We constructed two breast cancer risk estimation models based on the NMD format descriptors to aid radiologists in breast cancer diagnosis. Our results show that the combination of a logistic regression model and radiologists’ assessment performs better than either alone in discriminating between benign and malignant lesions. The ROC curve of Model-1, which only includes demographic factors and mammography observations, overlaps and intersects with the radiologists at certain points in the curve, showing that one is not always better than the other. On the other hand, Model-2, which also includes radiologists’ impression, clearly dominates the other two ROC curves indicating better sensitivity and specificity at all threshold levels. Adding radiologists’ overall impression (BI-RADS category) in Model-2, we could identify more malignant lesions and avoid false positive cases as compared to the performance of Model-1 and radiologists alone.
Our computer model is different in various ways when compared to the existing mammography computer models. The existing models in literature can be categorized in the following ways: (1) for detecting abnormalities present on the mammograms, (2) for estimating the risk of breast cancer based on the mammographic observations and patient demographic information, and (3) for predicting the risk of breast cancer to identify high risk population. The first category of models is used to identify abnormalities on the mammograms, whereas, our model provides the interpretation of mammography observations after they are identified. The models in the second category, in which we classify our model, have used (a) suspicious findings recommended for biopsy for training and evaluation and/or (b) biopsy results as the reference standard. For example, one study constructed a Bayesian Network using 38 BI-RADS descriptors and by training the model on 111 biopsies performed on suspicious calcifications, they found Az
= 0.919 [37
]. Another study developed linear discriminant analysis and artificial neural network models using a combination of mammographic and sonographic features, and found Az
= 0.92 [16
]. In contrast, our computer model was trained and evaluated on consecutive mammography examinations and used registry match as the reference standard. The third category of models (risk prediction models) have been built using consecutive cases, but they only included demographic factors and breast density in their model [19
]; and cannot be directly compared to our model. In addition, our model differs from these risk prediction models by estimating the risk of cancer at a single time point (i.e. at the time of mammography) instead of risk prediction over an interval in the future (e.g. over the next 5 years). In contrast to their findings, our model did not find breast density as a significant predictor of breast cancer. This could be due to the fact that the risk of breast cancer is explained by more informative mammographic descriptors in our logistic regression model. Our model reinforces previously known mammography predictors of breast cancer – irregular mass shape, ill-defined and spiculated mass margins, fine linear calcifications, and clustered, linear and segmental calcification distributions [38
]. In addition, we found increasing mass size and high mass density as significant predictors, which have not been demonstrated in the literature to our knowledge. Of note, our results reflect a single practice and must be viewed with some caution with respect to their generalizability as significant variability has been observed in interpretive performance of screening and diagnostic mammography [5
We developed two risk estimation models by excluding (Model-1) and including (Model-2) BI-RADS assessment codes. Though Model-2 performed significantly better than Model-1 in discriminating between benign and malignant lesions, Model-2 may have weaknesses as a stand-alone risk estimation tool if the assessed BI-RADS category is incorrect. If the BI-RADS assessment category does not agree with the findings, Model-1 and Model-2 used jointly will show a high level of disagreement in the prediction of breast cancer (as in example case 2) and potentially indicate this error. When the radiologist’s BI-RADS code is correct (i.e. when there is an agreement between the prediction of Model-1 and Model-2), Model-2 would be a better model for breast cancer prediction. In future work, we plan to estimate the level of disagreement between the two models and investigate the possible use of these models as complimentary tools.
Our secondary model (Model-3) showed that the exclusion of the BI-RADS descriptors significantly impairs the performance of the logistic regression model, underscoring the need for the collection of these variables at a clinical practice.
It is common for clinical data sets to contain a substantial number of “missing” data. While complete data is ideally better, it is rarely encountered in the real world. There is no perfect way to handle missing data but there are two possibilities: (1) impute the missing descriptor depending on the fraction of various possible values of the descriptor or (2) assume that the missing descriptor was not observed by radiologists and mark it as “not present”. While building the model, we made the decision to label all of the missing data as “not present”; therefore, while testing/applying the model on a new case the missing descriptors should be treated as “not present”. Our approach to handle missing data is appropriate for mammography data where radiologists often leave the descriptors blank if nothing is observed on the mammogram.
To the best of our knowledge, no prior studies discuss a logistic regression based CADx model incorporating mammography descriptors from consecutive mammograms from a breast imaging practice. The use of logistic regression model has some attractive features when compared with artificial intelligence prediction tools (e.g. artificial neural networks, Bayesian networks, support vector machines). Logistic regression can identify important predictors of breast cancer using odds ratios and generate confidence intervals which provide additional information for decision-making.
Our models’ performance depends on the ability of the radiologists to accurately identify findings on mammograms. Therefore, based on literature, the performance may be higher in facilities where the majority of the mammograms are read by mammography-subspecialists as compared to general radiologists[39
]. However, with appropriate training [40
], general radiologists in combination with the model may approach the accuracy of subspecialty trained mammographers. Decreasing variability in mammography interpretation, one of the underlying motivations of this research, can only be realized with further development of tools such as our model and research to validate accuracy, effectiveness, and generalizability. We consider this work only a first step toward this goal.
We could not compare practice parameters directly with the literature because screening and diagnostic examinations could not be separated for this database. Our prediction Model-2 shows a significant improvement over radiologists’ assessment in classifying abnormalities when built on a mix of screening and diagnostic data. The model’s performance may differ when built separately on screening and diagnostic mammograms. For screening mammograms, the incidence is low and descriptors are less exact due to general imaging protocols, hence may result in less accurate model parameters. In contrast, for diagnostic mammograms, the model parameters may be more accurate since more descriptors can be observed because of additional specialized views. In addition, the performance our existing model may differ when tested on screening and diagnostic mammograms separately. The model may perform better when tested on the diagnostic exams, but worse when tested on the screening exams.
Our risk estimation models are designed to aid radiologists, not act as a substitute. The improvement in the model’s performance by adding BIRADS assessments in this manuscript indeed suggests that the radiologist integration of the imaging findings summarized by the BIRADS assessment categories does augment predictions based on the observed mammographic features. However, the LR model contributes an additional measure of accuracy over and above that provided by the BI-RADS assessment categories as evidenced by improved performance as compared to the radiologists alone.
The objective of our model is to aid decision-making by generating a risk prediction for a single point in time (at mammography). As we were designing the study, we did not want to increase the probability of breast cancer based on future events but only on variables identified at the time of mammography. For this reason, we excluded unmatched BI-RADS 1 cases from our analyses, which represented either undetected cancer (present on the mammogram but not seen) or an interval cancer (not detectable on the mammogram). The inclusion of these cases may have erroneously increased the probability of malignancy by considering future risks rather than making a prediction at a single time point based on mammography features alone. However, the exclusion of these cases may have erroneously decreased the estimated probability of malignancy, given that at least some of the false negative cancers were likely present at the time of the mammogram - especially those in women with dense breasts; which is a limitation of our model.
Our models provide the probability of cancer as the outcome that can be used by radiologists for making appropriate patient management decisions. The use of such models has a potential to reduce the mammography interpretive variability across practices and radiologists. Our models also facilitate shared decision-making by providing probability of cancer, which can be better understood by patients than BI-RADS categories. In the future, we will test our models’ performance on other mammography practices to evaluate their generalizability. We will also include potentially important interaction effects that deserve particular attention. Note that including interaction effects will further improve the performance of our models.
In conclusion, we found that our logistic regression models (Model-1 and Model-2) can effectively discriminate between benign and malignant lesions. Furthermore, we have found that the radiologist alone or the logistic regression model incorporating only mammographic and demographic features (Model-1) are inferior to Model-2 which incorporates the model, the features, and the radiologist’s impression as captured by the BI-RADS assessment categories. Our study supports that further research is needed to define how radiologists and computational models can collaborate, each adding valuable predictive features, experience and training to improve overall performance.