Lymph node infiltration, parallel metastasis and treatment success in breast cancer

Background: The number of axillary positive lymph nodes (pLN) is the most important clinical prognostic factor in breast cancer (BC). To date, there is limited knowledge of LN-spreading and metastasization (MET). Patients and methods: In the Munich Cancer Registry, 30,170 hormone receptor positive BC patients were analysed for the variation in tumor diameter (TD) and number of pLNs. A total of 144 combinations were described with Gompertz functions for each LN-subgroup and linked with patient outcomes, MET and 20-years survival. Results: Every additional millimeter of BC diameter decreased the likelihood of 0pLN-status by 1.6%–0.3%. The infiltration accelerates from the 1pLN and the percentage of successive pLNs subgroups becomes smaller. BCs with increasing TDs continuously reduce the proportion of 0pLN-status and increase it with >10pLNs. The proportion of 1–10 pLNs at 10 mm is 16% and increases to 50% with prognostically favorable 1-2pLNs of 75% and 40%, respectively. After 20 years, tumor-specific mortality is about 17% for 0pLNs, twice that for 1pLN, and 3 times higher for 4–5 pLNs. The more LNs are positive, the less survival is affected. The subgroups with 0/1pLNs cause 41/16% of all cancer related death. Conclusion: The number of pLNs is an epiphenomenon of the onset and chronometer for the duration of TCs disseminating from growing BCs. METs are initiated parallel to LNs by PTs and not caused by pLNs. This LN process without cascade-like MET initiation should be generalizable to all common solid tumors.