Endocrine therapy is a cornerstone in hormone-dependent breast cancer treatment. Despite the effectiveness of this type of treatment, a significant percentage of tumours develop resistance, and hence, patients relapse. This raises the question of which mechanisms are activated by hormone-dependent tumours to become resistant to antihormonal therapy. The aim of this review is to summarise the current knowledge on structure and mechanisms of action of oestrogen receptors and the possible mechanisms of resistance known to date, focusing on the existing crosstalk between oestrogen receptor and growth factor receptor pathways as well as the influence of drug metabolism in its effectiveness. Finally, the clinical evidence of hormonal therapy resistance and the future directions for optimising breast cancer treatment is also discussed.
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