Iyengar NM, et al. - Authors analyzed the relationship between body fat and breast cancer risk in women with normal body mass index (BMI) in this ad hoc secondary analysis of the Women’s Health Initiative clinical trial and observational study cohorts. They noted an association of relatively high body fat levels with an elevated risk of invasive breast cancer and altered levels of circulating metabolic and inflammatory factors in postmenopausal women with normal BMI. An inadequate proxy for the risk of breast cancer in postmenopausal women may be normal BMI categorization.

Methods

• Study participants included postmenopausal women aged 50-79 years, with BMI values ranging from 18.5 to 24.9, who were enrolled October 1, 1993, through December 31, 1998.
• Of these participants, body fat measurements were conducted among 3,460 with dual-energy x-ray absorptiometry (DXA) at 3 US designated centers with follow-up.
• At a median follow-up of 16 years (range, 9-20 years), they ascertained 182 incident breast cancers, of which 146 were estrogen receptor (ER)-positive.
• They completed the follow-up on September 30, 2016, and data from October 1, 1993, through September 30, 2016, were analyzed August 2, 2017, through August 21, 2018.
• They measured the body fat levels at baseline and years 1, 3, 6, and 9 using DXA.
• They collected the information on demographic data, medical history, and lifestyle factors at baseline.
• Central review of medical records by physician adjudicators was done to confirm invasive breast cancers.
• They measured blood analyte levels in subsets of participants.

Results

• Multivariable-adjusted hazard ratios for the risk of invasive breast cancer were 1.89 (95% CI, 1.21-2.95) for the highest quartile of whole-body fat and 1.88 (95% CI, 1.18-2.98) for the highest quartile of trunk fat mass among study participants.
• For ER-positive breast cancer, the corresponding adjusted hazard ratios were 2.21 (95% CI, 1.23-3.67) and 1.98 (95% CI, 1.18-3.31), respectively.
• In time-dependent covariate analyses, similar positive associations were observed for serial DXA measurements.
• Overall, they noted higher circulating levels of insulin, C-reactive protein, interleukin 6, leptin, and triglycerides, whereas levels of high-density lipoprotein cholesterol and sex hormone–binding globulin were lower in those in the uppermost vs lowest quartiles of trunk fat mass.