Primary resistance to anti-HER2 therapy: mechanisms of development and ways to overcome

G.A. Dashyan, E.S. Dzhelialov, V.V. Konstantinova, Yu.A. Gronskaya, A.D. Murskikh, R.M. Akhmedov, A.E. Tyusenko, A.A. Olchonova, Z.V. Dyakonenko, O.A. Sereda, A.M. Belousov

Clinic of High Medical Technologies n.a. N.I. Pirogov, St. Petersburg State University, St. Petersburg, Russia

Breast cancer (BC) is the most common tumor in women. Human epidermal growth factor receptor type 2 (HER2) – positive tumors account for approximately 25–30% of all breast cancer subtypes and are correlated with a poor prognosis. Trastuzumab, a monoclonal antibody, has been used for many years to inhibit HER2 activity. The introduction of this drug into clinical practice has made a real revolution in the world of treatment of HER2-positive breast cancer. However, today there are cases of primary resistance to anti-HER2 therapy. In this regard, identifying mechanisms of resistance and exploring new therapeutic agents may lead to the development of more effective blockade of HER family receptor signaling. Over the past few years, many mechanisms of resistance have been studied, and attempts to introduce new therapeutic drugs to treat patients with resistance to trastuzumab-containing therapy are regularly made, but adequate effectiveness has not been achieved to date. In this regard, the purpose of this article was to review the mechanisms of resistance to anti-HER2 therapy and ways to overcome it, as well as demonstrate clinical experience in managing a patient with a similar condition.

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About the Authors

Corresponding author: Garik A. Dashyan, Dr. Sci. (Med.), Head of the Oncology Department № 1 (surgical methods for the treatment of tumors of the breast, skin and soft tissues), Clinic of High Medical Technologies n.a. N.I. Pirogov, St. Petersburg State University, St. Petersburg, Russia; dgarik@mail.ru

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