Increased breast tissue receptor activator of nuclear factor-κB ligand (RANKL) gene expression is associated with higher mammographic density in premenopausal women.

Adetunji T Toriola,Jingqin Luo,Catherine M Appleton,Christopher A Maher,Ha X Dang,Graham A Colditz,Ian S Hagemann

doi:10.18632/oncotarget.17909

Adetunji T Toriola, Jingqin Luo + Show 5 more

Open Access

https://doi.org/10.18632/oncotarget.17909

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Abstract

Increased mammographic breast density is associated with a 4–6-fold increased risk of breast cancer, yet lifestyle factors that can reduce dense breasts are yet to be identified, and viable prevention strategies to reduce breast density-associated breast cancer development are yet to be developed. We investigated the associations of breast tissue receptor activator of nuclear factor-κB (RANK) pathway gene expression with mammographic density in 48 premenopausal women, with no previous history of cancer. Gene expression levels were measured in total RNA isolated from formalin-fixed paraffin-embedded breast tissue samples, using the NanoString nCounter platform. Mammographic density was classified based on the American College of Radiology Breast Imaging Reporting and Data (BI-RADS). Linear regression was used to evaluate associations between gene expression and mammographic density. The mean age of participants was 44.4 years. Women with higher breast tissue RANKL (TNFSF11) (p-value = 0.0076), and TNF (p-value = 0.007) gene expression had higher mammographic density. Our finding provides mechanistic support for a breast cancer chemoprevention trial with a RANKL inhibitor among high-risk premenopausal women with dense breasts.

Highlights

Increased mammographic breast density is associated with a 4–6-fold increased risk of breast cancer [1,2,3]
We investigated the associations of breast tissue receptor activator of nuclear factor-κB (RANK) pathway gene expression with mammographic density in 48 premenopausal women, with no previous history of cancer
Findings were similar in sensitivity analyses (P-value for RANK ligand (RANKL) gene expression was 0.012) where we re-categorized the women into lower mammographic density and higher mammographic density

Summary

Introduction

Increased mammographic breast density is associated with a 4–6-fold increased risk of breast cancer [1,2,3]. Each 1% increase in percent mammographic density is associated with a 3% increase in breast cancer risk among women using estrogen plus progestin [1]. Estimates of attributable risk suggest that having dense breasts may account for 28–33% of breast cancer cases [4]. 2.4 million premenopausal women in the United States have extremely dense breasts [5]. Providing targeted prevention to these women could have a major impact on reducing breast cancer incidence. Lifestyle factors that can reduce dense breasts are yet to be identified, and viable prevention strategies to reduce mammographic breast density-associated breast cancer development are yet to be developed

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