Abstract 3249: Differential impact of body mass index (BMI) on absolute and percent breast density; implications regarding their use as breast cancer risk (BCR) biomarkers
Authors: Schetter Susann , Hartman Terryl , Liao Jason , Richie John P. , Prokopczyk Bogdan , Dubrock Cynthia , Signori Carina , Hamilton Christopher , Demers Laurence M. , El-Bayoumy Karam , Manni Andrea 
Published: May 2015

Abstract
Percent breast density (PBD) is a commonly used biomarker of BCR. However, its use is greatly confounded by the strong influence of non-dense breast tissue on its measurement and factors, such as BMI, which have a direct impact on this non-dense tissue. Consequently, BMI, a potent BCR factor, is actually negatively correlated with PBD. We propose that absolute breast density (ABD), a more direct determinant of BCR which can be easily and accurately measured on a routine basis, is a more accurate and valid biomarker of BCR. To address this issue, we compared the correlation between PBD and ABD with baseline demographics (e.g., age, BMI, waist:hip ratio, reproductive parameters, family history of BC and personal history of breast biopsies) and dietary and physical activity variables (measured using a modified version of the NCI Diet History Questionnaire and the International Physical Activity Questionnaire, respectively) in a group of 169 healthy postmenopausal women enrolled in a chemoprevention trial testing the individual and combined effects of the antiestrogen Raloxifene and the omega-3 preparation Lovaza on BD used as a biomarker of BCR (NCT00723398). A volumetric breast density software (Volpara, Matakina, Wellington, New Zealand) was used for determination of ABD and PBD since it may be superior to the two-dimensional method in predicting BCR. As observed previously, a strong negative correlation between PBD and BMI was observed (Rho = -0.5, P&lt;5e-12) due to the strong positive correlation of BMI with non-dense breast. However, we also observed a strong positive correlation of BMI with ABD (Rho = 0.41, P&lt;2.5e-8), a relationship which is not well established in the literature and supports the use of ABD as a more accurate indicator of BCR. We also observed that correction of PBD by BMI did not frequently provide the same information as ABD, thus further indicating that the latter should be the gold standard for BD measurement. The strong positive association between BMI and ABD implies that even a modest change in BMI (as can be expected with dietary and physical activity manipulations) is likely to obscure the independent effect of an intervention on ABD. We indeed observed that many correlations between dietary variables and ABD did not emerge until adjustment was made for BMI. Our data support the following conclusions: 1) ABD instead of PBD (even after adjustment for BMI) should be used for assessment of BD; 2) based on our novel observation of the strong positive correlation between BMI and ABD, ABD should be adjusted for BMI when testing the influence of an intervention on BD as a biomarker of BCR. (Supported by grant KG081632 from Susan G. Komen for the Cure.)
Citation Format: Susann Schetter, Terryl Hartman, Jason Liao, John P. Richie, Bogdan Prokopczyk, Cynthia Dubrock, Carina Signori, Christopher Hamilton, Laurence M. Demers, Karam El-Bayoumy, Andrea Manni. Differential impact of body mass index (BMI) on absolute and percent breast density; implications regarding their use as breast cancer risk (BCR) biomarkers. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3249. doi:10.1158/1538-7445.AM2014-3249