Purpose: In breast cancer (BC), the duration of endocrine adjuvant therapies (AT) has been extended continuously up to 10 years. We present an alternative explanation for the effect, which could enable shorter treatments.
Method: The relevant literature on chemoprevention and (neo-)adjuvant therapy was reviewed. Data for initiation and growth of primary and contralateral BCs and their metastases (MET) were considered. Also, population-based data from the Munich Cancer Registry for MET-free survival, time trends of MET patterns, and survival achieved by improved ATs are used to estimate all events in the long-term follow-up.
Results: Extended ATs (EAT) that continue after 1, 2, or 5 years reduce mortality only slightly. The effect is delayed, occurring more than 5 years after extension. EATs does not affect the prognosis of 1stBCs, they preventively eradicate contralateral 2ndBCs and thus their future life-threatening METs. Because chemoprevention can eradicate BCs from the smallest clusters to almost detectable BCs, ATs can be temporarily suspended without imposing harm. Results equal to EATs can be achieved by short-term ATs of the 1stBC and by repeated neo-ATs targeted at the indefinitely developing 2ndBCs. Considering this potential in de-escalation, a 70-80% reduction of overtreatment seems possible.
Conclusion: Knowledge of initiation and growth of tumors with known effects of neo-ATs suggest that intermittent endocrine ATs may achieve the same results as EATs but with improved quality of life and survival because of fewer side effects and better compliance. The challenge for developments of repeated ATs becomes: how short is short enough.
Keywords: Breast cancer; Long-term endocrine adjuvant therapy; Metastasis; Over-treatment; Survival.