CDK and Body Composition Study

Total Adipose tissue (TAT) is defined as the sum of intramuscular adipose tissue (IMAT), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT) obtained from L3 cross section from CT scans. Only patients who complete 24 weeks of CDK 4/6 inhibitor treatment and have no radiological/clinical signs of disease progression will be included in the analysis of primary endpoint. Results will be calculated and summarized in area (cm²).

Body Fat Mass will be obtained from dual-energy x-ray absorptiometry (DEXA). The DEXA scan calculates the ratio of soft tissue attenuation at different X-ray energies. Results are measured and reported in kilograms (kg). DEXA scans are optional and will be performed only if available.

Body Lean Mass (BLM) will be obtained from dual-energy x-ray absorptiometry (DEXA). The DEXA scan calculates the ratio of soft tissue attenuation at different X-ray energies. Results are measured and reported in kilograms (kg). DEXA scans are optional and will be performed only if available.

Skeletal muscle index (SMI) will be obtained by dual-energy x-ray absorptiometry (DEXA). The DEXA scan will be used to measure the amount of lean muscle in the body. SMI is defined as muscle area at L3 cross section from CT scans in cm^2 divided by height in meters squared. DEXA scans are optional and will be performed only if available.

Fasting glucose levels in blood sera will be measured using a glucose blood sugar test. Normal ranges vary based on the health of the individual however standard glucose concentrations are between 70 mg/dL (3.9 mmol/L) -100 mg/dL (5.6 mmol/L). Glucose levels between 100-125 mg/dL (5.6-6.9 mmol/L) may be indicative of prediabetes. Fasting glucose levels >126 mg/dL on successive tests is correlated with diabetes. Results will be summarized and reported.

A lipid panel will be used to assess Total cholesterol, LDL Cholesterol, HDL Cholesterol, and triglyceride levels in blood sera samples. Each parameter has unique ranges and can vary by age, weight, and sex; however, High concentrations of Total cholesterol and LDL cholesterol increases the risk of coronary heart disease and atherosclerosis. HDL cholesterol ("good cholesterol") removes excess cholesterol from the body. High triglyceride levels also increase the risk of cardiovascular disease. Results for each parameter will be summarized and reported in mg/dL.

DHEAS levels in blood sera will be measured using a DHEA-sulfate (DHEAS) blood test. This test can be used to check the function of the adrenal glands. Normal ranges vary based on age, gender and laboratory; however, high concentrations could be indicative of adrenal tumors, Cushing's disease, polycystic ovary syndrome (PCOS), or adrenal hyperplasia. Results will be summarized and reported in ug/dL.

Insulin levels in blood sera will be measured using an insulin blood test. Insulin is a hormone that regulates glucose absorption. Normal ranges vary based on the type of test administered and the health of the individual; however, standard fasting insulin concentrations are usually <25 mIU/L. Higher concentrations can be indicative of insulin resistance. Results will be summarized and reported.

Leptin will be assessed using a leptin blood test that measures the concentration of leptin in blood sera. Leptin is a hormone that helps regulate appetite and energy levels. Standard ranges vary based on age, gender, body mass index, and other variables; however, ranges are generally between 0.5-15.2 ng/mL for females and 0.5-12.5 ng/mL for males. Results will be summarized and reported.

FLI will be assessed by blood test and calculated as the ratio of total leptin and soluble leptin receptor (sOB-R) concentrations. FLI is a biomarker of leptin resistance and the status of leptin action. High FLI is a risk factor for obesity and is associated with several chronic diseases. Results will be summarized and reported.

Adiponectin will be assessed using an adiponectin test that measures the concentration of adiponectin in the blood. Adiponectin is a protein hormone produced by fat cells that helps regulate blood sugar and fat metabolism. Lower levels of adiponectin in blood sera are often linked to conditions like obesity, type 2 diabetes, and heart disease. A normal adiponectin blood test result is generally 5-30 ug/mL but can vary depending on age and body mass index (BMI). Results will be summarized and reported.

hsCRP will be measured and reported by blood test. hsCRP measures the concentration of C-reactive protein (CRP) in blood. CRP is a protein that increases in response to inflammation and is correlated with adverse cardiovascular and cerebrovascular outcomes. Normal results are generally risk stratified with concentrations <1.0 mg/dL indicating a low risk of cardiovascular disease; concentrations between 1.0-3.0 mg/dL indicating an average risk of cardiovascular disease; and concentrations >3.0 mg/dL indicating a high risk of cardiovascular disease. Results will be summarized and reported.

BFM will be measured with the use of bioimpedance spectroscopy (BIS). BIS is a non-invasive method that takes measurements at 256 different frequencies and uses mathematical modeling to calculate electrical resistance throughout the body. Fat tissue has significantly higher resistance compared to lean muscle tissue. The total weight of body fat estimated by the BIS analysis will be expressed in kilograms and summarized for the group.

FFM will be derived based on the BFM readout obtained from the BIS analysis. The "fat-free mass" will be calculated by subtracting the total body weight minus the estimated BFM obtained by BIS analysis, based on electrical resistance through the body. This result will be expressed in kilograms and summarized for the group.

BMI will be determined by obtaining height and body weight measurements. It is calculated by dividing body weight in kilograms (kg) by height in meters squared (m^2). A BMI of 30 kg/m^2 or higher has been used to define obesity in most reports, including those showing an association between obesity and increased risk of cancers, cancer mortality, and mortality from all causes. Group results will be summarized and reported.

Skin fold thickness will be measured with the use of calipers. Skin fold thickness measurements will be obtained for the biceps, triceps, subscapular, and suprailiac sites. Calipers will be used to pinch the skin and lift it away from the muscle at each site and measure the thickness of skin folds at each location. Values will be summarized in millimeters (mm) for the group and reported. Skin fold thickness measurements provide an overall picture of subcutaneous fat distribution.

Abdominal circumference is a measurement of the horizontal distance around the abdomen. Abdominal circumference will be assessed by determining the midpoint between the lower rib margin and the iliac crest and measuring the circumference at the midpoint, in centimeters, with measuring tape while breathing normally. Group results will be summarized. An enlarged abdominal circumference can be a sign of obesity and a risk factor for disease.

Waist-to-hip ratio will be measured with measuring tape by measuring the narrowest part of the waist followed by the widest part of the hips and dividing the waist measurement by the hip measurement. While normal values can vary, a healthy waist-to-hip ratio is generally considered to be below 0.9 for men and 0.85 for women, according to the World Health Organization (WHO). Group results will be summarized.