Cirrus: An Automated Mammography-Based Measure of Breast Cancer Risk Based on Textural Features

Abstract

Background: We applied machine learning to find a novel breast cancer predictor based on information in a mammogram.

Methods: Using image-processing techniques, we automatically processed 46 158 analog mammograms for 1345 cases and 4235 controls from a cohort and case-control study of Australian women, and a cohort study of Japanese American women, extracting 20 textural features not based on pixel brightness threshold. We used Bayesian lasso regression to create individual- and mammogram-specific measures of breast cancer risk, Cirrus. We trained and tested measures across studies. We fitted Cirrus with conventional mammographic density measures using logistic regression, and computed odds ratios (OR) per standard deviation adjusted for age and body mass index.

Results: Combining studies, almost all textural features were associated with case-control status. The ORs for Cirrus measures trained on one study and tested on another study ranged from 1.56 to 1.78 (all P < 10^-6). For the Cirrus measure derived from combining studies, the OR was 1.90 (95% confidence interval [CI] = 1.73 to 2.09), equivalent to a fourfold interquartile risk ratio, and was little attenuated after adjusting for conventional measures. In contrast, the OR for the conventional measure was 1.34 (95% CI = 1.25 to 1.43), and after adjusting for Cirrus it became 1.16 (95% CI = 1.08 to 1.24; P = 4 × 10^-5).

Conclusions: A fully automated personal risk measure created from combining textural image features performs better at predicting breast cancer risk than conventional mammographic density risk measures, capturing half the risk-predicting ability of the latter measures. In terms of differentiating affected and unaffected women on a population basis, Cirrus could be one of the strongest known risk factors for breast cancer.

Figure 1.

Correlations between the 20 textural features.

Figure 2.

Distribution of the Cirrus measure created on the combined studies, adjusted for age and BMI, for cases (gray line) and controls (dark line). Risk increases with increasing Cirrus. The difference in the mean between cases and controls is equal to the log of the OR per standard deviation, which in turn is linearly related to the area under the receiver operator curve (AUC) in the range of 0.5 to 0.7; see theory and references in the Supplementary Methods (available online). See also Figure 3, which shows the corresponding receiver operator curve.

Figure 3.

Receiver operator curves based on fitting: Cirrus created on the combined studies (continuous line); homogeneity alone (dashed line); and percentage mammographic density (dotted line). The corresponding areas under the receiver operator curves are 0.662, 0.642, and 0.620, respectively.