Lois Shepherd, MDCM, FRCPC
Professor, Department of Pathology and Molecular Medicine
2012-2013 BCRF Project:
Queen's University, Kingston, Ontario
National Cancer Institute Canada Clinical Trials Group
Co-Investigator: Pamela J. Goodwin, MD, MSc., FRCP(C)
, Mount Sinai Hospital, University of Toronto
(made possible with generous support from ANN INC.)
The NCIC Clinical Trials Group is conducting a randomized phase III trial of metformin compared with placebo on recurrence and survival in early stage breast cancer. This is a study that is being conducted across North America and involves a variety of cooperative groups from the United States and the NCIC CTG in Canada. In the fall of 2012, participation by selected centers within the United Kingdom and Switzerland will begin. Metformin is a very old drug that is used in the treatment of maturity onset diabetes. Over the last decade there has been a growing body of evidence to suggest that insulin and insulin growth factor pathways may play a role in the development and recurrence of many malignancies including breast cancer. Metformin has both a direct and indirect mechanism of action on the insulin pathway and its potential use in preventing the recurrence of early stage breast cancer is being explored in the MA.32 study. The study was activated in the summer of 2010 and to date more than 2,000 women have been recruited to the trial, more than 1,300 of whom have been accrued from the US.
Mid-year Progress: The study has now successfully reached its accrual goal of 3,852 women from North America, 2,259 of whom were recruited from the United States. Ongoing follow-up continues. There has been no unexpected toxicity from the study medication to date, and both the trial steering committee and the Data Safety Monitoring Committee of the NCIC CTG have not identified any concerns with the conduct or safety aspects of the study.
There is a strong embedded correlative (translational research) component in MA.32 that will allow identification of both patient-related (host) and tumor-related predictors of metformin benefit and help to differentiate indirect, insulin mediated from direct, insulin independent metformin effects. This trial continues to represent a truly international collaboration involving many different partners and is supported by a wide variety of funding sources. It remains a superb example of a study which has no industry support, using an older and an established treatment for an entirely different disease than breast cancer. This is a novel, first in world, phase III study of metformin, and the results of this trial may provide another effective treatment option for women with early stage breast cancer. The successful accrual over 30 months is an indication of the widespread support and excitement this study has generated.
Dr. Shepherd is a Hematopathologist and Professor in the Department of Pathology and Molecular Medicine at Queen's University in Kingston, Ontario and has worked as a Physician Coordinator and Senior Investigator at the NCIC Clinical Trial Group since 1988. Dr. Shepherd has been responsible for oversight of the Breast and Hematology trial activity within the group for the last 20 years. As well, she is the Operational Director of the Tumour, Tissue and Data Repository established in 1997 which is the biorepository for tissue collected in association with the Group's clinical trials. Dr. Shepherd's interests are in hematologic malignancies, transfusion medicine, breast cancer, translational research and biobanking. She has more than 70 peer-reviewed publications.