title: Neural network analysis of follow-up data in primary breast cancer.
abstract: This paper reports on the performance of a recently developed neural network environment incorporating likelihood-based optimization and complexity reduction techniques in the analysis of breast cancer follow-up data with the goal of building up a clinical decision support system. The inputs to the neural network include classical factors such as grading, age, tumor size, estrogen and progesterone receptor measurements, as well as tumor biological markers such as PAI-1 and uPA. The network learns the structural relationship between these factors and the follow-up data. Examples of neural models for relapse-free survival are presented, which are based on data from 784 breast cancer patients who received their primary therapy at the Department of Obstetrics and Gynecology, Technische Universität München, Germany. The performance of the neural analysis as quantified by various indicators (likelihood, Kaplan-Meier curves, log-rank tests) was very high. For example, dividing the patients into two equally sized groups based on the neural score (i.e., cutoff = median score) leads to an estimated difference in relapse-free survival of 40% or better (80% vs. 40%) after 10 years in Kaplan-Meier analysis. Evidence for factor interactions as well as for time-varying impacts is presented. The neural network weights included in the models are significant at the 5% level. The use of neural network analysis and scoring in combination with strong tumor biological factors such as uPA and PAI-1 appears to result in a very effective risk group discrimination. Considerable additional comparison of data from different patient series will be required to establish the generalization capability more firmly. Nonetheless, the improvement of risk group discrimination represents an important step toward the use of neural networks for decision support in a clinical framework and in making the most of biological markers.
authors.affiliation: Department of Obstetrics and Gynecology, Technical University, Munich, Germany. nadia.harbeck@lrz.tum.de
authors.forename: N
authors.initials: N
authors.lastname: Harbeck
authors.forename: R
authors.initials: R
authors.lastname: Kates
authors.forename: K
authors.initials: K
authors.lastname: Ulm
authors.forename: H
authors.initials: H
authors.lastname: Graeff
authors.forename: M
authors.initials: M
authors.lastname: Schmitt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D016013:Likelihood Functions; D008875:Middle Aged; D016571:Neural Networks, Computer; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D015996:Survival Rate; D013997:Time Factors; D014568:Urokinase-Type Plasminogen Activator / Q000032:analysis
chemical_list: D014408:Biomarkers, Tumor; D017395:Plasminogen Activator Inhibitor 1; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D014568:Urokinase-Type Plasminogen Activator