There is very good evidence that deregulated insulin signaling, which is a feature of pre-diabetes, is associated with certain types of cancer. It’s also very clear that elevated fasting insulin levels are associated with an increased risk of breast cancer as well as a worse prognosis.
Based on emerging data, it’s clear that about 10% of the population really needs a cancer-directed / metabolic syndrome-directed intervention.
BMI is an imprecise measurement for any individual, because it doesn’t discriminate between muscle and fat. If you were to accept today’s definition of up to 25 for normal BMI, there will be an awful lot of people who are told they’re normal because they’re less than 25. But in fact, they’re at increased risk for diseases such as breast cancer and heart disease because they have excess adiposity, despite receiving the label of “normal” by their doctor.
BMI is the parameter that is typically used to categorize patients in large-scale, epidemiologic analyses of obesity and cancer. However, BMI fails to take into account fat distribution, percent body fat, and can be confounded by elevated muscle mass.
According to Rowan Chlebowski, weight loss of 15% or more was associated with a 37% reduction in breast cancer risk. That’s huge. At baseline, 34% of patients were overweight and 25% were obese (Presentation GS5-07, 2017 SABCS). This study probably started a long time ago. Those numbers would be higher now.
If we change body composition, I think we’ll be able to get people through chemotherapy better. And if we do that, then that should have a survival benefit.
Health issues related to metabo-oncology are an enormous problem. There are numerous estimates of the consequences of excess adiposity on the development and progression of cancer, so one can anticipate a tidal wave of new cancers on the horizon. Moreover, for any number of cancers, there’s evidence that excess adiposity is associated with worse outcomes.
In the WINS Study, we were able to show a statistically significant 24-percent reduction in breast-cancer recurrence risk through weight loss. The women went down to about 20 percent of calories from fat, but they were anxious to increase fat intake as soon as the intervention ended. In the primary prevention study, the women went from about 34 percent calories from fat to a little under 25 percent. This appeared to be a sustainable solution because it looks like people could do that through simple substitution.
BMI is not one-size-fits-all. It’s not the most exact way to measure what’s going on. Since there’s quite a large proportion of people in the U.S. who are overweight and obese, there is a growing interest in this area of investigation [metabo-oncology] in terms of cancer research. But it’s still in its infancy, and there is more work to be done.
If you are post-menopausal and have excess adiposity — even though you have a normal BMI — your risk of breast cancer increases. So, it may well be that some of the estimates of the significance of obesity or excess adiposity in the development and progression of cancer actually underestimate the magnitude of the problem.
Postmenopausal women who have a normal BMI, but excess adiposity as defined by DEXA, have about a doubling in their risk for the development of estrogen receptor-positive breast cancer. That indicates BMI is an inadequate proxy for risk of breast cancer.
Based on the epidemiologic evidence, getting anywhere from 60 to 400 minutes of exercise per week has been shown to be associated with significant reductions in the risk of dying from breast cancer.
As opposed to BMI, the key issue, as I see it, is hyperadiposity. For example, elevated visceral fat mass is associated with a variety of negative health outcomes. In particular, insulin resistance downstream of elevated visceral fat can drive tumor growth through elevated levels of circulating insulin. Increased levels of adipose tissue around or adipocytes within particular organs can also contribute to cancer growth via cross-talk with the tumor and the tumor microenvironment.
Diabetes and hyperinsulinemia are risk factors for tumor recurrence, particularly in the breast cancer setting.