Mammographic Density, Estrogen Receptor Status and Other Breast Cancer Tumor Characteristics

The aim of this study was to examine the relationship between mammographic density and histological characteristics of breast tumors within a case-control study population. This study was an expansion of a large size case-control study examining the relationship between breast density and breast cancer risk. Percent and area of breast density was assessed in 370 invasive breast cancer cases and 1904 age-matched controls, using a computer-assisted method. Associations between breast density and estrogen receptor (ER) status, histological grade, histological size, lymph node status, vascular invasion, disease extent, and Nottingham Prognostic Index were evaluated, using logistic regression. Women with 50% or greater mammographic density have a 2.63-fold risk (95% confidence interval [95% CI] = 1.78-3.87; p < 0.001) of developing breast cancer compared to women with less than 10% density. Increase in every category of percentage of breast density is also associated with a 1.45-fold risk in developing ER positive tumors relative to ER negative tumors (odds ratio [OR] = 1.02; 95% CI = 1.00-1.04; p = 0.048), and increase in every quartile of absolute area of density is associated with a 1.48-fold ER positive breast cancer risk [95% CI = 1.06-2.07; p = 0.020]. Furthermore, breast density was found to be associated with specifically ER positivity, invasion as well as invasion with in situ, histological grades 1 and 2, tumor size larger than 1.1 cm, lack of vascular invasion, lymph node positivity and negativity, and NPI less than 4.0. After stratifying the data according to mode of diagnosis, the relationship became slightly stronger in the interval cancer group. Similar results were in observed using percent density and absolute density readings. Mammographic density was a stronger risk factor for ER positive [OR = 2.94; 95% CI = 1.94-4.43; p < 0.001] than ER negative cancers when comparing breasts with greater than 50% dense region to those with less than 10% density. No other tumor characteristic had a significant correlation with breast density. These results suggest that mammographic percent density may be more strongly related to ER positive than ER negative breast cancer, but otherwise is a risk factor for breast cancer independent of other tumor characteristics.