Ian E. Smith, MD, FRCP, FRCPE
2012-2013 BCRF Project:
(made possible by generous support from The Estée Lauder Brands
Head of the Breast Unit
Professor of Cancer Medicine
The Royal Marsden Hospital
Institute of Cancer Research
London, United Kingdom
Co-Investigator: Mitch Dowsett, PhD, BSc
, The Royal Marsden Hospital and Institute of Cancer Research, London, United Kingdom
Drs. Smith and Dowsett previously demonstrated in a retrospective study that there are significant differences in the expression of estrogen-regulated
genes during the menstrual cycle, which could affect the interpretation of molecular profiling tests in premenopausal women and has the potential to be
used as a test of endocrine responsiveness. To extend this observation, this team is conducting a prospective study to collect paired tumor tissue and
blood samples in the same patient at different points of the menstrual cycle. They are also in collaboration with North American colleagues to analyze
samples from a study in Vietnam. When complete, these two sets of prospectively collected samples will enable the researchers to verify if the possibility
of using the changes in gene expression through the menstrual cycle is supported scientifically and is feasible within clinical practice.
Mid-year Progress: Drs. Dowsett and Smith have already demonstrated in a retrospective study that there are significant differences in the expression of four estrogen-regulated genes (ERG) during the menstrual cycle. This could affect the interpretation of molecular profiling tests in premenopausal women and have the potential to be used as a test of endocrine responsiveness.
Drs. Dowsett and Smith have now selected a larger set of ERGs, based on knowledge from their group's in vivo and in vitro studies, to investigate in the same retrospective samples. Gene expression assays on these genes will be performed using the nCounter Analysis System (Nanostring) which provides a highly sensitive and reproducible method for detecting gene expression in archival material. In order to validate the above work prospectively, these researchers are collecting paired tumor tissue and blood samples in the same premenopausal patients at different points of the menstrual cycle. This study has been extended to five other UK centers. Drs. Dowsett and Smith are also collaborating with North American and Vietnamese colleagues to determine whether change in ERGs through the menstrual cycle is predictive of response to neo-adjuvant endocrine therapy. When complete, these two sets of prospectively collected samples will enable the researchers to verify if the possibility of using the changes in gene expression through the menstrual cycle is supported scientifically and is feasible within routine clinical practice.
Ian Smith is Professor of Cancer Medicine at The Royal Marsden Hospital and Institute of Cancer Research, London, UK He is also Head of the Breast Unit at The Royal Marsden and was Medical Director there from 2000 to 2003
His initial medical training was in Edinburgh and then he came to the Royal Marsden, London for specialist training in cancer medicine. He also spent some time in Boston at the Dana Farber Cancer Institute and Harvard University. Over the years his principal clinical research interests have been in breast cancer, lung cancer and in new drug development. He has been involved in the early clinical development of several anti-cancer drugs which have subsequently proved effective in the clinic, including carboplatin, letrozole, mitozantrone and more recently Herceptin®. In the last decade he has become increasingly involved in neoadjuvant therapies and translational research. He is currently UK Principal Investigator for several international multi-center trials including HERA (Herceptin®), BIG1-98 (Letrozole) and ALTTO (Lapatinib), and he is international co-chair of the FACE trial (letrozole v anastrozole)
Professor Smith is Chairman of the newly formed UK Breast Trials Intergroup and Chairman of the British Breast Group. He has been past Chairman of several national professional bodies including the Association of Cancer Physicians, the Royal College of Physicians Specialist Advisory Committee for Medical Oncology, and the NCRI Lung Cancer Clinical Studies Group. He is currently a member of the NCRI Breast Cancer Study Group and is a member of numerous international cancer societies and pharmaceutical advisory boards. He is currently on the Scientific Review Committee for the San Antonio Breast Cancer Symposium and has published around 300 peer reviewed scientific papers, and lectures widely around the world.