The CDK4/6 Inhibitor Dosing Knowledge (CDK) Study

Inclusion Criteria:

1. Hormone receptor positive (HR+) HER2 negative metastatic breast cancer. Cut-offvalues for positive/negative staining should be as per standard practice inaccordance with ASCO/CAP (American Society of Clinical Oncology/College of AmericanPathologists) guidelines. Verification of histology is preferred at the time ofrecurrence and where not possible or necessary in the judgment of the treatingphysician, the study will accept histology from the initial diagnosis.

2. Candidate for planned endocrine therapy in combination with 1st use of palbociclibor ribociclib, in the metastatic setting. The planned endocrine partner can be anaromatase inhibitor (letrozole, anastrozole, exemestane) or fulvestrant, selectedthrough patient/provider choice.

3. Aged 65 years or older

4. Adequate bone marrow and organ function.

• Absolute neutrophil count ≥ 1,000/µL

• Platelets ≥ 100,000/µL

• Hemoglobin ≥ 9g/dL

• Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (participantswith documented Gilbert's disease are allowed total bilirubin up to 5X ULN)

• AST (SGOT)/ALT (SGPT) <3 x institutional ULN, or ≤ 5 x ULN for subjects withdocumented metastatic disease to the liver.

• Creatinine ≤ institutional ULN or creatinine clearance ≥ 30 mL/min/1.73 m2 forsubjects with creatinine levels above institutional ULN.

• Baseline QTc ≤ 480 ms (only for ribociclib patients)

5. Ability to understand and the willingness to sign a written informed consentdocument.

Exclusion Criteria:

1. Previous treatment with a CDK4/6 inhibitor for metastatic breast cancer, or previoustreatment within the past 12 months with a CDK4/6 inhibitor in the neo/adjuvantbreast cancer setting.

2. May have received no more than 30 days of the endocrine therapy agent planned as thepartner to the CDK4/6 inhibitor in the study.

3. Known history of intolerance or allergy to the planned agents used in this trial.

4. Uncontrolled intercurrent illness that, as evaluated by the treating clinician,would hinder compliance with study requirements.

5. Concurrent therapy with other investigational agents.

6. Rapidly progressive brain metastases.

7. Active or chronic Hepatitis B or C are eligible provided they meet liver functionlaboratory criteria and are not on medication with a known interaction with thestudy agents.

8. Current use of drugs known to prolong the QT interval. 10. Prior or concurrentmalignancies that are undergoing active treatment.