Iyengar NM, et al. - Researchers examined the relationship between body fat and breast cancer risk in a cohort of 3460 postmenopausal women with normal body mass index (BMI) enlisted in the Women’s Health Initiative (WHI) randomized clinical trial and observational study. Findings suggested 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. Normal categorization of BMI in postmenopausal women may be an inadequate proxy for the risk of breast cancer.

Methods

•  This ad hoc secondary analysis of the WHI clinical trial and observational study cohorts was limited to postmenopausal participants with a BMI between 18.5 to 24.9.
• From October 1, 1993, to December 31, 1998, women aged 50 to 79 years were enrolled.
• Of these, 3460 study participants had body fat measurement with dual-energy x-ray absorptiometry (DXA) at 3 US designated centers with follow-up.
• One hundred eighty-two incident breast cancers had been ascertained and 146 were ER positive at a median follow-up of 16 years (range, 9-20 years).
• The follow-up was completed on September 30, 2016, and data from October 1, 1993, through September 30, 2016, was analyzed August 2, 2017, through August 21, 2018.
• Using DXA, body fat levels were measured at baseline and years 1, 3, 6, and 9.
• At baseline, information on demographic data, medical history, and lifestyle factors was collected.
• Invasive breast cancers were confirmed by physician adjudicators through a central review of medical records.
• In subsets of participants, blood analyte levels were measured.

Results

• Among the 3,460 women involved in the analysis (mean [SD] age, 63.6 [7.6] years), 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.
• Researchers found that the corresponding adjusted hazard ratios for ER-positive breast cancer were 2.21 (95% CI, 1.23-3.67) and 1.98 (95% CI, 1.18-3.31).
• Similar positive associations were observed in time-dependent covariate analyses for serial DXA measurements.
• Data reported that circulating levels of insulin, C-reactive protein, interleukin 6, leptin, and triglycerides were higher.
• On the other hand, 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.