PALbociclib CoLlaborative Adjuvant Study

Inclusion Criteria:

   - Signed informed consent prior to study specific procedures.

   - Age ≥18 years (or per national guidelines).

   - Pre- and postmenopausal women or men with Stage II (Stage IIA limited to max. 1000
   patients) or Stage III early invasive breast cancer

   - Patients with multicentric and/or multifocal and/or bilateral early invasive breast
   cancer are eligible if all histopathologically examined tumors meet pathologic
   criteria for ER+ and/or PR+ and HER2-.

   - Patients must have histologically confirmed ER+ and/or PR+, HER2-, early invasive
   breast cancer.

   - Patients must have undergone adequate (definitive) breast surgery for the current
   malignancy.

FFPE tumor tissue block must be confirmed to be received at the central sample repository
prior to randomization.

   - ECOG performance status 0-1.

   - Patients must be able and willing to swallow and retain oral medication.

   - Serum or urine pregnancy test must be negative in premenopausal women within 14 days
   of randomization, or in women with amenorrhea of less than 12 months at time of
   randomization.

   - Patients who received neo/adjuvant therapy must be after last dose of chemotherapy
   and/or biologic therapy and must have sufficient resolution of side effects.

   - Patients who received breast/axilla/post-mastectomy chest wall radiotherapy must be
   after last dose of radiotherapy and must have sufficient resolution of side effects.

   - Patients must have sufficient resolution of any surgical side effects (no active wound
   healing complications).

-Patients must either be initiating or have already started adjuvant hormonal treatment. -

   - Patients who already received neo/adjuvant endocrine therapy are eligible as long as
   they are enrolled within 12 months of initial histological diagnosis and after
   completing no more than 6 months of adjuvant endocrine therapy.

   - Absolute neutrophil count ≥ 1,500/µL

   - Platelets ≥ 100,000/ mm3

   - Hemoglobin ≥ 10g/dL

   - Total serum bilirubin ≤ ULN; or total bilirubin ≤ 3.0 × ULN with direct bilirubin
   within normal range in patients with documented Gilbert's Syndrome.

   - Aspartate amino transferase (AST or SGOT) and alanine amino transferase (ALT or SGPT)
   ≤ 1.5 × institutional ULN.

   - Serum creatinine below the upper limit of the institutional normal range (ULN) or
   creatinine clearance ≥ 60 mL/min/1.73 m2 for patients with serum creatinine levels
   above institutional ULN.

Exclusion Criteria:

   - Concurrent therapy with other Investigational Products.

   - Prior therapy with any CDK inhibitor.

   - Patients with Stage I or IV breast cancer are not eligible.

   - History of allergic reactions attributed to compounds of chemical or biologic
   composition similar to palbociclib.

   - Patients receiving any medications or substances that are potent inhibitors or
   inducers of

   - CYP3A isoenzymes within 7 days of randomization.

   - Uncontrolled intercurrent illness that would limit compliance with study requirements.

   - Pregnant women, or women of childbearing potential without a negative pregnancy test
   within 14 days prior to randomization.

   - Patients with a history of any malignancy are ineligible

   - Patients who previously received endocrine therapy within 5 years prior to diagnosis
   of the current malignancy.

   - Patients on antiretroviral therapy.

   - Patients with clinically significant history of any chronic liver disease.

   - Patients receiving concurrent exogenous hormone therapy (topical vaginal estrogen
   therapy is allowable).