Background: Overexpression and amplification of the human epidermal growth
factor receptor 2 (HER2) occur in 20% of total breast carcinomas. HER2-overexpression is
implicated in disease initiation and progression and associated with poor prognosis. Trastuzumab,
a humanized monoclonal antibody, is the standard HER2-targeted therapy for early
and metastatic HER2-amplified breast cancer patients. Trastuzumab has significantly increased
clinical benefit in HER2+ metastatic and adjuvant settings; however, it is not effective
for many patients due to primary or acquired resistance to the drug. During the last decade,
many studies have revealed a number of novel molecular traits of HER2+ breast cancer, allowing
us to uncover the molecular mechanisms involved in trastuzumab resistance and develop
strategies to overcome resistance to therapy.
Objective: In this review, we comprehensively addressed the current achievements in preclinical
studies; we discussed molecular mechanisms of acquired trastuzumab resistance in
HER2+ breast cancer models and potential therapeutic approaches based on the molecular
features for HER2+ breast cancer.
Conclusion: Enhanced understanding of the molecular profiles in HER2+ breast cancer may
lead to the identification of novel biomarkers for the development of diagnostic approaches
and improvement of therapeutic targets for the prevention and treatment of trastuzumab resistant
HER2+ breast cancer.