CDK4/6 and PI3K inhibitors: A new promise for patients with HER2-positive breast cancer

Background: HER2-positive (HER2+) breast cancer represents a heterogeneous breast cancer subtype, including both oestrogen receptor (ER) positive and negative tumours. A deeper understanding of the crosstalk between ER and HER2 receptor pathways has led to the development of treatment strategies consisting of a simultaneous blockade of both signalling pathways, as a reasonable approach to prevent the onset of mechanisms of resistance. Methods: This review was based on the material searched on PubMed, MEDLINE and Embase databases and on conference proceedings from major oncology conferences up to 15 December 2020. The search strategy included the following keywords: ‘HER2-positive breast cancer’, ‘CDK4-6 inhibitors’ and ‘PI3K inhibitors’, and was adapted for use with different bibliographic databases. Results: CDK4/6 and PI3K inhibitors are two classes of agents already approved in patients with hormone receptor positive, HER2-negative breast cancer. Recently, promising data with their use have been also shown in HER2+ disease. Results from preclinical and clinical studies are shedding light on the role of these classes of agents in HER2+ breast cancer, and are paving the road for a forthcoming change in clinical practice. Conclusions: Treatment landscape for HER2+ breast cancer is rapidly changing, and CDK4/6 and PI3K inhibitors represent a new promising strategy to improve patients’ outcomes.