Alternative Dosing Schedule of Palbociclib in Metastatic Hormone Receptor Positive Breast Cancer

Inclusion Criteria:

• Histologically confirmed metastatic ER+ and/or PR+ and HER2- breast cancer who arecandidates for palbociclib in combination with either letrozole or fulvestrant pertreating physician.
• Presence of measurable or non-measurable disease by RECIST 1.1 criteria.
• One prior systemic therapy in the metastatic setting is allowed, but patients who havenot had any prior systemic therapies in the metastatic setting are also eligible. *Note: patients who were started on endocrine therapy monotherapy as their 1st line or 2nd line systemic therapy in the metastatic setting for no more than 28 days andwithout clinical progression prior to the initiation of the study drug therapy areallowed to enroll on the study as their 1st line or 2nd line therapy, respectively.
• At least 18 years of age.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
• Normal bone marrow and organ function as defined below:
• Absolute neutrophil count ≥ 1,500/mcl
• Platelets ≥ 100,000/mcl
• Total bilirubin ≤ institutional upper limit of normal (IULN) or total bilirubin ≤ 3.0x IULN with direct bilirubin within normal range in patients with documented Gilbert'ssyndrome
• AST(SGOT)/ALT(SGPT) ≤ 1.5 x IULN (up to 5 x IULN in patients with liver disease)
• Creatinine ≤ IULN OR creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serumcreatinine levels above institutional normal (calculated by Creatinine ClearanceEstimate by Cockcroft-Gault Equation)
• Pre- or post-menopausal women are allowed. If pre- or peri-menopausal, concurrentovarian suppression for pre- or peri-menopausal women is required.
• Women of childbearing potential must agree to use adequate contraception (hormonal orbarrier method of birth control, abstinence) prior to study entry and for the durationof study participation. Should a woman become pregnant or suspect she is pregnantwhile participating in this study, she must inform her treating physician immediately.
• Able to swallow and retain oral medication.
• Washout of at least 3 weeks from prior chemotherapy or targeted therapy that inducesmyelosuppression and recovery of treatment related adverse events to grade 1 or less,with the exception of alopecia, is required prior to the start of palbociclib.
• Ability to understand and willingness to sign an Institutional Review Board (IRB)approved written informed consent document (or that of legally authorizedrepresentative, if applicable).

Exclusion Criteria:

• Prior therapy with any CDK inhibitor.
• Currently receiving any other investigational agents.
• Currently receiving exogenous estrogen replacement (topical vaginal estrogen therapyis allowed).
• Known brain metastases. Patients with known brain metastases must be excluded fromthis clinical trial because of their poor prognosis which could affect the evaluationof all-cycle adverse events.
• A history of allergic reactions attributed to compounds of similar chemical orbiologic composition to palbociclib or other agents used in the study.
• Receiving any medications or substances that are potent inhibitors or inducers ofCYP3A isoenzymes within 7 days prior to registration.
• Clinically significant history of liver disease.
• A condition that would interfere with enteric absorption.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or activeinfection, symptomatic congestive heart failure, unstable angina pectoris, or cardiacarrhythmia.
• Pregnant and/or breastfeeding. Women of childbearing potential must have a negativepregnancy test within 7 days of study entry.
• Known HIV-positivity on combination antiretroviral therapy because of the potentialfor pharmacokinetic interactions with palbociclib. In addition, these patients are atincreased risk of lethal infections when treated with marrow-suppressive therapy.Appropriate studies will be undertaken in patients receiving combinationantiretroviral therapy when indicated.