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Mammographic Features and Subsequent Risk of Breast Cancer: A Comparison of Qualitative and Quantitative Evaluations in the Guernsey Prospective Studies

Mammographic features are known to be associated with breast cancer but the magnitude of the effect differs markedly from study to study. Methods to assess mammographic features range from subjective qualitative classifications to computer-automated quantitative measures. We used data from the UK Guernsey prospective studies to examine the relative value of these methods in predicting breast cancer risk. In all, 3,211 women ages ≥35 years who had a mammogram taken in 1986 to 1989 were followed-up to the end of October 2003, with 111 developing breast cancer during this period. Mammograms were classified using the subjective qualitative Wolfe classification and several quantitative mammographic features measured using computer-based techniques. Breast cancer risk was positively associated with high-grade Wolfe classification, percent breast density and area of dense tissue, and negatively associated with area of lucent tissue, fractal dimension, and lacunarity. Inclusion of the quantitative measures in the same model identified area of dense tissue and lacunarity as the best predictors of breast cancer, with risk increasing by 59% [95% confidence interval (95% CI), 29-94%] per SD increase in total area of dense tissue but declining by 39% (95% CI, 53-22%) per SD increase in lacunarity, after adjusting for each other and for other confounders. Comparison of models that included both the qualitative Wolfe classification and these two quantitative measures to models that included either the qualitative or the two quantitative variables showed that they all made significant contributions to prediction of breast cancer risk. These findings indicate that breast cancer risk is affected not only by the amount of mammographic density but also by the degree of heterogeneity of the parenchymal pattern and, presumably, by other features captured by the Wolfe classification.