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BCRF Grantee Since

2004

Donor Recognition

The Estée Lauder Companies Brands Award in Memory of Evelyn H. Lauder

Pamela J. Goodwin, MD, MSc, FRCPC

Scientist, Samuel Lunenfeld Research Institute
Marvelle Koffler Chair in Breast Research
Professor of Medicine
University of Toronto/Mount Sinai Hospital
Toronto, Ontario, Canada

Current Research

Dr. Goodwin has initiated a study that will involve 100 women with metastatic 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. This research could lead to studies that explore whether improving obesity-associated physiologic profiles will reduce CTCs, and potentially improve patient outcomes. Specific activities have included protocol finalization, ethics approval, expansion of Dr. Goodwin’s study to additional cancer centers in Ontario, and enrolment of 20 women February to May 2013. She anticipates completion of this study in 2013-14.

Dr. Goodwin also continued research into quality of life (QOL) in long term breast cancer survivors; QOL 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 (in press Journal of Clinical Oncology). Her team has also conducted a series of biochemical assays on this survivorship cohort and has shown that a marker of inflammation (called CRP) does not predict cancer recurrence or death, and is not associated with fatigue. Finally, BCRF funds supported initial biochemical analyses of metabolic factors (insulin, leptin, CRP) in blood obtained in a large international trial (NCIC CTG MA.32) examining potential benefits of metformin (an anti-diabetes drug) on breast cancer outcomes. This group’s analyses, which confirm beneficial effects of metformin on metabolism, provide scientific support for the continuation of this important trial. Results of the latter two activities were presented at the Annual Meeting of the American Society of Clinical Oncology in June 2013. Initial BCRF funded analyses have confirmed beneficial effects of metformin on metabolism and provided scientific support for the continuation of this important trial. The expanded assays now being proposed will allow Dr. Goodwin’s team to examine these same factors as predictors of metformin benefit and they will allow exploration of a range of obesity-associated physiologic factors that may mediate adverse effects of obesity in breast cancer outcomes.

Mid-Year Summary

Dr. Goodwin reports that she and her team are continuing to successfully enroll women onto a study that will involve 100 women with metastatic breast cancer (BC) to investigate whether obesity-associated physiologic profiles of BC 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. This research could lead to studies that explore whether improving obesity-associated physiologic profiles will reduce CTCs, and potentially improve BC outcomes. As of January 1, 2014, 51 women have been enrolled at 3 participating centers; Dr. Goodwin anticipates accrual will be complete by August 2014, with final blood analyses 3 to 6 months later.

Her team also continued research into quality of life (QOL) in long-term BC survivors; QOL 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 BC (published in Journal of Clinical Oncology 2013, highlighted in several press reports). They also conducted a series of biochemical assays on this survivorship cohort and showed that a marker of inflammation (called CRP) does not predict cancer recurrence or death, and is not associated with fatigue (published in Breast Cancer Research and Treatment 2013).

Finally, the BCRF funds supported initial biochemical analyses of metabolic factors (insulin, leptin, CRP) in blood obtained in a large international trial (NCIC CTG MA.32) examining potential benefits of metformin (an anti-diabetes drug) on BC outcomes. The analyses, which confirm beneficial effects of metformin on metabolism, provide scientific support for the continuation of this important trial. The researchers are now doing these analyses in an expanded group of patients enrolled onto this trial; ultimately these data will be examined as predictors of metformin benefit and markers of BC outcomes (once trial outcomes have matured).

2) Co-Investigator: Lois Shepherd, MDCM, FRCPC, Queen's University The National Cancer Institute of Canada Clinical Trials Group (NCIC CCTG) 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, the United Kingdom, and Switzerland, and it involves a variety of cooperative groups from the United States and the NCIC CTG in Canada. Metformin is a very old drug which is used in the treatment of adult 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 closed to accrual in North American on January 22, 2013, six months ahead of the projected date. To date, 2,259 of the final sample size of 3,649 women were recruited from the United States with 1,203 women from Canada and an additional 187 women from the UK and Switzerland. Ongoing follow-up continues. Some early biological studies conducted on blood samples collected from participants have demonstrated that metformin has achieved the anticipated effect on body mass index, weight, glucose and insulin levels.

Mid-Year Summary:
Ongoing follow-up continues in this novel phase III trial of metformin in the adjuvant breast cancer setting, the results of which may provide another effective treatment option with early stage breast cancer. Some early biological studies conducted on blood samples collected from participants have demonstrated that metformin has achieved the anticipated effect on body mass index, weight, glucose and insulin levels.

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 tumor 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 at the Samuel Lunenfeld Research Institute of 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 160 research articles in leading journals. She is also active in the clinical management of breast cancer patients.

Co-Investigators

MDCM, FRCPC