Modern concepts of the natural history of breast cancer: a guide to the design and publication of trials of the treatment of breast cancer.

The design, analysis and interpretation of randomised controlled trials for the management of early breast cancer are to some extent predicated on the prevailing conceptual model of the disease based on its biology and cellular kinetics. Real progress became possible from the early 1970s following the challenge to a mechanistic view of the disease going back to the time of Virchow and Halsted. Improvements in local and systemic therapy that have reduced the surgical morbidity and improved on survival followed the biological revolution lead by Dr. Bernard Fisher. The rate of progress has now slowed down and a number of outlying clinical observations suggest that the time is ripe for a new revolutionary model of breast cancer with greater explanatory power. The application of non-linear mathematics (chaos theory) that is emerging in the new science of the disease suggests a new set of guidelines for the design, analysis and interpretation of clinical trials of therapy that might lead to the next stepwise progression in the management of early breast cancer.