Simultaneous targeting of estrogen receptor and HER2 in breast cancer

Abstract

Approximately 50% of HER2-positive breast cancers express estrogen receptor (ER) and these tumors are characterized by short-lived responses to hormonal agents. Preclinical models have shown that dual targeting of ER and HER2 could reverse and delay the development of drug resistance. Two studies (TAnDEM & EGF3008) have recently been published addressing the combined use of an aromatase inhibitor (AI) and an anti-HER2-targeted agent. Both studies showed that the combined approach is associated with improvement in response rate and progression-free survival compared with an AI alone with an acceptable toxicity profile. These results would indeed extend the treatment options for patients with ER/HER2-positive metastatic breast cancer. In this article, we discuss how the improved understanding of the complex cross-talk between ER and HER2 has resulted in better clinical outcomes. We analyze clinical evidence regarding the combined use of AIs and anti-HER2-targeted agents. We also touch on possible mechanisms of resistance and ways to improve research in this field.

Keywords::

• aromatase inhibitors
• cross-talk
• estrogen receptor
• HER2
• lapatinib
• resistance
• trastuzumab

Acknowledgements

The authors would like to thank Dr Stephen Johnston for giving permission to reproduce his figure.

Financial & competing interests disclosure

Hatem A Azim Jr received a PhD grant from the Université Libre De Bruxelles (ULB). Martine J Piccart is a consultant for and recieves honorarium from Roche/GSK/Novartis/Pfizer. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Writing assistance was utilized in the production of this manuscript. The authors would like to thank Carolyn Straehle for her editorial assistance during the preparation of the manuscript.