Christine B. Ambrosone, PhD

2012-2013 BCRF Project:
Co-Investigator: Chi-Chen Hong, PhD, Roswell Park Cancer Institute, Buffalo, NY

Psychosocial factors such as stressful life events and perceived stress may play a role in the progression of breast cancer and may be mediated in part by effects on the anti-tumor immune system, angiogenesis, and tumor invasion. Among breast cancer patients, pre- and post-treatment immune function, particularly soon after surgery, may be important for tumor control by playing a role in eliminating residual disease and/or micrometastasis. Stressful events are well known to be immunosuppressive and have been linked to changes in immune function, although much less is known on how subjective psychosocial experiences relate to physiological parameters that may contribute to long-term disease prognosis in breast cancer patients.

Only a handful of studies to date have used a longitudinal approach to examine stress and/or mood on immune function. Building on their previous work on vitamin D and body immune functions in the development of breast cancer, Drs. Ambrosone and Hong undertook a new project in 2011-2012 to examine prospectively the relationships between a comprehensive set of psychosocial factors and signaling molecules affecting immune function, in a cohort of newly diagnosed breast cancer patients, participating in the Women's Health After Breast Cancer (ABC) Study at Roswell Park Cancer Institute.

In 2012-2013, Drs. Ambrosone and Hong will continue their work to understand, in-depth, the roles of vitamin D and a number of biomarkers indicative of body immune functions in the development of breast cancer, particularly the type of aggressive breast cancer that is difficult to treat and leads to high mortality. Their study to date shows that two distinct types of immune response coupled with each other are associated with markedly lower risk of aggressive breast cancer. The research team has also observed interactions between immune biomarkers and vitamin D in relation to breast cancer. Based upon these results, they plan to examine the complex cross-talk among vitamin D, immune biomarkers, telomere length, and psychological stress. They will also continue enrolling and following-up patients in the Women's Health ABC Study.

Mid-year Progress: In this funding period, Drs. Ambrosone and Hong advanced their work to understand relationships between psychosocial factors and biomarkers indicative of immune function. They showed that at the time of cancer diagnosis, prior to treatment, feelings of psychological distress and limitations in social activities due to emotional problems were associated with immune markers related to general immune suppression and promotion of tumor growth in 448 newly diagnosed breast cancer patients. In contrast, those with higher levels of biomarkers indicative of a more robust anti-tumor immune response were less likely to report low levels of resilience or low levels of either mental or physical health. Drs. Ambrosone and Hong will extend these findings to prospectively examine how factors related to psychosocial adaptation impacts immune changes following treatment, and examine their interrelationships with vitamin D, circulating biomarkers responsive to stress, and telomere length. They have published two meeting abstracts and submitted one manuscript for publication since June.

Bio:
After positions at the National Center for Toxicological Research in Arkansas and Mount Sinai School of Medicine in New York City, Dr. Christine Ambrosone joined the faculty of Roswell Park Cancer Institute (RPCI) in 2002, where she now serves as Chair of the Department of Cancer Prevention and Control.

Dr. Ambrosone is an internationally recognized leader in molecular epidemiology and is co-founder and past Chairperson of the Molecular Epidemiology Group of the American Association for Cancer Research. She is also active in Southwest Oncology Group (SWOG), where she is Co-Chair of the Molecular Epidemiology Committee. Her research focuses primarily on breast cancer, and elucidating relationships among exposures, genetic susceptibility and cancer risk and outcomes. One of her main areas of interest in breast cancer is why African-American women with breast cancer are more likely to be diagnosed at a younger age and to have more aggressive disease characteristics.

Dr. Ambrosone's research also focuses on breast cancer prognosis. Working with SWOG clinicians, Dr. Ambrosone has several ongoing studies targeted at understanding why women with similar disease characteristics and general health status experience different outcomes from chemotherapy, examining the role of inherited differences in metabolism of chemotherapy drugs, as well as modifiable factors, such as vitamin supplements, diet and physical activity. Dr. Ambrosone is Past Senior Editor for Cancer Research and is on the Board of Scientific Advisors to the Director of the National Cancer Institute.

Dr. Christine Ambrosone, along with colleagues from the University of North Carolina and Boston University, has been awarded a five-year, $19.3 million grant from the National Cancer Institute to investigate the causes of breast cancer in African-American women. "We are so excited about this work - and BCRF played a LARGE role in getting the preliminary data to begin the study," said Dr. Ambrosone. "We are so grateful for BCRF support!" Read more