Pamela J. Goodwin, MD, MSc, FRCPC

2012-2013 BCRF Projects:
1) (made possible by generous support from The Estée Lauder Companies Brands)
Many women with advanced breast cancer have circulating tumor cells (CTCs) in their blood. These cells can be readily identified using FDA approved technology; their presence has been associated with poor response to treatment and more rapid disease progression in advanced breast cancer. Dr. Goodwin's ongoing research aims to determine whether measurement of CTCs can be used to make more effective treatment decisions. Her team plans to build on their previous clinical research showing that obesity and related physiologic factors (such as insulin) are associated with poor outcomes in breast cancer patients and a large body of basic research conducted by other investigators that has demonstrated an important role of a range of obesity associated factors in cancer biology (such as invasiveness and new blood vessel formation) that could lead to higher numbers of CTCs in the circulation.

In 2012-2013, Dr. Goodwin's team will conduct a pilot study in 100 women with advanced breast cancer to investigate whether obesity-associated physiologic profiles of breast cancer patients are associated with higher levels of CTCs. If important associations are seen, this research could lead to more definitive studies to explore whether improving obesity-associated physiologic profiles will reduce CTCs, and possibly improve breast cancer outcomes.

Mid-year Progress: Dr. Goodwin's group has initiated a pilot study involving 100 women with advanced breast cancer to investigate whether obesity-associated physiologic profiles of breast cancer patients are associated with higher levels of circulating tumor cells (CTCs). CTCs have been associated with poor response to treatment and more rapid disease progression in advanced breast cancer. This research could lead to more definitive studies to explore whether improving obesity-associated physiologic profiles will reduce CTCs, and possibly improve breast cancer outcomes. Reflecting the proposed timelines, specific activities have included protocol finalization, ethics approval, expansion of the study to additional cancer centers in Ontario and initiation of enrolment.

Dr. Goodwin's team has also continued research into quality of life in long-term breast cancer survivors. They have found that quality of life improves over time and, at an average of 11 years post diagnosis, is similar in most respects to that of age-matched women who have never had breast cancer. The investigators have conducted a series of biochemical assays on this survivorship cohort; early results show that a marker of inflammation (called CRP) does not predict cancer recurrence or death and is not associated with levels of fatigue. Finally, BCRF funds have supported biochemical analyses of metabolic factors (insulin, leptin, CRP) in blood samples obtained in a large international trial (NCIC CTG MA.32) examining potential benefits of metformin (an anti-diabetes drug) on recurrence and survival in breast cancer. The team's analyses have confirmed beneficial effects of metformin on metabolism and they provide scientific support for the continuation of this important trial.

2) On behalf of the NCIC Clinical Trials Group
Co-investigator: Lois Shepherd, MDCM, FRCP(C), Queen's University, Kingston, Ontario

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.

Bio:
Dr. Pamela Goodwin has been actively involved in research relating to host factors in breast cancer for the past 25 years. Early in her career, she became intrigued with the possibility that host (patient-related) factors, especially obesity, might impact outcomes of women diagnosed with breast cancer. She began a program of research that has focused on the role of these factors, including obesity, nutrition, exercise, and related factors in the clinical course of breast cancer. She has led a number of studies which investigate the complex interactions between body size, nutrition, exercise and physiologic mediators such as insulin, IGF-I and vitamin D, examining the impact of these factors on risk and survival of women diagnosed with breast cancer. Dr. Goodwin has expanded this work to investigate the status of long-term breast cancer survivors and the influences of hereditary factors, vitamin D and metformin on breast cancer outcomes. She currently leads a large international phase III trial (NCIC MA.32) which examines the impact of an insulin lowering drug, metformin, on breast cancer outcomes and has an active translational research program examining the interface between host factors and tumour biology in both early and advanced breast cancer.

Dr. Goodwin is a Professor of Medicine at the University of Toronto, with cross appointments in the Department of Health Policy, Management and Evaluation and in the School of Graduate Studies. She is a Senior Scientist in the Samuel Lunenfeld Research Institute at Mount Sinai Hospital, Director of the hospital's Marvelle Koffler Breast Centre and holder of the Marvelle Koffler Chair in Breast Research. Dr. Goodwin is an Associate Editor of the Journal of Clinical Oncology, the leading clinical oncology journal in the world, and she has published over 150 research articles in leading journals. She is also active in the clinical management of breast cancer patients.