Poor metabolic health increases post-menopausal breast cancer risk

Postmenopausal women who are metabolically unhealthy have a higher risk of breast cancer compared with metabolically healthy women, a study has found.

Metabolic health refers to how the body processes nutrients such as glucose, and can be measured according to the levels of the hormone insulin. Obesity is strongly associated with poor metabolic health, but the new study found that poor metabolic health was a risk factor for breast cancer in both overweight and normal-weight postmenopausal women.

The study was a collaborative project between Dr Marc Gunter from the School of Public Health at Imperial College London and Dr Howard Strickler, Professor of Epidemiology at Albert Einstein College of Medicine, New York City, and colleagues at multiple other institutions. The findings are published in Cancer Research, a journal of the American Association for Cancer Research.

Given that being overweight or obese significantly increases an individual's risk of being metabolically unhealthy, it remains important that we all keep a healthy weight throughout life, says Dr Marc Gunter, School of Public Health.
''Obesity is a significant risk factor for a number of types of cancer including postmenopausal breast cancer. ''Most, but not all, individuals 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. 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. However, given that being overweight or obese significantly increases an individual's risk of being metabolically unhealthy, it remains important that we all keep a healthy weight throughout life.''

The researchers analysed data from 3,327 non-diabetic women enrolled in the Women's Health Initiative, 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 enrolment, as was a sample of fasting blood. Women with a BMI at enrolment of 25 or more were classed as overweight. Metabolic health was assessed using two measures: fasting insulin levels and an assessment for quantifying insulin resistance.

The researchers found that women who were overweight and insulin-resistant had an 84 per cent 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 Dr 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 awarded to Dr Strickler. The WHI programme is funded by the National Heart, Lung, and Blood Institute.