TARGET AUDIENCE
This activity is intended for medical oncologists, hematologist-oncologists and other healthcare providers involved in the treatment of breast cancer.

OVERVIEW OF ACTIVITY
Breast cancer remains the most frequently diagnosed neoplasm in women, and in 2020 in the United States alone the disease will culminate in an estimated 279,100 new cases and 42,690 deaths. The current clinical management of breast cancer is multidisciplinary and includes surgical resection of local disease with or without radiation therapy and the treatment of microscopic or macroscopic systemic disease with cytotoxic chemotherapy, endocrine therapy, biologic therapy or combinations of these approaches. The indications for and potential utility of these local and systemic options are largely based on a number of prognostic and predictive risk factors detectable in the patient’s tumor at the time of diagnosis. In fact, as the field of oncology is challenged to improve the precision with which malignant cells are targeted, biomarker-driven treatment algorithms have become the norm for many tumor types, particularly breast cancer.

In recent years breast cancer diagnosis has included molecular subtype, derived from either gene microarray analysis or immunohistochemical cell-receptor expression profiles. While several factors are routinely considered in therapeutic decision-making, HER2 status and the presence or absence of hormone receptors perhaps play the most significant and substantial roles. Importantly, the recent observation and definitive documentation that patients with breast cancer harboring distinct genomic abnormalities or other biomarkers, such as BRCA mutations, PIK3CA mutations and ESR1 mutations, derive therapeutic benefit from particular agents has increased the complexity of selecting and sequencing therapy for estrogen receptor (ER)-positive metastatic breast cancer. Although several consensus- and evidence-based treatment guidelines are available to assist clinicians in this dynamic environment, many areas of controversy persist within academic and community settings. This CME activity uses the perspectives of clinical investigators on key challenges and controversies in the selection and sequencing of therapy for patients with ER-positive, HER2-negative metastatic breast cancer to address existing management uncertainties and help keep clinician learners up to date so they can optimize their care of patients.

LEARNING OBJECTIVES

• Assess the recommendations of clinical investigators regarding first-line endocrine-based treatment options, including CDK4/6 inhibitors, for patients with de novo metastatic disease or those who develop metastases during or after adjuvant endocrine therapy.
• Compare and contrast the efficacy and tolerability of the 3 approved CDK4/6 inhibitors, and consider this information when selecting among these agents for the treatment of ER-positive metastatic breast cancer.
• Understand clinical investigator assessments of the side-effect profiles of palbociclib, ribociclib and abemaciclib for patients with ER-positive, HER2-negative breast cancer.
• Evaluate the approaches taken by clinical investigators to therapy for patients experiencing disease progression on a CDK4/6 inhibitor.

ACCREDITATION STATEMENT
Research To Practice is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
CME credit is no longer available for this issue

AMERICAN BOARD OF INTERNAL MEDICINE (ABIM) — MAINTENANCE OF CERTIFICATION (MOC)
CME credit is no longer available for this issue

HOW TO USE THIS CME ACTIVITY
This CME activity consists of a text component.
CME credit is no longer available for this issue

CONTENT VALIDATION AND DISCLOSURES
Research To Practice (RTP) is committed to providing its participants with high-quality, unbiased and state-of-the-art education. We assess conflicts of interest with faculty, planners and managers of CME activities. Conflicts of interest are identified and resolved through a conflict of interest resolution process. In addition, all activity content is reviewed by both a member of the RTP scientific staff and an external, independent physician reviewer for fair balance, scientific objectivity of studies referenced and patient care recommendations.

FACULTY — The following faculty (and their spouses/partners) reported relevant conflicts of interest, which have been resolved through a conflict of interest resolution process:

Carey K Anders, MD
Medical Director of the Duke Center for Brain and Spine Metastases
Duke Cancer Institute
Durham, North Carolina

Advisory Committee and Consulting Agreements: AstraZeneca Pharmaceuticals LP, Eisai Inc, Genentech, a member of the Roche Group, Ipsen Biopharmaceuticals Inc, Seattle Genetics; Contracted Research: G1 Therapeutics, Lilly, Merck, Nektar, Puma Biotechnology Inc, Seattle Genetics, Tesaro, A GSK Company; Data and Safety Monitoring Board/Committee: Genentech, a member of the Roche Group; Royalties: Jones & Bartlett Learning.

Aditya Bardia, MD, MPH
Director, Precision Medicine
Center for Breast Cancer
Attending Physician
Massachusetts General Hospital Cancer Center
Harvard Medical School
Boston, Massachusetts

Consulting Agreements: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Immunomedics Inc, Merck, Novartis, Pfizer Inc, Puma Biotechnology Inc, Radius Health Inc, Sanofi Genzyme, Spectrum Pharmaceuticals Inc; Contracted Research: bioTheranostics Inc, Genentech, a member of the Roche Group, Immunomedics Inc, Merck, Novartis, Pfizer Inc, Radius Health Inc, Sanofi Genzyme.

Erika Hamilton, MD
Director, Breast and Gynecologic Research Program
Sarah Cannon Research Institute
Nashville, Tennessee

Consulting Agreements: AstraZeneca Pharmaceuticals LP, Black Diamond Therapeutics Inc, Boehringer Ingelheim Pharmaceuticals Inc, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, Lilly, Mersana Therapeutics, NanoString Technologies, Novartis, Pfizer Inc, Puma Biotechnology Inc, Silverback Therapeutics; Contracted Research: AbbVie Inc, Acerta Pharma — A member of the AstraZeneca Group, Aravive Inc, ArQule Inc, Arvinas, AstraZeneca Pharmaceuticals LP, BerGenBio ASA, Black Diamond Therapeutics Inc, Boehringer Ingelheim Pharmaceuticals Inc, Clovis Oncology, Compugen, Curis Inc, CytomX Therapeutics, Daiichi Sankyo Inc, Deciphera Pharmaceuticals Inc, eFFECTOR Therapeutics Inc, Eisai Inc, EMD Serono Inc, Fochon Pharmaceuticals Ltd, Fosun Orinove PharmaTech Inc, FUJIFILM Pharmaceuticals USA Inc, G1 Therapeutics, Genentech, a member of the Roche Group, H3 Biomedicine, Harpoon Therapeutics, Hutchison MediPharma, Immunomedics Inc, InventisBio, Karyopharm Therapeutics, Leap Therapeutics Inc, Lilly, Lycera, MacroGenics Inc, Marker Therapeutics Inc, Medivation Inc, a Pfizer Company, Mersana Therapeutics, Merus BV, Molecular Templates, Novartis, NuCana, OncoMed Pharmaceuticals Inc, Pfizer Inc, Puma Biotechnology Inc, Radius Health Inc, Regeneron Pharmaceuticals Inc, Rgenix, Seattle Genetics, Sermonix Pharmaceuticals, Silverback Therapeutics, Stemcentrx, Sutro Biopharma, Syndax Pharmaceuticals Inc, Syros Pharmaceuticals Inc, Taiho Oncology Inc, Takeda Oncology, Tesaro, A GSK Company, Torque Therapeutics, Unum Therapeutics, Verastem Inc, Zenith Epigenetics Ltd, Zymeworks.

Sara Hurvitz, MD
Associate Professor of Medicine
David Geffen School of Medicine at UCLA
Director, Breast Cancer Clinical Research Program
Co-Director, Santa Monica-UCLA Outpatient Oncology Practice
Santa Monica, California

Consulting Agreement: NKMax America; Contracted Research: Ambrx, Amgen Inc, Arvinas, Bayer HealthCare Pharmaceuticals, Daiichi Sankyo Inc, Dignitana, Genentech, a member of the Roche Group, GlaxoSmithKline, Immunomedics Inc, Lilly, MacroGenics Inc, Novartis, OBI Pharma Inc, Pfizer Inc, Pieris Pharmaceuticals, Puma Biotechnology Inc, Radius Health Inc, Roche Laboratories Inc, Sanofi Genzyme, Seattle Genetics; Paid Travel: Lilly.

Virginia Kaklamani, MD, DSc
Professor of Medicine
Ruth McLean Bowman Bowers Chair in Breast Cancer Research and Treatment
AB Alexander Distinguished Chair in Oncology
Associate Director for Clinical Research
Leader of the Breast Cancer Program
UT Health San Antonio
The University of Texas MD Anderson Cancer Center
San Antonio, Texas

Consulting Agreements: Amgen Inc, AstraZeneca Pharmaceuticals LP, Athenex, Celldex Therapeutics, Eisai Inc, Puma Biotechnology Inc; Contracted Research: Eisai Inc; Speakers Bureau: Celgene Corporation, Eisai Inc, Genentech, a member of the Roche Group, Genomic Health Inc, Novartis, Pfizer Inc, Puma Biotechnology Inc.

Ruth O’Regan, MD
Endowed Professor of Medicine
Chief, Division of Hematology/Oncology and Palliative Medicine
University of Wisconsin Carbone Cancer Center
Madison, Wisconsin

No relevant conflicts of interest to disclose.

Joyce O’Shaughnessy, MD
Celebrating Women Chair in Breast Cancer Research
Baylor University Medical Center
Director, Breast Cancer Research Program
Texas Oncology
US Oncology
Dallas, Texas

Advisory Committee and Consulting Agreements: AbbVie Inc, Agendia Inc, Amgen Inc, AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Company, Celgene Corporation, Daiichi Sankyo Inc, Eisai Inc, Genentech, a member of the Roche Group, Genomic Health Inc, GRAIL, Halozyme Inc, Heron Therapeutics, Immunomedics Inc, Ipsen Biopharmaceuticals Inc, Jounce Therapeutics, Lilly, Merck, Myriad Genetic Laboratories Inc, Novartis, Odonate Therapeutics, Pfizer Inc, Puma Biotechnology Inc, Roche Laboratories Inc, Seattle Genetics, Syndax Pharmaceuticals Inc.

Mark D Pegram, MD
Susy Yuan-Huey Hung Professor of Medicine
Director of the Breast Oncology Program
Associate Dean, Clinical Research Quality
Associate Director for Clinical Research
Stanford Cancer Institute
Stanford University School of Medicine
Stanford, California

Consulting Agreements: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Genentech, a member of the Roche Group, MacroGenics Inc, Merck, Novartis, Odonate Therapeutics, Pfizer Inc, Puma Biotechnology Inc, Samsung Bioepis, Seattle Genetics, Zymeworks Inc; Contracted Research: AstraZeneca Pharmaceuticals LP, Daiichi Sankyo Inc, Pfizer Inc, Zymeworks Inc; Data and Safety Monitoring Board/Committee: Roche Laboratories Inc; Employment (Spouse): Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company.

Sara M Tolaney, MD, MPH
Associate Director, Susan F Smith Center for Women’s Cancers
Director of Clinical Trials, Breast Oncology
Director of Breast Immunotherapy Clinical Research
Senior Physician
Breast Oncology Program
Dana-Farber Cancer Institute
Assistant Professor of Medicine
Harvard Medical School
Boston, Massachusetts

Consulting Agreements: AbbVie Inc, AstraZeneca Pharmaceuticals LP, Athenex, Bristol-Myers Squibb Company, Celldex Therapeutics, Eisai Inc, G1 Therapeutics, Genentech, a member of the Roche Group, Immunomedics Inc, Lilly, Merck, NanoString Technologies, Nektar, Novartis, Odonate Therapeutics, OncoPep, Paxman, Pfizer Inc, Puma Biotechnology Inc, Sanofi Genzyme, Seattle Genetics, Silverback Therapeutics; Contracted Research: AstraZeneca Pharmaceuticals LP, Bristol-Myers Squibb Company, Cyclacel Pharmaceuticals Inc, Eisai Inc, Exelixis Inc, Genentech, a member of the Roche Group, Immunomedics Inc, Lilly, Merck, NanoString Technologies, Nektar, Novartis, Odonate Therapeutics, Pfizer Inc, Sanofi Genzyme, Seattle Genetics.

EDITOR — Dr Love is president and CEO of Research To Practice. Research To Practice receives funds in the form of educational grants to develop CME activities from the following commercial interests: AbbVie Inc, Acerta Pharma — A member of the AstraZeneca Group, Adaptive Biotechnologies, Agendia Inc, Agios Pharmaceuticals Inc, Amgen Inc, Array BioPharma Inc, Astellas, AstraZeneca Pharmaceuticals LP, Bayer HealthCare Pharmaceuticals, Biodesix Inc, bioTheranostics Inc, Blueprint Medicines, Boehringer Ingelheim Pharmaceuticals Inc, Boston Biomedical Inc, Bristol-Myers Squibb Company, Celgene Corporation, Clovis Oncology, Daiichi Sankyo Inc, Dendreon Pharmaceuticals Inc, Eisai Inc, EMD Serono Inc, Exelixis Inc, Foundation Medicine, Genentech, a member of the Roche Group, Genmab, Genomic Health Inc, Gilead Sciences Inc, GlaxoSmithKline, Guardant Health, Halozyme Inc, ImmunoGen Inc, Incyte Corporation, Infinity Pharmaceuticals Inc, Ipsen Biopharmaceuticals Inc, Janssen Biotech Inc, administered by Janssen Scientific Affairs LLC, Jazz Pharmaceuticals Inc, Kite, A Gilead Company, Lexicon Pharmaceuticals Inc, Lilly, Loxo Oncology Inc, a wholly owned subsidiary of Eli Lilly & Company, Merck, Merrimack Pharmaceuticals Inc, Myriad Genetic Laboratories Inc, Natera Inc, Novartis, Oncopeptides, Pfizer Inc, Pharmacyclics LLC, an AbbVie Company, Prometheus Laboratories Inc, Puma Biotechnology Inc, Regeneron Pharmaceuticals Inc, Sandoz Inc, a Novartis Division, Sanofi Genzyme, Seattle Genetics, Sirtex Medical Ltd, Spectrum Pharmaceuticals Inc, Taiho Oncology Inc, Takeda Oncology, Tesaro, A GSK Company, Teva Oncology, Tokai Pharmaceuticals Inc and Tolero Pharmaceuticals.

RESEARCH TO PRACTICE CME PLANNING COMMITTEE MEMBERS, STAFF AND REVIEWERS — Planners, scientific staff and independent reviewers for Research To Practice have no relevant conflicts of interest to disclose.

This educational activity contains discussion of published and/or investigational uses of agents that are not indicated by the Food and Drug Administration. Research To Practice does not recommend the use of any agent outside of the labeled indications. Please refer to the official prescribing information for each product for discussion of approved indications, contraindications and warnings. The opinions expressed are those of the presenters and are not to be construed as those of the publisher or grantors.

This activity is supported by educational grants from AstraZeneca Pharmaceuticals LP, Celgene Corporation, Genentech, a member of the Roche Group, Merck, Novartis and Puma Biotechnology Inc.

Hardware/Software Requirements:
A high-speed Internet connection
A monitor set to 1280 x 1024 pixels or more
Internet Explorer 11 or later, Firefox 56 or later, Chrome 61 or later, Safari 11 or later, Opera 48 or later
Adobe Flash Player 27 plug-in or later
Adobe Acrobat Reader
(Optional) Sound card and speakers for audio

Release date: May 2020
Expiration date: May 2021