ESMO E-Learning: Present and Emerging Treatment Options in Her-2/neu Overexpressing Metastatic Breast Cancer

Learning Objectives

  • To summarise data of molecular characteristics relevant for HER2 targeting and data from recent clinical studies in metastatic breast cancer
  • To understand present and emerging treatment strategies in HER2 overexpressing metastatic breast cancer
  • To discuss the current evidence and perspectives for ameliorated efficacy of HER2 targeting in metastatic breast cancer
Title Duration Content CME Points CME Test
Present and Emerging Treatment Options in Her-2/neu Overexpressing Metastatic Breast Cancer 37 min min. 46 slides 1 Take Test
Zielinski Christoph
Christoph C. Zielinski
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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. Trastuzumab and other HER2 directed agents have been developed for treatment use, creating an array of therapeutic options for patients with breast cancer. This E-Learning module focuses on present and emerging treatment options in HER2-overexpressing metastatic breast cancer.

The module starts by providing evidence for targeted monotherapy (trastuzumab, lapatinib, T-DM1) and targeted combinations (trastuzumab plus lapatinib, trastuzumab plus pertuzumab). HER2 gene amplification is associated with increased tumour proliferation, high-grade disease, nodal metastases, tumour size, and it’s inversely correlated with ER status. HER2 activates ER in the presence of low estrogen, ER activates intracellular signalling potentiating HER-2 activity and downregulates HER2 expression. This negative loop is neutralised by HER2 overexpression. It is also known that tumour proliferation is linked to RAS/MAPK cascade. Increased cell migration and lymph node involvement are linked to Akt/PI3 kinase. Starting by understanding molecular pathways and clinical characteristics of breast cancer, the module provides a rationale for targeted therapies in HER2-positive breast cancer.

This module summarises details from randomised, phase III non-inferiority study which compared Pharmacokinetics, efficacy and safety of subcutaneous and intravenous formulations of trastuzumab; it also provides the subgroup analysis from the same study. After covering a novel formulation of an old drug, the author discusses new treatment options, including a mechanism of action of HER2 directed therapies, pertuzumab and T-DM1. Furthermore, the module provides in depth results from phase III study of docetaxel/trastuzumab with or without pertuzumab in HER2-overexpressing metastatic breast cancer, and then analyses T-DM1 efficacy according to the line of treatment: pre-treated patients (T-DM1 vs. lapatinib/capecitabine) and first-line treatment of HER2-positive metastatic breast cancer (T-DM1 vs. trastuzumab/docetaxel).

By covering HER2 somatic Mutations in breast cancer and the mechanisms of resistance to trastuzumab, the author continues on alternative mechanisms of lapatinib action, and provides details on the first direct comparison of trastuzumab vs. lapatinib in metastatic breast cancer (prospective randomised phase III study of trastuzumab plus taxane vs. lapatinib plus taxane). Furthermore he provides rationale for and results from studying lapatinib in the setting of brain metastases. The module concludes with data on dual HER2 inhibition in metastatic breast cancer.

Last update: 28 May 2013

The author has reported honoraria from Roche and Celgen, advisory uncompensated role for GSK