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Review
. 2021 Oct;17(10):594-604.
doi: 10.1200/OP.21.00172. Epub 2021 Jun 2.

Current and Future Management of HER2-Positive Metastatic Breast Cancer

Olga Martínez-Sáez  1   2   3 , Aleix Prat  1   2   3   4   5
Affiliations
Review

Current and Future Management of HER2-Positive Metastatic Breast Cancer

Olga Martínez-Sáez et al. JCO Oncol Pract. 2021 Oct.

Abstract

Human epidermal growth factor receptor 2 (HER2) is overexpressed and/or amplified in approximately 20% of breast cancers, conferring an aggressive tumor behavior but also an opportunity for targeted therapies. In the advanced setting, the prognosis of patients suffering from this disease has greatly improved after the introduction of new anti-HER2 drugs beyond trastuzumab. For most patients, a taxane combined with trastuzumab and pertuzumab in the first-line setting, followed by trastuzumab-emtansine in second line, should be considered the standard of care today. However, chemo-free anti-HER2 strategies in hormone receptor-positive, HER2-positive breast cancer could also be considered in selected patients. In the third-line setting and beyond, several emerging anti-HER2 therapies are becoming available, including tucatinib, fam-trastuzumab deruxtecan-nxki (DS-8201a), neratinib, and margetuximab-cmkb. In addition, new compounds and combinations are showing promising results in the late-line setting. The treatment landscape of HER2-positive advanced disease is evolving constantly, active drugs such as pertuzumab and trastuzumab-emtansine are moving to early-stage, many biomarkers, including quantification of HER2 itself, are being explored to improve patient selection, and patient populations with specific needs are emerging, such as those with brain metastasis. Here, we provide an overview of the current and future management of HER2-positive advanced breast cancer.

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Conflict of interest statement

Olga Martínez-SáezConsulting or Advisory Role: RocheSpeakers' Bureau: EisaiTravel, Accommodations, Expenses: Pfizer Aleix PratEmployment: NovartisStock and Other Ownership Interests: Reveal GenomicsHonoraria: Pfizer, Novartis, Roche, MSD Oncology, Lilly, Daiichi Sankyo, Amgen, Guardant HealthConsulting or Advisory Role: NanoString Technologies, Amgen, Roche, Novartis, Pfizer, Bristol Myers Squibb, Boehringer Ingelheim, Puma Biotechnology, Oncolytics Biotech, Daiichi Sankyo, AbbVie, AstraZenecaResearch Funding: Roche, Novartis, Incyte, Puma BiotechnologyPatents, Royalties, Other Intellectual Property: PCT/EP2016/080056: HER2 as a Predictor of Response to Dual HER2 Blockade in the Absence of Cytotoxic Therapy, WO/2018/096191. Chemoendocrine score (CES) based on PAM50 for breast cancer with positive hormone receptors with an intermediate risk of recurrence, HER2DX filingTravel, Accommodations, Expenses: Daiichi SankyoOther Relationship: Oncolytics, PeptomycNo other potential conflicts of interest were reported.

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