Scientific Objective and Rationale for the Proposal: During the last decade, a number of population studies have shown an association between green tea consumption, obesity, and breast cancer risk. Studies also suggest that this association is seen only in women who slowly metabolize the bioactive components of tea and thus have increased exposure. The proposed research study will be the first long-term clinical study to assess the effects of green tea catechins on obesity and energy balance-related biomarkers associated with breast cancer risk such as body weight, and the first to evaluate these effects in women with genetic variations that influence green tea metabolism.

Career Goals: The proposed research will prepare me well for my future goal of pursuing a career as clinical researcher studying dietary prevention of breast cancer. After finishing my Ph.D., my plan is to secure a faculty position in which I can continue research in this area. I was originally inspired to follow applied human research in cancer prevention by an oncology traineeship in Ameer hospital in Tehran. I was recruited to the University of Minnesota specifically to study the effects of reproductive hormones on breast cancer in the laboratory of Dr. Mindy S. Kurzer. Under her mentorship, I have already helped received all the necessary regulatory documents for approval of the parent study, and during the next 3-4 years, I will keep on participating in all study aspects of the study, from recruiting, collecting, and analyzing samples during clinic visits at the University of Minnesota Clinical Research Unit to interpreting data and writing manuscripts. Dr. Kurzer will provide training in all areas of implementation of clinical trials on diet and breast cancer prevention as well as biomarker analyses. This study will also introduce me to a distinguished group of researchers within the University of Minnesota Cancer Center and outside the state. Douglas Yee, M.D. is a medical oncologist and director of the University of Minnesota Cancer Center who will facilitate my participation in weekly and monthly meetings with Cancer Center clinicians, radiologists, surgeons, and researchers, specifically focusing on breast cancer. These activities will expose me to clinical breast cancer issues and will help me to understand the clinical applicability of my study results. I will also continue to work with Tim Emory, M.D., our study radiologist, in order to learn about screening potential subjects at the breast clinic, and I will work closely with other collaborators, such as Drs. Giske Ursin, Frank Stanczyk, and Anna Wu, well-known breast cancer researchers at the University of Southern California, and Dr. C.S. Yang, a world renowned green tea expert at Rutgers University. Along with my nutrition studies, I plan to take additional courses in cancer incidence, biology, and prevention to enhance my basic knowledge of important cancer-related topics. Training by experienced mentors, access to excellent resources and facilities, and involvement in a rich academic program will strongly support my career goal to become a breast cancer researcher. At the end of my doctoral studies, I will be fully trained and capable of carrying out clinical trials of dietary interventions for reduction of breast cancer risk.

Ultimate Research Applicability, Outcomes, and Contribution: Results of this research study will help researchers and clinicians understand the mechanisms by which green tea consumption exerts cancer-preventive, anti-obesity, and anti-inflammatory effects in postmenopausal women. This information is very important, because understanding mechanisms will lead to further studies to determine the optimal dosage, timing, and form of the green tea for breast cancer prevention. It may also lead to development of additional strategies for cancer prevention that target these mechanisms. The results will also help identify a subgroup of women who are particularly likely to benefit from green tea consumption. This is extremely important because most drugs are not effective in all people, and identifying responsive people will help clinicians target their recommendations and will help development of dietary supplements or drugs for obesity and breast cancer prevention that can be targeted to specific groups in which they will be most effective. The results of this study are especially important since to date no effective chemopreventive agent against breast cancer has been identified. Development of an effective chemopreventive agent for use by high-risk women may significantly reduce the rate of morbidity and mortality from breast cancer. The results of this trial will lead to future studies to determine the optimal dose and may ultimately lead to dietary recommendations and/or the development of dietary supplements for obesity and cancer prevention. The study itself will take approximately 4 years to carry out. Clinical recommendations could follow immediately after publication of the results.