Aromatase inhibitors (AIs) have become one of the mainstays of treatment of postmenopausal women with hormone receptorpositive
breast cancer. However, acquired resistance to treatment continues to be a significant clinical challenge. There is increasing evidence
from preclinical studies that activation of growth factor signaling pathways, as well as cross-talk between these pathways and estrogen
receptor-alpha signaling pathways are important mechanisms that contribute to AI resistance. These preclinical studies have been
the foundation for multiple randomized clinical trials that have evaluated combination targeted therapy in patients with advanced breast
cancer. While the clinical benefit observed in these trials has been variable, the preclinical studies were successful in predicting clinical
outcomes. This review focuses on mechanisms of acquired AI resistance and describes preclinical studies that have evaluated combination
targeted therapy to overcome AI resistance, as well as clinical trials that have translated this information to the clinical setting.
Keywords: Breast cancer, aromatase inhibitors, acquired endocrine resistance.
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