[Comment] Of surrogate endpoints, shortcuts, and safety

Adjuvant and neoadjuvant systemic drug therapy prevents recurrence and premature death in patients with breast cancer by treating undetectable micrometastatic disease.1 For less toxic treatments, prevention of metastases alone can justify therapy because patients should experience improved quality of life without metastases, but for more toxic or risky treatments improved overall survival might be required.2 When improving overall survival is the agreed-upon goal, both regulators and clinicians must balance the harms from delaying access to treatments later confirmed as improving overall survival (leaving aside the question of magnitude) against the harms of over-treating many patients who they later learn derived no improvement in survival.