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Open Access 01-03-2022 | Breast Cancer | Clinical

Anti-HER2 therapy in metastatic breast cancer: many choices and future directions

Authors: Carrie S. Wynn, Shou-Ching Tang

Published in: Cancer and Metastasis Reviews | Issue 1/2022

Abstract

Metastatic HER2 + breast cancer is an expanding area of drug development and research, with three new drugs approved in 2020 alone. While first-line therapy is well-established for metastatic HER2 + breast cancer, the standard of care for second-line therapy will likely be changing soon based on the results of the DESTINY-Breast03 trial. In the third-line setting, many options are available. Considerations in choosing between regimens in the third-line include resistance to trastuzumab, the presence of brain metastases, and tolerability. High rates of resistance exist in this setting particularly due to expression of p95, a truncated form of HER2 that constitutively activates downstream signaling pathways. We suggest a tyrosine kinase inhibitor (TKI)-based regimen because of the activity of TKIs in brain metastases and in p95-expressing tumors. Attempts to overcome resistance to anti-HER2 therapies with PI3K inhibitors, mTOR inhibitors, and CDK 4/6 inhibitors are an active area of research. In the future, biomarkers are needed to help predict which therapies patients may benefit from the most. We review the many new drugs in development, including those with novel mechanisms of action.

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Title: Anti-HER2 therapy in metastatic breast cancer: many choices and future directions
Authors: Carrie S. Wynn
Shou-Ching Tang
Publication date: 01-03-2022
Publisher: Springer US
Keywords: Breast Cancer
Tyrosine Kinase Inhibitors
Breast Cancer
Tyrosine Kinase Inhibitors
Lapatinib
Neratinib
Trastuzumab
Published in: Cancer and Metastasis Reviews / Issue 1/2022
Print ISSN: 0167-7659
Electronic ISSN: 1573-7233
DOI: https://doi.org/10.1007/s10555-022-10021-x

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Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

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Prof. Fabrice Barlesi

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Keynote webinar | Spotlight on antibody–drug conjugates in cancer