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Recent Developments in HER2-Directed Therapy in Breast Cancer

  • Clinical Trials (JE Lang, Section Editor)
  • Published:
Current Breast Cancer Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This review will discuss recent important trials for the treatment of HER2-positive breast cancer, emphasize ongoing areas of development, and highlight areas of unmet need.

Recent Findings

Advances for early-stage treatment have been driven by key clinical trials with pertuzumab, neratinib, and TDM-1. In the adjuvant setting, dual HER2 targeting with trastuzumab and pertuzumab has demonstrated modest improvement in disease-free survival. Neratinib also showed modest benefit in the extended adjuvant setting after prior trastuzumab. Finally, for patients who did not achieve pathologic complete response to neoadjuvant therapy, adjuvant therapy with TDM-1 showed significant disease-free survival benefit over trastuzumab. In advanced disease, neratinib appears to have activity beyond standard second line treatment. Promising compounds with early-phase data reviewed are tucatinib, margetuximab, and antibody-drug complexes. Immunotherapy in HER2-positive disease also has early-phase data. Endocrine therapy in combination with CDK4/6 inhibition and HER2-targeted therapy is in evaluation. Two areas of unmet need include CNS disease and disease treatment in the elderly population.

Summary

In the wake of recent practice changing clinical trials, HER2-directed therapy is rapidly evolving. Future advances in therapy are anticipated with ongoing studies.

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Funding

The project described was supported in part by award number P30CA014089 from the National Cancer Institute.

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Authors and Affiliations

  1. Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA

    Irene Kang, Stephen Dong, Janice Lu & Bing Xia

  2. Norris Comprehensive Cancer Center, University of Southern California, 1441 Eastlake Ave., Suite 3444, Los Angeles, CA, 90033, USA

    Irene Kang, Stephen Dong, Janice Lu & Bing Xia

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  1. Irene Kang
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  2. Stephen Dong
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  3. Janice Lu
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Correspondence to Irene Kang.

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Conflict of Interest

Irene Kang reports personal fees from Puma Biotechnology, and personal fees from Pfizer Inc. outside the submitted work. Janice Lu reports advisory roles for Novartis, Pfizer, Puma, Radius, and Daiichi outside the submitted work. Bing Xia reports personal fees from Genentech, personal fees from AstraZeneca, and other from Bristol-Myers Squibb outside the submitted work. Stephen Dong declares no conflicts of interest relevant to this manuscript.

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Kang, I., Dong, S., Lu, J. et al. Recent Developments in HER2-Directed Therapy in Breast Cancer. Curr Breast Cancer Rep 11, 311–325 (2019). https://doi.org/10.1007/s12609-019-00347-x

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