ESR1 and breast cancer: As fulvestrant, a selective ER down-regulator, remains active in HER2+ breast cancer cells that are resistant to other endocrine treatments and is licensed for advanced breast cancer in postmenopausal women after recurrence or progression despite previous endocrine treatments, it is possible that HER2 amplification or overexpression may have a different impact upon the activity of fulvestrant compared with tamoxifen or other hormone-regulating drugs[39–42].