Exploring the prediction performance for breast cancer risk based on volumetric mammographic density at different thresholds

Background: The percentage of mammographic dense tissue (PD) defined by pixel value threshold is a well-established risk factor for breast cancer. Recently there has been some evidence to suggest that an increased threshold based on visual assessment could improve risk prediction. It is unknown, however, whether this also applies to volumetric density using digital raw mammograms.
Method: Two case-control studies nested within a screening cohort (age 46-73y) from Manchester UK were used. In the first study (317 cases and 947 controls) cases were detected at the first screen; whereas in the second study (318 cases and 935 controls), cases were diagnosed after the initial mammogram. Volpara software was used to estimate dense tissue height at each pixel point, and from these, volumetric and area based PD were computed at a range of thresholds. Volumetric and area based PDs were evaluated using conditional logistic regression, and their predictive ability was assessed using the Akaike information criterion (AIC) and matched concordance index (mC).
Results: The best performing volumetric PD was based on a threshold of 5mm of dense tissue height (which we refer to as VPD5), and the best area PD was at a threshold level of 6mm (which we refer to as APD6), using pooled data, as well as in both studies separately. VPD5 showed a modest improvement in prediction performance compared to the original volumetric PD by Volpara with ΔAIC=5.90 for the pooled data. APD6, on the other hand, shows much stronger evidence for better prediction performance, with ΔAIC=14.52 for the pooled data, and mC increased slightly from 0.567 to 0.577.
Conclusion: These results suggest that imposing a 5mm threshold on dense tissue height for volumetric PD could result in better prediction of cancer risk. There is stronger evidence that area-based density with a 6mm threshold gives better prediction than the original volumetric density metric.