Biomarkers and Clinical Features of Metastatic Breast Cancer in Patients Treated With CDK4/6 Inhibitors

Will be summarized by ciclib treatment regimen using the appropriate descriptive statistics. Differences will be evaluated using the Kruskal-Wallis and Chi-square tests, as appropriate.

Will be summarized by treatment regimen using standard Kaplan-Meier methods, with comparisons made using the log rank test. Cox regression models with time-dependent variables may be considered to account for changing treatment regimens and other patient characteristics.

Will be summarized by treatment regimen using standard Kaplan-Meier methods, with comparisons made using the log rank test. Cox regression models may be considered to adjust for prior therapies and other patient characteristics.

Will be summarized by treatment regimen using standard Kaplan-Meier methods, with comparisons made using the logrank test. Cox regression models may be considered to adjust for prior therapies and other patient characteristics.

Development of and location of metastatic disease will be summarized using the appropriate descriptive statistics.

Will be summarized by ciclib treatment regimen using frequencies and relative frequencies. Comparisons may be made using Fisher's exact test. Associations between toxicity rates and patient demographic/clinical characteristics may be evaluated using logistic regression models.

Will be summarized in the overall sample and by treatment regimen using the appropriate descriptive statistics and graphical summaries. The association between these genetic features and toxicity and survival outcomes will be evaluated using stratified Cox regression models, where genotype will be the stratification factor. Additional models may be considered to account for other demographic or clinical characteristics. Hazard ratios with 95% confidence intervals will be obtained from model estimates.

Will be summarized in the overall sample and by treatment regimen using the appropriate descriptive statistics and graphical summaries. The association between baseline biomarkers and survival outcomes will be evaluated using stratified Cox regression models, where treatment regimen will be the stratification factor. Additional models may be considered to account for other demographic or clinical characteristics. Hazard ratios with 95% confidence intervals will be obtained from model estimates.

Will be evaluated to functionally assess the mechanisms occurring with resistance. No formal statistical analyses will be performed in regards to the development of organoid and patient-derived xenograft (PDX) models.

Will be elucidated clinically in the Roswell Park catchment area. Treatment regimens and sequences may be summarized by patient demographic and socio-economic characteristics using frequencies and relative frequencies. Associations may be evaluated using Chi-square tests.

Will involve interrogating ciclib treatment patterns, treatment choices post progression, toxicities, clinical responses following progression, and ultimately differences in overall survival.

Will examine biomarkers of response/resistance and association with long term outcomes relative to pretreatment controls.

Blood will be collected to interrogate single-nucleotide polymorphisms in CYP3A4 and related genes associated with metabolism of ciclib compounds. These polymorphisms will be related to dose limiting toxicities and dose interruptions. Blood samples for pharmacokinetic and pharmacogenomic analysis will be drawn during regular laboratory blood draws.

Serial peripheral blood samples will be prospectively collected at specified time points and processed for cfDNA and circulating tumor cells (CTC) isolation. CTCs will be utilized for the development of 3-dimensional (3D) organoid cultures and CTC-derived xenograft models.

Will only employ tissues and /or body fluids that are being discarded or do not involve any additional procedures for the patients. This includes, excess tissue that is not required for diagnosis or pleural effusions or peritoneal ascites. Cells isolated from the samples will be used for the development of organoid or PDX models.