Managing

Breast Cancer
Risk
 Managing
Breast Cancer
Risk
MONICA MORROW, MD
Professor of Surgery
Director, Lynn Sage Breast Center

V. CRAIG JORDAN, OBE, PhD, DSc

Diana, Princess of Wales Professor of Cancer Research
Director, Lynn Sage Breast Cancer Research Program

both of

Northwestern University
Feinberg School of Medicine
Chicago, Illinois

2003
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Notice: The authors and publisher have made every effort to ensure that the patient care recommended herein, including choice of drugs
and drug dosages, is in accord with the accepted standard and practice at the time of publication. However, since research and regula-
tion constantly change clinical standards, the reader is urged to check the product information sheet included in the package of each
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contained herein is not intended as, and should not be employed as, a substitute for individual diagnosis and treatment.
To our parents, Maxine and J. Robert Morrow, and Cynthia Jordan,
for teaching us what is important in life
 PREFACE

T
en years ago there was no need for this book. The emphasis in cancer was on early treatment, and
prophylactic mastectomy was the only option to reduce risk for the high-risk woman. In the past
decade, breast cancer genetics has become a reality, tamoxifen is clinically available to reduce breast
cancer risk, and risk assessment is an active area of clinical research. Breast cancer risk assessment and man-
agement is a true multidisciplinary endeavor. It requires an understanding of epidemiology, genetics, imag-
ing, and drugs traditionally associated with cancer treatment, as well as surgery and psychology. Even in ma-
jor cancer centers, multidisciplinary teams devoted to risk management are uncommon. The purpose of this
book is to bring together a multidisciplinary group of experts to address breast cancer risk in a clinically
meaningful way. Chapters providing detailed information on individual risk factors are accompanied by a
discussion of models that integrate multiple factors for a more complete assessment of risk. Traditional
strategies for risk management, including surveillance and prophylactic surgery, are reviewed, and the data
on newer techniques such as ductal lavage and screening with magnetic resonance are presented. The ra-
tionale for chemoprevention with selective estrogen receptor modulators (SERMs) is discussed, and the ev-
idence for tamoxifen as a chemopreventive is updated. The potential for chemoprevention with newer
SERMs and the aromatase inhibitors is reviewed. Finally, the critical (and often ignored) areas of quality of
life and symptom management are addressed.

This book is a single source for information needed by primary care physicians, nurses, and gynecolo-
gists, as well as oncologic specialists who deal with women who are concerned about breast cancer.

Monica Morrow, MD and V. Craig Jordan, OBE, PhD, DSc

July 2003
 CONTENTS

Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii
Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii

Section One: Evaluation of Risk

1. Overview of Clinical Risk Assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Julia Tchou, MD, PhD, Monica Morrow, MD
2. Familial and Genetic Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 26
Claudine Isaacs, MD, FRCPC, Beth N. Peshkin, MS, CGC, Marc Schwartz, PhD
3. Endocrine Risk Factors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Leslie Bernstein, PhD
4. Benign Breast Disease and Breast Cancer Risk . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 57
Elizabeth L. Wiley, MD
5. Lifestyle, Environmental Factors, and Breast Cancer Risk . . . . . . . . . . . . . . . . . . . . . . 70
Susan M.Gapstur, PhD, MPH
6. Breast Cancer Risk in the Context of Overall Health . . . . . . . . . . . . . . . . . . . . . . . . . . 80
Aarati Didwania, MD, Aparna Priyanath, MD, MPH

Section Two: Risk Management Strategies

Surveillance
7. Outcome of Routine Surveillance of the High-Risk Woman . . . . . . . . . . . . . . . . . . . 103
Valerie L. Staradub, MD
8. Newer Imaging Approaches to the High-Risk Woman . . . . . . . . . . . . . . . . . . . . . . . . 116
R. Edward Hendrick, PhD, FACR, Jean R. Paquelet, MD, FACR,
Ellen B. Mendelson, MD, FACR
9. Role of Breast Epithelial Sampling Techniques in High-Risk Women . . . . . . . . . . . . 138
Mehra Golshan, MD, Seema A. Khan, MD

Chemoprevention
10. Biologic Basis for Breast Cancer Risk Reduction with Pharmacologic Agents . . . . . . 159
V. Craig Jordan, OBE, PhD, DSc
11. Tamoxifen for Chemoprevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 175
D. Lawrence Wickerham, MD, Joseph P. Constantino, DrPH
12. SERMs Other Than Tamoxifen for Chemoprevention . . . . . . . . . . . . . . . . . . . . . . . 186
Ruth M. O’Regan, MD, William J. Gradishar, MD, FACP
x Contents

13. Aromatase Inhibitors for Chemoprevention . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199

Paul E. Goss, MD, PhD, FRCPC, FRCP (UK), Kathrin Strasser-Weippl, MD
14. Quality of Life Issues with Endocrine Chemoprevention . . . . . . . . . . . . . . . . . . . . . . 214
Stephanie R. Land, PhD, Patricia A. Ganz, MD
15. Improving Quality of Life for Women at High Risk for Breast Cancer:
Symptom Management without Estrogen . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 227
Tait D. Shanafelt, MD, Charles Loprinzi, MD

Surgical Prevention
16. Prophylactic Mastectomy and Oophorectomy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 241
Faina Nakhlis, MD, Monica Morrow, MD
17. Breast Reconstruction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 259
Neil A. Fine, MD, FACS, Robert M. Saltzmann, BA

Section Three: Practical Management Guidelines

18. Practical Management Guidelines . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 289
Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 294
 Acknowledgments

The authors acknowledge the invaluable assistance of Burton Korman,

who helped make this book a reality.
 CONTRIBUTORS

LESLIE BERNSTEIN, PhD WILLIAM J. GRADISHAR, MD, FACP

Professor and AFLAC Inc., Associate Professor, Medicine
Chair in Cancer Research Director, Breast Medicine Oncology
Preventive Medicine Feinberg School of Medicine
Keck School of Medicine Northwestern University
University of Southern California Chicago, Illinois
Los Angeles, California
R. EDWARD HENDRICK, PhD, FACR
JOSEPH P. CONSTANTINO, DrPH Research Professor, Radiology
Professor, Biostatistics Director, Breast Imaging Research
Graduate School of Public Health Lynn Sage Breast Center
Pittsburgh, Pennsylvania Feinberg School of Medicine
AARATI DIDWANIA, MD Northwestern University
Clinical Instructor, Internal Medicine Chicago, Illinois
Feinberg School of Medicine CLAUDINE ISAACS, MD, FRCPC
Northwestern University Associate Professor of Medicine and Oncology
Chicago, Illinois Georgetown University Medical Center
NEIL A. FINE, MD, FACS Washington, District of Columbia
Assistant Professor, Plastic Surgery
V. CRAIG JORDAN, OBE, PhD, DSc
Feinberg School of Medicine
Diana, Princess of Wales Professor of Cancer Research
Northwestern University
Director, Lynn Sage Breast Cancer Research Program
Chicago, Illinois
Feinberg School of Medicine
PATRICIA A. GANZ, MD Northwestern University
Professor, Hematology / Oncology Chicago, Illinois
Director, Cancer Prevention and Control Research
SEEMA A. KHAN, MD
UCLA Schools of Medicine and Public Health
Associate Professor, Surgery
Jonsson Comprehensive Cancer Center at UCLA
Feinberg School of Medicine
Los Angeles, California
Northwestern University
SUSAN M. GAPSTUR, PhD, MPH Chicago, Illinois
Associate Professor, Preventive Medicine
Feinberg School of Medicine STEPHANIE R. LAND, PhD
Northwestern University Research Assistant Professor, Biostatistics
Chicago, Illinois University of Pittsburgh
Pittsburgh, Pennsylvania
MEHRA GOLSHAN, MD
Fellow, Breast Surgery CHARLES LOPRINZI, MD
Feinberg School of Medicine Professor and Chair, Medical Oncology
Northwestern University Mayo Clinic
Chicago, Illinois Rochester, Minnesota

PAUL E. GOSS, MD, PhD, FRCPC, FRCP (UK) ELLEN B. MENDELSON, MD, FACR
Professor, Medicine Professor, Radiology
Director, Breast Cancer Prevention Program Director, Breast Imaging
Princess Margaret Hospital Lynn Sage Breast Center
University Health Network Feinberg School of Medicine
University of Toronto Northwestern University
Toronto, Ontario Chicago, Illinois
xiv Contributors

MONICA MORROW, MD MARC SCHWARTZ, PhD

Professor, Surgery Associate Professor of Oncology
Director, Lynn Sage Breast Center Co-Director, Cancer Control
Feinberg School of Medicine Lombardi Cancer Center
Northwestern University Georgetown University Medical Center
Chicago, Illinois Washington, District of Columbia

FAINA NAKHLIS, MD TAIT D. SHANAFELT, MD

Fellow, Breast Surgery Clinical Instructor, Oncology
Feinberg School of Medicine Mayo Clinic
Northwestern University Rochester, Minnesota
Chicago, Illinois KATHRIN STRASSER-WEIPPL, MD
RUTH M. O’REGAN, MD Medical Oncology
Assistant Professor, Medicine Wilhelminen Hospital
Feinberg School of Medicine Vienna, Austria
Northwestern University VALERIE L. STARADUB, MD
Chicago, Illinois Assistant Professor, Surgical Oncology
Lynn Sage Breast Center
JEAN R. PAQUELET, MD, FACR
Feinberg School of Medicine
Director, Breast Imaging
Northwestern University
Department of Radiology
Chicago, Illinois
Grant Medical Center
Columbus, Ohio JULIA TCHOU, MD, PhD
Fellow, Breast Surgery
BETH N. PESHKIN, MS, CGC Lynn Sage Breast Center
Senior Certified Genetic Counselor Feinberg School of Medicine
Research Assistant Professor of Oncology and Medicine Northwestern University
Georgetown University Medical Center Chicago, Illinois
Washington, District of Columbia
D. LAWRENCE WICKERHAM, MD
APARNA PRIYANATH, MD, MPH Associate Professor, Human Oncology
Clinical Instructor, Internal Medicine Associate Chairman, NSABP
Feinberg School of Medicine Drexal University School of Medicine
Northwestern University Allegheny General Hospital
Chicago, Illinois Pittsburgh, Pennsylvania
ROBERT M. SALTZMANN, BA ELIZABETH L. WILEY, MD
Feinberg School of Medicine Associate Professor, Surgical Pathology
Northwestern University Feinberg School of Medicine
Chicago, Illinois Northwestern University
Chicago, Illinois