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Hormone receptor positive (HR+) HER2 negative metastatic breast cancer. Cut-off values for positive\u002Fnegative staining should be as per standard practice in accordance with ASCO\u002FCAP (American Society of Clinical Oncology\u002FCollege of American Pathologists) guidelines. Verification of histology is preferred at the time of recurrence and where not possible or necessary in the judgment of the treating physician, the study will accept histology from the initial diagnosis.\n2. Candidate for planned endocrine therapy in combination with 1st use of palbociclib or ribociclib, in the metastatic setting. The planned endocrine partner can be an aromatase inhibitor (letrozole, anastrozole, exemestane) or fulvestrant, selected through patient\u002Fprovider choice.\n3. Aged 65 years or older\n4. Adequate bone marrow and organ function. Laboratory values must be within normal institutional limits, or within ranges as indicated below, or demonstrate minor abnormalities that are deemed clinically non-significant by the investigator.\n\n   * Absolute neutrophil count ≥ 1,000\u002FµL\n   * Total bilirubin ≤ 1.5 x institutional upper limit of normal (ULN) (participants with documented Gilbert's disease are allowed total bilirubin up to 5X ULN)\n   * AST (SGOT)\u002FALT (SGPT) \\\u003C3 x institutional ULN, or ≤ 5 x ULN for subjects with documented metastatic disease to the liver.\n5. Baseline QTc ≤ 480 ms (only for ribociclib patients)\n6. Ability to understand and the willingness to provide informed consent. Note: Remote consent is allowed per institutional guidelines.\n\nExclusion Criteria:\n\n1. Previous treatment with a CDK4\u002F6 inhibitor for metastatic breast cancer, or previous treatment within the past 12 months with a CDK4\u002F6 inhibitor in the neo\u002Fadjuvant breast cancer setting.\n2. Received greater than 30 days (in the metastatic setting) of the specific endocrine therapy agent planned as partner to the CDK4\u002F6 inhibitor in the study at the time of randomization.\n3. Known history of intolerance or allergy to the planned agents used in this trial.\n4. Uncontrolled intercurrent illness that, as evaluated by the treating clinician, would hinder compliance with study requirements.\n5. Concurrent therapy with other investigational agents.\n6. Rapidly progressive brain metastases.\n7. Active or chronic Hepatitis B or C are eligible provided they meet liver function laboratory criteria and are not on medication with a known interaction with the study agents.\n8. Current use of drugs that have known potential to prolong the QT interval (e.g., antiarrhythmic drugs), for patients on ribociclib. Note: If concomitant use cannot be avoided, monitor ECG when initiating, during concomitant use, and as clinically indicated. Refer to crediblemeds.org as a resource.\n9. Prior or concurrent malignancies that are undergoing active treatment.","ALL","65 Years",{"count":1005,"type":1006},500,"ESTIMATED","INTERVENTIONAL",[1009],"PHASE3","The purpose of this study is to generate evidence on an alternative dosing strategy for CDK4\u002F6 inhibitors to help more patients with Metastatic Breast Cancer (MBC) (age ≥ 65 years) tolerate side effects and stay on treatment longer, to derive the most clinical benefit from these drugs.\n\nThe primary objective of the CDK Study is to compare time to treatment discontinuation (TTD) on the approved dosing for palbociclib (125 mg orally daily on days 1-21 of 28-day cycle) or ribociclib (600 mg orally daily on days 1-21 of 28-day cycle) vs. TTD using titrated dosing approach with the same schedule but starting at a lower dose of palbociclib (100 mg or 75 mg) or ribociclib (400 mg or 200 mg) and escalating the dose if well-tolerated in combination with provider\u002Fpatient choice endocrine therapy (aromatase inhibitor (AI) or fulvestrant) in patients age 65 or older with HR+\u002FHER2- MBC. 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