Breast cancer is a disease of aging, and almost half of all newly diagnosed cases are found in women aged 60 and older. Chemotherapy is an essential component of curative treatment for most patients with early stage breast cancer. However, this treatment comes with a cost for older patients who are at increased risk of chemotherapy-induced toxicity and treatment-related mortality. One of the greatest challenges facing oncologists is identifying which older adults are at increased risk for toxicity and chronological age itself is a poor predictor of the risk. Although clinical markers of aging, such as obtained through a comprehensive geriatric assessment can improve our ability to identify those at risk additional tools are needed. This is particularly true for those patients who have limited functional reserve, which would only be unmasked in the setting of a stressor such as chemotherapy. The field of geriatrics has discovered biomarkers of aging that can identify older adults at risk for functional decline and mortality. These biomarkers include peripheral blood proinflammatory markers (interleukin-6 [IL-6], C-reactive protein [CRP]), a coagulation marker (D-dimer), and a marker of cellular senescence (telomere length) which identify older adults at risk for functional decline and mortality. However, the ability of these markers to identify older adults at risk for chemotherapy toxicity or chemotherapy associated functional decline is unknown. We hypothesize that these molecular markers of aging (IL-6, CRP, D-dimer, and telomere length) are associated with pre-chemotherapy functional status, as well as risk for chemotherapy toxicity and chemotherapy-associated functional decline in older individuals with breast cancer. The overall goal of this study is to identify the association between the biomarkers of aging and pre-chemotherapy functional status, chemotherapy toxicity, and functional decline in patients with breast cancer. This research leverages an ongoing prospective longitudinal study which will enroll 200 adult women with breast cancer across all age groups undergoing chemotherapy, who had blood collected at baseline (prior to chemotherapy). These pre-chemotherapy samples will be analyzed for IL-6, CRP, D-dimer, and leukocyte telomere length. The findings from the proposed study will fill an important knowledge gap in geriatric oncology and provide a bridge for melding laboratory-based biomarkers of aging with geriatric oncology research in older women with breast cancer. The proposed study will also provide preliminary data and a platform for a future larger scale prospective longitudinal study evaluating molecular biomarkers of aging and their role in predicting chemotherapy toxicity in older adults with breast cancer. This unique research opportunity will provide the PI with a foundation for melding aging and oncology research and also provide critical support for the PI's career development in aging research.
The overall goal of this study is to identify the association between biomarkers of aging and baseline functional status, chemotherapy toxicity, and functional decline in patients with breast cancer. The proposed study is a translational research project evaluating potential molecular markers of aging including proinflammatory markers (IL-6, CRP), coagulation marker (D-dimer), and leukocyte telomere length in older women with breast cancer undergoing chemotherapy. This unique research opportunity will provide the PI with a foundation for melding aging and oncology research and also provide critical support for the PI's career development in aging research.
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