How can we identify women at risk for a masked cancer, who may benefit from supplemental screening?

PURPOSE The sensitivity of mammograms is low for women with dense breasts, since cancers may be masked by dense tissue. In this study, we investigate methods to identify women with density patterns associated with a high masking risk. Three methods based on quantitative volumetric breast density analysis are compared to an area based density measure. METHOD AND MATERIALS We used the last negative screening mammograms of 87 women who subsequently presented an interval cancer (IC) and, as controls, 870 randomly selected normal screening exams from women without cancer. Volumetric breast density maps (VBDMs) were computed using software provided by Matakina (Wellington, New Zealand). These maps provide dense tissue thickness for each pixel location. We used the VBDMs to compute three masking measures: 1) Volume of glandular tissue (VGT), 2) Percent dense volume (PDV), and 3) Percent area where dense tissue thickness exceeds 1cm (PA1). In addition, we determined percentage dense area (PDA) after classifying pixels automatically in dense and nondense classes (random forest classifier). Methods were applied to MLO views and averaged per exam. For each method, we selected cases with the highest masking measure (by thresholding) and computed the fraction of ICs as a function of the fraction of controls selected. We used the Volpara Density Grade (VDG, threshold on PDV) to distinguish women with nondense breasts from dense breasts (VDG3+4). In practice women with dense breasts are offered supplemental screening. We determined the fraction of controls corresponding to this categorization, and determined sensitivity of our masking measures to select women with masked cancers. RESULTS Using VDG, 38% of the controls have dense breasts. When offering 38% of the women supplemental screening, 55%, 66%, 71% and 60% of the women with IC would be included using VGT, PDV, PA1 and PDA respectively. The sensitivity of PA1 was significantly higher compared to VGT and PDA (p-value <0.05). CONCLUSION Measures based on volumetric density maps are a promising tool to identify women with a high risk for a masked cancer. Novel masking risk measures have a higher sensitivity than often used measures such as percent dense volume and area. CLINICAL RELEVANCE/APPLICATION When offering supplemental screening to women with a high risk for masked cancer, the response of this group should be as high as possible to make supplemental screening feasible and cost efficient.