The combined effect of mammographic texture and density on breast cancer risk: a cohort study

Texture patterns have been shown to improve breast cancer risk segregation in addition to area-based mammographic density. The additional value of texture pattern scores on top of volumetric mammographic density measures in a large screening cohort has never been studied. Volumetric mammographic density and texture pattern scores were assessed automatically for the first available digital mammography (DM) screening examination of 51,400 women (50-75 years of age) participating in the Dutch biennial breast cancer screening program between 2003 and 2011. The texture assessment method was developed in a previous study and validated in the current study. Breast cancer information was obtained from the screening registration system and through linkage with the Netherlands Cancer Registry. All screen-detected breast cancers diagnosed at the first available digital screening examination were excluded. During a median follow-up period of 4.2 (interquartile range (IQR) 2.0-6.2) years, 301 women were diagnosed with breast cancer. The associations between texture pattern scores, volumetric breast density measures and breast cancer risk were determined using Cox proportional hazard analyses. Discriminatory performance was assessed using c-indices. The median age of the women at the time of the first available digital mammography examination was 56 years (IQR 51-63). Texture pattern scores were positively associated with breast cancer risk (hazard ratio (HR) 3.16 (95% CI 2.16-4.62) (p value for trend <0.001), for quartile (Q) 4 compared to Q1). The c-index of texture was 0.61 (95% CI 0.57-0.64). Dense volume and percentage dense volume showed positive associations with breast cancer risk (HR 1.85 (95% CI 1.32-2.59) (p value for trend <0.001) and HR 2.17 (95% CI 1.51-3.12) (p value for trend <0.001), respectively, for Q4 compared to Q1). When adding texture measures to models with dense volume or percentage dense volume, c-indices increased from 0.56 (95% CI 0.53-0.59) to 0.62 (95% CI 0.58-0.65) (p < 0.001) and from 0.58 (95% CI 0.54-0.61) to 0.60 (95% CI 0.57-0.63) (p = 0.054), respectively. Deep-learning-based texture pattern scores, measured automatically on digital mammograms, are associated with breast cancer risk, independently of volumetric mammographic density, and augment the capacity to discriminate between future breast cancer and non-breast cancer cases.