Palbociclib in Estrogen Receptor Positive (ER+) Human Epidermal Growth Factor Receptor 2 Positive (HER2+) Metastatic Breast Cancer

• Palbociclib 75mg (Drug), also known as Ibrance: Oral Administration
• Letrozole 2.5mg (Drug), also known as Femara: Oral Adminstration
• T-DM1 (Drug), also known as Ado-trastuzumab Emtansine, Kadcyla: Intravenous Administration
• Palbociclib 100mg (Drug), also known as Ibrance: Oral Administration
• Palbociclib 125mg (Drug), also known as Ibrance: Oral Administration
• Palbociclib (Drug), also known as Ibrance: Oral Administration

Primary outcomes

• Rate of Overall Response [From the time of first documented complete response or appearance of one or more new lesions, until the first documented date of recurrent or progressive disease, whichever came first, assessed up to 5 years]: Determine overall response rate (ORR), defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

Secondary outcomes

• Proportion of participants with complete response (CR). [Up to 5 years]: Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Proportion of participants with partial response (PR). [Up to 5 years]: Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Proportion of participants with stable disease (SD). [Up to 5 years]: Defined per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
• Proportion of participants with Grade 3 or higher adverse event. [Up to 5 years]: Defined per Common Terminology Criteria for Adverse Events (CTCAE) v4.03
• Number of patients with adverse events [Up to 5 years]: Determine safety and tolerability of the intervention, defined per Common Terminology Criteria for Adverse Events (CTCAE) v4.03.
• Number of participants with a worsening Patient Reported Outcomes of Adverse Events (PRO-AE) score [At baseline and Day 1 of each cycle, up to 5 years (each cyle is 21 days)]: PRO-AE score defined per Patient Reported Outcome Measurement Information System (PROMIS) and Breast Cancer Prevention Trial (BCPT) Symptom Checklist.
• Peak observed plasma concentration [Cycle 1, Day 1: 0 ,2,4 and 8 hours post treatment; Cycle 1, Day 15: 0 hours post treatment (each cyle is 21 days)]: Defined per maximum observed concentration (Cmax) and time of Cmax (Tmax).

Sex: Female, ages: 18 Years to any

Inclusion Criteria:

* Pathologically confirmed diagnosis of Estrogen Receptor (ER) positive and HER2 (human epidermal growth factor receptor 2) positive metastatic breast cancer based on local laboratory results.
* Prior treatment with a taxane (including paclitaxel, docetaxel and/or nanoparticle protein-bound paclitaxel).
* Prior treatment with trastuzumab with or without pertuzumab.
* Measurable or non-measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) criteria version 1.1.
* Eastern Cooperative Oncology Group Performance Status of 0-2
* Adequate organ and marrow function
* Women must be post-menopausal
* Must be able to swallow pills

Exclusion Criteria:

* Current or anticipated use of other investigational agents
* Prior therapy with a cyclin-dependent kinase 4/6 inhibitor
* Subject has received chemotherapy or radiotherapy within 14 days prior to Cycle 1, Day 1 of the study or has not recovered from adverse events due to agents administered more than 14 days earlier
* Subject has leptomeningeal disease
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to palbociclib or other agents used in study
* Subject has other illness or disease that the investigator believes will interfere with study requirements.

• Lauren Nye, MD, Principal investigator, KUCC