Optimal Chemotherapy Combinations with Trastuzumab: Are Anthracyclines Obsolete?

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Table of Contents

• A Word From the Editor
• Introduction
• Role Of Anthracyclines in Her2 Positive Breast Cancer
• Efficacy Of Anthracycline and Nonanthracycline Adjuvant Trastuzumab Clinical Trials
• Cardiotoxicity of Anthracycline vs Nonanthracycline Adjuvant Trastuzumab Clinical Trials
• Concurrent Anthracycline and Trastuzumab Neoadjuvant Therapy
• Topoisomerase II as a Predictor of Anthracycline Benefit Her2 Positive Breast Cancer
• Conclusion
• Key Points
• References

Dear Colleague:

We are pleased to introduce the third of four E-Updates that will be presented this year in the series entitled HER1 and HER2 Targeting in Breast Cancer.  This clinically focused update concerns the optimal chemotherapy combinations with trastuzumab, a presentation that endeavors to determine whether anthracyclines are now obsolete in the setting of HER2+ disease. This is a particularly thorny issue for the clinician, so we are fortunate to have it addressed and analyzed by Dr. Maysa Abu-Khalaf, Assistant Professor of Medical and Gynecologic Oncology at the Yale Comprehensive Cancer Canter, and by her colleague, Dr. Lyndsay Harris, Director of the Breast Disease Unit at the Yale Comprehensive Cancer Center.

Among other key clinical considerations, the authors describe the cardiotoxicity risk factors that must be recognized and considered when considering therapy with adjuvant trastuzumab.

The fourth and final E-Update in this series will present the current and future roles of lapatinib in HER2 breast cancer. We hope that taken together these four updates focused on HER2-directed therapy will improve the clinicians understanding of how to maximize the benefits of HER2 targeting in breast cancer and minimize side effects and serious toxicities.

Sincerely,

Matthew J. Ellis, MB, BChir, PhD, FRCP
Director, Breast Cancer Program
Anheuser Busch Tenured
Associate Professor of Medicine
Washington University School of Medicine
St. Louis, Missouri

INTRODUCTION

HER2 (human epidermal growth factor receptor 2) is a 185 kDa member of the erb-B receptor tyrosine kinase family and is overexpressed in 25% to 30% of breast cancer patients. HER2 overexpression is an adverse prognostic factor in early breast cancer, and is associated with an increased risk of distant relapse and death.[1] The presence of HER2 on the cell surface makes it a logical target for antibody therapy, leading to the development of trastuzumab (Herceptin) — a humanized monoclonal antibody against the extracellular domain of the HER2 protein. Trastuzumab was first approved in 1998 for first-line treatment of HER2 positive metastatic breast cancer in combination with paclitaxel.[2] Trastuzumab has been found to improve survival for women with metastatic breast cancer, and subsequently, adjuvant trials showed substantial benefits for patients with early-stage HER2 positive breast cancer. This review focuses on discussing the efficacy and cardiotoxicity of anthracycline and trastuzumab combination regimens compared to nonanthracycline and trastuzumab regimens.