Abstract

Abstract Background: Obesity is an established risk factor for postmenopausal breast cancer and is associated with poor outcomes. Accumulating evidence suggests crown-like structures in the breast adipose tissue (CLS-B), a marker of local inflammation, play a role in explaining the obesity-breast cancer association. However, it is unknown whether breast tissue composition (i.e., the amount of fibroglandular tissue in the breast relative to fat) is related to CLS-B. Objective: We evaluated whether breast tissue composition, as reflected by mammographic breast density, is associated with breast adipose tissue inflammation, as indicated by the presence of CLS-B, and whether the combination of breast density and obesity increases the presence of CLS-B among newly diagnosed breast cancer patients. Methods: We examined the presence of CLS-B, detected by CD68 immunohistochemistry, in breast adipose tissue obtained via mastectomy from a quadrant uninvolved by tumor among 254 women with stage I–III breast cancer treated at Emory University Hospitals (2007–2012). Patient characteristics, including mammographic breast density (assessed on a mammogram up to 5 years before breast surgery) and body mass index (BMI) at diagnosis, were abstracted from electronic medical records. Mammographic density was assessed using the Breast Imaging Reporting and Data System (BI-RADS) density classification (1=almost entirely fat; 2=scattered fibroglandular densities; 3=heterogeneously dense; and 4=extremely dense); density was further categorized as fatty (BI-RADS 1-2) and dense (BI-RADS 3-4). Age and multivariable (MV)-adjusted logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the independent and joint associations of breast density (dense vs. fatty) and obesity (BMI ≥30 kg/m2 vs. < 30 kg/m2) on the presence of CLS-B. Multivariable models adjusted for age (continuous, years) and parity (nulliparous, parous) with mutual adjustment of BMI (continuous, kg/m2) or mammographic breast density (dense, fatty) depending on the model. Results: Women with obesity were more likely to have fatty breasts than women without obesity (52% vs. 27%). Obesity was strongly associated with the presence of CLS-B in age-adjusted (OR=3.11, 95% CI: 1.79, 5.48) and multivariable models (MV-OR=3.70, 95% CI: 1.96, 7.15). There was no apparent association between dense breast tissue and presence of CLS-B in the age-adjusted model (OR=1.04, 95% CI: 0.59, 1.85). After additional adjustment for BMI and parity, we noted that women with dense breasts had higher odds of having CLS-B compared to those with fatty breasts (MV-OR=2.13, 95% CI: 1.07, 4.41). MV-ORs from the joint model (common referent: not obese, fatty breasts) were 1.54 (95% CI: 0.62, 4.24) for women without obesity but with dense breasts, 3.18 (95% CI: 1.15, 9.56) for women with obesity and fatty breasts, and 6.24 (95% CI: 2.23, 19.2) for women with obesity and dense breasts. Conclusions: Our findings suggest that dense rather than fatty breast tissue is associated with breast adipose tissue inflammation among women with breast cancer. Results of the joint analyses suggest obesity is more strongly predictive of CLS-B presence than breast density. However, density may be an important risk factor for CLS-B among women without obesity while patients with obesity and dense breast tissue are the most likely to have CLS-B present. Future studies may consider the mechanisms by which density leads to increased presence of CLS-B. Joint Associations Table Table 1. Joint associations between mammographic breast density (MD) and body mass index (BMI) on the presence of crown-like structures in breast adipose tissue (CLS-B) among 254 women diagnosed with invasive breast cancel (stage I-III) at Emory University between 2007 and 2012 Citation Format: Maret L. Maliniak, Rebecca L. Seidel, Kimberly Bertrand, Lauren E. McCullough. Joint associations of mammographic breast density and obesity on the presence of crown-like structures in the breast adipose tissue of breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P5-03-08.

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