PS-341, now known as bortezomib (Velcade[Millenium Pharmaceuticals, Inc., Cambridge, MA; and Johnson & Johnson Pharmaceutical Research & Development, LLC, Spring house, PA]), is a proteasome inhibitor approved for the treatment of refractory multiple myeloma. Preclinical and early clinical studies showed PS-341 to be effective in solid tumors, one of which was breast cancer. We conducted a single institution, phase II study using PS-341 in the treatment of patients with metastatic breast cancer. The primary objective of this study was to determine the objective tumor response in patients with metastatic breast cancer (MBC) receiving PS-341. The secondary objectives were to estimate progression-free survival of patients receiving single-agent PS-341 and to evaluate toxicity related to PS-341. In all 12 patients who met criteria for enrollment, there were no observed objective responses. Further, all 12 patients progressed while receiving therapy with PS-341. This study was terminated after the first stage due to the lack of any objective response.