 The Investigators propose a 3x3 dose-escalation trial to assess the safety and efficacy of Fulvestrant and three dose levels of MLN9708 2.3, 3, and 4mg Subjects will be treated with Fulvestrant 500mg once every four weeks on day 1. The dose of MLN9708 will start at 2.3mg, which is about 50 of the phase 3 dose in another ongoing study. If 2.3mg MLN9708 does not induce any grade 3 non-hematologic toxicity, or any grade 4 hematologic toxicity by CTCAE v4.0 Common Terminology Criteria for Adverse Events, version 4.0 in any of the 3 subjects treated for 1 cycle, the Investigators will treat another 3 subjects with the combination of Fulvestrant and MLN9708 3mg; and if no grade 3 non-hematologic toxicity, or any grade 4 hematologic toxicity by CTCAE v4.0 is seen over the first cycle, the Investigators will treat another 3 subjects with Fulvestrant and MLN9708 4mg, which is the phase 3 dose. If dose-limiting toxicity is observed in 13 subjects, the Investigators will treat an additional 3 subjects at that same dose. If dose-limiting toxicity is seen in 2 of 6 subjects at any dose level, that dose level will be considered the maximum tolerated dose, and a total of 6 subjects will be treated at the prior dose. Plasma pharmacokinetic profiles of MLN9708 will be determined over 21 days after the first dose of the combination. 