Effects of Ribociclib and Palbociclib on Tumor and Blood Characteristics in Patients With Metastatic Breast Cancer

Inclusion Criteria:

* Patients with histological confirmed breast adenocarcinoma who meet the following criteria:
* Age: \>= 18 years and are post-menopausal
* Estrogen receptor positive (ER+) and human epidermal growth factor receptor 2 (HER2) negative breast cancer patients who prospectively may undergo evaluation for Cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), ribociclib or palbociclib, as part of first-line therapy. Retrospective cohorts will be built to include either ribociclib or palbociclib treated patients with known clinical outcome
* During routine standard of care procedure, tumor that is accessible for ultrasound guided biopsy (from breast, lymph node, subcutaneous tumor, or selected liver metastasis per treating physician's discretion) or skin punch biopsy (for dermal metastasis) will be collected
* Available tumor tissue or planning on biopsy prior to initiation of CDK4/6i treatment
* Available tumor tissue or planning on biopsy at time of progression, prior to initiating subsequent therapy
* Willing to provide consent for extra tissue and blood samples

Exclusion Criteria:

* Patient received prior treatment with any CDK4/6 inhibitor
* Prior treatment with any chemotherapy for metastatic disease
* Patient is cognitively impaired
* Lung or bone metastasis only (not accessible by ultrasound guided biopsy)
* Patients with central nervous system (CNS) involvement unless they meet ALL the following criteria:

  * Untreated brain metastases (e.g., lesions \< 1cm) not needing immediate local therapy
  * Previously treated brain metastases not needing immediate local therapy
  * At least 4 weeks from prior therapy completion (including radiation and/or surgery) to starting the study treatment

    * Clinically stable CNS tumor at the time of screening and not receiving steroids and/or enzyme-inducing anti-epileptic medications for brain metastases
* Clinically significant, uncontrolled heart disease and/or cardiac repolarization abnormalities, including any of the following:
* Patient is currently receiving any of the following medications and cannot be discontinued 7 days prior to starting study drug:

  * Known strong inducers or inhibitors of CYP3A4/5, including grapefruit, grapefruit hybrids, pummelos, star-fruit, and Seville oranges
  * That have a narrow therapeutic window and are predominantly metabolized through CYP3A4/5
  * Herbal preparations/medications, dietary supplements
  * Warfarin or other coumadin-derived anticoagulant for treatment, prophylaxis or otherwise. Therapy with heparin, low molecular weight heparin (LMWH), newer anticoagulation agents such as direct factor Xa inhibitors, or fondaparinux is allowed
* Patient is currently receiving or has received systemic corticosteroids =\< 2 weeks prior to starting study drug, or who have not fully recovered from side effects of such treatment

  * The following uses of corticosteroids are permitted: single doses, topical applications (e.g., for rash), inhaled sprays (e.g., for obstructive airways diseases), eye drops or local injections (e.g., intra-articular)