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While the Altocumulus measures of dense area appear to be better predictors of risk, the Cumulus measures of percent dense area might be better predictors of masking.
The intra-class correlation coefficients for the Altocumulus and Cirrocumulus measures of dense area were 0.93 and 0.80 cf. 0.98 for the Cumulus measure [ 19].
Quantitative measures of dense and non-dense breast area and possibly other image factors need to be standardized if they are to be used in clinical practice.
The total breast area was then classified into dense and lucent tissues using an interactive greyscale threshold, from which percent density (100 × dense area/total breast area) and absolute measures of dense and lucent areas were calculated.
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The result is a measure of the total area of the breast and a measure of dense area, which, when subtracted, gives the nondense area.
The use of an absolute rather than relative measure of dense area can reduce or eliminate confounding by BMI (Assi et al, 2012).
In the absence of an established biological gold-standard measure of the quantity of dense tissue in the breast, we evaluated the performance of our MRI-based method via direct comparison with two mammography-based methods and by assessing correlations with known anthropometric and hormonal determinants of breast density.
More recently, measures of the volumetric amount of dense tissue have been proposed as more accurate representations of the underlying fibroglandular tissue content and, as such, potentially better predictors of risk [ 21, 25– 29].
Overall, this may suggest that area and volume density could reflect different aspects of a woman's breast density and parenchymal pattern, with volumetric density measures reflecting the total amount of dense tissue and area-based density being indicative of the extent of the distribution of the dense tissue within the breast, with an increase in either suggesting increased risk.
Of these, compound 4 was selected as a starting point for SAR studies, as it showed acceptable potency in the primary assay measuring inhibition of dense granule release (IC50 = 1 10 μM).
The preferred MD measure for breast cancer risk prediction is debated, although recent studies show that the proportion of dense breast tissue may have a stronger predictive value than the absolute amount of dense tissue, thus suggesting non-dense tissue as a contributing risk factor [ 30, 31].
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