Anne McTiernan, MD, PhD
Public Health Sciences Division
University of Washington
Fred Hutchinson Cancer Research Center, Seattle, Washington
2013-2014 BCRF Project:
(The Delta Air Lines Award)
Women who are overweight or obese are at increased risk for developing breast cancer after menopause, the most common type of breast cancer. Little is known about why these women are at increased risk, however. Women who are overweight or obese tend to have high levels of blood hormones such as estrogens, and high levels of blood markers of inflammation. These blood factors are associated with increased breast cancer risk but do not fully explain all of the connections between obesity and cancer. One under-studied but potential mechanism may be vitamin D deficiency that is very common in overweight or obese women. A recent study that combined results from several large prospective studies found that women with low levels of vitamin D have increased risk for breast cancer, and a new report from the Women’s Health Initiative clinical trial suggests that supplementation with vitamin D and calcium significantly reduces breast cancer risk by 20 percent.
Dr. McTiernan and colleagues have shown that Vitamin D deficiency is also very common in breast cancer survivors, and recent reports suggest that low vitamin D levels may negatively affect breast cancer prognosis. This group now wants to investigate whether supplementation of vitamin D at a high enough dose to bring vitamin D to a healthy blood level can reduce breast cancer risk factors in overweight or obese women. Over two-thirds of U.S. women are overweight or obese, and more than 75% have vitamin D levels below 30 ng/mL, which are considered insufficient. Therefore, discovering links among these factors and cancer-related biomarkers has high potential for reducing breast cancer risk.
The work on this study rests upon a completed randomized clinical trial that is testing the effect of vitamin D plus weight loss on indicators of breast cancer risk in postmenopausal overweight women. That trial is completed, and the primary data have been analyzed. A manuscript from these data is under review at the American Journal of Clinical Nutrition. An intriguing finding was that women whose vitamin D levels rose the highest with a standard dose of vitamin had the greatest changes in weight and an inflammation factor. Dr. McTiernan’s laboratory work funded through BRCF includes testing hormones and additional inflammation-related factors in blood samples from this trial. The inflammation-related factor assays have been completed for all participants’ samples at the University of Washington Wener lab, and Dr. McTiernan’s team is conducting statistical analyses to compare change in these factors in women who took vitamin D compared with those who took placebo. The hormones, which include estrogens and testosterone, are being measured now at Dr. Frank Stanczyk’s lab at University of Southern California. When all of the samples have been analyzed, the researchers will conduct statistical analyses. Additional laboratory work has been completed at Dr. Makar’s lab at the Fred Hutchinson Cancer Research Center, to identify genetic variability that might affect how vitamin D changes breast cancer risk indicators. Data analyses will be performed in the second half of the grant year. As results become available, manuscripts will be developed and submitted to scientific journals.
Dr. Anne McTiernan has been involved in breast cancer research for the past 25 years and focuses on prevention and survivorship. She served as co-Project Director for the Women’s Health Initiative (WHI) Clinical Coordinating Center at the Fred Hutchinson Cancer Research Center (FHCRC), where she led the development and implementation of the WHI low-fat dietary pattern, hormone replacement therapy, and calcium/vitamin D clinical trials, as well as the Observational Study. She is the principal investigator of the first two National Cancer Institute (NCI) funded trials to test exercise and weight loss interventions on breast cancer biomarkers in postmenopausal women, in which she and colleagues found that an one-year moderate intensity aerobic exercise intervention resulted in statistically significant reductions in blood markers related to breast cancer risk including estrogens, androgens, inflammation, insulin, and prolactin. She further found that a mean 10% weight loss from dietary calorie reduction in postmenopausal women over one year produces statistically significant reductions in blood estrogens, inflammation markers, insulin resistance, and adipokines, all of which have been linked to increased breast cancer risk.
Dr. McTiernan is also principal investigator of the Seattle site of a multi-site cohort study in breast cancer patients (HEAL) that has followed 1,183 women with breast cancer for over ten years to determine the effects of weight, body composition, physical activity, diet, genetics, and serum hormones on recurrence and survival. The HEAL study has provided seminal information on host factors predicting prognosis. In particular, women with elevated inflammation markers, insulin resistance, lower adipokines, or low levels of physical activity had statistically significantly poorer breast cancer-specific and all-cause survival.
In addition, Dr. McTiernan led the Seattle site of the ExCel trial, a NCI of Canada-led trial testing exemestane vs. placebo on breast cancer incidence in high risk women. Other breast-cancer related projects that she has led include a completed trial testing aspirin effects on mammogram density in postmenopausal women, and a trial testing Yoga on weight and quality of life in breast cancer survivors. She is co-investigator on at least 10 additional active or completed projects related to breast cancer. Of her approximately 340 published peer-reviewed scientific manuscripts, more than half are focused on breast cancer. Dr. McTiernan edited two scientific volumes focused on obesity, physical activity and cancer, and was first author on a book written for the lay audience (with Dr. Julie Gralow and Lisa Talbott): Breast Fitness: An Optimal Exercise and Health Plan for Reducing Your Risk of Breast Cancer. Dr. McTiernan is internationally recognized reputation for leadership in energy balance and breast cancer prevention and survivorship. Dr. McTiernan has served on several guideline committees and working groups relevant to breast cancer and has chaired and participated in several NIH grant review groups and study sections. Dr. McTiernan is Member (Professor) in the Division of Public Health Sciences at FHCRC, and Research Professor in the University of Washington School of Public Health (Epidemiology) and Medicine (Geriatrics). At the FHCRC, she founded and directed until 2013 the Prevention Center, a state-of-the art center that supports small and large-scale prevention and survivorship oriented studies, and includes an ambulatory clinic, nutrition laboratory, and exercise testing and training center.