Clinical and Biological Predictors of Chemotherapy Toxicity in Older Adults

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.

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