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

Study Overview
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Brief Summary
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This study investigates the clinical course of CDK4/6 inhibitor treated patients in the real-world setting among patients with breast cancer. CDK4/6 inhibitors may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Studying samples of blood, tissue, ascites or pleural effusions, and fresh body fluids or fresh biopsy, from patients with breast cancer that has spread to the other places in the body (metastatic) may help doctors learn more about cancer and the development of drug resistance in patients, and predict how well patients will respond to treatment.

Detailed Description
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PRIMARY OBJECTIVES: I. Delineate clinical features of disease progression and responses to subsequent therapy following progression on ciclib-based therapy. II. Define pharmacogenomics relationships that could provide a more precise approach to drug dosing. III. Interrogate biomarkers related to response and acquired resistance in standard clinical practice. IV. Develop patient-derived models from resistant disease to functionally assess the mechanisms occurring with resistance. V. Elucidate the socio-demographic features related to the use of ciclibs clinically in the Roswell Park catchment area. OUTLINE: Patients electronic medical records are reviewed to capture clinical information, and patients undergo collection of blood, tissue, ascites or pleural effusions, and fresh body fluids or fresh biopsy samples for diagnosis/treatment decision, biomarker assessments, and description of mechanisms of resistance/response related to ciclib-therapy.

Official Title
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The Roswell Park Ciclib Study: A Prospective Study of Biomarkers and Clinical Features of Advanced/Metastatic Breast Cancer Treated With CDK4/6 Inhibitors

Conditions
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Anatomic Stage IV Breast Cancer AJCC v8, Metastatic Breast Carcinoma, Prognostic Stage IV Breast Cancer AJCC v8

Intervention / Treatment
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* Other: Cytology Specimen Collection Procedure
* Other: Diagnostic Laboratory Biomarker Analysis
* Other: Medical Chart Review


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All adult patients with ER+/HER2- metastatic breast cancer or HR+/HER2-node positive, high risk early breast cancer who are being or have been treated with ciclib-based therapies are eligible for inclusion in this study This includes patients receiving standard of care therapy for ER+/HER2- metastatic breast cancer, as well as those who would be eligible to participate in a non-interventional study while on a clinical study open at Roswell Park or St. Vincent's Hospital Screening will occur in breast oncology clinic, by review of patient medical records for the pending, ongoing, or past treatment with ciclib-based therapy Participant must understand the prospective nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form Exclusion Criteria: Pregnant of nursing female subjects Unwilling or unable to follow protocol requirements

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Basic science (medical chart review, biospecimen collection)<br>Patients electronic medical records are reviewed to capture clinical information, and patients undergo collection of blood, tissue, ascites or pleural effusions, and fresh body fluids or fresh biopsy samples for diagnosis/treatment decision, biomarker assessments, and description of mechanisms of resistance/response related to ciclib-therapy. | Other: Cytology Specimen Collection Procedure<br>* Undergo collection of blood, tissue, ascites or pleural effusions, and fresh body fluids or fresh biopsy samples<br>* Other names: Cytologic Sampling;Other: Diagnostic Laboratory Biomarker Analysis<br>* Correlative studies<br>Other: Medical Chart Review<br>* Patient's electronic health records are reviewed<br>* Other names: Chart Review;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Collection of clinical characteristics | 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. | Up to 5 years | 
| Overall survival on ciclib | 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. | Up to 15 years | 
| Progression-free survival on ciclib | 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. | Up to 15 years | 
| Progression-free survival on subsequent therapies | 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. | Up to 15 years | 
| Site of the metastatic disease and time to progression | Development of and location of metastatic disease will be summarized using the appropriate descriptive statistics. | Up to 5 years | 
| Incidence of treatment related toxicities | 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. | Up to 5 years | 
| Genetic variance of genes associated with ciclib metabolism | 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. | Up to 5 years | 
| Quantitative biomarker expressions | 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. | Up to 5 years | 
| Development of patient-derived models from resistant disease | 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. | Up to 5 years | 
| Socio-economic features related to the use of ciclibs | 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. | Up to 5 years | 
| Clinical course of CDK4/6 inhibitor treated patients in the real-world setting | Will involve interrogating ciclib treatment patterns, treatment choices post progression, toxicities, clinical responses following progression, and ultimately differences in overall survival. | Up to 5 years |