T-DM1 and Palbociclib for Metastatic HER2 Breast Cancer

Inclusion Criteria: 1. Be informed of the investigational nature of the study and all pertinent aspects of the trial 2. Sign and provide written consent in accordance with institutional and federal guidelines. 3. ECOG Performance status of 0-2 4. Recurrent or metastatic HER2-positive breast cancer (HER2 positive is defined per ASCO-CAP guidelines) 5. Adequate cardiac reserve (EF≥50%) 6. Serum creatinine ≤ 1.5 x institutional upper limit of normal (IULN), bilirubin ≤ 2.0, and an SGOT/SGPT/alkaline phosphatase ≤ 2.0 x IULN 7. Adequate bone marrow function (ANC ≥1000, Platelets ≥100,000/ml, Hemoglobin ≥10gm/dL) 8. Be willing and able to comply with scheduled visits, treatment plan, laboratory tests and other trial procedures 9. Been treated with pertuzumab previously (neoadjuvant or metastatic setting). Patients who weren't able to tolerate pertuzumab due to side effects can be eligible for study upon discussion with the study PI 10. No more than 2 lines of therapy in the metastatic disease setting Exclusion Criteria: 1. HER2 negative tumors 2. Prior treatment with T-DM1 3. Prior treatment with CDK 4/6 inhibitors 4. Known active CNS metastases or carcinomatous meningitis. Patients with stable CNS metastases including brain metastases who have completed a course of radiotherapy are eligible for the study provided they are clinically stable. However, oral corticosteroids for control of CNS symptoms are not allowed on study 5. Known documented or suspected hypersensitivity to the components of the study drug(s) or analogs. 6. Uncontrolled systemic illness, including but not limited to ongoing or active infection 7. Symptomatic congestive heart failure, unstable angina pectoris, stroke or myocardial infarction within 3 months 8. Be pregnant or breast feeding. Female subjects must be surgically sterile or be postmenopausal, or must agree to use effective contraception during the period of therapy. All female subjects with reproductive potential must have a negative pregnancy test (serum or urine) prior to enrollment and must agree to use effective contraception during the period of therapy 9. Concurrent hormonal or other anti-neoplastic therapy is not allowed. Patients can receive supportive therapy like bone-directed therapy including bisphosphonates or denosumab