Thomas E. Rohan, MD, PhD
Harold and Muriel Block Chair in Epidemiology and Population Health
Professor and Chairman,
Department of Epidemiology and Population Health
2013-2014 BCRF Project:
(The Estée Lauder Companies Brands Award)
Elucidation of the molecular basis of breast cancer development has the potential not only to lead to further improvements in breast cancer treatment but also to assist with breast cancer prevention. To date, cancer genome studies have largely focused on documenting mutations in primary tumors. However, it is recognized that there is a need to create a mutational atlas of the natural history of cancer, and that to do so, comprehensive genomic analysis of preneoplastic lesions is required. Furthermore, such efforts need to expand beyond the sequencing of DNA changes to encompass changes in gene expression as well. To that end, using benign breast disease (BBD) tissue samples from an epidemiologically well-characterized cohort of women who had a biopsy for BBD, for whom formalin-fixed, paraffin-embedded (FFPE) breast tissue is available, and who are being followed up to determine the occurrence of breast cancer subsequent to the BBD biopsy, Dr. Rohan is evaluating the feasibility of using next generation sequencing of DNA and RNA extracted from the tissue to identify changes related to risk of progression to breast cancer. The data that his team will acquire through this project should lay the additional groundwork needed to proceed to a full-scale study. Dr. Rohan’s ultimate goal is to enhance approaches to the prediction of breast cancer risk and to the clinical management of women at risk. For the Canadian Study of Diet, Lifestyle, and Health, a prospective study that includes ~39,000 women, Dr. Rohan’s team is undertaking analyses of factors related to breast cancer development.
For the component of this project that is focused on prediction of breast cancer risk using next generation sequencing of DNA and RNA, Dr. Rohan and his team have extracted DNA from benign breast tissue and matching normal tissue from 42 women who had benign breast disease and developed subsequent invasive breast cancer and similarly from 42 women who had BBD but did not develop breast cancer. For most of the samples they have determined the amount of DNA available. Furthermore, they have selected a set of genes that they intend to test for the presence of mutations and have optimized methods for working with the relatively small amounts of DNA that can be obtained from the tissue available for this study. Therefore, all of the pieces are now in place to enable the researchers to move forward to address the goal of the project, namely to compare the mutational profile of benign breast lesions in women who progress to invasive breast cancer with the profile of the benign lesions of women who do not progress to invasive breast cancer. In addition to this, the Rohan team is well advanced in their work to optimize sequencing of three types of small RNA species (microRNA, PiwiRNA, and TinyRNAs).
With respect to their ongoing cohort study, the Canadian Study of Diet, Lifestyle, and Health, they found no association between any smoking exposure and risk of breast cancer in an analysis involving 1,077 women with incident, invasive breast cancer and 3,217 women without breast cancer. Although these results cannot rule out an association between smoking and breast cancer, they do agree with current literature suggesting that if an association does exist, it is relatively weak. In other cohorts Dr. Rohan and colleagues have recently shown that adherence to all of the American Cancer Society cancer prevention guidelines is associated with a substantial reduction in breast cancer risk, and that estradiol, insulin, and C-reactive protein (a marker of inflammation) are associated with strong increases in risk of benign proliferative breast disease (BPBD), a putative breast cancer precursor, and that adiponectin, a protein with anti-inflammatory activity, is associated with a strong reduction in risk of BPBD.These findings suggest that the estrogen, insulin and inflammation pathways are associated with the early stages of breast cancer development. Manuscripts describing the results of these cohort analyses have been submitted for publication.
Dr. Thomas Rohan is Chairman of the Department of Epidemiology and Population Health at the Albert Einstein College of Medicine in New York, Associate Director for Population Sciences in the Albert Einstein Cancer Center, and a member of the National Cancer Institute Board of Scientific Counselors. He is a cancer epidemiologist with extensive experience in the design, conduct, and analysis of studies of genetic/molecular, nutritional, and hormonal factors in the etiology and pathogenesis of breast cancer. He has published widely on these topics, and he has co-edited books on cancer precursors and on cervical cancer. Dr. Rohan also has extensive experience in conducting translational studies that involve multiple investigators and require careful planning and coordination.