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Disclaimer: CME certification for these activities has expired. All information is pertinent to the timeframe in which it was released.


New Approaches to the Treatment of Breast Cancer


GOAL
To provide medical/surgical oncologists and oncology nurses with up-to-date information on the treatment and management of patients with breast cancer.

TARGET AUDIENCE
This activity is designed for medical/surgical oncologists and oncology nurses. No prerequisites required.

LEARNING OBJECTIVES
At the conclusion of this activity, the participant should be able to:

  • Assess current treatment guidelines for women with hormone receptor-positive breast cancer.
  • Describe the mechanism of action of current pharmacotherapeutics used to treat breast cancer, such as selective estrogen receptor modulators, aromatase inhibitors, estrogen receptor antagonists, and human epidermal growth factor receptor 2-targeted monoclonal antibodies.
  • Discuss the status of other chemotherapies and novel therapeutics that may play a  role in managing breast cancer in the future.

The Johns Hopkins University School of Medicine and The Institute for Johns Hopkins Nursing take responsibility for the content, quality, and scientific integrity of this CE activity.

ACCREDITATION STATEMENT
This activity has been planned and implemented in accordance with the Essential Areas and Policies of the Accreditation Council for Continuing Medical Education through the joint sponsorship of The Johns Hopkins University School of Medicine and The Institute for Johns Hopkins Nursing. The Johns Hopkins University School of Medicine is accredited by the ACCME to provide continuing medical education for physicians.

The Institute for Johns Hopkins Nursing is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center’s Commission on Accreditation.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 AMA PRA Category 1 Credit(s)™. Physicians should only claim credit commensurate with the extent of their participation in the activity.

This 1.4 contact hour Educational Activity (Provider Directed/Learner Paced) is provided by The Institute for Johns Hopkins Nursing. Claim only those contact hours actually spent in the activity.

The estimated time to complete this educational activity: 2 hours. After reading this monograph, participants may receive credit by completing the CE test, evaluation, and receiving a score of 70% or higher.

Release date: December 15, 2007. Expiration date: December 15, 2009.

DISCLAIMER STATEMENT
The opinions and recommendations expressed by faculty and other experts whose input is included in this program are their own. This enduring material is produced for educational purposes only. Use of The Johns Hopkins University School of Medicine and The Institute for Johns Hopkins Nursing names implies review of educational format, design, and approach. Please review the complete prescribing information of specific drugs or combinations of drugs, including indications, contraindications, warnings, and adverse effects, before administering pharmacologic therapy to patients.

This program is supported by an educational grant from AstraZeneca LP, Genentech, Inc, and Pfizer, Inc.

Full Disclosure Policy Affecting CE Activities:
As a provider accredited by the Accreditation Council for Continuing Medical Education (ACCME), it is the policy of the Johns Hopkins University School of Medicine to require the disclosure of the existence of any significant financial interest or any other relationship a faculty member or a provider has with the manufacturer(s) of any commercial product(s) discussed in an educational presentation. The Program Directors and Participating Faculty reported the following:

PROGRAM DIRECTORS

Vered Stearns, MD
Associate Professor of Oncology
Breast Cancer Program
Sidney Kimmel Comprehensive Cancer Center
Baltimore, Maryland
Dr Stearns reports receiving grants/research support from Novartis and Pfizer, Inc; and serving as a consultant for Wyeth.

Kathleen A. Griffith, PhD, CRNP
Postdoctoral Fellow
Johns Hopkins School of Nursing
Baltimore, Maryland
Dr Griffith reports having no significant financial or advisory relationships with corporate organizations related to this activity.

PARTICIPATING FACULTY

Kimberly Blackwell, MD
Associate Professor of Medicine and Radiation Oncology
Director, Clinical Trials Program in Breast Cancer
Duke University Comprehensive Cancer Center
Durham, North Carolina
Dr Blackwell reports having no significant financial or advisory relationships with corporate organizations related to this activity.

Maura N. Dickler, MD
Assistant Attending Physician
Breast Cancer Medicine Service
Memorial Sloan-Kettering Cancer Center
New York, New York
Dr Dickler reports receiving grants/research support from, serving as a consultant for, and receiving honoraria from Genentech, Inc, GlaxoSmithKline, and Novartis.

Matthew J. Ellis, MD, PhD
Director, Breast Cancer Program
Washington University
St. Louis, Missouri
Dr Ellis reports receiving grants/research support from AstraZeneca, GlaxoSmithKline, Novartis, and Taiho; serving as a consultant for and receiving honoraria from AstraZeneca, Genentech, Inc, GlaxoSmithKline, and Novartis; and serving on the speakers’ bureau for GlaxoSmithKline.

Claudine Isaacs, MD
Director of Clinical Breast Cancer Program
Lombardi Comprehensive Cancer Center
Georgetown University
Washington, DC
Dr Isaacs reports serving on the speakers’ bureau for Abraxis, Genentech, Inc, and Genomic Health.

Ann Partridge, MD, MPH
Department of Medical Oncology
Dana-Farber Cancer Institute
Boston, Massachusetts
Dr Partridge reports serving as a consultant for AstraZeneca and Novartis.

Antonio C. Wolff, MD, FACP
Associate Professor of Oncology
The Sidney Kimmel Comprehensive Cancer Center
Johns Hopkins University School of Medicine
Baltimore, Maryland
Dr Wolff reports receiving grants/research support from Roche.

Notice: The audience is advised that articles in this CE activity may contain reference(s) to unlabeled or unapproved uses of drugs or devices.

Dr Dickler—bevacizumab for metastatic breast cancer.

All other faculty have indicated that they have not referenced unlabeled or unapproved uses of drugs or devices.

Johns Hopkins Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. Johns Hopkins Advanced Studies in Medicine does not provide disclosure information from authors of abstracts and poster presentations. The reader shall be advised that these contributors may or may not maintain financial relationships with pharmaceutical companies.

New Approaches to the Treatment of Breast Cancer
Vered Stearns, MD,* and Kathleen A. Griffith, PhD, CRNP†

Breast cancer has a considerable impact on women’s health in the United States. The incidence of breast cancer has been in decline since 2001, partly as a result of a decrease in the use of estrogen replacement therapy,1 but it is still the most prevalent cancer in women and claims more than 40 000 lives each year.2

Considerable public awareness campaigns and funding have resulted in important treatment advances that have improved the prognosis of individuals diagnosed with breast cancer. Chemotherapy regimens improved over the past 3 decades with the introduction of advanced combination strategies, as well as anthracycline and taxane agents, all of which progressively conferred additional survival benefits.3,4 Targeted endocrine therapy in patients with breast cancer with hormone receptor (HR)-positive tumors has also improved with the advent of tamoxifen, a selective estrogen receptor modulator, and aromatase inhibitors that inhibit the conversion of androgens to estrogen. The introduction of trastuzumab, an agent that targets human epidermal growth factor receptor 2 (HER2), has likewise expanded treatment options in patients with HER2-positive tumors. Although the introduction of new agents has considerably improved the ability of clinicians to offer tailored therapies in breast cancer management, clinicians are still challenged by important considerations when making therapeutic decisions, such as the potential for cardiac dysfunction with trastuzumab therapy and the compounded toxicity of combination strategies.

Questions also remain in determining the ideal regimen of endocrine therapy in those with HR-positive disease. Endocrine therapy is often administered for a course of 5 years or longer after the initial diagnosis of breast cancer. Clinicians are currently faced with the prospect of offering longer courses of therapy to further protect against disease recurrence while balancing the benefits of these agents with the potential for toxicity issues. For instance, aromatase inhibitors have been associated with bone loss, osteoporosis, and possibly dyslipidemia,5-9 which can have a considerable clinical impact in the patient population that is commonly affected by breast cancer.

As breast cancer research continues, new agents have been developed that hold promise in progressively improving patient outcomes. Bevacizumab, an agent that inhibits vascular endothelial growth factor (VEGF), has been shown to be effective in the treatment of solid tumors and is considered a first-line therapy for metastatic colorectal cancer and non–small-cell lung cancer.10,11 Bevacizumab is still under investigation in breast cancer, as preliminary trials have demonstrated improved progression-free survival, but no significant effect on overall survival (study results are expected to be publised in the New England Journal of Medicine soon).12 Novel HER1-targeted agents are also under evaluation in combination with chemotherapy to improve outcomes in patients with breast cancer with tumors that are negative for estrogen receptors, progesterone receptors, or HER2 receptors. Other agents that target both HER1 and HER2, as well as novel anti-HER2 agents, are also being investigated for their therapeutic value in breast cancer.

Although the development of novel therapies continues, ongoing research is also investigating the value of combination regimens that target multiple pathways, such as VEGF and HER2. In addition, new formulations of established chemotherapy agents are also being developed in an ongoing effort to maximize efficacy and minimize the substantial toxicity associated with these therapies.

The advent of new potential treatment options is exciting from a therapeutic standpoint, but raises questions regarding the best sequence of therapy, the potential for greater toxicity as combination regimens are explored, and the best therapeutic course as predicted by HR and HER2 status. Overall, the advent of new therapies will require a continuing commitment to advanced diagnostic strategies and the utilization of predictive markers to guide therapy and realize the best possible clinical outcomes in each individual patient.

This issue of Johns Hopkins Advanced Studies in Medicine is the result of a recent roundtable discussion that addressed the present and projected future treatment options for the management of breast cancer. Kimberly Blackwell, MD, of the Duke University Comprehensive Cancer Center opened the discussion with a review of current treatment options, including chemotherapy regimens, endocrine therapy, and HER2-targeted agents. Matthew J. Ellis, MD, PhD, of Washington University in St. Louis, Missouri, discussed the role that endocrine therapy plays in the management of breast cancer, including the challenges in determining the best sequence of endocrine therapy with chemotherapy, and the importance of balancing between protective benefits and toxicity risks in patients receiving these treatments over long periods of time. Therapeutic advances that have the potential to impact future breast cancer management, including agents that target VEGF, novel HER1- and HER2-targeted agents, new combination strategies, and new chemotherapy formulations, were addressed by Maura N. Dickler, MD, of Memorial Sloan-Kettering Cancer Center. These presentations, as well as the final presentation of relevant case studies by Dr Ellis, were followed by discussion sessions with all participating faculty members, including Claudine Isaacs, MD, of Georgetown University, Ann Partridge, MD, MPH, of the Dana-Farber Cancer Institute, and Antonio C. Wolff, MD, FACP, of the Johns Hopkins University School of Medicine. These discussion sessions are summarized in the monograph to provide greater attention to the relevant issues addressed by the panel. After the completion of this educational monograph, participants should recognize the role that standard chemotherapy, endocrine therapy, and targeted agents play in the management of breast cancer, and should have a better understanding of therapies currently under investigation to improve outcomes in patients diagnosed with the disease.

REFERENCES
1.    Ravdin PM, Cronin KA, Howlader N, et al. The decrease in breast-cancer incidence in 2003 in the United States. N Engl J Med. 2007;356:1670-1674.
2.    American Cancer Society. Cancer facts and figures 2007. Available at: http://www.cancer.org/downloads/STT/CAFF2007PWSecured.pdf. Accessed October 8, 2007.
3.    Early Breast Cancer Trialists’ Collaborative Group. Polychemotherapy for early breast cancer: an overview of the randomised trials. Lancet. 1998;352:930-942.
4.    Giordano SH, Duan Z, Kuo Y, et al. The impact of CALGB 9344 on adjuvant taxane (T) use for breast cancer (BC). 2005 ASCO Annual Meeting Proceedings. J Clin Oncol. 2005;23:669.
5.    Breast International Group (BIG) 1-98 Collaborative Group, Thürlimann B, Keshaviah A, et al. A comparison of letrozole and tamoxifen in postmenopausal women with early breast cancer. N Engl J Med. 2005;353:2747-2757.
6.    Coombes RC, Hall E, Gibson LJ, et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004;350:1081-1092.
7.    McCloskey E, Eastell R, Lakner G, et al. Initial results of the LEAP Study: The first direct comparison of safety parameters between aromatase inhibitors (AIs) in healthy postmenopausal women. Presented at: 28th Annual San Antonio Breast Cancer Symposium; December 8-11, 2005; San Antonio, Texas. Abstract 2052.
8.    Baum M, Buzdar A, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer. 2003;98:1802-1810.
9.    Goss PE, Ingle JN, Martino S, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003;349:1793-1802.
10.    Hurwitz H, Fehrenbacher L, Novotny W, et al. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004;350:2335-2342.
11.    Sandler A, Gray R, Perry MC, et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N Engl J Med. 2006;355:2542-2550.
12.    Miller KD, Wang M, Gralow J, et al. A randomized phase III trial of paclitaxel versus paclitaxel plus bevacizumab as first-line therapy for locally recurrent or metastatic breast cancer: a trial coordinated by the Eastern Cooperative Oncology Group (E2100). Presented at: 28th Annual San Antonio Breast Cancer Symposium; December 8-11, 2005; San Antonio, Texas. Abstract 3.

The content in this monograph was developed with the assistance of a staff medical writer. Each author had final approval of his or her article and all its contents.

*Associoate Professor of Oncology, Breast Cancer Program, Sidney Kimmel Comprehensive Cancer Center, Baltimore, Maryland.
†Postdoctoral Fellow, Johns Hopkins School of Nursing, Baltimore, Maryland.
Address correspondence to: Vered Stearns, MD, Associate Professor of Oncology, Breast Cancer Program, Sidney Kimmel Comprehensive Cancer Center, Cancer Research Building I, Suite 145, 1650 Orleans Street, Baltimore, MD  21231. E-mail: vstearn1@jhmi.edu.





Johns Hopkins Advanced Studies in Medicine (ISSN-1558-0334), is published by Galen Publishing, LLC, d/b/a ASiM, PO Box 340, Somerville, NJ 08876. (908) 253-9001. Copyright ©2012 by Galen Publishing. All rights reserved. No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, without first obtaining permission from the publisher. ASiM is a registered trademark of The Healthcare Media Group, LLC.