Gad Rennert, MD, PhD

2012-2013 BCRF Project:
Dr. Rennert's study is aimed at identifying unique natural history patterns for subsets of breast cancer patients defined according to a variety of germline and tumor biological/genetic characteristics as well as behavioral/environmental factors. Some of the genetic events are inherited, some are acquired and some are evident only in the tumor. Dr. Rennert believes that women with different patterns will also have different survival patterns and varying probability of developing other tumors, recurrence of tumors or metastases and response to treatment.

Physicians' ability to identify sub-groups of tumor behavior depends on the recruitment of sufficient women into the study and ensuring that the recruited participants are representative of all the women with breast cancer (the target population). Dr. Rennert's team has thus far recruited over 5,000 women with breast cancer into the study and has collected demographic and risk factor data, as well as blood samples, from all of them. They are carrying out an extensive molecular analysis of the blood samples of each participating woman and are extensively evaluating all the medical records and histological reports of each patient. More than 100,000 genetic tests have already been performed on the study participants. When enough women with enough diversity are collected, Dr. Rennert's team will be able to compare clinical patterns between various sub-groups. The results of this effort will allow the researchers to provide better follow-up, potentially point at better treatment options and better prediction of survival.

With their current data, Dr. Rennert's team has managed to identify the use of a group of bone drugs called bisphosphonates as possibly associated with reduced risk of breast cancer, and reported it in the Journal of Clinical Oncology. They have also identified a mutation in a gene called MUTYH in North African women, which carries an increased risk of breast cancer, and reported it in the journal Cancer. They are further evaluating the response to hormonal treatments given differences between women in their hormone-inducing genes and are able for the first time to provide preliminary survival curves.

In the coming year, Dr. Rennert's team will continue recruiting new cases (and controls), retrieving more oncology follow-up records, retrieving more bloods and tissue blocks, analyzing blood and tissue for more molecular and other markers. They will also focus their efforts on women with triple negative breast tumors and women presenting at early stage but developing an aggressive disease. With BRCA results available for all of the Ashkenazi Jewish participants, Dr. Rennert's team stands a good chance of being able to demonstrate differences in clinical behavior of the different molecular subgroups in women with triple negative tumors, with special interest in osteoporosis, use of bisphosphonates, vitamin D metabolism, and breast cancer risk. Another aspect that their study will be able to evaluate is the field accuracy of panels such as the Oncotype DX diagnostic test, extensively used in Israel. With longer periods of follow up, Dr. Rennert's team will be able to compare the predictive recurrence score with the actual recurrence rate.

Mid-year Progress:Much of this work, aimed to identify sub-groups of tumor behavior, depends on the researchers' ability to recruit enough women into the study and to make sure that the recruited participants are representative of all the women with breast cancer (the target population). Dr. Rennert's team has thus far recruited over 6,000 women with breast cancer into the study and has collected demographic and risk factor data, as well as blood samples, from all of the participants. This is now one of the largest cohorts in the world of women with breast cancer who have been consecutively recruited in a population-based manner.

Dr. Rennert's team is carrying out an extensive molecular analysis of the blood samples of each participating woman and is extensively evaluating all the medical records and histological reports of each patient. More than 100,000 genetic tests have already been performed in the study participants. When enough women with enough diversity are collected, the investigators will be able to compare clinical patterns between various sub-groups. The results of this effort will allow researchers to provide better follow-up, potentially point at better treatment options and better prediction of survival. With their current data Dr. Rennert's team is now ready to present data that associates bisphosphonate use with improved survival from breast cancer.

Bio:
Dr. Rennert is the Director of the CHS National Cancer Control Center in Israel and of the National Breast and Colorectal Cancer Detection Programs of Israel. He is also the Chairman of the Department of Epidemiology and Community Medicine at Carmel Medical Center and the School of Medicine of the Technion - Israel Institute of Technology in Haifa.

Dr. Rennert's research is mainly focused on population-based molecular epidemiology studies of gene-environment interactions in the etiology of cancer, mainly of breast, colon, lung and gynecological cancers. His research group takes special interest in the unique genetic make-up of the Israeli population and its influence on the risk of cancer, on the development of means of cancer prevention and on the natural history of the disease, including the diagnostic process and response to treatment.

Dr. Rennert received his MD degree from the Ben-Gurion University of the Negev Medical School and his PhD in Epidemiology from the University of North Carolina School of Public Health in Chapel Hill.