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


Current Endocrine Therapy Options for Postmenopausal Women with Early-Stage Hormone Receptor-Positive Breast Cancer


GOAL
To provide oncologists up-to-date information on the role of adjuvant hormone therapy to reduce the risk of tumor recurrence for postmenopausal women with hormone receptor-positive breast cancer.

TARGET AUDIENCE
This activity is designed for oncologists.

LEARNING OBJECTIVES
The Johns Hopkins University School of Medicine takes responsibility for the content, quality, and scientific integrity of this CME activity. At the conclusion of this activity, participants should be able to:

  • Discuss the mechanisms of current treatment options in the treatment of breast cancers for postmenopausal women with hormone receptor-positive breast cancer
  • Evaluate the efficacy of various monotherapies in breast tumor regression
  • Define new directions in treatment protocols for women with advanced breast cancer
  • Assess the efficacy of recent clinical trials in switching treatment modalities for the treatment of breast cancer

ACCREDITATION STATEMENT
The Johns Hopkins University School of Medicine is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

CREDIT DESIGNATION STATEMENT
The Johns Hopkins University School of Medicine designates this educational activity for a maximum of 2 category 1 credits toward the AMA Physician's Recognition Award. Each physician should claim only those credits that he/she actually spent in the activity. The estimated time to complete this educational activity: 2 hours.

Release date: October 15, 2005.
Expiration date: October 15, 2007.

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 name 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 Pfizer, Inc.

Full Disclosure Policy Affecting CME 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 sponsor 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

Deborah K. Armstrong, MD
Associate Professor of Oncology, and Obstetrics and Gynecology
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Johns Hopkins Oncology Center
Baltimore, Md
Dr Armstrong reports having no financial or advisory relationship with corporate organizations related to this activity.

Antonio C. Wolff, MD, FACP
Associate Professor of Oncology
The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Johns Hopkins Oncology Center
Baltimore, Md
Dr Wolff reports having no financial or advisory relationship with corporate organizations related to this activity.

PARTICIPATING FACULTY

Andrea Eisen, MD, FRCPC
Head of Preventive Oncology
Medical Oncologist
Toronto Sunnybrook Regional Cancer Centre
Assistant Professor
University of Toronto
Toronto, Ontario
Dr Eisen reports receiving grants/research support from Novartis Pharmaceuticals Corporation, and honoraria from Novartis Pharmaceuticals Corporation, Pfizer Inc, and Aventis Pharmaceutical.

William J. Gradishar, MD
Associate Professor of Medicine
Division of Hematology and Medical Oncology
Director of Breast Medical Oncology
Co-Director, Lynn Sage Breast Program Northwestern University
Chicago, Ill
Dr Gradishar reports having no financial or advisory relationship with corporate organizations related to this activity.

Carolyn B. Hendricks, MD
Medical Oncologist
Suburban Specialty Care Physicians, PC
Bethesda, Md
Dr Hendricks reports having no financial or advisory relationship with corporate organizations related to this activity.

Eleftherios P. Mamounas, MD, MPH, FACS
Aultman Health Foundation
Canton, Ohio
Dr Mamounas reports that he has served as a consultant for and has received honoraria from AstraZeneca LP, Pfizer Inc., and Novartis Pharmaceuticals Corporation.

Eric P. Winer, MD
Director, Breast Oncology Center
Dana-Farber Cancer Institute
Associate Professor of Medicine
Harvard Medical School
Boston, Mass
Dr Winer reports receiving grants/research support from AstraZeneca. He has attended the advisory boards for AstraZeneca LP, Pfizer Inc, and Novartis Pharmaceuticals Corporation during the past 2 years.

Notice: The audience is advised that articles in this CME activity contain no reference(s) to unlabeled or unapproved uses of drugs or devices.

Advanced Studies in Medicine provides disclosure information from contributing authors, lead presenters, and participating faculty. 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.

Current Endocrine Therapy Options for Postmenopausal Women with Early-Stage Hormone Receptor-Positive Breast Cancer
Deborah K. Armstrong, MD*; Antonio C. Wolff, MD, FACP†

Tamoxifen has long been a mainstay of adjuvant breast cancer therapy. Randomized, double-blind clinical trials have demonstrated that 5 years of treatment with tamoxifen reduced the risk of breast cancer recurrence among estrogen receptor-positive women by 47%, with a 26% reduction in mortality.1 When used for cancer prevention, tamoxifen also has been shown to reduce the incidence of invasive and noninvasive tumors in women at high risk of developing breast cancer.2 Limitations to tamoxifen treatment have also been recognized. Extending tamoxifen treatment beyond 5 years did not confer any additional benefit,3 and tamoxifen is associated with a number of clinically significant side effects, including endometrial cancer, vaginal bleeding, and thromboembolism.4

Tamoxifen is thought to produce its beneficial effects on breast cancer recurrence by blocking the effects of estrogen at estrogen receptors. Although the precise mechanisms by which estrogen promotes cancer risk are not completely understood, estrogen promotes the proliferation of estrogen-sensitive tissues, and estrogen metabolites also may directly contribute to DNA damage and tumor formation.4 During the last few years a new class of medications, the aromatase inhibitors (AIs), has emerged as an important alternative to tamoxifen for the treatment of postmenopausal women with breast cancer. AIs block the activity of the enzyme aromatase, which converts androgens to estrogens in peripheral tissues. The aromatase-mediated conversion of androgens to estrogens occurs primarily in adipose tissue, muscle, skin, and breast tissue, and is the source of estrogens in postmenopausal women.5 AIs reduce both circulating estrogen and the synthesis of estrogen within breast tumors.6

Three “third-generation” AIs are approved for use in the United States: 2 nonsteroidal agents (anastrozole and letrozole), and 1 steroidal agent (exemestane).6 All of the third-generation AIs suppress the production of estrone, estradiol, and estrone sulfate by approximately 80% to 98%, although the degree of inhibition of the different estrogens varies somewhat from agent to agent.4 Recent clinical trials have examined the efficacy and safety of AIs as primary therapy (in place of tamoxifen), as sequential therapy following initial tamoxifen treatment for 2 to 3 years, and as extended therapy following 5 years of tamoxifen.7 These studies have shown that AIs reduce the risk of breast cancer recurrence among postmenopausal women, and that they may be more effective than tamoxifen. The American Society of Clinical Oncology (ASCO) has recently recommended that postmenopausal women with estrogen-sensitive tumors should receive an AI either as initial treatment or following treatment with tamoxifen.8 At present, the optimal treatment strategies to incorporate AIs into oncology practice are not well defined, and a number of important questions remain.

This issue of Advanced Studies in Medicine, which is based on proceedings of a roundtable held in Baltimore on June 28, 2005, entitled “Current Endocrine Therapy Options for Postmenopausal Women With Early-Stage Hormone Receptor-Positive Breast Cancer,” provides an update on the use of AIs as adjuvant therapy for postmenopausal women with breast cancer. William J. Gradishar, MD, director of Breast Medical Oncology and codirector of the Lynn Sage Breast Program at Northwestern University, reviews evidence from recent clinical trials that have examined whether chemotherapy offers an added benefit when combined with hormone therapy. Dr Gradishar, also reviews the use of biomarkers to identify women who are most likely to benefit from endocrine therapy. His review is followed by a panel discussion in which experts on the management of breast cancer discuss the current standard of care for adjuvant hormone therapy, the incorporation of AIs into the management of patients with breast cancer, and the management of toxicities associated with AI therapy. The issue concludes with a summary of the recent ASCO Technology Assessment on the role of AI therapy by Eric P. Winer, MD, Director of the Breast Oncology Center of the Dana-Farber Cancer Institute.

This educational activity will provide oncologists with an overview of recent research and expert opinion regarding strategies for the adjuvant treatment of breast cancer with AIs.

Editor's Note: As of October 7, 2005 three aromatase inhibitors, anastrazole, letrozole, and exemestane, are approved by the US Food and Drug Administration for the adjuvant treatment of postmenopausal women with estrogen receptor-positive early breast cancer.

REFERENCES

1. Early Breast Cancer Trialists’ Collaborative Group. Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet. 1998;351:1451-1467.
2. Fisher B, Costantino JP, Wickerham DL, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90:1371-1388.
3. Fisher B, Dignam J, Bryant J, Wolmark N. Five versus more than five years of tamoxifen for lymph node-negative breast cancer: updated findings from the National Surgical Adjuvant Breast and Bowel Project B-14 randomized trial. J Natl Cancer Inst. 2001;93:684-690.
4. Osborne C, Tripathy D. Aromatase inhibitors: rationale and use in breast cancer. Annu Rev Med. 2005;56:103-116.
5. Michaud LB. Adjuvant use of aromatase inhibitors in postmenopausal women with breast cancer. Am J Health Syst Pharm. 2005;62:266-273.
6. Kudachadkar R, O’Regan RM. Aromatase inhibitors as adjuvant therapy for postmenopausal patients with early stage breast cancer. CA Cancer J Clin. 2005;55:145-163.
7. Burstein HJ. Hormonal therapy for breast cancer. Available at: www.medscape.com/viewarticle/506529. Accessed September 8, 2005.
8. Winer EP, Hudis C, Burstein HJ, et al. American Society of Clinical Oncology technology assessment on the use of aromatase inhibitors as adjuvant therapy for postmenopausal women with hormone receptor-positive breast cancer: status report 2004. J Clin Oncol. 2005;23:619-629.

*Associate Professor of Oncology and Obstetrics & Gynecology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Oncology Center, Baltimore, Maryland.
†Associate Professor of Oncology, The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Johns Hopkins Oncology Center, Baltimore, Maryland.

Address correspondence to: Antonio Wolff, MD, CRB 189 - Oncology, 1650 Orleans St, Baltimore, MD 21231. E-mail: awolff@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.