PALbociclib CoLlaborative Adjuvant Study: A Randomized Phase III Trial of Palbociclib With Standard Adjuvant Endocrine Therapy Versus Standard Adjuvant Endocrine Therapy Alone for Hormone Receptor Positive (HR+) / Human Epidermal Growth Factor Receptor 2 (HER2)-Negative Early Breast Cancer

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).