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Principal Investigator: Carolyn Stigge Harris
Organization: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
Fiscal Year: 2024
Award: $161,556
Funding agency: National Cancer Institute
PROJECT SUMMARY/ABSTRACT
The psychological symptom cluster is a common problem that impacts women receiving breast cancer
treatment and is associated with several negative outcomes, including reduced functional status and quality of
life. Unfortunately, the mechanism(s) that underlie this cluster are unknown which limits the development of
targeted interventions. Mounting evidence suggests that individual (e.g., age, education) and community-level
determinants of health (e.g., neighborhood deprivation, pollution) increase psychological symptoms in women
with breast cancer. While exercise can improve psychological symptoms in women with breast cancer, it is
unknown if individual or community-level factors impact this relationship. Given that exercise, individual, and
community-level factors can alter DNA methylation, evaluation of epigenetic regulation may provide new
mechanistic insights. Investigation into the epigenomic, individual, and community-level factors associated with
a psychological symptom cluster in women with breast cancer within the context of a randomized clinical trial
for a moderate-intensity aerobic exercise intervention will clarify these relationships and inform the
development of targeted interventions. The overarching goal of this research is to alleviate symptoms in cancer
patients, which is a research priority of the NCI’s Division of Cancer Prevention. The aims of the K99 study are
to (1) test the hypotheses that epigenomic, individual, and community-level factors are associated with
psychological symptom cluster severity profiles in women with breast cancer prior to the start of aromatase
inhibitor therapy; and (2) test the hypotheses that epigenomic, individual, and community-level factors are
associated with worsening psychological symptom cluster severity profiles following six months of aromatase
inhibitor therapy in women with breast cancer, while exercise and epigenomic factors mitigate this effect. The
candidate will extend this line of research to immunotherapy, which is rapidly emerging as an adjuvant therapy
for breast cancer. The detailed training plan, exceptional team of mentors, and research-intensive environment
of the University of Pittsburgh will provide the candidate with the mentored training, support, and research
experience needed to conduct this research. Through this training plan, the candidate will develop: proficiency
in epigenomics; competency in analysis and bioinformatics of longitudinal epigenomic data; proficiency in the
evaluation of social determinants of health in symptom science; expertise in the mechanisms of
immunotherapy-related symptoms; and knowledge and skills for professional career development. The aims of
the R00 study are to: (1) identify symptom cluster profiles of women with breast cancer receiving
immunotherapy over time; and (2) evaluate for epigenomic, individual, interpersonal, community, and societal-
level factors associated with symptom cluster severity profiles of women with breast cancer receiving
immunotherapy over time. Findings from these projects will provide new knowledge to guide clinical
assessment and the development of targeted interventions to mitigate the severity common symptom clusters.
Terms: <Address><Adjuvant Therapy><Aerobic Activity><Aerobic Exercise><Aerobic Training><Aerobic fitness><Age><Androstenedione Aromatase Inhibitor><Anxiety><Aromatase Inhibitors><Bio-Informatics><Bioinformatics><Biological><Blood Sample><Blood specimen><Breast Cancer><Breast Cancer Treatment><Breast Cancer therapy><Cancer Patient><Cancer Survivor><Cancer Treatment><Cancers><Clinical Trials><Clinical assessments><Communities><Competence><DNA Methylation><Data><Development><Distress><Division of Cancer Prevention><Education><Educational aspects><Employment><Environment><Estrogen Synthase Inhibitor><Estrogen Synthetase Inhibitor><Evaluation><Exercise><Fatigue><Genes><Goals><Health Disparities Research><Health disparities related research><Immune mediated therapy><Immunologically Directed Therapy><Immunotherapy><Individual><Intervention><Intervention Strategies><Investigation><Knowledge><Knowledge acquisition><Lack of Energy><Maintenance><Malignant Breast Neoplasm><Malignant Neoplasm Therapy><Malignant Neoplasm Treatment><Malignant Neoplasms><Malignant Tumor><Measures><Mediating><Mental Depression><Mentors><Methylation><Molecular><NCMHD><NIMHD><National Center on Minority Health and Health Disparities><National Institute of Minority Health and Health Disparities><National Institute on Minority Health and Health Disparities><Neighborhoods><Oncology><Oncology Cancer><Outcome><Pathway interactions><Patient outcome><Patient-Centered Outcomes><Patient-Focused Outcomes><Patients><Policy Developments><Pollution><Preventative strategy><Prevention strategy><Preventive strategy><QOL><Quality of life><Race><Races><Randomized><Research><Research Priority><Risk><Risk Factors><Role><Severities><Sleep disturbances><Socio-economic status><Socioeconomic Status><Symptoms><Testing><Time><Training><United States><Universities><Woman><aberrant sleep><adjuvant treatment><ages><alleviate symptom><ameliorating symptom><anti-cancer therapy><associated symptom><biologic><cancer therapy><cancer type><cancer-directed therapy><care as usual><career development><co-morbid symptom><co-occuring symptom><common symptom><community factor><community-level factor><comorbid symptom><concurrent symptom><cooccuring symptom><decrease symptom><depression><deprivation><developmental><disrupted sleep><disturbed sleep><epigenetic regulation><epigenomics><exercise intervention><experience><fewer symptoms><functional status><health determinants><health disparities science><immune therapeutic approach><immune therapeutic interventions><immune therapeutic regimens><immune therapeutic strategy><immune therapy><immune-based therapies><immune-based treatments><immuno therapy><impaired sleep><improved><inhibitor drug><inhibitor therapeutic><inhibitor therapy><innovate><innovation><innovative><insight><interventional strategy><irregular sleep><malignancy><malignant breast tumor><methylome><mortality><neoplasm/cancer><novel><pathway><patient oriented outcomes><physical activity intervention><pre-doc><pre-doctoral><predoctoral><psychological symptom><racial><racial background><racial origin><randomisation><randomization><randomized, clinical trials><randomly assigned><reduce symptoms><relieves symptoms><skill acquisition><skill development><skills><sleep disruption><sleep dysregulation><social><social health determinants><social influence><social role><socio-economic position><socioeconomic position><symptom alleviation><symptom association><symptom cluster><symptom comorbidity><symptom reduction><symptom relief><symptom science><treatment as usual><usual care>