The association between DXA-derived body fat measures and breast cancer risk among postmenopausal women in the Women's Health Initiative.

Rhonda S Arthur,Andrew J Dannenberg,Thomas E Rohan,Dorothy S Lane,Xiaonan Xue,Kathy Pan,Marian L Neuhouser,Gloria Y F Ho,Hailey Banack,Michael Simon,Juhua Luo,Aladdin H Shadyab,Rowan T Chlebowski,Sylvia Wassertheil‐Smoller,Victor Kamensky,Kerryn W Reding

doi:10.1002/cam4.2690

Abstract

BackgroundMost studies demonstrating an association between excess adiposity and postmenopausal breast cancer have used anthropometric measures, particularly body mass index (BMI). However, more direct body fat measures may more accurately determine the relationship between body fat distribution and breast cancer risk.MethodsCox proportional hazards regression models were created to examine the associations of dual‐energy x‐ray absorptiometry (DXA) body fat measures (at baseline and during follow‐up) with breast cancer risk among 10 931 postmenopausal women from the Women's Health Initiative cohort. A total of 639 incident invasive breast cancer cases (including 484 estrogen receptor positive (ER+) cases) were ascertained after a median follow‐up of 15.0 years.ResultsExcess whole body fat mass and trunk fat mass were positively associated with risk invasive breast cancer risk. These associations persisted even after additional adjustment for standard anthropometric measures. In time‐dependent analyses, we observed that both whole body fat mass and trunk fat mass, in the highest versus lowest category, were associated with a doubling of risk of invasive breast cancer overall (HR: 2.17; 95% CI: 1.54‐3.05 and 2.20; 1.55‐3.14, respectively) and of ER+ breast cancer (2.05; 1.37‐3.05 and 2.03; 1.34‐3.07, respectively). The remaining DXA measures were also positively associated with breast cancer risk in baseline and time‐dependent analyses.ConclusionThese findings suggest that DXA‐derived body fat measures are positively associated with breast cancer risk after adjustment for BMI and other conventional breast cancer risk factors.

Highlights

Among women with trunk fat mass in the highest octile, mean levels of body mass index (BMI), waist circumference (WC), and WHR were highest while mean physical activity level and alcohol intake were lowest
Whole body fat mass, trunk fat mass, and the body fat indices in the highest octile had more than a doubling of the risk of invasive breast cancer compared to women in the lowest octile (HR: 2.13, 95% confidence intervals (CIs): 1.52-2.98; 2.58, 1.83-3.65; 2.14, 1.53-3.01, and 2.17, 1.523.07, respectively) (Table 2)
The multivariable models demonstrated positive associations of all of the anthropometric measures with risk of invasive breast cancer overall and with ER+ breast cancer, but these associations did not persist after further adjustment for whole body fat mass or trunk fat mass (Tables S1-S2)

Summary

Introduction

Excess adiposity is believed to contribute to carcinogenesis through several mechanisms, including chronic inflammation, hyperinsulinemia, elevated leptin and reduced adiponectin levels, hyperlipidemia and abnormal sex steroid hormone metabolism.[1,2] The preponderance of epidemiologic studies examining the association of body fat with risk of breast cancer (including hormone receptor-positive breast cancer) have used body mass index (BMI) as the exposure of interest.[3,4,5,6,7,8] These studies have provided consistent evidence to support a role for excess adiposity, as defined by having a BMI >25.0 kg/m2 (overweight/obesity), in the development of breast cancer among postmenopausal women.[3,4,5,6,7,8]As a measure of adiposity, BMI is limited, in that it does not truly reflect one's body fat distribution,[9] and, may not precisely estimate breast cancer risk among persons with excess adiposity. In an attempt to better capture the influence of body fat distribution on risk of breast cancer, several epidemiological studies have investigated the associations of waist circumference (WC) and waist-to-hip-ratio (WHR),[4,8,10,11] indicators of central adiposity, with risk of postmenopausal breast cancer In most studies, both measures have been positively associated with risk,[4,8,10,12] and some studies have suggested that these measures may better predict the risk of postmenopausal breast cancer than BMI.[4,8] BMI fails to adequately account for differences in metabolic phenotypes among persons within the same BMI category.[13,14,15] Consistent with these limitations, some women with normal BMI have enlarged adipocytes and elevated levels of leptin, suggestive of a hyperadipose state.[16]. In time-dependent analyses, Cancer Medicine. 2020;9:1581–1599.

Results

Discussion

Conclusion