Toxicity will be assessed using the Common Terminology Criteria of Adverse Events (CTCAE) version 4.0 grading scale. Dose- limiting toxicity-DLT is defined as any drug-related grade 3 non-hematologic toxicity or grade 4 hematologic toxicity lasting >28 days after the last day of therapy. If two patients experience drug-related DLT, the maximal tolerated dose (MTD) for the combination in HER2-positive breast cancer patients has been exceeded, enrollment to that dose will stop, and the next lower dose will be designated the MTD. An additional 15 patients will be treated at the MTD or the maximal 200mg po daily PD-0332991 dose in combination with T-DM1 to confirm safety. Treatment cycles will continue until disease progression or withdrawal from study.