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Evolution of neural networks in prediction of recurrent

events in breast cancer


Vlad Ana-Maria
Abstract
Breast cancer is the most common cancer among women today and the
second cause of women death. It can return after primary treatment and sometimes
it is harder to diagnose recurrent events than the initial one. In this paper we are
trying to see an evolution of medical diagnosis of breast cancer using neural networks
and whether neural networks are a useful tool in diagnosing recurrent events or not.
First, in 2008, it was used a dataset obtained from Ljubljana Oncology Institute
to show that both multi-layer perceptron and radial basis function have strong
classication performances, and then, in 2010 the neural networks are tested to
two dierent datasets. It has shown that the best performing algorithm strongly
depends on the features of the dataset.
1 Introduction
Today, breast cancer represents about 23% of all feminine cancers and is the leading
cause of death among women with ages between 40 and 44 years, with a 19% mortality
rate. The American Cancer Society estimates that one woman in eight has breast cancer
or she will develop it in her lifetime. Sometimes, a diagnosis of the recurrent cancer is
more challenging than the initial one. It is very important to nd whether the patient
will suer from a recurrence of her disease or not. Basically, in this paper, it is created
a simple neural network for clinically predictions . Neural Network Analysis is a form of
computer-simulated articial intelligence that has actually outperformed other analytic
techniques because it learns to distinguish dierent classes of events. The results are com-
pared to the actual clinically diagnosis. We will see either if the accuracy of detecting
breast cancer methods has improved from 2008 to 2010 or not. This paper is organized
as follows. One section compares methods and datasets used in both experiments and
the second section presents a report of the study and its validity.
2 Methods and datasets
An articial neural network works in the way human brain does. A large number
of interconnected units called neurons are working together to solve specic problems.
This system is capable to detect and solve articial intelligence problems in an ecient
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way, even if they seem too complex for the human brain. The principal elements for
a Neural Network are called neurons and as the biological ones they have connections
that are modeled as weights. All inputs are summed together with the weights and
passed into an activation function. The activation function turns the neurons output to
a nite value. Basically there are 2 types of frameworks : single-layer and multi-layer.
The rst has only an input and an output layer, unlike the latter that can have one or
more hidden layers. The most common architecture used is the multi-layer perceptron
(MLP) and although a MLP with only two hidden layers is sucient to model a real-
life problem, in this paper is adopted a three-layer perceptron. . There are two phases
needed to process neural information: training phase and testing phase. The Dataset
used in 2008 was from Ljubljana Oncology Institute(UCI Machine Learning repository
http://archive.ics.uci.edu/ml/datasets/Breast+Cancer), which contains attributes from
286 patients and a binary decision class: non-recurrent events totaling 201 instances
and recurrent-events totaling 85 instances.In Table 1 below we can see how categorical
attributes are coded into numerical values. The attributes are listed in correspondence
with their type, range and codes.
In 2010, beside the Ljubljana Dataset(LOI) it was used a signicantly dierent
breast cancer dataset, the Wisconsin Prognostic Breast Cancer(WPBC) . The WPBC
dataset (UCI Machine Learning repository : http://archive.ics.uci.edu/ml/machine-learning-
databases/breast cancer-wisconsin/) contains 34 input features concerning 198 patients
and a binary decision class : non-recurrent events totaling 151 instances and recurrent
events totaling 47 instances. We have only 12 selected attributes and displayed in Table
2, the most relevant to the study(the input features can contain relevant attributes and
redundant information for the NNs application, such errors, for instance).
Table 1: The Main Characteristics of the Ljubljana Breast Cancer Dataset
Attribute Type Range Codes
Age Categorical 10-19...90-99 average
Menopause Categorical lt40, ge40, premeno 1; 2; 3
Tumour-size Categorical 0-4...55-59 average
Invasive-nodes Categorical 0-2...36-39 average
Node-caps Categorical yes, no 0 / 1
Deg-malignancy Categorical 1, 2, 3 1; 2; 3
Breast Categorical left, right 0 / 1
Breast-quad Categorical
left-up, left-low,
right-up, right-low, central
-3; -2; 3
2; 0
Irradiation Categorical yes, no 0 / 1
Decision Categorical recurrent/ non-recurrent Y / N
2.1 Neural networks diagnosing performances with both datasets
Using the LOI dataset, an a priori statistical power analysis has been performed
to determine the appropriate sample size in order to achieve the adequate power. In
probabilistic terms, statistical power is the capability of a test to detect a signicant
eect. The a priori power is applied rst to determine an appropriate sample size. In
order to evaluate the NN classication eciency, two main metrics have been computed
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Table 2: The Main characteristics of the Wisconsin breast cancer dataset
Attribute Type Range
Radius(mean of distances from the centre to all points
on the perimeter)
Numerical (10.95, 27.22)
Texture (standard deviation of grey-scale values) Numerical (10.38, 39.28)
Perimeter Numerical (71.90. 182.10)
Area Numerical (361.60, 2250)
Smoothness(local variation Compactness (perimeter
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/area - 1.0) Numerical (0.046, 0.311)
Concavity (severity of concave portions of the contour) Numerical (0.024, 0.427)
Concave points (number of concave portions of the contour) Numerical (0.020, 0.201)
Symmetry Numerical (0.131, 0.304)
Fractal dimension (coastline approximation - 1) Numerical (0.050, 0.097)
Tumour size - diameter of the excised tumour in centimetres Numerical (0.400, 10.00)
Lymph node status - number of positive auxiliary
lymph nodes observed at the time of surgery
Numerical (0, 27)
: (a) the training performance (the proportion of cases that are correctly classied in the
training phase) and (b) the testing performance (the proportion of cases that are correctly
classied in the testing phase).The NN classication eciency is indicated by the testing
performance and it is interpreted as the diagnosis accuracy. The classication accuracy
training/testing is computed 10 times, each time leaving out one of the sub-samples from
the computation and using that sub-sample as a test sample for cross-validation, so that
each sub-sample is used 9 times as training sample and just once as testing sample.
Technically, 260 cases were randomly selected each time for training and the remaining
26 cases for testing. To complete this cross-validation cycle, the procedure is repeated 10
times, more precisely there are made 10 runs of the NN model.
In Table 3 below are listed the results of the neural network diagnosing performances, in
terms of average and standard deviation , computed over 106 computer runs.
Table 3: NN Diagnosing performances over 106 runs
NN type
Average/
Std.no. hidden neurons
Average/
Std. testing performance
Average/
Std. testing performance
Running time
per cycle
MLP 5/3 87.23 / 5.08 76.19 / 5.38 02:45
It can be seen from the above table that the mean number of hidden processing
units (neurons for MLP) in networks equal to: 5 for MLP, with relatively high standard
deviations, equaling 3 for MLP. This means that a three-layer perceptron with 5 hidden
neurons in average is able to provide76 % classication accuracy. More importantly, it
shows that we can have a simple neural network structures and obtain a good enough
accuracy, i.e. a MLP model with 2 neurons. However, we notice that the MLP with
one neuron in each hidden layer provided the lowest performance (around 64%). We also
experimentally applied a MLP with one hidden layer to compare its performance with
the three-layer perceptron. Thus, the average training/testing performance reached 68%,
conrming the theoretical expectation. The above table also shows that the classication
accuracy will not further improve beyond 8 neurons for MLP. Thus, we can conclude
that it is possible to have a relatively simple network structure (i.e. a small number of
processing units), with a good performance.The results for MLP will be analysed in order
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to derive some insights into the behavioural dierences of these NN models, even though
they seemed to provide similar results. In Table 4 we can observe the total number of
cases in each class, cases of each class that were correctly (and incorrectly) classied and
nally, cases of that class which could not be classied at all (unknown cases). More
information about the misclassication is provided after the analyse.
Table 4: Overall and per-class statistics(MLP)
MLP
Training Testing
Non-recurrent Recurrent Non-recurrent Recurrent
Total 193 67 8 18
Correct 168 58 6 14
Wrong 25 9 2 4
Unknown 0 0 0 0
Non-recurrent 168 9 6 4
Recurrent 25 58 2 14
Using the LOI dataset we conclude that only the rst four attributes are needed
in order to obtain a good diagnosis accuracy, resulting in a smaller running time. Despite
the fact that the models were applied to a small categorical dataset, the MLP has provided
a good performance and the rate of unknown cases was zero.
In Table 5 we will see the Neural Networks performance for the WPBC dataset, which
has a dierent mean number of hidden processing units. In this case, we have also simple
NN structures and we can obtain a good enough accuracy.
Table 5: NN diagnose performances for WPBC over 106 runs
NN type
Mean/ Std no.
of hidden neurons
Mean/ Std training
performance (%)
Mean/Std testing
performance (%)
95% Condence
interval testing (%)
Running time
per cycle
MLP 9/ 2 69.11 /10.38 60.21/ 8.08 (58.65, 61.76) 01:05
The main observation on using dierent datasets is that for the WPBC, the hi-
erarchy of the NN classiers is reversed, the average testing performance reaches 60.21%
for MLP. The dierence between the results can be explained by the attributes of the two
datasets. The LOI dataset consists of categorical attributes only, such as age, menopause,
and degree of malignancy, whereas the WPBC consists of continuous attributes only, such
as digitized image data of the cell nuclei obtained by certain techniques. Another expla-
nation is based on the fact that there are two dierent points of view in identifying the
risk factors for breast cancer recurrence. This statistical analysis has as target the deriva-
tion of signicant insights into the behavioural dierences of the NN models, although
their results are similar. In order to give a more detailed view over the misclassication
provided for both datasets, an overall and per-class classication statistics are displayed
in Tables 6 and 7.
The sensitivity analysis for the LOI dataset regarding the importance of predictors
of recurrent events showed, in descending order, the hierarchy of the nine attributes.
The hierarchy was the same for all the three NN algorithms and is as follows: #1 deg-
malignancy, #2 irradiation, #3 node caps, #4 breast quad, #5 tumour size, #6 invasive
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Table 6: Overall and per-class statistics (MLP) - the LOI dataset
MLP
Training Testing
Non-recurrent Recurrent Non-recurrent Recurrent
Total 193 67 8 18
Correct 168 58 6 14
Wrong 25 9 2 4
Unknown 0 0 0 0
Non-recurrent 168 9 6 4
Recurrent 25 58 2 14
Table 7: Overall and per-class statistics (MLP) - the WPBC dataset
MLP
Training Testing
Non-recurrent Recurrent Non-recurrent Recurrent
Total 135 45 16 2
Correct 95 31 10 1
Wrong 40 14 6 1
Unknown 0 0 0 0
Non-recurrent 95 14 10 1
Recurrent 40 31 6 1
nodes, #7 age, #8 menopause and #9 breast.By rerunning the MLP algorithm on a
reduced dataset containing the rst attributes, there were obtained results that were not
signicantly dierent from the original ones, i.e. for the testing performance, there were
obtained 72.25 % prediction accuracies for MLP.
A similar sensitivity analysis for the WPBC dataset provided the following hierarchy, in
descending order, of the 12 attributes (again, the same for all the three NN algorithms):
#1 radius, #2 perimeter, # 3 area, #4 tumour size, #5 texture, # 6 concave points,
#7 lymph-node status, #8 smoothness, #9 fractal dimension, #10 compactness, #11
symmetry and #12 concavity.Analogously to the LOI dataset, rerunning the three NN
models on a reduced WPBC dataset containing the rst seven attributes provided 54.12%
testing accuracy for MLP.
3 Report of the study
No matter what dataset was used, Ljubljana Oncology Insitute or Wisconsin Prog-
nostic Breast Cancer it was found that Neural Network is a suitable methodology for
classyng recurrent events in breast cancer. The results of the classication is similar
to the highest results obtained using expensive medical imaging, such as MRI method.
Statistical power analyses was very useful in the determination of the optimal network
structures, and the statistical tests were very good tools in learning behaviours of the NN
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algorithms and the comparison of their performances.We found that the paper from 2010
extends and improves the version of 2008. The dataset used in the rst paper is dierent
and it is a very useful tool for validating the conclusions. An intelligent Neural Network
for breast cancer will certainly be able to give an acurrate diagonis and create a positive
inuence over the breast cancer tumors.
References
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dict recurrent events in breast cancer
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detection
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[5] Jerez, J.M. (2005). Improvement of breast cancer relapse prediction in high risk in-
tervals using articial neural networks
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bilistic neural networks
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and model selection
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[9] website: e-Instructiv.ro,
http://einstructiv.ro/Retele-neuronale/252597.html
[10] website: ceex.elth.pub.ro,
http://ceex.elth.pub.ro/invterm/lucrareATEE.pdf
[11] website: diagnijmegen.nl,
http://www.diagnijmegen.nl/index.php/Research
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