Poor metabolic health increases risk for postmenopausal breast cancer irrespective of BMI

Postmenopausal women who were metabolically unhealthy, as assessed by insulin abnormalities, were at increased risk for breast cancer compared with their metabolically healthy counterparts, according to a study published in Cancer Research (2015; doi: 10.1158/0008-5472.CAN-14-2317). This was the case for both overweight and normal-weight women.

Obesity is a significant risk factor for a number of types of cancer including postmenopausal breast cancer,” said Marc J. Gunter, PhD, associate professor of cancer epidemiology and prevention in the Department of Epidemiology and Biostatistics at Imperial College London's School of Public Health in the United Kingdom. “Most, but not all, [persons] who are obese have metabolic abnormalities including high levels of fasting insulin and insulin resistance, which means that their bodies produce the hormone insulin but do not use it effectively.

“We found that postmenopausal women who were overweight or obese and metabolically unhealthy were at increased risk for breast cancer, but their metabolically healthy counterparts were not,” Gunter continued. “We also found that postmenopausal women who were lean but metabolically unhealthy were at similarly increased risk for the disease.

“These results suggest that metabolic health evaluated by, for example, insulin resistance, might be a better predictor of breast cancer risk than being overweight or obese,” said Gunter. “However, given that being overweight or obese significantly increases [a person's] risk of being metabolically unhealthy, it remains important that we all keep a healthy weight throughout life.”

Gunter and colleagues analyzed data from 3,327 nondiabetic women enrolled in the Women's Health Initiative (WHI), a long-term study to investigate the most common causes of death, disability, and poor quality of life in postmenopausal women. Among this subcohort of women with available data on insulin resistance and body mass index (BMI), 497 received a breast cancer diagnosis over a mean of 8.2 years of follow-up.

Information on height and weight was collected at enrollment, as was a sample of fasting blood. Women with a BMI of 25 kg/m2 or higher at enrollment were classed as overweight. Metabolic health was assessed using two measures: fasting insulin levels and the homeostatic model assessment (HOMA-IR) method for quantifying insulin resistance.

The researchers found that women who were overweight and insulin-resistant had an 84% greater risk of breast cancer than women who were overweight but not insulin-resistant. When using fasting insulin levels to assess metabolic health, breast cancer risk more than doubled for those women who were overweight and had high fasting insulin levels. Further, breast cancer risk was twofold greater for women who were normal weight and had high fasting insulin levels, compared with those who were normal weight and had normal fasting insulin levels.

Breast cancer risk was no different for overweight and normal-weight women who were metabolically healthy by both measures of metabolic health.

“Our data suggest that insulin resistance may be a significant factor in the development of breast cancer, irrespective of whether a woman is overweight or normal weight,” said Gunter. “However, we need to conduct further larger-scale studies, preferably ones that allow us to follow a woman's metabolic health over time, to better understand this and to verify our current findings.”

The study was supported by funds from the National Cancer Institute. The WHI program is funded by the National Heart, Lung, and Blood Institute. Gunter declares no conflicts of interest.

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