1. 國立雲林科技大學 National Yunlin University of Science and Technology Intelligent Database Systems Lab 1 Self-organizing map for cluster analysis of a breast cancer database Mia K. Markey, Joseph Y. Lo, Georgia D. Tourassi, Carey E. Floyd Jr. Artificial Intelligence in Medicine 27 (2003) 113–127 Advisor : Professor Chung-Chian Hsu Reporter : Wen-Chung Liao 2006/5/17

2. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 2 Outline Motivation Objectives Data Methods Results Discussion Comments

3. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 3 Motivation The decision to biopsy is complicated  breast cancer can present itself in a variety of ways on a mammogram  considerable overlap in the appearance of benign and malignant lesions. Unsupervised learning may provide an alternate avenue to a priori knowledge for identifying subsets in the data that should be handled separately in the development or evaluation of computer-aided diagnosis or detection systems.

4. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 4 Objectives The purpose of this study was to identify and characterize clusters in a heterogeneous breast cancer computer-aided diagnosis database.  Identification of subgroups within the database could help elucidate clinical trends and facilitate future model building.

5. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 5 Data available data:4435  model development: 2258 (982 malignant) 751 suspicious breast lesions at Duke Univ. Med. Center  mammographers described each case using BI-RADS lexicon  each of the cases was read by one of seven readers :six BI- RADS features and the patient age.  260 (35%) were malignant. 501 from Univ. of Penn. Med. Center, 200 (40%) were malignant. 1006 lesions randomly selected from the Digital Database for Screening Mammography, 522 (52%) were malignant.  model validation: 2177  The overall malignancy fraction was 43%.

6. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 6 Methods Self-organizing map  using the SOM toolbox in MATLAB  2-D grid of 4 x 4 neurons, but different configurations were considered.  Features standardization  seven input features, the biopsy outcome was not provided to the SOM Constraint satisfaction neural network (CSNN)  determine the profiles of the clusters  1000 iterations, weights determined by auto-BP  Each category of BI-RADS features corresponded to a binary variable and associated neuron.  the mass margin with its five non-zero categories : five separate neurons  Patient age : five levels (<40, 40 ≦ x< 50, 50 ≦ x<60, 60 ≦ x<70, 70 ≦ )

7. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 7 Methods Back-propagation artificial neural network (BP-ANN)  predict the biopsy outcome from the mammographic findings and patient age.  Single hidden layer of 14 neurons  Logistic activation function  Input: 6 BI-RADS features and age  One output node to indicate malignancy ROC curves  show the trade-off in sensitivity and specificity achievable by a classifier by varying the threshold on the output decision variable sensitivity=t_pos/pos, specificity=t_neg/neg  The area under the ROC curve is often used as a measure of classifier performance.  Only techniques with high sensitivity would be acceptable. 98% sensitivity. Error

8. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 8 ROC Rf: Fawcett (2006). An introduction to ROC analysis. Pattern Recognition Letters 27.

9. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 9 Results Fig. 2 Fig. 3(d)

10. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 10 Results BP-ANN predict the biopsy outcome The SOM can do a malignancy prediction  For example, if a case belonged to cluster #4, then the classifier output for that case would be 0.83. Fig. 6 shows the ROC curve for the BP-ANN and SOM. The performance at the highest sensitivities was comparable. In particular, at 98% sensitivity  the SOM operates with 0.26±0.03 specificity  the BP-ANN operates with 0.25±0.03 specificity (P=0.93).

11. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 11 Results Fig. 7 lists the BP-ANN’s recommendations for follow up instead of biopsy on the subsets identified by the SOM (320 cases) A threshold was applied to the BP- ANN outputs such that  sensitivity = 98% (965/982)  specificity = 24% (303/1276).  In other words, 320 cases (303 actual negatives and 17 actual positives) fell below the threshold. The majority of the benign lesions that the BP-ANN would have spared biopsy (242/303=80%) were in the cluster defined by neuron #6. False NegativeTrue Positive False Positive True Negative 96517 303971 Fig. 7

12. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 12 Results A classification rule based on the cluster profiles (Figs. 4 and 5) of neuron #6 and a classification and regression tree (CART) The classification rule was:  if the mass margin was well-circumscribed or obscured and the age was less than 59 years and there were no calcifications, associated findings, or special findings, then do not biopsy, otherwise do biopsy.

13. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 13 Results On the 2258 training cases,  this rule gave 961/982=98% sensitivity and 336/1276=26% specificity.  this rule performed comparably to the BP-ANN with a threshold of 0.1842 (965/982=98% sensitivity, 303/1276=24% specificity). On the validation set,  the classification rule gave 886/904=98% sensitivity and 339/1273=27% specificity  the BP-ANN with a threshold of 0.1842 gave 884/904=98% sensitivity and 296/1273=23% specificity. Thus, both the BP-ANN and the rule-based approach generalized and they performed comparably at this high sensitivity point.

14. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 14 Discussion Considerable variability from cluster to cluster. One of the major goals of computer-aided diagnosis of breast cancer is  to identify very likely benign cases, in order to reduce the number of benign biopsies. It is possible to use the clusters and their malignancy fractions directly as a tool for predicting biopsy outcome. The SOM prediction method, similar to a case- based reasoning system. the SOMs with similar architectures showed substantial agreement in clustering the data.

15. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 15 Discussion The SOM prediction method in conjunction with the CSNN profiling method has the potential advantage  physicians may understand the intuition  the BP-ANN, which is often seen as a ‘‘black box’’. The successful separation of a priori known, coarse lesion types (masses, clustered microcalcifications, focal asymmetric densities, and architectural distortions) provided some quality assurance of the clustering.

16. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 16 Discussion Classification based on the SOM was competitive to that achieved by the BP-ANN at high sensitivity levels (Fig. 6). the SOM clustering and CSNN profiling technique could be used to provide the physician with an alternative description of what the BP-ANN does for certain types of cases. The identification of a single cluster that accounted for the majority of the cases that the BP-ANN would have recommended for follow up also suggests the investigation of rule-based methods to identify relatively simple diagnostic criteria which might be applied to these cases to aid the radiologists in their decision making process. Based on the profiles of the clusters (#6) identified by the SOM, a simple classification rule was developed and performed comparably to the BPANN

17. N.Y.U.S.T. I. M. Intelligent Database Systems Lab 17 Comments Advantage:  Divide and conquer approach  A good classification rule  A good example of knowledge discovery Disadvantage  high false positive rate: 971/1276=0.76  Low accuracy: (965+303)/2258=0.56 Solution: Remove cluster #6, then repeat the divide and conquer approach?  Such a research depends on domain knowledge heavily.