Beyond Breast Cancer: Mammographic Features and Mortality Risk in a Population of Healthy Women

Rachel A Murphy,Stephen B Kritchevsky,Tamara B Harris,Catherine Schairer,Mark E Sherman,Jingzhong Ding,Gretchen L Gierach,Celia Byrne,Thomas C Register,Olivia Fletcher

doi:10.1371/journal.pone.0078722

Abstract

BackgroundBreast fibroglandular (dense) tissue is a risk factor for breast cancer. Beyond breast cancer, little is known regarding the prognostic significance of mammographic features.MethodsWe evaluated relationships between nondense (fatty) breast area and dense area with all-cause mortality in 4,245 initially healthy women from the Breast Cancer Detection Demonstration Project; 1,361 died during a mean follow-up of 28.2 years. Dense area and total breast area were assessed using planimeter measurements from screening mammograms. Percent density reflects dense area relative to breast area and nondense area was calculated as the difference between total breast area and dense area. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by Cox proportional hazards regression.ResultsIn age-adjusted models, greater nondense and total breast area were associated with increased risk of death (HR 1.17, 95% CI 1.10-1.24 and HR 1.13, 95% CI 1.06-1.19, per SD difference) while greater dense area and percent density were associated with lower risk of death (HR 0.91, 95% CI 0.86-0.95 and HR 0.87, 95% CI 0.83-0.92, per SD difference). Associations were not attenuated with adjustment for race, education, mammogram type (x-ray or xerogram), smoking status, diabetes and heart disease. With additional adjustment for body mass index, associations were diminished for all features but remained statistically significant for dense area (HR 0.94, 95% CI 0.89-0.99, per SD difference) and percent density (HR 0.93, 95% CI 0.87-0.98, per SD difference).ConclusionsThese data indicate that dense area and percent density may relate to survival in healthy women and suggest the potential utility of mammograms beyond prediction of breast cancer risk.

Highlights

Tissue density, a reflection of the physical and biochemical composition of the tissue, can be estimated from the Hounsfield Unit of computed tomography images
Data was derived from the Breast Cancer Detection Demonstration Project (BCDDP), a study sponsored by the National Cancer Institute and the American Cancer Society
We focused on healthy women because the primary aim of this analysis was to determine whether mammographic measures are associated with mortality risk beyond breast cancer

Summary

Introduction

A reflection of the physical and biochemical composition of the tissue, can be estimated from the Hounsfield Unit of computed tomography images. Low skeletal muscle density is associated with insulin resistance and type 2 diabetes [3,4] as well as increased mortality risk [5], fracture [6]. Results: In age-adjusted models, greater nondense and total breast area were associated with increased risk of death (HR 1.17, 95% CI 1.10-1.24 and HR 1.13, 95% CI 1.06-1.19, per SD difference) while greater dense area and percent density were associated with lower risk of death (HR 0.91, 95% CI 0.86-0.95 and HR 0.87, 95% CI 0.83-0.92, per SD difference). Conclusions: These data indicate that dense area and percent density may relate to survival in healthy women and suggest the potential utility of mammograms beyond prediction of breast cancer risk

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