High Mammographic Breast Density Is Independent Predictor of Local But Not Distant Recurrence After Lumpectomy and Radiotherapy for Invasive Breast Cancer

Abstract

Biologically meaningful predictors for locoregional recurrence (LRR) in patients undergoing breast-conserving surgery (BCS) and radiotherapy (RT) are lacking. Tissue components, including extracellular matrix, could confer resistance to ionizing radiation. Fibroglandular and extracellular matrix components of breast tissue relative to adipose tissue can be quantified by the mammographic breast density (MBD), the proportion of dense area relative to the total breast area on mammography. We hypothesized that the MBD might be a predictor of LRR after BCS and RT for invasive breast cancer. We conducted a nested case-control study of 136 women with invasive breast cancer who had undergone BCS and RT and had had the MBD ascertained before, or at, diagnosis. Women with known recurrence were matched to women without recurrence by year of diagnosis. The median follow-up was 7.7 years. The percentage of MBD was measured using a computer-based threshold method. Patients with a high MBD (>/=75% density) vs. low (</=25%) were at increased risk of LRR (hazard ratio, 4.30; 95% confidence interval, 0.88-021.0; p = 0.071) but not distant recurrence. In addition, we found a complete inverse correlation between high MBD and obesity (body mass index, >/=30 kg/m(2)). In a multivariate Cox proportional hazards model, patients with MBD in the greatest quartile were at significantly greater risk of LRR (hazard ratio, 6.6; 95% confidence interval, 1.6-27.7; p = 0.01). Obesity without a high MBD also independently predicted for LRR (hazard ratio, 19.3; 95% confidence interval, 4.5-81.7; p < 0.001). The results of our study have shown that a high MBD and obesity are significant independent predictors of LRR after BCS and RT for invasive breast cancer. Additional studies are warranted to validate these findings.