Person:

Retsky, Michael

We review our work over the past 14 years that began when we were first confronted with bimodal relapse patterns in two breast cancer databases from different countries. These data were unexplainable with the accepted continuous tumor growth paradigm. To explain these data, we proposed that metastatic breast cancer growth commonly includes periods of temporary dormancy at both the single cell phase and the avascular micrometastasis phase. We also suggested that surgery to remove the primary tumor often terminates dormancy resulting in accelerated relapses. These iatrogenic events are apparently very common in that over half of all metastatic relapses progress in that manner. Assuming this is true, there should be ample and clear evidence in clinical data. We review here the breast cancer paradigm from a variety of historical, clinical, and scientific perspectives and consider how dormancy and surgery-driven escape from dormancy would be observed and what this would mean. Dormancy can be identified in these diverse data but most conspicuous is the sudden synchronized escape from dormancy following primary surgery. On the basis of our findings, we suggest a new paradigm for early stage breast cancer. We also suggest a new treatment that is meant to stabilize and preserve dormancy rather than attempt to kill all cancer cells as is the present strategy.

The combination of mathematics – queen of sciences – and the general utility of computers has been used to make important inroads into insight-providing breast cancer research and clinical aids. These developments are in two broad areas. First, they provide useful prognostic guidelines for individual patients based on historic evidence. Second, by suggesting numeric tumor growth laws that are correlated to clinical parameters, they permit development of biologically relevant theories and comparison with patient data to help us understand complex biologic processes. These latter studies have produced many new ideas that are testable in clinical trials. In this review we discuss these developments from a clinical perspective, and ask whether and how they translate into useful tools for patient treatment.