Targeting Breast Cancer Metabolism Through Exercise & Weight Control

breast cancer: breast cancerVIENNA, Austria—Women with breast cancer can benefit from exercise and weight control, but they should not be made to feel guilty that their lifestyles have caused their disease. “There's fairly consistent evidence that being more physically active is associated with better breast cancer outcomes and lower risk of breast cancer,” said Pamela J. Goodwin MD, MSc, FRCPC, Medical Oncologist, Clinical Epidemiologist, and Professor of Medicine at the University of Toronto and Mount Sinai Hospital, Toronto, Canada, at the St. Gallen International Breast Cancer Conference. She noted that targeting metabolism through exercise and weight control was clinically beneficial for patients with breast cancer. “There's also evidence suggesting that having a normal body weight is associated with a lower risk of [developing] postmenopausal hormone receptor-positive [breast cancer] and premenopausal triple negative breast cancer, and with generally better breast cancer outcomes,” she said, warning, however, that because these conclusions came from observational studies, it was not possible to know if BMI and physical activity levels were simply markers of general health rather than being actually “on the causal pathway.” Hormone receptor-positive breast cancer was more strongly associated with obesity, said Goodwin, while data were “less clear” for physical activity. When asked for her recommendations on the basis of currently available evidence, she re-emphasized that the associations were not proven to be causal. “We don't know if changing obesity or changing physical activity will improve outcomes,” she said, adding that randomized trials that should provide this information were ongoing. But the lack of final proof need not stand in the way of making cautious recommendations both for preventing cancer and delaying breast cancer relapse, Goodwin suggested. “I think until those trials are complete we can certainly recommend optimization of body weight and physical activity for general health and for symptom control. But we need to be very careful that we don't lead breast cancer patients to believe that doing those things has been proven to improve their outcome. Because it has not.” In her review at the conference, Goodwin explained some of the fascinating insights into physiology and metabolism that lead to a suggestion that changing metabolic factors by lifestyle is an approach to cancer management that could be fruitful—the biology linking obesity and physical activity to breast cancer was “pretty strong,” she said. “People who are overweight or obese have more adipose tissue. That adipose tissue has increased levels of inflammation and inflammatory cells. It secretes a number of compounds that can stimulate breast cancer growth and metastasis, and it's also associated with a change [of] physiology—higher insulin resistance, insulin, and glucose levels—insulin is a growth factor in breast cancer,” she stated. Because glucose can stimulate the growth of breast cancer even within the normal physiologic range, researchers have good evidence there is a biologic basis for its association with the disease. “What we don't know is whether changing it will change the outcome. It may be that breast cancers that develop in overweight and obese women are biologically more aggressive than those that develop in normal-weight women. And we may not be able to change that biological aggressiveness,” Goodwin noted. It was important to try to get phase III trials and high-level evidence showing that changing lifestyle would improve outcomes. “We don't want to be in the situation where women feel guilty that they're overweight and obese or physically inactive, and that they've caused a breast cancer recurrence. We're not there yet,” she explained. Risk Levels When asked for her summary of the most up-to-date knowledge of cancer risks from high body mass, Goodwin explained there was a 50-70 percent higher relative risk of postmenopausal hormone receptor-positive breast cancer and premenopausal triple negative breast cancer among women who are obese or overweight as compared with their contemporaries with BMI in the recommended range. “They also have about a one-third higher risk of recurrence once breast cancer is diagnosed,” she said. Necrotic Adipocytes Goodwin discussed evidence about mechanisms involving the interaction of adipose tissue with cancer. Specifically, she described the role of necrotic adipocytes that she noted were more prevalent in obese women. “As the fat cell dies, it attracts inflammatory cells. And those inflammatory cells secrete cytokines that can actually change the microenvironment of the tumor—promoting growth, invasion, and metastasis,” she said. When asked if there was a link between inflammation and mechanisms involved in causing or promoting breast cancer, Goodwin believed there was. “But we are not sure that's the primary factor mediating the obesity/cancer link or whether it's related to the insulin, glucose, and some of the other factors present in an obese individual as well.” Fatness or Fitness? When discussing whether the primary influence on factors causing breast cancer or promoting recurrence was high BMI or a lack of physical fitness, Goodwin explained it was hard to separate the two. “Physical activity by itself has been associated with lower breast cancer risk and better breast cancer outcomes. [But] there's always a correlation between physical activity and body size. And even though you try and tease it out, individuals [who] are physically active are more likely to have a lower BMI,” she noted. “But independent of BMI, physical activity changes some of those same factors that seem to be associated with the obesity/breast cancer link.” Insulin Glucose metabolism and insulin were also potential players in breast cancer growth, development, or recurrence, said Goodwin. “Whether it's diabetes or pre-diabetes, insulin is higher during the pre-diabetes phase and it tends to fall after diabetes has been diagnosed. Glucose has the opposite pattern. Together they seem to make a contribution, and I think we're not going to find one biologic responsible for this relationship,” she explained, adding that other factors could be involved. “I think we're going to find that multiple [factors] have additive effects—some more important in some types of breast cancer and some more important in other types of breast cancer.” While Goodwin acknowledged the connection between body mass, physical activity, and breast cancer remained controversial, there were two messages: Healthy women had good evidence of an association—though not necessarily causative—of high BMI and physical inactivity with breast cancer initiation. And patients with cancer could be increasingly confident that reducing body mass and increasing physical activity would add cancer inhibition to the many other health benefits this would bring. Peter M. Goodwin is a contributing writer.

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