The Hurria Older PatiEnts (HOPE) With Breast Cancer Study

Study Overview
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Brief Summary
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The goal of this study is to develop a bedside to bench model of clinical and biological predictors for toxicity to adjuvant and neoadjuvant chemotherapy in older adults with breast cancer. The investigators will develop a predictive model using clinical and biological predictors of toxicity to adjuvant and neoadjuvant chemotherapy in older adults with breast cancer. The investigators will also determine the association between clinical and biological factors and reduced relative dose intensity of the prescribed chemotherapy regimen. In addition, the investigators will explore specific chemotherapy toxicities associated with reduced relative dose intensity of a prescribed regimen.

Detailed Description
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Although cancer is a disease associated with aging, there is no standard tool in oncology practice that incorporates clinical and biological factors to identify older adults with cancer who may be more vulnerable to the toxicity of chemotherapy. It is generally recognized that chronological age tells relatively little about an older adult's physiological age. Oncologists allude to this when they describe an older adult as: a 'young' 80-year-old or an 'old' 80-year-old, implying factors other than age contribute to the health status of an older adult. Geriatricians address this by routinely performing a geriatric assessment, which measures independent clinical predictors of morbidity and mortality in older adults. In addition, several potential biomarkers of aging have been described that are associated with functional decline and mortality among older adults. This study will identify whether novel biomarkers of aging can predict risk of chemotherapy toxicity. The current proposal will fill this knowledge gap by melding the principles of geriatrics with those of oncology to create a tool to assess the clinical and biological risk factors for chemotherapy toxicity in older adults. Furthermore, this study will determine the association between chemotherapy toxicity and dose reductions and/or delays that decrease chemotherapy dose intensity. Maintenance of chemotherapy dose intensity is necessary to maintain chemotherapy efficacy. Older adults are at risk for chemotherapy toxicity and if this toxicity results in decreased dose intensity, the benefits of chemotherapy will be compromised. This study will identify the association between clinical and biological predictors of grade 2-5 toxicity and relative dose intensity. Furthermore, this study will identify the specific dose-limiting toxicities. These data will provide evidence-based criteria to identify those patients whose projected risk of toxicity would limit dose intensity and compromise the efficacy of standard treatment. These data could serve as the basis for vulnerable elderly trials which would study an alternate therapy regimen in patients who are predicted to have a significant risk of toxicity (and compromised efficacy) with the standard regimen. This proposal unites the fields of geriatrics and oncology, incorporating geriatric correlates of vulnerability and studying their impact in an aging oncology population. These data will be used to develop a predictive equation for the risk of chemotherapy toxicity that can be utilized in daily oncology practice. These data will facilitate decision-making regarding the risks and benefits of adjuvant chemotherapy in older adults with breast cancer and ultimately serve as a foundation on which to identify older adults at risk for chemotherapy toxicity in order to guide interventions to decrease this risk.

Official Title
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Clinical and Biological Predictors of Chemotherapy Toxicity in Older Adults

Conditions
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Breast Cancer

Participation Criteria
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Eligibility Criteria
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Patients with Breast Cancer: Inclusion Criteria: Patients with stages I-III breast cancer receiving adjuvant or neoadjuvant chemotherapy Able to understand English Able to provide informed consent Patients age ≥65 and of any performance status are eligible Exclusion Criteria: Patients with metastatic disease Breast Cancer Controls: Inclusion Criteria: Patients with stages I-III breast cancer Patient will not receive adjuvant or neoadjuvant chemotherapy Patients age ≥65 and of any performance status are eligible Able to understand English Able to provide informed consent Exclusion Criteria: Patients with metastatic disease Receipt of chemotherapy Healthy Controls: Inclusion Criteria: Patients age ≥65 and of any performance status are eligible No history of cancer (excluding non-melanoma skin cancer) Able to understand English Able to provide informed consent

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patients<br>All patients 65 years old with Stage I to III breast cancer who are beginning adjuvant or neo-adjuvant chemotherapy. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Develop a predictive model of clinical and biological predictors for grade 2-5 toxicity to adjuvant and neoadjuvant chemotherapy. |  | 6 months after completion of chemotherapy | 
| Understand the association between clinical and biological factors and reduced relative dose intensity (RDI) of the prescribed chemotherapy regimen. |  | 6 months after completion of chemotherapy | 
| Identify the specific chemotherapy toxicities associated with reduced relative dose intensity of the prescribed chemotherapy regimen. |  | 6 months after completion of chemotherapy | 
| Understand the association between the receipt of adjuvant chemotherapy and change in functional status from pre-chemotherapy to end of chemotherapy. |  | 6 months after completion of chemotherapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Assess potential biomarkers for physiologic age, including interleukin-6, C-reactive protein, D-dimer, and p16 expression. |  | 6 months after completion of chemotherapy |