ESR1 and breast cancer: First, promising alisertib single-agent activity was observed in ER-positive and HER2-negative patients as described above (41); second, Aurora A plays a role in the development of endocrine resistance through activation of SMAD5 nuclear signaling and down-regulation of ERα expression in initially ERα+ breast cancer cells (51); and third, aromatase inhibitors (AIs) are used for treatment of ER-positive breast cancer though resistance to AI is a major obstacle to optimal patient outcome.