Breast cancer: Emerging principles of metastasis, adjuvant and neoadjuvant treatment from cancer registry data

AbstractBackgroundGrowing primary breast cancers (PT) can initiate local (LR), regional (pLN), and distant metastases (MET). Characteristics of these progressions such as initiation, frequency, growth duration and treatment success describe principles of these processes. They are bottlenecks through which scientific and molecular biological concepts and hypotheses must fit.MethodsPopulation-based data from the Munich Cancer Registry over 4 time periods since 1978 with the most important prognostic factors and an up to date follow-up are analyzed. With 66.818 patients, reliable data are obtained on initiation on METs, growth time und survival even in small subgroups. Together with results of clinical trials on prevention and adjuvant treatment (AT) principles for tumor growth, MET process and AT are derived.ResultsThe median growth periods for PT/ MET/LR/pLN result in 12.5/8.8/5/3.5 years. Even if 30% of METs only appear after 10 years of MET-free time, a delayed initiation or cascade like initiation of METs, e.g. from pLNs cannot be derived from the data. That is an immediate MET initiation principle by PT. The growth rate of the PT can vary by a factor of 10 or more and can be transferred to the MET. Nevertheless, the relation of the growth times PT/MET results in a less varying value of 1.4. Principles of AT are the 50% eradication of 1st and 2ndPTs, the selective and partial eradication of bone and lung METs with successful ATs, which cannot be improved by extending the duration of ATs. These principles reveal, among other things, that there is no rationale for the accepted for long-term endocrine ATs, breast cancer risk by hormone replacement therapies, or cascading initiation of METs.ConclusionA paradigm with ten principles for the MET process and ATs can be derived from real world data and clinical trials. The principles show limits and opportunities for innovation also through alternative interpretations of well-known studies. The outlined MET process should be generalizable to all solid tumors.