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REVIEW

Daniel Morgensztern Ramaswamy Govindan Siddhartha Devarakonda Nikolaos A. Trikalinos

DeVita, Hellman, and Rosenberg’s Cancer Principles & Practice of Oncology REVIEW

DeVita, Hellman, and Rosenberg’s Cancer Principles & Practice of Oncology REVIEW 5th Edition

Editors Daniel Morgensztern, MD Professor of Medicine Division of Oncology Alvin J. Siteman Cancer Center Washington University School of Medicine St. Louis, Missouri Ramaswamy Govindan, MD Professor of Medicine Anheuser Busch Chair in Medical Oncology Director, Section of Medical Oncology Division of Oncology Washington University School of Medicine St. Louis, Missouri

Siddhartha Devarakonda, MD Assistant Professor of Medicine Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri Nikolaos A. Trikalinos, MD, MS Assistant Professor of Medicine Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri

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5th edition

4th edition Copyright © 2016 Wolters Kluwer. 3rd edition Copyright © 2012 and 2nd edition Copyright © 2009 by Lippincott Williams & Wilkins, a Wolters Kluwer business. Copyright © 2005 by Lippincott Williams & Wilkins. All rights reserved. This book is protected by copyright. No part of this book may be reproduced or trans mitted 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 permission 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. government employees are not covered by the above-mentioned copyright. To request permission, please contact 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).

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DEDICATION To our contributors.

CONTRIBUTORS

Foluso C. Ademuyiwa, MD, MPH Associate Professor Department of Medicine Washington University School of Medicine St. Louis, Missouri Douglas R. Adkins, MD Professor Department of Internal Medicine Washington University School of Medicine St. Louis, Missouri Olivia Aranha, MD, PhD Assistant Professor Internal Medicine, Division of Oncology Siteman Cancer Center St. Louis, Missouri Matthew Austin, MD Fellow, Medical Oncology Medical Oncology Section, Department of Internal Medicine Yale School of Medicine, Yale University New Haven, CT Dhruv Bansal, MD, MBA Fellow Department of Oncology Washington University School of Medicine St. Louis, Missouri Ron Bose, MD, PhD Associate Professor of Medicine Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri Omar Hameed Butt, MD, PhD Fellow Department of Neurology Washington University School of Medicine St. Louis, Missouri Jian L. Campian, MD, PhD Assistant Professor of Medicine and Neurosurgery Internal Medicine, Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri

Katherine Clifton, MD Assistant Professor Department of Medicine Washington University School of Medicine St. Louis, Missouri Siddhartha Devarakonda, MD Assistant Professor of Medicine Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri Haley Ellis, MD Resident Physician Department of Medicine Washington University School of Medicine St. Louis, Missouri Armin Ghobadi, MD Associate Professor Department of Medicine Washington University School of Medicine St. Louis, Missouri Scott R. Goldsmith, MD Fellow Division of Oncology Washington University School of Medicine St. Louis, Missouri Ramaswamy Govindan, MD Professor of Medicine Anheuser Busch Chair in Medical Oncology Director, Section of Medical Oncology Division of Oncology Washington University School of Medicine St. Louis, Missouri Patrick Grierson, MD, PhD Assistant Professor Department of Medical Oncology Washington University School of Medicine St. Louis, Missouri Sasha Haarberg, PharmD, BCOP Clinical Oncology Pharmacist Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri

vii

Contributors

Jennifer Hedgecorth, PharmD, BCOP Clinical Oncological Pharmacist Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri Leonel Hernandez-Aya, MD Assistant Professor Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri Brett H. Herzog, MD, PhD Fellow Department of Medicine Washington University School of Medicine St. Louis, Missouri Angela C. Hirbe, MD, PHD Assistant Professor of Medicine Assistant Professor of Pediatrics Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri Shu (Joy) Jiang, PhD Assistant Professor Division of Public Health Sciences Washington University School of Medicine St. Louis, Missouri Ramon Jin, MD, PhD Clinical Fellow Division of Oncology Department of Internal Medicine Washington University School of Medicine St. Louis, Missouri Jessica Ley, BS Clinical Research Specialist Department of Medical Oncology Washington University School of Medicine St. Louis, Missouri Joshua T. Loesche, PharmD Clinical Oncological Pharmacist Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri Esther Lu, MS, PhD Assistant Professor Department of Surgery Washington University School of Medicine St. Louis, Missouri

Cynthia X. Ma, MD, PhD Professor of Medicine Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri Prabhat Singh Malik, MD, DM Associate Professor Department of Medical Oncology All India Institute of Medical Sciences New Delhi, India (Visiting Scholar, Washington University School of Medicine, November 2019) Janelle E. Mann, PharmD, BCOP Manager, Clinical Pharmacy Services Clinical Oncological Pharmacist Department of Medicine Washington University School of Medicine St. Louis, Missouri Neha Mehta-Shah, MD, MSCI Assistant Professor of Medicine Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri Daniel Morgensztern, MD Professor of Medicine Division of Oncology Alvin J. Siteman Cancer Center Washington University School of Medicine St. Louis, Missouri Ashley E. Morton, MSN, ANP-BC Nurse Practitioner Division of Oncology, Section of Medical Oncology Department of Internal Medicine Washington University School of Medicine St. Louis, Missouri David G. Mutch, MD Vice Chairman of Gynecology Division of Gynecologic Oncology Department of Obstetrics and Gynecology Washington University School of Medicine St. Louis, Missouri Peter Oppelt, MD Assistant Professor Department of Medicine Washington University School of Medicine St. Louis, Missouri

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Contributors

Russell K. Pachynski, MD Assistant Professor Division of Oncology Department of Medicine Washington University School of Medicine St. Louis, Missouri Kevin T. Palka, MD Assistant Professor Department of Internal Medicine Washington University School of Medicine St. Louis, Missouri Internal Medicine, Division of Oncology Washington University School of Medicine St. Louis, Missouri Katrina S. Pedersen, MD, MS Assistant Professor of Medicine Washington University School of Medicine St. Louis, Missouri Department of Obstetrics and Genecology Washington University School of Medicine St. Louis, Missouri Elizabeth Prsic, MD Associate Professor Department of General Internal Medicine Yale University New Haven, Connecticut William Rafelson, MD Division of Hematology/Oncology Department of Medicine Alpert Medical School, Brown University Providence, Rhode Island Haeseong Park, MD, MPH Assistant Professor Matthew A. Powell, MD Associate Professor

Nikolaos A.Trikalinos, MD, MS Assistant Professor of Medicine Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri Danielle K.Turlington, PharmD, BCOP Clinical Oncological Pharmacist Division of Medical Oncology Department of Medicine Washington University School of Medicine St. Louis, Missouri Brian A. Van Tine, MD, PhD Associate Professor of Medicine Associate Professor of Pediatrics Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri Ravi Vij, MD, MBA Professor of Medicine Division of Medical Oncology Washington University School of Medicine St. Louis, Missouri Fei Wan, PhD Assistant Professor Department of Surgery Washington University School of Medicine St. Louis, Missouri

Saiama N. Waqar, MBBS, MSCI Associate Professor

Internal Medicine, Division of Oncology Washington University School of Medicine St. Louis, Missouri

Alice Zhou, MD, PhD Hematology Oncology Fellow

Divisions of Hematology and Oncology Washington University School of Medicine St. Louis, Missouri

David Russler-Germain, MD, PhD Hematology/Oncology Fellow Department of Internal Medicine Barnes-Jewish Hospital St. Louis, Missouri

Benjamin R.Tan, Jr, MD Associate Professor Department of Internal Medicine Washington University School of Medicine St. Louis, Missouri

PREFACE

The past decade has witnessed numerous advances in cancer therapy. Even since the publication of the previous edition of Cancer: Principles & Practice of Oncology (PPO) , or simply known as the “DeVita book,” several new drugs have been approved for cancer therapy. Immunotherapy plays a significant role in many advanced malignancies. Cancer Genome Sequencing projects increasing ly incorporate proteomics and single-cell sequencing. Molecular mechanisms that underline the course of several cancer types and responses to specific therapies are understood better than before. This companion review book, now in its fifth edition, is an attempt to cull out the key learning points from the massive tome of the “DeVita book” that captures all these advances in a timely manner. While these review books are often seen as “study aids” for last-minute cramming for the board examinations, we hope this book would serve to highlight key points from each chapter of PPO. Each chapter in the review book corresponds to one or more chapters in the main textbook, just as they were in the first edition. We hope you find this book valuable and informative. Please do not hesitate to contact us with comments, criticisms, and suggestions. You can reach us by e-mail at rgovindan@wustl.edu or danielmorgensztern@wustl.edu.

Ramaswamy Govindan, MD Daniel Morgensztern, MD

PREFACETO PREVIOUS EDITION

We are pleased to publish the fourth edition of the companion review book for DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology , 10th edition (PPO) . While these re view books are often seen as study aids for last-minute cramming for the board examinations, we hope this book will enable readers to learn key points from each chapter of the PPO textbook. Each chapter in the review book corresponds to one or more chapters in the main textbook just as they were in the first three editions. We hope you find this book useful and informative. Please do not hesitate to contact us with comments, criticisms, and suggestions.

Ramaswamy Govindan, MD Daniel Morgensztern, MD

ACKNOWLEDGMENTS

I would like to extend my sincerest thanks to Dr. Govindan for the opportunity to contribute to this book and his mentorship, my coeditors, contributors, and publishers for the time and effort they have dedicated to this project. I am also grateful to my family for their unconditional love and support.

Siddhartha Devarakonda

I would like to extend my gratitude to Dr. Ramaswamy Govindan for including me in this ambi tious project and to the coeditors Dr. Morgensztern and Dr. Devarakonda for their guidance and constructive input. Also, many thanks to the talented physicians/scientists of Washington University in St. Louis who graciously contributed to the chapters of this book.

Nikolaos A. Trikalinos

I want to thank the contributors for their diligence, time, and patience. My special thanks to my coeditors for their hard work, dedication, and commitment to make this project successful. Special thanks to Dr. Morgensztern for coordinating manuscript submission and revision. I am grateful to our contributors for their support. I want to thank the staff at Wolters Kluwer for their support. Needless to say, these projects take a sizable amount of time away from family. I will always be grateful to my wife Prabha and my two children, Ashwin and Akshay.

Ramaswamy Govindan

I would like to thank my mentor Ramaswamy Govindan, my colleagues and new editors Sid Devarakonda and Nikos Trikalinos, and the authors for their excellent chapters. I am also very grateful to my parents Silvia and Felipe, my lovely wife Marcela, and my three delightful children Alan, David, and Michael.

Daniel Morgensztern

CONTENTS

Contributors ....................................................... vi Preface ............................................................ ix Preface to Previous Edition ............................................ x Acknowledgments .................................................. xi 1. MolecularBiologyofCancer. . . . . . . . . . . . . . . . . . . . . . 1 David Russler-Germain and Olivia Aranha 2. Design and Analysis of Clinical Trials . . . . . . . . . . . . . . . . . . 8 Esther Lu, Fei Wan, and Shu (Joy) Jiang 3.CancerTherapy...........................15 Joshua T. Loesche, Janelle E. Mann, and Danielle K. Turlington 4. Central Nervous System Neoplasms and Brain Metastases. . . . . . . . 23 Alice Zhou, Omar Hameed Butt, and Jian L. Campian 5. CanceroftheHeadandNeck. . . . . . . . . . . . . . . . . . . . . 36 Peter Oppelt, Kevin T. Palka, Jessica Ley, and Douglas R. Adkins 6.ThoracicCancers..........................47 Brett H. Herzog, Haley Ellis, Prabhat Singh Malik, Saiama N. Waqar, Siddhartha Devarakonda, Ramaswamy Govindan, and Daniel Morgensztern 7.BreastCancer........................... 60 Katherine Clifton, Foluso O. Ademuyiwa, Ron Bose, and Cynthia X. Ma 8. EsophagealandGastricCancer. . . . . . . . . . . . . . . . . . . . 71 Ramon Jin and Haeseong Park 9. Small Intestine Cancers and Gastrointestinal Stromal Tumors. . . . . . . 82 Katrina S. Pedersen and Nikolaos A. Trikalinos 10. Pancreas and Hepatobiliary Cancer . . . . . . . . . . . . . . . . . . 92 Patrick Grierson and Katrina S. Pedersen 11. ColorectalandAnalCancer. . . . . . . . . . . . . . . . . . . . . 109 Ashley E. Morton and Benjamin R. Tan, Jr. 12.GenitourinaryCancer.. . . . . . . . . . . . . . . . . . . . . . .119 Russell K. Pachynski 13.SkinCancer............................133 Leonel Hernandez-Aya 14. Sarcoma. . . . . . . . . . . . . . . . . . . . . . . . . . . . .146 Brian A. Van Tine and Angela C. Hirbe xii

xiii

Contents

15. Endocrine and Neuroendocrine Tumor. . . . . . . . . . . . . . . . . 155 Nikolaos A. Trikalinos 16.GynecologicCancer........................ 167 Matthew A. Powell and David G. Mutch 17. Leukemias and Myelodysplastic Syndrome . . . . . . . . . . . . . . 176 Dhruv Bansal and Armin Ghobadi 18. Lymphomas. . . . . . . . . . . . . . . . . . . . . . . . . . . 198 Neha Mehta-Shah 19.PlasmaCellNeoplasms.. . . . . . . . . . . . . . . . . . . . . .210 Ravi Vij and Scott R. Goldsmith 20.CancerScreening......................... 229 Olivia Aranha 21.CancerPain............................235 Elizabeth Prsic and William Rafelson 22. Oral and Gastrointestinal Complications. . . . . . . . . . . . . . . . 248 Sasha Haarberg and Jennifer Hedgecorth 23. OncologicEmergencies.. . . . . . . . . . . . . . . . . . . . . .256 Elizabeth Prsic and Matthew Austin

Index ............................................................ 267

7 Katherine Clifton, Foluso C. Ademuyiwa, Ron Bose, and Cynthia X. Ma Breast Cancer

QUESTIONS

Each of the numbered items below is followed by lettered answers. Select the ONE lettered answer that is BEST in each case unless instructed otherwise. Question 7.1 What percentage of breast cancers is caused by germline mutations? A. 20% B. 10% C. 15% D. 2%

Question 7.2 BRCA1 mutations are most commonly associated with: A. Triple-negative breast cancers. B. Estrogen receptor (ER)-positive breast cancers.

C. Pancreatic cancer and melanoma. D. Autosomal recessive inheritance.

Question 7.3 Li–Fraumeni syndrome is characterized by which clinical features? A. Lobular breast cancer, gastric cancer B. Breast cancer, soft tissue sarcoma, central nervous system tumors, adrenocortical cancer, leukemia, prostate cancer C. Breast cancer, hamartoma, thyroid cancer, oral mucosa cancer, endometrial cancer, brain tumors D. Male breast cancer, pancreas cancer, gall bladder cancer, pharynx cancer, gastric cancer, melanoma, prostate cancer Question 7.4 Which of the following statements about luminal A subtype is TRUE? A. It is more common in premenopausal black women. B. Luminal A breast cancers frequently carry TP53 mutations. C. It is characterized by high-expression levels of ER-related genes and low expression of the HER2 cluster and proliferation-associated genes. D. It has a worse prognosis than do other molecular subtypes of breast cancer.

opyright © 2021 Wolters Kluwer, Inc. Unauthorized reproduction of the content is prohibited Corresponding chapters in DeVita, Hellman, and Rosenberg’s Cancer: Principles & Practice of Oncology , Eleventh Edition: 78 (Molecular Biology of Breast Cancer), 79 (Malignant Tumors of the Breast), and 80 (Genetic Testing in Breast Cancer).

Chapter 7 Breast Cancer

Question 7.5 A 42-year-old female undergoes mastectomy and sentinel lymph node biopsy. Final pathology reveals a 1.5-cm invasive ductal carcinoma that is ER positive, progesterone receptor positive and HER2 1 + by immunohistochemistry (IHC), with intermediate grade. Two

sentinel lymph nodes are negative. Treatment recommendations include: A. Adjuvant radiation followed by 5–10 years of endocrine therapy. B. 5–10 years of letrozole alone. C. Oncotype DX testing and 5–10 years of endocrine therapy. D. HER2-based therapy followed by 5–10 years of tamoxifen.

Question 7.6 Which of the following factors is a risk factor for developing breast cancer? A. Cowden syndrome B. Early age at first full-term pregnancy

C. Breast density < 10% D. Simple breast cysts

Question 7.7 American Cancer Society (ACS) guidelines for magnetic resonance imaging (MRI) screening are supported for which of the following patients? A. A 47-year-old woman with a deleterious mutation in BRCA1 B. A 60-year-old woman with biopsy-proven lobular carcinoma in situ (LCIS) C. A 55-year-old woman with a personal history of ER-positive breast cancer treated 8 years ago D. A 65-year-old woman who underwent chest radiation at age 60 years Question 7.8 Which of the following scenarios are considered a contraindication to the use of tamoxifen? A. Major surgical procedure within the previous 6 months B. A history of deep vein thrombosis, stroke, pulmonary embolism, or transient ischemic attack C. A 60-year-old woman with bilateral asymptomatic cataracts D. A 65-year-old woman currently on a selective serotonin reuptake inhibitor (SSRI) for hot flashes Question 7.9 A 44-year-old woman presents to your office with a new palpable breast mass. A biopsy has been recommended on the basis of the results of mammogram and ultrasound. In general, the most appropriate way to diagnose suspected invasive carcinoma is: A. Circulating tumor DNA. B. An excisional biopsy. Question 7.10 You are advising a 42-year-old premenopausal woman with a history of atypical hyperplasia on prevention strategies. Which of the following is CORRECT? A. Tamoxifen reduces the risk only in premenopausal women. B. Oophorectomy reduces the risk by 50%–65%. C. Bilateral mastectomy completely eliminates her risk of breast cancer. D. Raloxifene provides similar benefit compared with tamoxifen. C. Diagnosis by core needle biopsy. D. A fine-needle aspiration biopsy.

Cancer: Principles & Practice of Oncology Review

Question 7.11 The Gail model includes which of the following risk factors? A. Second-degree relatives with breast cancer B. Previous breast biopsies C. Age at first pregnancy conception D. Age at menopause

Question 7.12 Which of the following statements about ductal carcinoma in situ (DCIS) is TRUE? A. DCIS accounts for 15%–30% of mammographically detected cancers. B. DCIS is most common in women aged 40–49 years. C. Younger women have a lower rate of local recurrence after local therapy. D. Sentinel lymph node biopsy should be performed routinely during breast-conservation surgery for nonpalpable DCIS. Question 7.13 The use of radiation therapy (RT) after lumpectomy in patients with DCIS: A. Improves overall survival (OS). B. Reduces the risk of recurrent DCIS, but not invasive disease, in the treated breast. C. Does not decrease local recurrence when tamoxifen therapy is administered. D. None of the above. Question 7.14 According to the AJCC (American Joint Committee on Cancer) eighth edition, which factor is not included in breast cancer staging in addition to traditional TNM (tumor, node, metastasis) staging: Question 7.15 Which of the following statements concerning local recurrences after breast-conserving therapy is FALSE? A. The underlying molecular subtype is the most significant determinant of the likelihood of local recurrence after breast-conserving therapy and mastectomy, particularly when negative margins are achieved. B. Women initially treated with breast-conserving surgery may be offered salvage mastectomy. C. Local recurrences do not require systemic staging because very few patients with local recurrences have concurrent metastatic disease. D. Chemotherapy after local recurrence improves survival in ER-negative tumors. Question 7.16 Which of the following is an absolute contraindication to breast-conserving surgery requiring RT? A. RT during pregnancy B. Diffuse suspicious or malignant-appearing microcalcifications C. Widespread disease that cannot be incorporated by local excision through a single incision that achieves negative margins with a satisfactory cosmetic result D. All of the above A. ER expression B. Tumor grade C. Ki 67 D. Oncotype DX if applicable

Chapter 7 Breast Cancer

Question 7.17 Identify the CORRECT statement. A. Patients aged 70 and older with stage 1, ER-positive breast cancer treated by lumpectomy and tamoxifen alone have no difference in locoregional recurrence rates relative to those who receive the addition of whole-breast radiation. B. Preoperative chemotherapy has a long-term survival advantage relative to adjuvant chemotherapy. C. Concurrent use of pertuzumab with trastuzumab and chemotherapy is appropriate in women receiving preoperative chemotherapy for HER2-positive breast cancer. D. All of the above.

Question 7.18 The gains associated with adjuvant tamoxifen: A. Are independent of patient age. B. Are less in patients who also receive adjuvant chemotherapy. C. Are dependent on patient menopausal status. D. Decline 10 years after diagnosis.

Question 7.19 Identify the patient most appropriate for ovarian suppression. A. A 31-year-old female with T2N1 triple-negative breast cancer B. A 38-year-old female with T1cN1 ER-positive HER2 negative-breast cancer C. A 47-year-old female with a T1cN0 ER-positive HER2 negative-breast cancer with an Oncotype DX score of 11 D. A 75-year-old female with T2N0 ER-positive HER2 negative-breast cancer with a history of osteoporosis with prior hip fracture Question 7.20 Identify the CORRECT statement regarding the use of taxanes in the adjuvant setting. A. Concurrent administration of docetaxel/doxorubicin/cyclophosphamide chemotherapy is better tolerated than is sequential dose-dense AC (Adriamycin and Cyclophosphamide) followed by paclitaxel due to lower rates of neutropenia. B. Weekly paclitaxel is associated with increased grades 3 and 4 neutropenia relative to dose-dense paclitaxel. C. Weekly paclitaxel is associated with increased grades 3 and 4 neuropathy relative to dose-dense paclitaxel. D. Incorporation of gemcitabine into adjuvant anthracycline- and taxane-based chemotherapy improves efficacy. Question 7.21 Risk factors for cardiac dysfunction with trastuzumab include: A. Preexisting cardiac disease, age older than 65 years. B. Non–anthracycline-based chemotherapy, age older than 60 years. C. Age older than 65 years, current aspirin use for cardio protection, hyperthyroidism. D. None of the above.

Cancer: Principles & Practice of Oncology Review

Question 7.22 A 57-year-old woman has been taking anastrozole as adjuvant therapy for a moderately differentiated T1N1 stage II breast cancer for 3 years. During a routine follow-up visit you recommend: A. History and physical examination and complete blood count and liver function tests. B. History and physical examination, complete blood count and liver function tests, and cancer antigen 15-3. C. History and physical examination. D. History and physical examination, complete blood count and liver function tests, cancer antigen 15-3, and yearly computed tomography scans. Question 7.23 Regarding inflammatory breast cancer (IBC), which of the following is TRUE?”: A. Patients presenting with clinical features of IBC but no discrete palpable breast mass may forego systemic staging. B. The presence of dermal lymphatic involvement indicates IBC regardless of the clinical features. C. Adjuvant radiation is not necessary in patients with IBC who achieve a pathologic complete response to neoadjuvant systemic therapy. D. None of the above. Question 7.24 With regard to the clinical and pathologic characteristics of male breast cancer, which of the following is TRUE? A. Male breast cancer is found, more often than is female breast cancer, to be estrogen receptor negative. B. Liver cirrhosis and mumps orchitis are associated with a decreased risk of male breast cancer. C. The median age of onset is 10 years younger than is the median age of onset for females. D. Sentinel node biopsy is the preferred treatment for clinically node-negative patients. Question 7.25 Regarding bone metastases, which of the following is TRUE? A. The optimal duration of receptor activator of nuclear factor- κβ (RANK)-ligand inhibition is 2 years. B. Intravenous bisphosphonates and RANK-ligand inhibitors lessen the pain associated with bone metastases. C. Bone-directed therapies in patients with widespread bone metastases improve OS. D. Only patients with asymptomatic sclerotic bone metastases benefit from bone-directed therapies. Question 7.26 A 58-year-old woman has a history of T2N1 ER-positive HER2 negative-breast cancer and underwent mastectomy followed by adjuvant chemotherapy. She has been on letrozole for the past 3 years. During an evaluation for mild hip pain, she was found to have bone only metastatic disease. First-line treatment includes: A. Anastrozole alone. B. Palbociclib and fulvestrant. C. Paclitaxel. D. Everolimus and exemestane.

Chapter 7 Breast Cancer

Question 7.27 What is the most common side effect associated with alpelisib? A. Neutropenia B. Diarrhea C. Hyperglycemia D. Fatigue Question 7.28 What is a rare toxicity of poly (ADP-ribose) polymerase (PARP) inhibitors? A. Myelodysplastic syndrome/acute myeloid leukemia (MDS/AML) B. Squamous cell carcinomas of the skin C. Hepatitis D. Hypophysitis Question 7.29 Which patient is eligible for immunotherapy? A. A 31-year-old female with T3N1 triple-negative breast cancer undergoing neoadjuvant chemotherapy B. A 65-year-old female with metastatic ER-positive breast cancer who has progressed on CDK 4/6 inhibitors, PD-L1 > 1% C. A 55-year-old female with unresectable triple-negative breast cancer with PD-L1 > 1% D. A 32-year-old female with metastatic triple-negative breast cancer who has progressed on multiple lines of chemotherapy, PD-L1 is negative Question 7.30 A 44-year-old female presents with isolated right axillary lymphadenopathy. No breast mass is palpable on examination. Mammogram is negative. The next step involves: A. Next-generation sequencing of axillary biopsy. B. Upper endoscopy. C. Breast MRI. D. Positron emission tomography (PET) scan.

Cancer: Principles & Practice of Oncology Review

ANSWERS

Question 7.1 The correct answer is B. Approximately 10% of all breast cancers are associated with germline mutations, whereas the rest occur sporadically. Question 7.2 The correct answer is A. BRCA1 -associated breast cancers usually are characterized by a “triple-negative” phenotype (ER, PR, and HER2 negative). BRCA2 is associated with pancreatic cancer and melanoma as well as ER-positive breast cancer. BRCA1 and BRCA2 mutations are inherited in an autosomal dominant manner. Question 7.3 The correct answer is B. Li–Fraumeni syndrome is characterized by TP53 mutations leading to breast cancer, soft tissue sarcoma, central nervous system tumors, adrenocortical cancer, leukemia, and prostate cancer. Question 7.4 The correct answer is C. Luminal A breast cancer is characterized by high-expression levels of ER-related genes and low expression of the HER2 cluster and proliferation-associated genes. It rarely has mutations in TP53 , and has an overall better prognosis than do other forms of breast cancer. Question 7.5 The correct answer is C. Clinical practice guidelines support consideration for multigene testing to guide the addition of combination chemotherapy to standard hormone therapy for hormone receptor–positive patients with T1–3 tumors who are node negative based on the TAILORx trial (Trial Assigning Individualized Options for Treatment). 1 Because the HER2 is negative, HER2-based therapy would not be recommended. There is no indication for postmastectomy radiation in this patient. Question 7.6 The correct answer is A. Cowden syndrome, which is associated with germline mutations in PTEN , confers a 25% to 50% lifetime risk of breast cancer. Other risk factors include late age (after age 30) at first full-term pregnancy, > 75% breast density, and proliferative breast lesions. Question 7.7 The correct answer is A. The ACS guidelines for MRI screening of breast cancer include individuals with BRCA mutations; untested first-degree relative of BRCA carrier; those with lifetime risk of breast cancer from 20% to 25%; radiation to the chest between ages 10 and 30 years; Li–Fraumeni, Cowden, or Bannayan–Riley–Ruvalcaba syndromes; and first-degree relatives of patients with breast cancer. A recent study showed that the addition of MRI screening in women with dense breast tissue resulted in significantly fewer interval cancers than did mammography alone, although it is unclear how this will impact clinical practice. 2

Chapter 7 Breast Cancer

Question 7.8 The correct answer is B. History of deep vein thrombosis, stroke, pulmonary embolism, or transient ischemic attacks are considered contraindications to the use of tamoxifen and raloxifene. Tamoxifen has been reported to increase the risks of cataracts. Some SSRIs, particularly paroxetine, fluoxetine, and bupropion, are strong CYP2D6 inhibitors that may decrease the conversion of tamoxifen to its active form. Question 7.9 The correct answer is C. Core needle biopsy is the most appropriate way to diagnose suspected invasive disease. Fine-needle aspiration does not reliably distinguish invasive cancer from DCIS. Excisional biopsy as a diagnostic technique should be reserved for patients with imaging abnormalities that cannot be targeted by core biopsy. Circulating tumor DNA in screening and diagnosis of breast cancer remains investigational. Question 7.10 The correct answer is B. Both tamoxifen and raloxifene have been associated with a decrease in the risk of breast cancer in patients with atypical hyperplasia. However, although the risk reduction for tamoxifen may be seen in both premenopausal and postmenopausal women, the data with the raloxifene is restricted to postmenopausal women. The risk reduction by tamoxifen is 84%. Oophorectomy before menopause decreases the risk of breast cancer by 50% to 65% depending on age at the time of surgery. Although bilateral mastectomy decreases the risk by more than 90%, the risk is not completely eliminated. Question 7.11 The correct answer is B. The Gail model includes first-degree relatives with breast cancer, previous breast biopsies, age at menarche, age at first live birth, race, and ethnicity. Question 7.12 The correct answer is A. DCIS accounts for 15% to 30% of mammographically detected cancers, and is most common among women aged 49 to 69 years. Several studies have reported an increased risk of local recurrence in younger women. The routine use of sentinel lymph node biopsy is not recommended due to the low rates of axillary involvement (1%–2%) and recurrence despite the lack of axillary surgery ( < 0.1%). Nevertheless, selected patients at high risk for axillary lymph node involvement may benefit from sentinel node biopsy. Question 7.13 The correct answer is D. The use of RT after breast-conserving therapy for DCIS reduces both invasive and noninvasive recurrences, but does not alter OS. Question 7.14 The correct answer is C. According to the AJCC eighth edition, in addition to traditional TNM staging, ER, PR, and HER2 expression, as well as tumor grade and Oncotype DX are incorporated into breast cancer staging.

Cancer: Principles & Practice of Oncology Review

Question 7.15 The correct answer is C. The underlying molecular subtype is the most significant determinant of the likelihood of local recurrence after breast-conserving therapy or mastectomy, particularly when a negative margin is achieved. Patients with local regional recurrences warrant restaging, and more than 60% will eventually develop metastatic disease. Women initially treated with breast-conserving therapy may be offered salvage mastectomy. Chemotherapy reduces the risk of subsequent cancer recurrence and improves OS, especially in ER-negative tumors. Question 7.16 The correct answer is D. All of the above are absolute contraindications to breast-conserving therapy followed by RT. Question 7.17 The correct answer is C. In 2013, the U.S. Food and Drug Administration (FDA) approved concurrent use of pertuzumab with trastuzumab and chemotherapy in women receiving preoperative chemotherapy for HER2 positive breast cancer. Patients aged 70 and older with stage I, ER-positive breast cancer treated by lumpectomy and tamoxifen alone have no difference in OS relative to those who receive the same therapy with the addition of whole-breast radiation, although the latter approach is associated with an improvement in locoregional recurrence. Preoperative chemotherapy has no long-term survival advantage relative to adjuvant chemotherapy. Question 7.18 The correct answer is A. Adjuvant tamoxifen results in an improvement in OS for at least 15 years. The benefits are independent of age, menopausal status, and the use of chemotherapy. Question 7.19 The correct answer is B. According to the trials SOFT 3 (Suppression of Ovarian Function Trial) and TEXT (Tamoxifen and Exemestane Trial), 4 younger premenopausal patients with ER-positive, node-positive breast cancers who need adjuvant chemotherapy should receive ovarian suppression with either tamoxifen or an aromatase inhibitor. The addition of ovarian suppression to tamoxifen improves OS. Premenopausal women with low-risk breast cancer may receive tamoxifen without ovarian suppression. Question 7.20 The correct answer is B. Weekly paclitaxel is associated with increased grades 3 and 4 neutropenia relative to dose-dense paclitaxel because pegfilgrastim support is not administered with the former, whereas dose-dense paclitaxel is associated with increased grades 3 and 4 neuropathy. Incorporation of gemcitabine into adjuvant anthracycline- and taxane-based chemotherapy does not improve efficacy. Question 7.21 The correct answer is A. Preexisting cardiac disease, age older than 65 years, anthracycline-based chemotherapy, borderline left ventricular ejection fraction, and hypertension are all risk factors for cardiac dysfunction with adjuvant trastuzumab.

Chapter 7 Breast Cancer

Question 7.22 The correct answer is C. Complete blood counts and liver function tests, cancer antigen 15-3, and yearly computed tomography scans are not indicated in routine surveillance for patients with early-stage breast cancer. Question 7.23 The correct answer is D. All patients presenting with clinical features of IBC should undergo full-staging workup due to the substantial risk of metastatic disease. Involvement of dermal lymphatics in the absence of clinical findings does not indicate IBC because it is a clinical diagnosis. Due to the high risk of local recurrence, all patients with IBC should undergo postmastectomy radiation regardless of the response to neoadjuvant therapy. Question 7.24 The correct answer is D. Male breast cancer is found, more often than is female breast cancer, to be ER positive. Chronic liver disorders, Klinefelter syndrome (XXY), BRCA1 or 2 mutations, mumps orchitis, undescended testis, testicular injury, and feminization are all associated with an increased risk of male breast cancer. The median age of onset is later than that in females. The same considerations regarding nodal surgery pertain for men as for women. Question 7.25 The correct answer is B. The optimal duration of intravenous bisphosphonates or RANK-ligand inhibitors is not well characterized. Intravenous bisphosphonates and RANK-ligand inhibitors lessen the pain associated with bone metastases and prevent skeletal-related complications, such as hypercalcemia and fractures. Bone-directed therapies in patients with widespread bone metastases do not impact OS. Question 7.26 The correct answer is B. Frontline therapy for hormone-positive metastatic breast cancer includes a CDK 4/6 inhibitor. Because this patient had a recurrence while on endocrine therapy with an aromatase inhibitor, treatment includes a CDK 4/6 inhibitor with fulvestrant. Question 7.27 The correct answer is C. In the SOLAR-1 trial, the most common grade 3 toxicity from alpelisib was hyperglycemia. 5 Question 7.28 The correct answer is A. A rare ( < 1%–1.5%), but potentially fatal, side effect of PARP inhibitors is the development of MDS or AML. Patients should be monitored closely for hematologic toxicity. 6 Question 7.29 The correct answer is C. The only current approval for immunotherapy in breast cancer is in patients with unresectable locally advanced or metastatic triple-negative breast cancer that is PD-L1 positive. 7

Cancer: Principles & Practice of Oncology Review

Question 7.30 The correct answer is C. Isolated axillary metastases can be an uncommon presentation of breast cancer. Initial evaluation includes breast MRI if mammogram finding is negative. References 1. Sparano JA, Gray RJ, Makower DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med. 2018;379:111–121. 2. Bakker MF, de Lange SV, Pijnappel RM, et al. Supplemental MRI screening for women with extremely dense breast tissue. N Engl J Med. 2019;381:2091–2102. 3. Francis PA, Regan MM, Fleming GF, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med . 2015;372:436–446. 4. Pagani O, Regan MM, Walley BA, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. N Engl J Med . 2014;371:107–118. 5. André F, Ciruelos E, Rubovszky G, et al. Alpelisib for PIK3CA-mutated, hormone receptor–positive advanced breast cancer. N Engl J Med. 2019;380:1929–1940. 6. Litton JK, Rugo HS, Ettl J, et al. Talazoparib in patients with advanced breast cancer and a germline BRCA mutation. N Engl J Med. 2018;379:753–763. 7. Schmid P, Adams S, Rugo HS, et al. Atezolizumab and nab-paclitaxel in advanced triple-negative breast cancer. N Engl J Med. 2018;379:2108–2121.

Oncology

Editors: Daniel Morgensztern, MD Ramaswamy Govindan, MD Siddhartha Devarakonda, MD Nikolaos A. Trikalinos, MD, MS

REVIEW

5 th edition

Prepare for the oncology boards with confidence! This comprehensive review book closely follows the contents of DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology, 11th Edition , including brand-new, state-of-the-art topics. Hundreds of multiple choice and case-based questions cover medical, radiation, and surgical oncology, as well as hematology, diagnosis and staging, molecular biology, immunotherapy, targeted therapy, and more. The questions are also available online in an interactive format, allowing you to study and review anytime, anywhere! • All questions have been completely revised to mimic the common formats you’ll see on the exam. • Detailed answers with explanations are provided for every question, helping you understand the “how” and “why” behind each correct response. • Content reflects the most current information from the leading oncology text , with corresponding chapters to DeVita, Hellman, and Rosenberg’s Cancer: Principles and Practice of Oncology, 11th Edition provided for further review. Enrich Your eBook Reading Experience • Read directly on your preferred device(s) , such as computer, tablet, or smartphone. • Easily convert to audiobook , powering your content with natural language text-to-speech.

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