Elevated levels of body fat in postmenopausal women were associated with an increased risk of invasive breast cancer, despite the presence of a normal body mass index (BMI), according to research published in JAMA Oncology.

A team of US-based investigators conducted a long-term prospective study in an ad hoc secondary analysis of the Women’s Health Initiative (ClincalTrials.gov Identifier, NCT00000611) to determine whether there was a link between elevated body fat level and risk of breast cancer in women with normal BMIs.

Demographic information, medical history, and lifestyle factors were recorded at the start of the analysis and body fat levels of eligible participants were measured with dual-energy x-ray absorptiometry (DXA) at baseline and 1, 3, 6, and 9 years. Review of medical records confirmed invasive breast cancer cases.

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A total of 3460 postmenopausal women with BMI varying between 18.5 mg/k2 and 24.9 mg/k2 underwent DXA measurements with a median follow-up of 16 years (range, 9-20 y); 182 breast cancer cases were reported and 146 were estrogen-receptor positive. For the highest quartile of whole-body fat and trunk fat mass, multivariable-adjusted hazard ratios for risk of invasive breast cancer were 1.89 and 1.88, respectively.

For estrogen-receptor positive breast cancer, adjusted hazard ratios were 2.21 and 1.98 for whole-body fat and trunk fat mass, respectively.

Women in the highest quartile of trunk fat mass had elevated circulating levels of insulin, C-reactive protein, interleukin 6, leptin, and triglycerides, and lower levels of high-density lipoprotein cholesterol and sex hormone-binding globulin.

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“When considering an individual’s health, physicians generally assess BMI by absolute categorical levels,” the authors wrote. “As such, increased adiposity in an individual categorized as having normal BMI is likely to remain clinically unrecognized,” they continued. “Future studies are needed to determine whether interventions that reduce fat mass, such as diet and exercise programs, or medications (including aromatase inhibitors), might lower the elevated risk of breast cancer in this population with normal BMI.”


Iyengar NM, Arthur R, Manson JE, et al. Association of body fat and risk of breast cancer in postmenopausal women with normal body mass index: a secondary analysis of a randomized clinical trial and observational study [published online December 6, 2018]. JAMA Oncol. doi: 10.1001/jamaoncol.2018.5327