<br>        Inclusion Criteria (Preliminary Screening)<br><br>          1. Signed Preliminary Screening Informed Consent Form obtained prior to any study<br>             specific assessments and procedures<br><br>          2. Age =18 years (or per national guidelines)<br><br>          3. Patients must have histologically confirmed invasive breast cancer that is metastatic<br>             or not amenable for resection or radiation therapy with curative intent. Histological<br>             documentation of metastatic/recurrent breast cancer is not required if there is<br>             unequivocal evidence for recurrence of the breast cancer.<br><br>          4. Patients must have histologically confirmed HER2+ and hormone receptor positive (ER+<br>             and/or PR+), metastatic breast cancer. ER, PR and HER2 measurements should be<br>             performed according to institutional guidelines, in a CLIA-approved setting in the US<br>             or certified laboratories for Non-US regions. Cut-off values for positive/negative<br>             staining should be in accordance with current ASCO/CAP (American Society of Clinical<br>             Oncology/College of American Pathologists) guidelines.<br><br>          5. Patients must agree to provide a representative formalin-fixed paraffin-embedded<br>             (FFPE) tumor tissue block (preferred) from primary breast or metastatic site<br>             (archival) OR at least 15 freshly cut unstained slides from such a block, along with a<br>             pathology report documenting HER2 positivity and hormone receptor positivity.<br><br>          6. Patients should be willing to provide a representative tumor specimen obtained from<br>             recently biopsied metastatic disease if clinically feasible. This is recommended but<br>             optional tissue.<br><br>             Inclusion Criteria (Randomization Screening)<br><br>          7. Signed Main Informed Consent Form obtained prior to any study specific assessments and<br>             procedures<br><br>          8. Age = 18 years (or per national guidelines)<br><br>          9. ECOG performance status 0-1<br><br>         10. Patients must be able and willing to swallow and retain oral medication without a<br>             condition that would interfere with enteric absorption.<br><br>         11. Serum or urine pregnancy test must be negative within 7 days of randomization in women<br>             of childbearing potential. Pregnancy testing does not need to be pursued in patients<br>             who are judged as postmenopausal before randomization, as determined by local<br>             practice, or who have undergone bilateral oophorectomy, total hysterectomy, or<br>             bilateral tubal ligation. Women of childbearing potential and male patients randomized<br>             into the study must use adequate contraception for the duration of protocol treatment<br>             which is 6 months after the last treatment with palbociclib if they are in Arm A and<br>             for 7 months after last treatment with trastuzumab if in either Arm A or Arm B<br>             Adequate contraception is defined as one highly effective form (i.e. abstinence,<br>             (fe)male sterilization OR two effective forms (e.g. non-hormonal IUD and condom /<br>             occlusive cap with spermicidal foam / gel / film / cream / suppository).<br><br>         12. Resolution of all acute toxic effects of prior induction anti-HER2-based chemotherapy<br>             regimen to NCI CTCAE version 4.0 Grade =1 (except alopecia or other toxicities not<br>             considered a safety risk for the patient at investigator's discretion) 12 weeks<br>             between last dose of chemotherapy-anti-HER2therapy and randomization are allowed.<br>             Endocrine therapy could start before study randomization.<br><br>         13. Willingness and ability to comply with scheduled visits, treatment plan, laboratory<br>             tests, and other study procedures<br><br>             Prior Treatment Specifics<br><br>         14. Patients may or may not have received neo/adjuvant therapy, but must have a<br>             disease-free interval from completion of anti-HER2 therapy to metastatic diagnosis =6<br>             months.<br><br>         15. Patients must have received an acceptable, standard, chemotherapy containing anti-HER2<br>             based induction therapy for the treatment of metastatic breast cancer prior to study<br>             enrollment. For this study, chemotherapy is limited to a taxane or vinorelbine (only<br>             for trastuzumab-based regimen). Eligible patients are expected to have completed 6<br>             cycles of chemotherapy containing anti-HER2-therapy treatment. A minimum of 4 cycles<br>             of treatment is acceptable for patients experiencing significant toxicity associated<br>             with treatment as long as they are without evidence of disease progression (i.e. CR,<br>             PR or SD). The maximum number of cycles is 8. Patients can randomize immediately<br>             following completion of their induction therapy, or for those who have already<br>             completed induction, a gap of 12 weeks between their last infusion/dose of induction<br>             therapy and the C1D1 visit is permitted. Patients are eligible provided they are<br>             without evidence of disease progression by local assessment (i.e. CR, PR or SD).<br><br>         16. Patients with a history or presence of asymptomatic CNS metastases are eligible,<br>             provided they meet all of the following criteria:<br><br>               -  Disease outside the CNS is present.<br><br>               -  No evidence of interim progression between the completion of induction therapy<br>                  and the screening radiographic study<br><br>               -  No history of intracranial hemorrhage or spinal cord hemorrhage<br><br>               -  Not requiring anti-convulsants for symptomatic control<br><br>               -  Minimum of 3 weeks between completion of CNS radiotherapy and Cycle 1 Day 1 and<br>                  recovery from significant (Grade = 3) acute toxicity with no ongoing requirement<br>                  for corticosteroid<br><br>             Baseline Body Function Specifics<br><br>         17. Absolute neutrophil count = 1,000/mm3<br><br>         18. Platelets = 100,000/mm3<br><br>         19. Hemoglobin = 10g/dL<br><br>         20. Total serum bilirubin = ULN; or total bilirubin = 3.0 × ULN with direct bilirubin<br>             within normal range in patients with documented Gilbert's Syndrome.<br><br>         21. Aspartate aminotransferase (AST or SGOT) and alanine aminotransferase (ALT or SGPT) =<br>             3 × institutional ULN (=5 x ULN if liver metastases are present).<br><br>         22. Serum creatinine below the upper limit of normal (ULN) of the institutional normal<br>             range or creatinine clearance = 60 mL/min/1.73 m2 for patients with serum creatinine<br>             levels above institutional ULN.<br><br>         23. Left ventricular ejection fraction (LVEF) = 50% at baseline as determined by either<br>             ECHO or MUGA<br><br>        Exclusion Criteria (Randomization)<br><br>          1. Concurrent therapy with other Investigational Products.<br><br>          2. Prior therapy with any CDK 4/6 inhibitor.<br><br>          3. History of allergic reactions attributed to compounds of chemical or biologic<br>             composition similar to palbociclib.<br><br>          4. Patients receiving any medications or substances that are strong inhibitors or<br>             inducers of CYP3A isoenzymes within 7 days of randomization (see Section 8.6.3 for<br>             list of strong inhibitors or inducers of CYP3A isoe