Hormonal treatment combined with targeted therapies in endocrine-responsive and HER2-positive metastatic breast cancer

Approximately 50% of HER2 positive breast cancer cases are also estrogen receptor (ER) positive. Data supports a role for close cross-talk between the ER and HER2 signaling pathways as an important contributor to the development of de novo or acquired resistance to hormone therapies. Therefore a strategy that simultaneously blocks both signaling pathways is a reasonable approach to prevent or overcome either endocrine or anti-HER2 therapy resistance. Moreover, preclinical data support the idea that PI3K inhibitors and CDK4/6 could be an attractive target that functions downstream of both ER and HER2 pathways. We conducted a literature review of the results of phase II and III studies testing targeted therapies in metastatic breast cancer with HER2-positive and hormonal-receptor-positive disease. The analyses included efficacy and toxicity data from earlier studies with a single anti-HER2 drug combined with hormonal therapy up to more recent studies testing new molecules targeting these signaling pathways. The aims of this review are to summarize current knowledge and to discuss research development including the possibility to spare chemotherapy in this subgroup of HER2-positive breast cancer patients.