Contralateral Breast Background Parenchymal Enhancement: A Physiologic Marker, not a Predictor of ER Status

Breast MRI, specifically background parenchymal enhancement (BPE), plays a crucial role in evaluating breast cancer risk and tumor biology. BPE, influenced by vascularity, permeability, and hormonal status, reflects the physiological state of the breast tissue. This study investigates the relationship between quantitative BPE in the contralateral, non-tumor breast and estrogen receptor (ER) status in early-stage invasive ductal carcinoma (IDC), alongside factors like age, breast density, and menopausal status. It also compares quantitative BPE to qualitative BI-RADS assessments.

This retrospective study included 233 women with pathologically confirmed early-stage IDC undergoing preoperative breast MRI. BPE was quantitatively assessed using MATLAB-based segmentation techniques, measuring initial, overall, late enhancement, and area under the enhancement curve (AUC). The data were compared to qualitative BI-RADS BPE categories (minimal, mild, moderate, marked). Statistical analyses were performed using Spearman's rank correlation and Kruskal-Wallis tests, with significance set at p<0.05.

Out of 233 patients, 187 (median age 49.6, range 43.1-57.3) had ER+ cancer, while the remaining 46 (median age 52.4, range 46.9-60.6) had early-stage ER- cancer. Significant correlation between quantitative BPE values and qualitative BPE categories was observed; specifically, increasing median values of BPE enhancement curve parameters (p<0.001) and mean values of the top 10% of pixels (p<0.02) were observed across qualitative BPE categories from minimal to marked BPE. Quantitative BPE was independent of breast density (p>0.11), while qualitative BPE was influenced by breast density, with an increase from minimal (median=0.33, IQR=0.21-0.41) compared with marked BPE (median=0.39, IQR=0.28-0.55) (p=0.04). Quantitative BPE values decreased with age and menopausal status (p<0.02). Quantitative BPE was not associated with ER status, even when stratified by age.

The study found that quantitative BPE of the contralateral breast increased across qualitative BI-RADS BPE categories, independent of breast density, and decreased with age and post-menopausal status, but did not distinguish ER+ from ER- cancers. Published literature demonstrates age and hormone-associated effects on BPE, whereas the correlations with molecular subtype, cancer risk, and treatment response are not clear, highlighting its potential and limitations as a biomarker.

While BPE reflects hormonal influences, its role in predicting tumor ER expression in early-stage cancer is limited. However, it provides a reproducible method for assessing breast tissue physiology, with potential utility in evaluating treatment response and hormonal effects. Furthermore, the study also delineates the need for larger, multicenter investigations to explore BPE's potential as a complementary biomarker for breast cancer characterization and treatment response.