 Subjects with metastatic ERHER2- breast cancer with disease progression on Fulvestrant, for whom continuation of endocrine therapy would be an appropriate treatment, will be treated with the combination of MLN9708 proteasome inhibitor and Fulvestrant anti-estrogen. Subjects with visceral or soft tissue disease will have a tumor biopsy while on treatment with Fulvestrant but prior to initiation of MLN9708 to confirm ERPRHER2 status, and to provide a baseline specimen for molecular analysis. A biopsy of the same tumor will be obtained after 2 days of treatment with MLN9708 plus Fulvestrant i.e. on day 3. Patients with bone-only disease will be eligible for the study, but will not be biopsied. 