Assessing the usefulness of a novel MRI-based breast density estimation algorithm in a cohort of women at high genetic risk of breast cancer: the UK MARIBS study

Abstract

Introduction: Mammographic breast density is one of the strongest known risk factors for breast cancer. We present a novel technique for estimating breast density based on 3D T1-weighted Magnetic Resonance Imaging (MRI) and evaluate its performance, including for breast cancer risk prediction, relative to two standard mammographic density-estimation methods.

Methods: The analyses were based on MRI (n = 655) and mammography (n = 607) images obtained in the course of the UK multicentre magnetic resonance imaging breast screening (MARIBS) study of asymptomatic women aged 31 to 49 years who were at high genetic risk of breast cancer. The MRI percent and absolute dense volumes were estimated using our novel algorithm (MRIBview) while mammographic percent and absolute dense area were estimated using the Cumulus thresholding algorithm and also using a 21-point Visual Assessment scale for one medio-lateral oblique image per woman. We assessed the relationships of the MRI and mammographic measures to one another, to standard anthropometric and hormonal factors, to BRCA1/2 genetic status, and to breast cancer risk (60 cases) using linear and Poisson regression.

Results: MRI percent dense volume is well correlated with mammographic percent dense area (R = 0.76) but overall gives estimates 8.1 percentage points lower (P < 0.0001). Both show strong associations with established anthropometric and hormonal factors. Mammographic percent dense area, and to a lesser extent MRI percent dense volume were lower in BRCA1 carriers (P = 0.001, P = 0.010 respectively) but there was no association with BRCA2 carrier status. The study was underpowered to detect expected associations between percent density and breast cancer, but women with absolute MRI dense volume in the upper half of the distribution had double the risk of those in the lower half (P = 0.009).

Conclusions: The MRIBview estimates of volumetric breast density are highly correlated with mammographic dense area but are not equivalent measures; the MRI absolute dense volume shows potential as a predictor of breast cancer risk that merits further investigation.

Figure 1

Relationship between MRI percentage dense volume and Cumulus percentage dense area (n = 509). The least-squares best-fit lines for women with cumulus percent dense areas < 30% and ≥ 30% are shown in grey.

Figure 2

Age-adjusted means and 95% confidence intervals for MRI percent dense volume, Cumulus percent dense area and visual assessment percent dense area by BRCA1/BRCA2 genetic status. P-values are for the comparisons with the group of women with uninformative BRCA1/2 genetic test results, as assessed by linear regression (P-values further adjusted for BMI and parity are given in parentheses). Arithmetic means are presented for the Cumulus and Visual measurements; geometric means are shown for the MRI measure (for which the regression analyses were based on log-transformed values). Box areas are proportional to sample size.

Figure 3

Age-adjusted means and 95% confidence intervals for MRI absolute dense volume and Cumulus absolute dense volume by BRCA1/BRCA2 genetic status. P-values are for the comparisons with the group of women with uninformative BRCA1/2 genetic test results, as assessed by linear regression (P-values further adjusted for BMI and parity are given in parentheses). Arithmetic means are presented for the Cumulus measurement; geometric means are shown for the MRI measure (for which the regression analyses were based on log-transformed values). Box areas are proportional to sample size.