My career goal is to become an independent cancer epidemiologist using molecular approaches, including molecular pathology, to understand cancer etiology in the population overall and between different racial and ethnic populations. Toward my career goal, the objective of this application is to gain training and develop expertise in molecular pathological epidemiology, with focus on the laboratory methods, advanced statistical methods, and tumor heterogeneity in breast cancer etiology. Obesity, in particular, central adiposity may play an important role in breast cancer risk among African-American (AA) women, and this association may differ be- tween tumor subtypes; however, the underlying mechanisms are largely unclear. The phosphatidylinositol 3- kinase/Akt/mammalian target of the rapamycin (PI3K/AKT/mTOR) pathway, which is important in regulation of cell growth and proliferation, can be activated by obesity, and aberrant activation of this pathway has been implicated in estrogen receptor negative (ER-) and basal-like breast cancers, commonly seen in breast cancers of AA women. To better understand the role of the mTOR pathway in the association between obesity and breast cancer subtypes, we will conduct a molecular pathological epidemiology study leveraging tumor tissue and data from 1,400 AA and 422 European-American (EA) women with breast cancer in the Women's Circle of Health Study (WCHS).
We aim to examine differences in mTOR pathway activities between ER+ and ER- breast tumors and intrinsic subtypes among AA women (Aim 1), to assess the association of mTOR pathway activities with obesity among AA women (Aim 2), and compare these associations between AA and EA women. The expectation of this research is to provide a better understanding of which key components of obesity (general obesity, central adiposity, body composition, and weight gain) are associated with mTOR pathway activities and whether the associations are more frequently observed for specific breast cancer subtypes. The results of this project will serve as a stepping stone to developing a highly competitive R01 project in a large consortium of AA women. This project is well tailored for me to apply the knowledge and skills that will be obtained from training activities and my mentors: 1) molecular pathological epidemiology and breast cancer pathology (Dr. Thaer Khoury, Co-Mentor); 2) advanced statistical methods (Dr. Song Liu, Co-Mentor); and 3) breast cancer etiology with emphasis on body size and race (Dr. Christine Ambrosone, Primary Mentor, and Dr. Elisa Bandera, Co-Mentor). The training activities include molecular pathological and statistical courses, a six-month rotation in pathology laboratories and regular office-based rotations with Dr. Khoury, regular attendance and presentations at institute and at international meetings, continue publication in breast cancer sub- types and R03 and R01 grant writing, and participation in molecular pathological epidemiological research pro- jects. Roswell Park Cancer Institute and the University at Buffalo, SUNY, both provide an outstanding environment for me to achieve my career goal.
African-American women have the highest prevalence of obesity in the U.S. (58.6% with body mass index >30 kg/m2) and are affected most by obesity and having unfavorable breast cancer subtypes (ER-; triple-negative; and basal-like tumors). The results from this study will add in causal inference for body size and breast cancer subtypes and in the design of public health interventions. This project also serves as an excellent vehicle for developing research skills that the candidate needs towards development as an independent investigator.
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