Palbociclib and Letrozole or Fulvestrant in Treating Patients With Estrogen Receptor Positive, HER2 Negative Metastatic Breast Cancer

This phase II trial studies the side effects and how well palbociclib and letrozole or fulvestrant works in treating patients aged 70 years and older with estrogen receptor positive, HER2 negative breast cancer that has spread to other places in the body. Palbociclib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as letrozole or fulvestrant, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving palbociclib and letrozole or fulvestrant may work better in treating patients with breast cancer. The trial will explore factors other than chronologic age that can affect toxicity rates as identified using a cancer-specific geriatric assessment.

PRIMARY OBJECTIVES:

I. To estimate the safety and tolerability (adverse event rate) of the combination of palbociclib and letrozole or fulvestrant in adults age 70 or older with estrogen receptor-positive, HER2-negative metastatic breast cancer.

SECONDARY OBJECTIVES:

I. To describe the full toxicity profile including all grade 2 and higher adverse events (per National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events \[CTCAE\] version \[v.\] 5.0), specifically estimating the rate of grade 2 and higher myelosuppression (neutropenia, leukopenia, thrombocytopenia, and anemia), neutropenic fever, gastrointestinal (GI) side effects (nausea, diarrhea, decreased appetite, vomiting, mucositis-oral), fatigue, neuropathy, and thromboembolism.

II. To describe rates of dose reductions, dose holds, and hospitalizations. III. To estimate median time to treatment failure, including progression free survival and overall survival.

IV. To estimate the rate of adherence to palbociclib, letrozole and fulvestrant.

V. To explore factors other than chronologic age that can affect toxicity rates as identified using a cancer-specific geriatric assessment.

VI. To describe the results of the Overall Treatment Utility (OTU). VII. To determine the degree of agreement between patient-reported adverse events (AEs) using Patient Reported Outcomes (PRO)-CTCAE measures and those reported using traditional collections for AEs.

VIII. To examine the association between sarcopenia and the development of toxicity and adverse events.

OUTLINE:

Patients receive palbociclib orally (PO) once daily (QD) on days 1-21. Patients also receive letrozole PO QD on days 1-28 or fulvestrant intramuscularly (IM) on days 1 and 15 of course 1 and on day 1 of subsequent courses per Doctor of Medicine (MD) discretion. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for up to 5 years.

Eligibility Criteria:
Inclusion Criteria:

* Documentation of disease: estrogen receptor positive and/or progesterone receptor (PR) positive, HER2 negative metastatic breast cancer; histologic confirmation is required
* Measurable disease or non-measurable disease
* Planning to begin palbociclib for metastatic disease; one prior line of endocrine therapy and/or chemotherapy for metastatic disease is allowed; patients may begin or have already begun endocrine therapy before they start palbociclib treatment, but no more than two weeks prior to registration
* No prior therapy with a CDK inhibitor
* Resolution of all acute toxic effects of prior therapy or surgical procedures to CTCAE grade =\< 1 (except alopecia) or to baseline toxicities prior to previous therapy or surgical procedures, prior to registration
* No untreated brain metastases; patients with treated brain metastases must have completed treatment with steroids to be eligible
* No known interstitial lung disease
* No second malignancies other than non-melanoma skin cancers or cervical carcinoma in situ; however, patients are not considered to have a "currently active" malignancy if they have completed therapy and are free of disease for \>= 3 years
* No active infection requiring treatment with antibiotics
* Patients must be able to swallow and retain oral medication
* Eastern Cooperative Oncology Group (ECOG) performance status 0, 1 or 2
* Patients must be able to read and comprehend English or Spanish
* Absolute neutrophil count (ANC) \>= 1500/mm\^3 (1.5 x 10\^9/L)
* Platelet count \>= 100,000/mm\^3 (100 x 10\^9/L)
* Creatinine clearance \>= 30 ml/min calculated using the Cockcroft-Gault formula
* Total serum bilirubin =\< 1.5 upper limit of normal (ULN) (\< 3 ULN if Gilbert's disease)
* Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) =\< 3 x ULN (=\< 5.0 x ULN if liver metastases present)
* Alkaline phosphatase =\< 2.5 x ULN (=\< 5 x ULN if bone or liver metastases present)