Pilot Study Assessing the Effect of Cyclin-dependent Kinase 4/6 Inhibitors on Body Composition in Patients With ER+/HER2- Metastatic Breast Cancer

The goal of this study is to evaluate changes in body composition among patients who are
treated with cyclin-dependent kinase (CDK) 4/6 inhibitors (abemaciclib, ribociclib, or
palbociclib). There is preliminary data suggesting that these drugs have more effect on body
fat mass than body muscle mass. These drugs have already been approved by U.S Food and Drug
Administration (FDA) to treat ER+/HER2- metastatic breast cancer. The investigators will
follow up body composition changes among patients who receive CDK 4/6 inhibitors as part of
their standard of care. Body composition changes will be measured from CT or PET/CT scans
that are part of standard of care treatment, and from DEXA scans (as part of proposed study).
The investigators will also conduct body measurements with measuring tape, and will draw
blood tests to assess for fat biomarkers.

Inclusion Criteria:

- Histologically confirmed adenocarcinoma of the breast that is ER and/or PR positive,
Her2 negative based on current ASCO-CAP guidelines

- Metastatic or locally advanced/inflammatory, unresectable breast cancer not amenable
to potentially curative surgery.

- Measurable and/or non-measurable as defined by RECIST 1.1 criteria

- Patients must be a candidate to start an FDA approved CDK 4/6 inhibitor (palbociclib,
ribociclib, abemaciclib) as part of standard of care treatment.

- Female, or male patients, and age >18 years.

- ECOG performance status 0-2.

- Ability to understand and the willingness to sign a written informed consent document.

- At least 30 days from major surgery before study enrollment, with full surgical wound
healing and return to baseline performance status.

- Concomitant therapy with bisphosphonates, RANKL inhibitors or
growth-colony-stimulating factor (G-CSF) is allowed as per physician decision.

Exclusion Criteria:

- History of allergic reactions attributed to compounds of similar chemical or biologic
composition to CDK 4/6 inhibitors or other agents used in the study (e.g.,
fulvestrant, letrozole, anastrozole, exemestane).

- BMI < 18.5

- Prior CDK 4/6 use in any setting.

- Inability to undergo anthropometric measurements.

- Inability to undergo CT scan imaging.

- Recent radiation or chemotherapy within 4 weeks

- Women of child-bearing potential must not be pregnant or breast feeding. They must
also agree to use adequate contraception (hormonal or barrier method of birth control)
and not be breast feeding prior to study entry, for the duration of study
participation, and for up to 10 days after completion of all protocol therapy. Should
a woman become pregnant or suspect she is pregnant while participating in this study
or up to 10 days after completion of protocol therapy, she should inform her treating
physician immediately.

- Intercurrent illness that would substantially increase the risk of treatment
associated complications (e.g., active infection, uncontrolled diabetes mellitus or
hypertension)

- Psychiatric illness/social situations that would interfere with the patient's ability
to comply with the treatment regimen.

- Patients with untreated brain metastasis are excluded. Patients with a prior history
of brain metastasis are eligible if they have received prior brain radiation (whole
brain or stereotatactic radiosurgery) or surgery, have stable intracranial disease for
at least 3 months after completion of local therapy, and are not taking
corticosteroids for treatment of brain metastasis.

- Treatment with bevacizumab, other targeted therapies, or other investigational agents
within the past 4 weeks.

- Patients who have not recovered (i.e., CTCAE Grade ≤1 or baseline) from an adverse
event due to a previously administered agent, excluding alopecia.

- Patients with inability to swallow and retain pills

- Malabsorption syndrome or other gastrointestinal illness that could affect oral
absorption.