"Abstract

Background

Much of the existing literature reporting associations of breast density with breast cancer risk has evaluated the density of the entire breast. However, density is not homogeneously distributed throughout the breast, and tumors are more likely to arise in areas of dense tissue. This study describes novel measures of local breast density and evaluates their association with participant characteristics and risk of breast cancer.

Methods

Among a cohort of women aged 40–65 years who underwent image-guided breast biopsy following an abnormal mammogram from 2007 to 2010 (n = 808), absolute fibroglandular volume (FGV, cm³) and percentage fibroglandular volume (%FGV) of the entire breast (global) and local to the biopsy site (lesional, perilesional) were assessed from pre-biopsy raw digital mammograms using Volpara® software. Associations of participant characteristics with density measures were evaluated using multivariable linear regression models. Associations of density measures with prevalent (baseline) breast cancer and risk of incident (during 10-years of follow-up) breast cancer were evaluated using multivariable logistic and Cox proportional hazard regression models respectively, adjusted for age at mammogram, body mass index, reason for mammogram and self-reported lump prior to mammogram.

Results

Global and local density measures shared similar patterns of associations with participant characteristics. %FGV was not associated with prevalent or risk of incident breast cancer. However, absolute FGV was positively associated with prevalent breast cancer (n = 177 cases; odds ratio (OR) per 0.25 standard deviation (SD) increase for global FGV: OR 2.74, 95% confidence interval (CI) 1.07–7.00; lesional FGV: OR 1.43, 95% CI 1.16–1.76; perilesional FGV: OR 1.11, 95% CI 1.01–1.23). Additionally, local absolute FGV was associated with increased risk of incident breast cancer (n = 31 cases) during follow-up, with a hazard ratio (HR) per 0.25 SD increase for lesional FGV of 2.05, 95% CI 1.53–2.76 and for perilesional FGV of 1.42, 95% CI 1.14–1.77.

Conclusion

Among women biopsied following an abnormal mammogram, higher global and local absolute FGV were associated with prevalent breast cancer. Additionally, elevated absolute FGV local to the biopsy site was associated with increased risk of breast cancer during follow-up. These findings may assist with risk stratification of women undergoing diagnostic breast biopsy."