75% of breast cancers are hormonal receptor-positive and in these tumours there is a possibility of using hormone therapy, which significantly reduces the risk of death in both adjuvant and palliative treatment. Efficiency of the treatment is proportional to the level of hormone receptor expression. An important problem connected with hormone therapy is primary or secondary resistance to the treatment. About 50% of patients with metastatic breast cancer are not responsive to hormone therapy with selective oestrogen receptor modulators (SERMs). According to clinical observations, patients with coexpression of hormonal receptors and human epidermal growth factor receptor 2 (HER2) have an especially poor response to hormone therapy. Classical and non-classical nuclear-initiated steroid signalling of oestrogen receptors as well as their membrane-initiated steroid signalling crosstalk with signal pathways of growth factor receptors. This phenomenon can be seen in healthy cells, but in cancer cells with HER2 overexpression it is so intense that hormone resistance can develop.