Defined as the proportion of patients with documentation of grade 3 - 5 toxicity (regardless of attribution using the National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] version [v.] 5.0 criteria). A 95% binomial confidence interval for single proportions will be constructed for the severe toxicity rate during treatment. Univariate relationships between the primary endpoint and various pre-treatment patient characteristics such as anemia, self-assessed functional status, or social support will be described via cross-tabulation and Fisher's exact testing. Exploratory logistic regression modeling, with limited generalizability due to the modest sample size, will be used to assess the relative contributions of these variables impact the likelihood of developing a severe toxicity during treatment. The strength of this association will be expressed in terms of an odds ratio and its associated 95% confidence interval.

patients meeting the eligibility criteria who have not withdrawn before treatment and have adverse event data available are considered evaluable for the primary endpoint.

Measured by National Cancer Institute [NCI] Common Terminology Criteria for Adverse Events [CTCAE] v. 5.0. Reported in this section is the percentage of patients that experienced a grade 3 or higher toxicity.

All treated patients.

Dosing interruption and/or dose reductions are recommended based on individual safety and tolerability.

Palbociclib cycle length will remain 28 days (± 2 days) (despite a delay in initiating a new cycle of palbociclib); endocrine therapy may continue to be administered per the preplanned schedule.

• Dose holds/reductions of letrozole or fulvestrant will occur per the package insert and the treating investigator's discretion.
• Dose escalation will not be permitted in this study.
• Palbociclib doses missed for toxicity will not be made up.
• The initiation of a new cycle may be delayed for up to 7 days

Distributions time to treatment failure will be estimated using Kaplan-Meier methodology. Treatment failure is defined as a severe adverse event, disease progression or patient refusal to continue assigned treatment. Any reason that treatment is discontinued to time to treatment failure and not censor patients will be included. The reason for treatment discontinuation will be captured.

Patients to be included in the analysis cohort will be those patients who have taken one or more doses of the study treatment. Those patients will be considered adherent to study treatment. For each of the first 3 cycles, an estimate of the proportion of patients who meet the criteria for adherence and its corresponding 95% confidence interval will be determined.

The response rate is defined as the proportion of patients whose disease status met Response Evaluation Criteria in Solid Tumors (RECIST) criteria for complete response (CR) or partial response (PR) on 2 consecutive evaluations at least 8 weeks apart. A 95% binomial confidence interval for the response rate will be constructed.

All treated patients with measurable disease.

Distributions of progression free survival (PFS) times will be estimated using Kaplan-Meier methodology. The PFS time is calculated as the time between a patients start of treatment and their disease progression or death.

Distributions of overall survival (OS) times will be estimated using Kaplan-Meier methodology. OS time is calculated as the time between the date a patient started treatment and their death.

OTU is a novel composite endpoint developed by investigators of the FOCUS2 trial to assess the outcome of palliative chemotherapy. The patient will be given either an overall score of "good", "intermediate", or "poor". A 95% binomial confidence interval will be constructed for the percentage of patients that scored "good" on the OTU.

All treated patients that completed both the onstudy and end of treatment assessments.

Will examine variables associated with skeletal muscle loss during treatment and whether skeletal muscle loss during treatment is associated with the presence of grade 3-5 toxicity and adverse events. Sarcopenia will be treated as a binary variable using the Skeletal Muscle Index (SMI) (SMI < 41 cm^2/m^2 vs. SMI > 41 cm^2/m^2) and differences in grades chemotherapy toxicity and adverse events will be analyzed using two group t-tests and fisher's exact test. The number of patients with and without sarcopenia grouped by patients with or without grade 3+ Adverse Events (AE's) will be also be reported.

European Quality of Life Five Dimension Three Level Questionnaire (EQ-5D-3L) is comprised of 5 dimensions. Mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 levels, no problems, some problems, extreme problems. The EQ-5D-3L can be converted to a single summary index, 0-1, where higher scores mean better health. The median and range of this total score will be reported.

All treated patients that completed the EQ5D-3L questionnaire