Inferring the natural time history of breast cancer: implications for tumor growth rate and early detection.

This review analyzes the results of 692 breast cancer patients from the Norwegian Radium Hospital. All cases were diagnosed during the period 1951-1959 and the average follow-up time was just under eight years. All patients received a radical mastectomy and had their diagnoses pathologically confirmed by a separate reviewer. The purpose of this paper is to apply a novel method of analysis in order to infer the longitudinal course of the disease as if it had not been interrupted by treatment. The method allows one to estimate the average times between changes in the biological factors which characterize the natural history of the disease. Applying this method to the Norwegian data has resulted in identifying three pathways of the natural history of the disease. The tumor growth rates differ for these pathways and are in the approximate ratio 1:5:27. Furthermore, we can estimate the potential benefit from earlier diagnosis. Two of the three pathways would seem to benefit from earlier detection.