Over-using chemotherapy in the adjuvant setting.

Avoidance of unnecessary or ineffective treatment should be one of the main goals in adjuvant breast oncology today. Unfortunately, both patients and doctors hunt for tiny statistical differences in survival curves. This search could not only lead to an oncological approach of unlimited addition that we will not be able to afford, but would also end inevitably in indeterminate overtreatment with substantial risks of unexpected toxic effects eating away whatever progress we might make. "Do not harm" remains the main principle in medicine. To be able to follow this rule, we need to better understand the biology of breast cancer. The mistake of "one treatment fits all" can only be changed when we critically review trial designs of adjuvant breast oncology. The risk of overtreatment is there and selection of precisely defined cohorts for phase 3 trials is necessary, despite pressure of scientific ambition, pragmatism, and demands of industry. The "add on" clinical trial design model accepts the inability to confirm that standard therapy is still necessary if a positive result from the addition of the new therapy is obtained. The same model can be applied to "extended" adjuvant treatments in breast cancer subtypes. Addition of "miraculin" to the standard of care should generate a new standard. Such trials that show a modest benefit on average at a population level take us a step away from refining care for the individual, and might support the use of multiple and costly interventions with potential short and long term side effects. It is essential to escalate treatment when necessary and to de-escalate when un-necessary.