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Principles and Practice of Gynecologic Oncology

EIGHTH EDITION

Dennis S. Chi Dineo Khabele Don S. Dizon Catheryn Yashar

PRINCIPLES AND PRACTICE OF GYNECOLOGIC ONCOLOGY

EIGHTH EDITION

PRINCIPLES AND PRACTICE OF GYNECOLOGIC ONCOLOGY

Dennis S. Chi, MD Ronald O. Perelman Chair in Gynecologic Surgery Deputy Chief, Gynecology Service Head, Ovarian Cancer Surgery Department of Surgery Memorial Sloan Kettering Cancer Center New York, New York Don S. Dizon, MD, FACP Professor of Medicine and Professor of Surgery Brown University Director, The Pelvic Malignancies Program Lifespan Cancer Institute Director of Medical Oncology Rhode Island Hospital Associate Director, Community Outreach and Engagement Legorreta Cancer Center at Brown University Providence, Rhode Island

Catheryn Yashar, MD, FACRO, FACR, FABS, FASTRO Professor and Vice-Chair of Clinical Affairs, Radiation Medicine Chief Medical Officer, UC San Diego Health University of California, San Diego San Diego, California Dineo Khabele, MD, FACOG, FACS Mitchell and Elaine Yanow Professor Chair, Department of Obstetrics and Gynecology Washington University School of Medicine in St Louis St Louis, Missouri

Acquisitions Editor: Joe Cho Development Editor: Barton Dudlick Editorial Coordinator: Venugopal Loganathan Editorial Assistant: Kristen Kardoley Marketing Manager: Phyllis Hittner Production Project Manager: Justin Wright Manager, Graphic Arts & Design: Stephen Druding Manufacturing Coordinator: Lisa Bowling Prepress Vendor: S4Carlisle Publishing Services Eighth Edition Copyright © 2025 Wolters Kluwer.

Copyright © 2017, 2013, 2009, 2005, 2001, 1996, 1992 by Lippincott Williams & Wilkins, A Wolters Kluwer business. All rights reserved. This book is protected by copyright. No part of this book may be reproduced or transmitted in any form or by any means, including as photocopies or scanned-in or other electronic copies, or utilized by any information storage and retrieval system without written per mission from the copyright owner, except for brief quotations embodied in critical articles and reviews. Materials appearing in this book prepared by individuals as part of their official duties as U.S. govern ment employees are not covered by the above-mentioned copyright. To request permission, please con tact Wolters Kluwer at Two Commerce Square, 2001 Market Street, Philadelphia, PA 19103, via email at permissions@lww.com, or via our website at shop.lww.com (products and services). 9 8 7 6 5 4 3 2 1 Printed in the United States of America Library of Congress Cataloging-in-Publication Data Names: Chi, Dennis S., editor. | Dizon, Don S., editor. | Yashar, Catheryn M., editor. | Khabele, Dineo, editor. Title: Principles and practice of gynecologic oncology / [edited by] Dennis S. Chi, Don S. Dizon, Catheryn Yashar, Dineo Khabele.

Description: Eighth edition. | Philadelphia: Lippincott Williams & Wilkins, [2025] | Includes bibliographical references and index. Identifiers: LCCN 2023028582 (print) | LCCN 2023028583 (ebook) | ISBN 9781975183271 (hardback) | ISBN 9781975183288 (ebook) Subjects: MESH: Genital Neoplasms, Female | BISAC: MEDICAL / Oncology / General | MEDICAL / Gynecology & Obstetrics Classification: LCC RC280.G5 (print) | LCC RC280.G5 (ebook) | NLM WP 145 | DDC 616.99/465—dc23/eng/20230929 LC record available at https://lccn.loc.gov/2023028582 LC ebook record available at https://lccn.loc.gov/2023028583

This work is provided “as is,” and the publisher disclaims any and all warranties, express or implied, including any warranties as to accuracy, comprehensiveness, or currency of the content of this work. This work is no substitute for individual patient assessment based upon healthcare professionals’ exam ination of each patient and consideration of, among other things, age, weight, gender, current or prior medical conditions, medication history, laboratory data and other factors unique to the patient. The publisher does not provide medical advice or guidance and this work is merely a reference tool. Health care professionals, and not the publisher, are solely responsible for the use of this work including all medical judgments and for any resulting diagnosis and treatments. Given continuous, rapid advances in medical science and health information, independent professional verification of medical diagnoses, indications, appropriate pharmaceutical selections and dosages, and treatment options should be made and healthcare professionals should consult a variety of sources. When prescribing medication, healthcare professionals are advised to consult the product information sheet (the manufacturer’s package insert) accompanying each drug to verify, among other things, condi tions of use, warnings and side effects and identify any changes in dosage schedule or contraindications, particularly if the medication to be administered is new, infrequently used or has a narrow therapeutic range. To the maximum extent permitted under applicable law, no responsibility is assumed by the pub lisher for any injury and/or damage to persons or property, as a matter of products liability, negligence law or otherwise, or from any reference to or use by any person of this work. shop.lww.com

Dedication

T his book is dedicated to our families: Hae-Young Chi and children Jessica, Stephanie, and Andrew Chi; Henry Stoll and children Isabelle, Harrison, and Sophia Dizon-Stoll; Arnold Yashar and children William, Jacob, and Drew Yashar. Their patience, good humor, encouragement, and love have inspired us throughout our careers. In this regard, they have each made signif icant contributions to this book. We would also like

learned from, and taught us over the years. The Gynecologic Oncol ogy community that the readers of this book belong to is dedicated to the advancement of knowledge in the field and its application to out standing patient care. The considerable progress we have achieved together in the understanding, diagnosis, treatment, and prevention of these cancers is presented in this book. On behalf of the Gyne

cologic Oncology com munity, we dedicate this edition of Principles and Practice of Gynecologic Oncology to the brave and courageous patients we all serve, and take in spiration in the oath we all share.

to express our gratitude to our own esteemed professors who guided and mentored us, and to all of the colleagues we have worked alongside,

HIPPOCRATIC OATH

I swear to fulfill, to the best of my ability and judgment, this covenant: ✜ I will respect the hard-won scientific gains of those physicians in whose steps I walk, and gladly share such knowledge as is mine with those who are to follow. ✜ I will apply, for the benefit of the sick, all measures which are required, avoiding those twin traps of overtreatment and therapeutic nihilism. ✜ I will remember that there is art to medicine as well as science, and that warmth, sympathy, and understanding may outweigh the surgeon’s knife or the chemist’s drug. ✜ I will not be ashamed to say “I know not,” nor will I fail to call in my colleagues when the skills of another are needed for a patient’s recovery. ✜ I will respect the privacy of my patients, for their problems are not disclosed to me that the world may know. Most especially must I tread with care in matters of life and death. Above all, I must not play at God. ✜ I will remember that I do not treat a fever chart, a cancerous growth, but a sick human being, whose illness may affect the person’s family and economic stability. My responsibility includes these related problems, if I am to care adequately for the sick. ✜ I will prevent disease whenever I can, for prevention is preferable to cure. ✜ I will remember that I remain a member of society, with special obligations to all my fellow human beings, those sound of mind and body as well as the infirm. ✜ If I do not violate this oath, may I enjoy life and art, respected while I live and remembered with affection thereafter. May I

Copyright © 2024 Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited. always act so as to preserve the finest traditions of my calling and may I long experience the joy of healing those who seek my help.

Preface

T he publication in 2017 of the seventh edition of Principles and Practice of Gynecologic Oncology marked the 25th an niversary of the creation of this textbook. The founding ed itors, William J. Hoskins, Carlos A. Perez, and Robert C. Young, represented the disciplines of Gynecologic Oncology, Radiation Oncology, and Medical Oncology. They created the first multidisci plinary textbook in the field and, in their words, “strove to produce a definitive reference written at the expert level.” The focus on mul tidisciplinary approaches to treatment and a detailed presentation of the literature on which clinical care is based continue to be a guiding principle. The second set of editors, Richard R. Barakat, Maurie Markman, Marcus Randall, and for two editions Andrew Berchuck, also rep resented Gynecologic, Medical, and Radiation Oncology. Over the course of several editions, they incorporated new chapters that re flected dramatic progress in the understanding and treatment of women’s cancers. Simultaneously, advances in technology facilitat ed the use of full color throughout the book as well as increasing ly user-friendly online versions that allow access to cutting-edge information at the point of care. As the editors of Principles and Practice of Gynecologic Oncology , we owe a debt of gratitude to our predecessors. We are proud to con tinue their tradition of bringing together multidisciplinary expertise that also includes Pathology, Radiology, and Basic/Translational Sci ence colleagues. Given the pace of discovery and change within the field, we strove to ensure that this new edition reflects the many ad vances in the field. To this end, this edition includes updates on the numerous advances in molecular, immunologic, and targeted thera pies. With an overwhelming amount of information on gynecologic cancers available on the internet combined with limited time to read, study, and digest all the new studies and approaches, we worked to reorganize the book to make it more reader-friendly and focused on

disease sites. Rather than having the sections of the book devoted to general oncologic principles and then one section dedicated specifi cally to a dozen or so disease sites, in this eighth edition each disease site is its own section. The sections are divided into separate chapters specific to the disease site such as surgery for cervical cancer, treat ment of persistent and recurrent endometrial cancer, and new ther apeutics for ovarian cancer. We hope these changes will decrease redundancy, focus the key aspects of each disease site, and provide the reader with a more expeditious reference source. We have given considerable thought to the issue of how best to maintain the relevance of the book between printed editions in an era of instant access to new information on the internet. Solutions include smartphone access to the content of the textbook with en hanced search capabilities, as well as more frequent online updates as new studies are reported. We also now include online access to a comprehensive library of surgical videos to ensure that surgical techniques are not only read but also visualized. The planning and organization of this eighth edition began just before the lockdowns of the COVID pandemic. With fear and uncertainty about global, national, and personal health, our con tributors persevered in taking care of patients, their families, and their communities. We are so thankful for their dedication and thoroughness. They volunteered their downtime to help us revamp this eighth edition and now, with the COVID pandemic hopefully behind us, we can all focus on our shared passion to cure and erad icate gynecologic cancers worldwide.

Dennis S. Chi, MD, FACOG, FACS Don S. Dizon, MD, FACP, FASCO Catheryn Yashar, MD, FACRO, FACR, FABS, FASTRO Dineo Khabele, MD, FACOG, FACS

vii

Acknowledgments

T he editors acknowledge the contributions of numerous individuals without whom this book would not have been possible. The talented staff of Wolters Kluwer, specifically production manager Justin Wright, editorial coordinator Venu gopal Loganathan, and development editor Barton Dudlick, pro vided invaluable encouragement, direction, and guidance during the creative process and in technical execution. Bharathi Sanjeev provided outstanding production services. From the Academic

Office of the Gynecology Service, Department of Surgery, Memo rial Sloan Kettering Cancer Center, we acknowledge the invalu able contributions of editors George Monemvasitis and Jenifer Levin. Their attention to detail, patience, and communication skills were of the utmost importance throughout the publication process. Our appreciation for all their efforts cannot be adequate ly expressed, but we hope they know how much we value their contributions.

Section Editors

Sushil Beriwal, MD, MBA, FASTRO, FABS Academic Chief and Professor

Amanda Nickles Fader, MD Professor of Gynecology and Obstetrics Professor of Oncology Vice-Chair, Gynecologic Surgical Operations Baltimore, Maryland Katherine Fuh, MD, PhD Associate Professor of Obstetrics and Gynecology Washington University St Louis, Missouri Theresa A. Graves, MD, FACS Clinical Director Lifespan Cancer Institute Breast Center Director, Center for Breast Care Brown Surgical Associates Associate Professor of Surgery The Warren Alpert Medical School of Brown University Providence, Rhode Island Laura J. Havrilesky, MD, MHSc Professor of Obstetrics and Gynecology Gynecologic Oncology Duke University Durham, North Carolina Mario M. Leitao Jr, MD Attending Surgeon Department of Surgery/Gynecologic Oncology Memorial Sloan Kettering Cancer Center New York, New York Ernst Lengyel, MD, PhD Professor and Chairman Section of Gynecologic Oncology Department of Obstetrics and Gynecology University of Chicago Chicago, Illinois

Allegheny Health Network Pittsburgh, Pennsylvania

Ross S. Berkowitz, MD William H. Baker Professor of Gynecology Harvard Medical School

Director of Gynecologic Oncology Brigham and Women’s Hospital Dana-Farber Cancer Institute Director of New England Trophoblastic Disease Center Boston, Massachusetts

Jubilee Brown, MD Professor, Wake Forest University Division Director of Gynecologic Oncology Atrium Health Levine Cancer Institute Charlotte, North Carolina Andrew R. Bruggeman, MD Assistant Professor Radiation Medicine and Applied Sciences UC San Diego Health La Jolla, California

Marcela G. del Carmen, MD, MPH Professor of Obstetrics, Gynecology and Reproductive Biology Division of Gynecologic Oncology Department of Obstetrics and Gynecology Massachusetts General Hospital

Harvard Medical School Boston, Massachusetts

Sean C. Dowdy, MD, FACS, FACOG Professor and Vice-Chair Department of Obstetrics and Gynecology Mayo Clinic College of Medicine Rochester, Minnesota

Ramez N. Eskander, MD Professor of Gynecologic Oncology Division of Gynecologic Oncology Department of Obstetrics, Gynecology and Reproductive Sciences Moores Cancer Center University of California, San Diego La Jolla, California

Contributors

Sunil J. Advani, MD Professor Radiation Medicine and Applied Sciences Co-Leader Cancer Biology and Signaling Program. Moores Cancer Center University of California, San Diego La Jolla, California

Agnes Julia Bilecz, MD, PhD Pathologist Department of Pathology University of Chicago Chicago, Illinois 2nd Department of Pathology Semmelweis University Budapest, Hungary

Ebtesam Ahmed, PharmD Clinical Professor Clinical Health Professions St. John’s University College of Pharmacy Queens, New York Shannon Dawn Armbruster, MD, MPH Assistant Professor Division of Gynecologic Oncology Virginia Tech Carilion School of Medicine Roanoke, Virginia Emeline M. Aviki, MD, MBA Assistant Attending, Gynecologic Surgery Department of Surgery Memorial Sloan Kettering Cancer Center New York, New York

Deborah Billmire, MD Professor of Surgery Department of Surgery, Division of Pediatric Surgery Indiana University School of Medicine Indianapolis, Indiana Teresa K. L. Boitano, MD Assistant Professor, Division of Gynecologic Oncology Department of Obstetrics and Gynecology

University of Alabama, Birmingham, Alabama

Antonio Braga, MD, PhD Director of Rio de Janeiro Trophoblastic Disease Center Department of Obstetrics and Gynecology Associated Professor, Rio de Janeiro Federal University and Fluminense Federal University Maternity School of Rio de Janeiro Federal University and Antonio Pedro University Hospital of Fluminense Federal University Full Professor, Vassouras University Rio de Janeiro, RJ, Brazil

Rani Bansal, MD, BA Oncology Fellow Division of Hematology/Oncology Brown University Providence, Rhode Island Meena Bedi, MD Radiation Oncologist Department of Radiation Oncology Medical College of Wisconsin Milwaukee, Wisconsin

Amy Bregar, MD Instructor of Obstetrics and Gynecology Division of Gynecologic Oncology Department of Obstetrics and Gynecology Massachusetts General Hospital

Harvard Medical School Boston, Massachusetts

Andrew Berchuck, MD Director, Division of Gynecologic Oncology Obstetrics and Gynecology Duke University Durham, North Carolina Sushil Beriwal, MD, MBA, FASTRO, FABS Academic Chief and Professor Priya Bhosale, MD Professor Department of Diagnostic Radiology Division of Diagnostic Imaging The University of Texas MD Anderson Cancer Center Houston, Texas Allegheny Health Network Pittsburgh, Pennsylvania

James J. Burke, II, MD, FACOG, FACS The Donald G. Gallup Scholar of Gynecologic Oncology Professor and Director, Gynecologic Oncology Mercer University School of Medicine, Savannah Campus Savannah, Georgia Robert Tucker Burks, MD Professor Department of Pathology and Laboratory Medicine Indiana University School of Medicine Indianapolis, Indiana

xiii

xiv Contributors

Susana M. Campos, MD, MPH Medical Oncologist

Christine Duffy, MD, MPH Director of Adult Cancer Survivorship Program

Lifespan Cancer Institute Providence, Rhode Island

Director of Clinical Pathways, Division of Gynecologic Oncology Director of Educational Initiatives, Division of Gynecologic Oncology Institute Physician Assistant Professor of Medicine Harvard Medical School

Kevin M. Elias, MD, FACOG Assistant Professor Division of Gynecologic Oncology Department of Obstetrics and Gynecology New England Trophoblastic Disease Center

Brigham and Women’s Hospital Dana Farber Cancer Institute Boston, Massachusetts

Brigham and Women’s Hospital Dana-Farber Cancer Institute Harvard Medical School Boston, Massachusetts

Fernanda Freitas Oliveira Cardoso, MD, PhD Rio de Janeiro Trophoblastic Disease Center Department of Obstetrics and Gynecology Affiliated Professor, Rio de Janeiro Federal University Maternity School of Rio de Janeiro Federal University Rio de Janeiro, RJ, Brazil Marcela G. del Carmen, MD, MPH Professor of Obstetrics, Gynecology and Reproductive Biology Division of Gynecologic Oncology Department of Obstetrics and Gynecology Massachusetts General Hospital

Lora Hedrick Ellenson, MD Attending Physician Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York, New York

Beth A. Erickson, MD Professor Department of Radiation Oncology Medical College of Wisconsin Milwaukee, Wisconsin

Harvard Medical School Boston, Massachusetts

Christine Chin, MD Assistant Professor of Radiation Oncology Columbia Irving Medical Center Vagelos College of Physicians and Surgeons New York, New York

Elizabeth Euscher, MD Professor Department of Pathology The University of Texas MD Anderson Cancer Center Houston, Texas Mary Anne Fenton, MD Clinical Associate Professor Lifespan Cancer Institute The Warren Alpert Medical School of Brown University Providence, Rhode Island

Rani Chudasama, MD, BA Oncology Fellow Division of Hematology/Oncology Brown University Providence, Rhode Island

David E. Cohn, MD, MBA, FACHE Chief Executive Officer (Interim), Chief Medical Officer, and Professor Division of Gynecologic Oncology The James Cancer Hospital Columbus, Ohio

Gini F. Fleming, MD Professor of Medicine

Section of Hematology/Oncology University of Chicago Medicine Chicago, Illinois

Lindsay Frazier Professor of Pediatrics, Harvard Medical School Institute Physician, Pediatric Hematology/Oncology Dana-Farber Cancer Institute/Boston Children’s Hospital Boston, Massachusetts Katherine Fuh, MD, PhD Associate Professor Department of Obstetrics and Gynecology Washington University School of Medicine in St Louis St Louis, Missouri David M. Gershenson, MD Professor Department of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Center Houston, Texas

Bradley R. Corr, MD Assistant Professor Division of Gynecologic Oncology Department Obstetrics and Gynecology University of Colorado Aurora, Colorado Allan Covens, MD, FRCSC Chair, Gynecologic Oncology Department of Obstetrics and Gynaecology University of Toronto Toronto, Ontario, Canada

Don S. Dizon, MD, FACP Professor of Medicine and Professor of Surgery Brown University Director, The Pelvic Malignancies Program Lifespan Cancer Institute Director of Medical Oncology Rhode Island Hospital Associate Director, Community Outreach and Engagement Legorreta Cancer Center at Brown University Providence, Rhode Island

Allison Gockley, MD Assistant Professor

Harvard Medical School Gynecologic Oncologist Massachusetts General Hospital Boston, Massachusetts

Contributors xv

Elizabeth L. Jewell, MD, MHSc, FACOG, FACS Associate Professor of Surgery Department of Surgery Weill Cornell Medical Center Vice-Chair, Regional Network and Affiliates Director of Surgery, MSK Monmouth and Basking Ridge Director of MSK Monmouth ORs Interim Associate Deputy Physician-in-Chief, Strategic Partnerships

Charlie Gourley, BSc, MB ChB, PhD, FRCP Professor and Honorary Consultant in Medical Oncology

CRUK Scotland Centre University of Edinburgh Edinburgh, Scotland, United Kingdom

Stephanie L. Graff, MD Director of Breast Oncology Assistant Professor of Medicine Division of Medical Oncology and Hematology Lifespan Cancer Institute The Warren Alpert Medical School of Brown University Providence, Rhode Island Theresa A. Graves, MD, FACS Clinical Director Lifespan Cancer Institute Breast Center Director, Center for Breast Care Brown Surgical Associates Associate Professor of Surgery The Warren Alpert Medical School of Brown University Providence, Rhode Island Andrea R. Hagemann, MD, MSCI Associate Professor of Obstetrics and Gynecology Division of Gynecologic Oncology Department of Obstetrics and Gynecology Washington University in St Louis School of Medicine St Louis, Missouri Matthew M. Harkenrider, MD Associate Professor Department of Radiation Oncology Stritch School of Medicine, Loyola University Medical Center Maywood, Illinois Jaroslaw T. Hepel, MD, FACRO Associate Professor Department of Radiation Oncology Lifespan Cancer Institute The Warren Alpert Medical School of Brown University Providence, Rhode Island R. Tyler Hillman, MD, PhD Assistant Professor and CPRIT Scholar in Cancer Research Department of Gynecologic Oncology and Reproductive Medicine Department of Genomic Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Neil S. Horowitz, MD Associate Professor of Obstetrics, Gynecology, and Reproductive Biology Harvard Medical School Co-Director, New England Trophoblastic Disease Center Laura J. Havrilesky, MD, MHSc Professor of Obstetrics and Gynecology Gynecologic Oncology Duke University Durham, North Carolina

Medical Director, Department of Surgery Memorial Sloan Kettering Cancer Center New York, New York

Jenna Kahn, MD Assistant Professor

Department of Radiation Medicine Oregon Health and Science University Portland, Oregon Josephine Kang, MD, PhD Assistant Professor Department of Radiation Oncology New York Presbyterian Weill Cornell Medical Center New York, New York Emily M. Ko, MD, MSCR Assistant Professor Division of Gynecologic Oncology Department of Obstetrics and Gynecology Division of Epidemiology and Community Health University of Minnesota School of Public Health Minneapolis, Minnesota Charles A. Kunos, MD, PhD Professor Radiation Medicine University of Kentucky Lexington, Kentucky Katherine C. Kurnit, MD, MPH Assistant Professor Section of Gynecologic Oncology Department of Obstetrics and Gynecology University of Chicago Chicago, Illinois Charles N. Landen Jr, MD, MS Associate Professor Department of Obstetrics and Gynecology University of Virginia Charlottesville, Virginia Carrie Langstraat, MD Associate Professor Department of Obstetrics and Gynecology Mayo Clinic Rochester, Minnesota Ricardo R. Lastra, MD Associate Professor of Pathology Department of Pathology University of Chicago Medical Center Chicago, Illinois University of Pennsylvania Philadelphia, Pennsylvania Shalini L. Kulasingam, PhD Professor

Brigham and Women’s Hospital Dana-Farber Cancer Institute Boston, Massachusetts

xvi Contributors

Barrett Lawson, MD Assistant Professor Department of Pathology The University of Texas MD Anderson Cancer Center Houston, Texas Charles A. Leath III, MD, MSPH Direction, Division of Gynecologic Oncology Ellen Gregg Shook Culverhouse Endowed Chair Department of Obstetrics and Gynecology University of Alabama at Birmingham Birmingham, Alabama Mario M. Leitao Jr, MD Attending Surgeon Department of Surgery/Gynecologic Oncology Memorial Sloan Kettering Cancer Center New York, New York Ernst Lengyel, MD, PhD Professor and Chairman Section of Gynecologic Oncology Department of Obstetrics and Gynecology University of Chicago Chicago, Illinois Margaret I. Liang, MD, MS Assistant Professor Division of Gynecologic Oncology Department of Obstetrics and Gynecology Cedars-Sinai Medical Center Los Angeles, California Diane C. Ling, MD Assistant Professor of Radiation Oncology Los Angeles, California Sanjana Luther, MD Fellow Department of Gastroenterology Mount Sinai New York, New York Izildinha Maestá, MD, PhD Director of Botucatu Trophoblastic Disease Center Department of Obstetrics and Gynecology Associated Professor, São Paulo State University Botucatu, SP, Brazil Martha B. Mainiero, MD Director of Breast Imaging Professor of Diagnostic Imaging Rhode Island Hospital The Warren Alpert Medical School of Brown University Providence, Rhode Island Giorgia Mangili, MD Senior Physician Gynaecology, Obstetric Unit IRCCS San Raffaele Scientific Institute Milan, Italy Department of Radiation Oncology University of Southern California

Koji Matsuo, MD, PhD, FACOG Associate Professor, Chief in Oncology Research

Division of Gynecologic Oncology University of Southern California Los Angeles, California

Jyoti Mayadev, MD Professor of Radiation Medicine and Applied Sciences University of California, San Diego La Jolla, California

Katherine M. McBride, MD, FACS Assistant Professor General Surgery

Associate Program Director Surgical Critical Care Fellowship Mercer University School of Medicine, Savannah Campus Savannah, Georgia

Diana Miao, MD Department of Gynecology and Obstetrics Johns Hopkins Hospital Baltimore, Maryland

Jeffrey C. Miecznikowski, PhD Associate Professor Department of Biostatistics SUNY University at Buffalo Buffalo, New York

Austin Miller, PhD Clinical Trials Development Division Director of Biostatistics Biostatistics and Bioinformatics Roswell Park Comprehensive Cancer Center Buffalo, New York

Chelsea Miller, MD Radiation Oncologist Department of Radiation Oncology Lifespan Cancer Institute The Warren Alpert Medical School of Brown University Providence, Rhode Island

Kathryn M. Miller, MD Fellow Department of Surgery Memorial Sloan Kettering Cancer Center New York, New York Kathryn A. Mills, MD Assistant Professor Department of Obstetrics and Gynecology University of Chicago Chicago, Illinois

Amir Momeni-Boroujeni, MD Gynecologic and Molecular Pathologist Department of Pathology and Laboratory Medicine Memorial Sloan Kettering Cancer Center New York, New York

Firas Mourtada, PhD, MSE, DABR, FAAPM, FABS, FASTRO Professor & Enterprise Medical Physics Director Department of Radiation Oncology, Sidney Kimmel Cancer Center Thomas Jefferson University Hospital Philadelphia, Pennsylvania

Emily J. Martin, MD, MS Assistant Clinical Professor Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, California

Contributors xvii

Dimitrios Nasioudis, MD Fellow Division of Gynecologic Oncology Department of Obstetrics and Gynecology

Michael W. Sill, PhD Senior Biostatistician Clinical Trials Development Division Roswell Park Comprehensive Cancer Center Buffalo, New York Priya K. Simoes, MD, CNSC Assistant Professor Division of Gastroenterology Department of Medicine Mount Sinai West and Mount Sinai Morningside New York, New York Olesya Solheim, MD, PhD Consultant in Gynaecology and Obstetrics Department of Gynaecological Oncology The Norwegian Radium Hospital Oslo University Hospital Oslo, Norway

University of Pennsylvania Philadelphia, Pennsylvania

Natsai C. Nyakudarika, MD Clinical Assistant Professor Division of Gynecologic Oncology Department of Obstetrics and Gynecology Los Angeles (UCLA) Medical Center Harbor-University of California Torrance, California Roisin E. O’Cearbhaill, MD Associate Professor Medicine Memorial Sloan Kettering Cancer Center Weill Cornell College of Medicine New York, New York M. H. M. Oonk, MD Gynecologic Oncologist Department of Obstetrics and Gynecology University Medical Center Groningen Groningen, The Netherlands Gabriela Paiva, MD Rio de Janeiro Trophoblastic Disease Center Department of Obstetrics and Gynecology

Anil K. Sood, MD Professor Department of Gynecologic Oncology and Reproductive Medicine The University of Texas MD Anderson Cancer Center Houston, Texas Sara Stoneham, MBBCh, FCPaeds SA, MRCPCH Paediatric and TYA Oncology Consultant Children’s and Young People Cancer Services, University College London Hospital, London, United Kingdom Sue Yazaki Sun, MD, PhD Director of São Paulo Hospital Trophoblastic Disease Center Department of Obstetrics Associated Professor, Universidade Federal de São Paulo São Paulo, SP, Brazil

Affiliated Professor, Rio de Janeiro Federal University Maternity School of Rio de Janeiro Federal University Rio de Janeiro, RJ, Brazil Russell K. Portenoy, MD Executive Director MJHS Institute for Innovation in Palliative Care New York, New York Professor of Neurology and Family and Social Medicine Albert Einstein College of Medicine Bronx, New York Allison M. Puechl, MD Assistant Professor of Gynecologic Oncology Atrium Health Levine Cancer Institute Charlotte, North Carolina Isabelle Ray-Coquard, PhD PU-PH Léon Bérard Center Lyon, France Laura Salama, MD Hematology Oncology Fellow Department of Hematology and Oncology Lifespan Cancer Institute The Warren Alpert Medical School of Brown University Providence, Rhode Island Angeles Alvarez Secord, MD, MHSc Professor Division of Gynecologic Oncology Department of Obstetrics and Gynecology Duke Health Durham, North Carolina Tiffany Y. Sia, MD Gynecologic Oncology Fellow Department of Surgery Memorial Sloan Kettering Cancer Center New York, New York

Brenna E. Swift, MD, MASc Gynecologic Oncology Fellow University of Toronto Toronto, Ontario, Canada

Charu Taneja, MD Clinical Assistant Professor of Surgery

Department of Surgery Rhode Island Hospital The Warren Alpert Medical School of Brown University Providence, Rhode Island Julia Tassinari, BS, MD Clinical Instructor of Surgery Department of Surgery The Warren Alpert Medical School of Brown University Providence, Rhode Island

Ashley Valenzula, DO, MBA Assistant Professor

Department of Gynecologic Oncology Mercer University School of Medicine Memorial Health University Medical Center Savannah, Georgia Willemijn L. van der Kolk, BSc PhD Candidate Department of Obstetrics and Gynaecology Cancer Research Center Groningen University Medical Center Groningen Groningen, The Netherlands

xviii Contributors

Akila N. Viswanathan, MD, MPH Professor and Director Radiation Oncology and Molecular Radiation Sciences Johns Hopkins University School of Medicine Baltimore, Maryland Michelle E. Wakeley, MD Resident Physician Department of Surgery The Warren Alpert Medical School of Brown University Providence, Rhode Island Dan Wang, MD Fellow Department of Obstetrics and Gynecology Peking Union Medical College Hospital Department of Pathology and Laboratory Medicine The Warren Alpert Medical School of Brown University Pathologist Department of Pathology Rhode Island Hospital Providence, Rhode Island Robert C. Ward, MD Assistant Professor of Diagnostic Imaging Department of Diagnostic Imaging The Warren Alpert Medical School of Brown University Providence, Rhode Island Yihong Wang, MD, PhD Associate Professor

Doreen L. Wiggins, MD, MHL Breast Surgery

Associate Professor of Surgery Clinician Education The Warren Alpert Medical School of Brown University Providence, Rhode Island

Casey W. Williamson, MD, MAS Assistant Professor Radiation Medicine Oregon Health and Science University Portland, Oregon

Evgeny Yakirevich, MD, DSc Professor

Department of Pathology and Laboratory Medicine The Warren Alpert Medical School of Brown University Pathologist Department of Pathology Rhode Island Hospital Providence, Rhode Island

Chinese Academy of Medical Science and Peking Union Medical College National Clinical Research Center for Obstetric and Gynecologic Diseases Beijing, People’s Republic of China

Robert H. Young, MD Robert E. Scully Professor of Pathology Massachusetts General Hospital Harvard Medical School Department of Pathology Massachusetts General Hospital Boston, Massachusetts

Dmitriy Zamarin, MD, PhD Translational Research Director, Gynecologic Medical Oncology Department of Medicine Memorial Sloan Kettering Cancer Center New York, New York

Catherine Watson, MD Assistant Professor Department of Obstetrics and Gynecology Vanderbilt University Medical Center Nashville, Tennessee

Oliver Zivanovic, MD Assisting Attending Gynecology Surgery Memorial Sloan Kettering Cancer Center New York, New York

Video List

Section 2 Vulva: Video 1 Sentinel inguinofemoral lymph node identification in vulvar cancer and the use of near-infrared imaging for sentinel lymph node detection Section 3 Cervix: Video 2 Radical abdominal trachelectomy Video 3 Extraperitoneal lymph node dissection Video 4 Robotic-assisted supralevator total pelvic exenteration Video 5 Total pelvic infralevator exenteration using Ligasure Video 6 Urinary reconstruction following cystectomy: the ileal conduit Video 7 Urinary reconstruction after pelvic exenteration: modi fied Indiana pouch Video 8 Modified rectus abdominis myocutaneous (RAM) flap for neovagina creation after exenteration Section 4 Uterine Corpus: Video 9 Sentinel lymph node mapping for uterine cancer: a prac tical illustration of injection and mapping techniques Video 10 Sentinel lymph node (SNL) mapping using robotic-assisted fluorescence imaging

Section 5 Ovary: Video 11 Robotic Xi infrarenal aortic node dissection with lower pelvic port placement Video 12 Retroperitoneal lymph node dissection (RPLND) for primary ovarian cancer Video 13 Surgical vascular anatomy on the upper abdomen Video 14 Vascular and ligamentous attachments Video 15 How to approach suspicious lymph nodes on the upper abdomen Video 16 Resection of tumor from the supragastric lesser sac with peritonectomy Video 17 Morison pouch peritonectomy in cytoreductive surgery Video 18 Diaphragm peritonectomy with resection of Glisson capsule for advanced ovarian cancer Video 19 Diaphragm peritonectomy with full-thickness resection for advanced ovarian cancer Video 20 Liver mobilization with diaphragm peritonectomy and liver wedge resection Video 21 Excision of tumor along ligamentum venosum Video 22 Excision of tumor along ligamentum teres Video 23 Mobilization of right liver with wedge resection seg ments 6 and 7

xix

Contents

Preface vii Acknowledgments ix

SECTION 3 VAGINAL CANCER 45 3.1 Vaginal Anatomy 47

Section Editors xi Contributors xiii Video List xix

Diana Miao, Josephine Kang, Amanda Nickles Fader, and Akila N. Viswanathan Vaginal Cancer: Etiology, Epidemiology, Risk Factors, Genetics, and Molecular Biology 49 Diana Miao, Josephine Kang, Amanda Nickles Fader, and Akila N. Viswanathan Symptoms and Diagnosis of Vaginal Intraepithelial Neoplasia and Vaginal Cancer 54 Diana Miao, Josephine Kang, Amanda Nickles Fader, and Akila N. Viswanathan Surgery for Vaginal Intraepithelial Neoplasia and Vaginal Cancer 57 Diana Miao, Josephine Kang, Akila N. Viswanathan, and Amanda Nickles Fader Prognostic Factors 59 Josephine Kang, Diana Miao, Amanda Nickles Fader, and Akila N. Viswanathan Therapeutic Approach for VAIN and Invasive Vaginal Disease 61 Josephine Kang, Diana Miao, Amanda Nickles Fader, and Akila N. Viswanathan Treatment of Persistent and Recurrent Vaginal Cancer 69 Josephine Kang, Diana Miao, Amanda Nickles Fader, and Akila N. Viswanathan Rare Histologies of Vaginal Cancer 70 Josephine Kang, Diana Miao, Amanda Nickles Fader, and Akila N. Viswanathan Vaginal Cancer: Follow-Up, Survivorship Issues, and Summary 78 Diana Miao, Josephine Kang, Amanda Nickles Fader, and Akila N. Viswanathan

SECTION 1 OVERVIEW OF BASIC BIOLOGY 1 1.1 Overview of Basic Biology 3

3.2

Katherine Fuh, Angeles Alvarez Secord, Charles Gourley, and Andrew Berchuck

3.3

SECTION 2 VULVAR CANCER 9 2.1

3.4

Epidemiology of Vulvar Cancer 11 Willemijn L. van der Kolk and M. H. M. Oonk Vulvar Cancer: Anatomy, Natural History, and Patterns of Spread 11 Willemijn L. van der Kolk and M. H. M. Oonk Vulvar Cancer: Etiology, Risk Factors, Genetics, and Molecular Biology 14 Diane C. Ling and Sushil Beriwal Vulvar Cancer: Preinvasive Disease 15 Willemijn L. van der Kolk Vulvar Cancer: Clinical Presentation, Diagnostic Evaluation, and Workup 16 Willemijn L. van der Kolk and M. H. M. Oonk Therapy for Vulvar Cancer: Radiation, Systemic Therapy, and Treatment of Persistent and Recurrent Disease 19 Diane C. Ling and Sushil Beriwal Surgery for Vulvar Cancer 28 Updated by Diane C. Ling and Sushil Beriwal Vulvar Cancer: Pathology and Prognostic Factors 34 Updated by Diane C. Ling and Sushil Beriwal Vulvar Cancer: Follow-Up and Survivorship Issues 43 Diane C. Ling and Sushil Beriwal Vulvar Cancer: Future Directions 44 Diane C. Ling and Sushil Beriwal

2.2

3.5

2.3

3.6

2.4

3.7

2.5

2.6

3.8

3.9

2.7

2.8

SECTION 4 CERVICAL CANCER 81 4.1

2.9

Cervix Uteri: Epidemiology, Etiology, Risk Factors, Anatomy, Natural History, and Patterns of Spread 83 Teresa K. L. Boitano and Charles A. Leath III

2.10

xxi

xxii Contents

4.2

Genetics and Molecular Biology of Cervical Cancer 87 Dmitriy Zamarin Cervical Cancer: Clinical Presentation and Diagnostic Evaluation 88 Charles A. Leath III and Teresa K. L. Boitano Surgery for Cervical Cancer 93 Charles A. Leath III and Teresa K. L. Boitano Cervical Cancer: Pathology 97 Charles A. Leath III and Teresa K. L. Boitano Radiation Therapy, Immunotherapy, and Targeted Therapies in Cervix Cancer 105 Dmitriy Zamarin, Charles A. Kunos, Casey W. Williamson, Jyoti Mayadev, and Ramez N. Eskander Treatment of Persistent or Recurrent Uterine Cervix Cancer 115 Charles A. Leath III and Teresa K. L. Boitano Survivorship Issues Following Treatment for Cervical Cancer 117 Laura Salama and Don S. Dizon Cervical Cancer: Future Directions 119 Charles A. Leath III and Teresa K. L. Boitano Endometrial Cancer: Introduction, Anatomy, Natural History, and Patterns of Spread 123 Amy Bregar Endometrial Cancer: Etiology, Epidemiology, Risk Factors, Genetics, and Molecular Biology 127 Amy Bregar Endometrial Cancer: Clinical Presentation, Diagnostic Evaluation, and Workup 130 Amy Bregar Endometrial Cancer: Pathology and Prognostic Factors 148 Christine Chin Therapy for Endometrial Cancer: Radiation, Chemotherapy, Targeted, Immunotherapy, and Other New and Novel Agents 159 Susana M. Campos and Marcela G. del Carmen Treatment of Persistent and Recurrent Endometrial Cancer 180 Susana M. Campos Endometrial Cancer: Special Conditions 181 Allison Gockley Endometrial Cancer: Follow-Up and Survivorship Issues 183 Allison Gockley Endometrial Cancer: Future Directions 185 Allison Gockley Surgery for Endometrial Cancer 133 Christine Chin

SECTION 6 CORPUS: MESENCHYMAL TUMORS 187 6.1 Mesenchymal Tumors: Introduction, Anatomy, Natural History, and Patterns of Spread 189 Tiffany Y. Sia and Mario M. Leitao Jr Mesenchymal Tumors: Etiology, Epidemiology, and Risk Factors 191 Tiffany Y. Sia, Mario M. Leitao Jr, and Lora Hedrick Ellenson 6.2 Mesenchymal Tumors: Clinical Presentation and Diagnostic Evaluation and Workup 193 Tiffany Y. Sia and Mario M. Leitao Jr Surgery for Newly Diagnosed Uterine Corpus Mesenchymal Tumors 197 Tiffany Y. Sia and Mario M. Leitao Jr Pathology of Uterine Mesenchymal Tumors 202 Amir Momeni-Boroujeni and Lora Hedrick Ellenson 6.4 6.5 Radiation Therapy for Uterine Corpus Mesenchymal Tumors 213 Matthew M. Harkenrider Chemotherapy for Uterine-Limited and Advanced Uterine Sarcomas 216 Kathryn M. Miller and Roisin E. O’Cearbhaill Surgery for Persistent and Recurrent Uterine Sarcomas 231 Tiffany Y. Sia and Mario M. Leitao Jr Uterine Sarcomas: Follow-Up, Survivorship Issues, and Future Directions 232 Tiffany Y. Sia and Mario M. Leitao Jr SECTION 7 GESTATIONAL TROPHOBLASTIC DISEASE: MOLAR PREGNANCY AND GESTATIONAL TROPHOBLASTIC NEOPLASIA 235 7.1 Epidemiology, Genetics, and Pathology in Gestational Trophoblastic Disease 237 Sue Yazaki Sun, Gabriela Paiva, and Antonio Braga 6.7 6.8 6.9 Management of Molar Pregnancy 247 Kevin M. Elias, Neil S. Horowitz, and Ross S. Berkowitz Management of Low-Risk Gestational Trophoblastic Neoplasia 251 Neil S. Horowitz, Ross S. Berkowitz, and Kevin M. Elias Management of High-Risk Gestational Trophoblastic Neoplasia 257 Antonio Braga, Fernanda Freitas Oliveira Cardoso, and Izildinha Maestá Gestational Trophoblastic Disease: Postdiagnosis and Treatment, Long-Term Sequelae, and Quality-of-Life Issues 267 Neil S. Horowitz, Kevin M. Elias, and Ross S. Berkowitz 7.3 7.4 7.5 6.3 6.6 7.2

4.3

4.4

4.5

4.6

4.7

4.8

4.9

SECTION 5 CORPUS: EPITHELIAL TUMORS 121 5.1

5.2

5.3

5.4

5.5

5.6

5.7

5.8

5.9

5.10

Contents xxiii

9.2

Malignant Ovarian Germ Cell Tumors: Etiology, Epidemiology, Risk Factors, Genetics, and Molecular Biology 405 Dimitrios Nasioudis, Emily M. Ko, Koji Matsuo, and Anil K. Sood Ovarian Germ Cell Tumors: Clinical Presentation and Diagnostic Evaluation and Workup 409 Allison M. Puechl, Priya Bhosale, Dimitrios Nasioudis, Emily M. Ko, and Sara Stoneham Surgery for Ovarian Germ Cell Tumors 414 Giorgia Mangili, Deborah Billmire, Dimitrios Nasioudis, and Emily M. Ko Ovarian Germ Cell Tumors: Pathology and Prognostic Factors 420 Elizabeth Euscher and Robert Tucker Burks Therapy for Ovarian Germ Cell Tumors: Radiation, Chemotherapy, Targeted Therapy, Immunotherapy, and Other New and Novel Agents 429 Brenna E. Swift, Dimitrios Nasioudis, and Allan Covens Treatment of Persistent and Recurrent Ovarian Germ Cell Tumors 436 Brenna E. Swift and Allan Covens

SECTION 8 EPITHELIAL OVARIAN CANCER 271 8.1 Epidemiology and Risk Factors 273 Shannon Dawn Armbruster and Ernst Lengyel Hereditary Ovarian Cancer: BRCA and HNPCC—Panel Testing 284 Shannon Dawn Armbruster and Ernst Lengyel 8.2

9.3

8.3

Natural History of the Disease: Patterns of Spread 295 Kathryn A. Mills and Ernst Lengyel Ovarian Cancer: Etiology, Genetics, and Molecular Biology 299 Charles N. Landen Jr and Ernst Lengyel Ovarian Cancer: Clinical Presentation and Diagnostic Workup 310 Ernst Lengyel and Kathryn A. Mills Surgery for Ovarian Cancer 326 Oliver Zivanovic and Ernst Lengyel Ovarian Cancer: Pathology 343 Agnes Julia Bilecz and Ricardo R. Lastra Epithelial Ovarian Cancer: Prognostic Factors 366 Kathryn A. Mills and Ernst Lengyel Management of Early-Stage Ovarian Cancer 371 Katherine C. Kurnit and Gini F. Fleming Management of Borderline Tumors and Low-Grade Serous Tumors 375 Katherine C. Kurnit and Gini F. Fleming Management of Advanced-Stage Ovarian Cancer 378 Katherine C. Kurnit and Gini F. Fleming Approach to Advanced and Recurrent Clear Cell, Mucinous, or Endometrioid Cancer 389 Katherine C. Kurnit and Gini F. Fleming Treatment of Ovarian Carcinosarcoma 391 Katherine C. Kurnit and Gini F. Fleming Ovarian Cancer: Survivorship Issues 392 Katherine C. Kurnit and Gini F. Fleming Treatment of Persistent and Recurrent Ovarian Cancer and Palliative Care 394 Katherine C. Kurnit and Gini F. Fleming

9.4

8.4

9.5

8.5

9.6

8.6

8.7

9.7

8.8

9.8

Ovarian Germ Cell Tumors: Special Conditions 438 Dan Wang and Bradley R. Corr

8.9

9.9

Ovarian Germ Cell Tumors: Follow-Up and Survivorship Issues 440 Olesya Solheim and David M. Gershenson Ovarian Germ Cell Tumors: Future Directions 444 Isabelle Ray-Coquard and Lindsay Frazier

8.10

9.10

8.11

SECTION 10 OVARIAN SEX CORD-STROMAL TUMORS 447 10.1

8.12

Ovarian Sex Cord-Stromal Tumors: Introduction, Anatomy, Natural History, and Patterns of Spread 449 R. Tyler Hillman and Carrie Langstraat Ovarian Sex Cord-Stromal Tumors: Etiology, Epidemiology, Risk Factors, Genetics, and Molecular Biology 450 R. Tyler Hillman Ovarian Sex Cord-Stromal Tumors: Clinical Presentation, Diagnostic Evaluation, and Surgery for Ovarian Sex Cord-Stromal Tumors 456 Carrie Langstraat Ovarian Sex Cord-Stromal Tumors: Pathology and Prognostic Factors 457 Robert H. Young and Barrett Lawson Workup 453 Carrie Langstraat

8.13

8.14

10.2

8.15

10.3

8.16

New Therapeutics 398 Katherine C. Kurnit and Gini F. Fleming

SECTION 9 OVARIAN GERM CELL TUMORS 401 9.1 Ovarian Germ Cell Tumors: Introduction, Anatomy, Natural History, and Patterns of Spread 403 Dimitrios Nasioudis and Emily M. Ko

10.4

10.5

xxiv Contents

10.6

11.11 Multidisciplinary Approach to Breast Cancer Care 530 Theresa A. Graves, Stephanie L. Graff, and Jaroslaw T. Hepel 11.12 Systemic Treatment for Metastatic Breast Cancer 532 Stephanie L. Graff and Mary Anne Fenton 11.13 Breast Cancer in the Older Patient 537 Theresa A. Graves and Mary Anne Fenton 11.14 Pregnancy-Associated Breast Cancer 539 Rani Bansal 11.15 Breast Cancer: Survivorship Issues 543 Christine Duffy and Don S. Dizon Clinical Trials Methodology and Analysis 553 Jeffrey C. Miecznikowski, Austin Miller, and Michael W. Sill Cost-Effective and Value-Based Gynecologic Cancer Care 571 Laura J. Havrilesky, Margaret I. Liang, Emeline M. Aviki, Shalini L. Kulasingam, Elizabeth L. Jewell, and David E. Cohn Nutrition Support of Patients With Gynecologic Cancer 635 Sanjana Luther and Priya K. Simoes Management of Pain 653 Russell K. Portenoy and Ebtesam Ahmed Palliative and Supportive Care 675 Emily J. Martin and Natsai C. Nyakudarika Hereditary Cancer Genetics 688 Catherine Watson and Andrea R. Hagemann Biologic and Physical Principles of Radiation Oncology 696 Jenna Kahn, Beth A. Erickson, Meena Bedi, Firas Mourtada, and Sunil J. Advani 12.2 12.3 Perioperative and Critical Care 590 James J. Burke II, Ashley Valenzuela, and Katherine M. McBride 12.4 12.5 12.6 12.7 12.8 SECTION 12 SPECIAL TOPICS 551 12.1

Therapy for Ovarian Sex Cord-Stromal Tumors: Radiation, Chemotherapy, Targeted Therapy, Immunotherapy, and Other New and Novel

Agents 464 R. Tyler Hillman

10.7 Treatment of Persistent or Recurrent Sex Cord Stromal Tumors 466 R. Tyler Hillman Ovarian Sex Cord-Stromal Tumors: Special Conditions 469 Carrie Langstraat Ovarian Sex Cord-Stromal Tumors: Follow-Up and Survivorship Issues 470 Carrie Langstraat 10.10 Ovarian Sex Cord-Stromal Tumors: Future Directions 470 R. Tyler Hillman 10.8 10.9

SECTION 11 BREAST CANCER 473 11.1

Breast Cancer: Introduction 475 Theresa A. Graves

11.2

Breast Cancer: Epidemiology, Risk Factors, Anatomy, and Natural History 475 Michelle E. Wakeley Breast Cancer: Clinical Presentation 478 Julia Tassinari

11.3

11.4

Breast Imaging 485 Martha B. Mainiero and Robert C. Ward Breast Pathology 490 Yihong Wang and Evgeny Yakirevich

11.5

11.6 Surgical Management of the Breast 502 Doreen L. Wiggins and Theresa A. Graves Surgical Management of the Axilla 507 Charu Taneja Endocrine Therapy for Breast Cancer 512 Mary Anne Fenton Approaches to Systemic Therapy for Breast Cancer: Neoadjuvant and Adjuvant Management 518 Stephanie L. Graff 11.10 Radiation Therapy for Breast Cancer 523 Jaroslaw T. Hepel and Chelsea Miller 11.7 11.8 11.9

Index 751

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