRICH, Jefferson Cancer Center, Jefferson Medical College, Thomas
Jefferson University, Philadelphia, PA
RoBERT CALLAHAN, Laboratory of Tumor Immunology and Biology, National Cancer
Institute, National Institutes ofH ealth, Bethesda, MD
PASQUALE CARACI, Universita di Torino, Dipartimento di Scienze Cliniche e
Biologiche, Torino, Italy
CARLO M. CROCE, Jefferson Cancer Center, Jefferson Medical College, Thomas
Jefferson University, Philadelphia, PA
KEVIN J. CuLLEN, Division ofH ematology/Oncology, Vincent T. Lombardi Cancer
Research Center, Washington, DC
LUIGI DoGLIOTTI, Universita di Torino, Dipartimento di Scienze C/iniche e
Biologiche, Torino, Italy
MITCHELL DowsETT, Department ofB iochemistry, Royal Marsden Hospital, London, UK
HEATHER SPENCER FEIGELSON, Norris Cancer Center, University ofS outhern California,
Los Angeles, CA
JoHN A. FoEKENS, Dr. Daniel den Hoed Cancer Center, Rotterdam Cancer Institute,
Rotterdam, The Netherlands
WILLIAM J. GRADISHAR, Breast Cancer Research Progam, Robert H. Lurie Cancer Center,
Northwestern University Medical School, Chicago, IL
GEOFFREY L. GREENE, The Ben May Institute for Cancer Research, The University of
Chicago, Chicago, IL
ANNE GuiOCHON-MANTEL, Unite de Recherches Hormones et Reproduction, Faculte de
Medicine de Bicetre, Universite Paris-Sud, Le Kremlin-Bicetre, France
KAREN R. HAMMOND, Department ofO bstetrics and Gynecology, Reproductive Biology
and Endocrinology, The University ofA labama at Birmingham School ofM edicine,
Birmingham, AL
HAROLD A. HARVEY, Division ofH ematology/Oncology, Pennsylvania State University
College ofM edicine, Hershey, PA
BRIAN E. HENDERSON, Norris Cancer Center, University ofS outhern California,
Los Angeles, CA
V. H. T. JAMES, Editor-in-Chief, Endocrine-Related Cancer, Bristol, UK
RoY A. JENSEN, Pathology Tumor Biology Research Laboratories, Vanderbilt
University School ofM edicine, Nashville, TN
V. CRAIG JoRDAN, Director, Breast Cancer Research Progam, Robert H. Lurie Cancer
Center, Northwestern University Medical School, Chicago, IL
SAHANA S. KAuP, Division ofH ematology/Oncology, Vincent T. Lombardi Cancer
Research Center, Washington, DC
ix