ESR1 and breast cancer: By blocking proteasome activity, bortezomib enhances cytoplasmic fulvestrant-mediated ER aggregation, leading to apoptotic cell death in a panel of ER-positive breast cancer cell lines, a tamoxifen-resistant cell line in vitro, and also augments tumor regression in a hormone resistant breast cancer xenograft model.9 When bortezomib is added to fulvestrant, the nuclear degradation of the ER is maintained.