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ESMO E-Learning: Present and Emerging Treatment Options in HER2/neu Overexpressing Metastatic Breast Cancer

ESMO members

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60 slides / 49 minutes

Learning objectives

  • To summarise data of molecular characteristics relevant for HER2 targeting and data from recent clinical studies in metastatic breast cancer
  • To provide an update on present and emerging treatment strategies in HER2-positive metastatic breast cancer
  • To present the current evidence and discuss perspectives for ameliorated efficacy of HER2 targeting in metastatic breast cancer


In recent decades, the human epidermal growth factor receptor 2 (HER2) oncogene, which is present in up to 30% of patients with breast cancer, has become a major therapeutic target. HER2 directed agents create an array of therapeutic options for patients with breast cancer. This E-learning module focuses on current and emerging treatment options in HER2-positive metastatic breast cancer and it represents a seriously performed update of a previously available ESMO E-Learning module that introduces different medical advances emerged in the field in the last 5 years.

This module, authored by two distinguished experts in the management of breast cancer, provides evidence for targeted treatments in HER2-positive metastatic breast cancer and is divided into 3 sections: current standards, specific treatment situations and novel approaches.

Each section is illustrated by molecular pathways observations relevant for activity and resistance to treatment and provides a summarised evidence from the clinical trials with either HER2 targeted monotherapy or HER2 targeted combinations.

After a general introduction about the trastuzumab treatment success story, the authors elaborate a subcutaneous formulation of trastuzumab and cover in depth the mechanisms of action of the more recently developed HER2 directed therapies, as well as the achievements from the clinical studies. In the section of current treatment standards, the authors discuss in detail the next five therapeutic scenarios in HER2-positive metastatic breast cancer: chemotherapy plus trastuzumab, chemotherapy plus rastuzumab/pertuzumab, T-DM1, trastuzumab/lapatinib, and lapatinib/capecitabine.

In the second part of the module, the authors discuss specific treatment situations such as HER2-directed therapy in combination with endocrine therapy, in particular trastuzumab or lapatinib plus aromatase inhibitors, as well as the systemic therapy for brain metastases in HER2-positive metastatic breast cancer.

In the third section, the authors give details of novel approaches, such as second- and third-generation tyrosine kinase inhibitors (neratinib, tucatinib), immune checkpoint inhibition in HER2 overexpressing breast cancers and optimised HER2-directed antibodies (margetuximab, ZW25, trastuzumab-deruxtecan).

The authors conclude the module summarising the evidence for ameliorated efficacy of HER2 targeting treatments for metastatic breast cancer and emphasizing the optimising definition of HER2 positivity.

This E-Learning module was published in 2019 and expired in 2021.

Last update: 24 Jan 2019

Prof Zielinski has reported consultancies and Speaker’s honoraria: Roche, Novartis, BMS, MSD, Imugene, Ariad, Pfizer, Merrimack/Shire, Merck KGaA, Fibrogen, AstraZeneca, Tesaro, Gilead, Servier, Eli Lilly, Amgen. Financial support for research to his Institution (CECOG); BMS, MSD, Pfizer, AstraZeneca, Merrimack/Shire.

Prof Bartsch has reported Advisory role: Astra-Zeneca, Celgene, Daiichi, Eisaii, Eli-Lilly, MSD, Novartis, Pfizer and Roche. Lecture honoraria: Astra-Zeneca, BMS, Celgene, Eli-Lilly, Novartis, Pfizer and Roche. Research support: Novartis and Roche.

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