Accelerating progress to innovation for patients: Trial design and risk stratification.

In early breast cancer, we integrate risk stratification and trial design, together with subtype, to focus on clinical questions in specific patient populations. In the past, trials enrolled an "all-comers," broadly-defined population. More recently, trials enroll low-to intermediate-risk populations for whom testing strategies to de-escalate therapy are appropriate, or intermediate-to high-risk populations for whom testing additional and novel therapeutic strategies are needed. For example, in patients who have triple-negative breast cancer, the presence of residual disease after neoadjuvant therapy has become an approach to risk stratification for defining a trial population testing approaches to adjuvant therapy. In patients with hormone receptor positive, HER2-negative breast cancer, trials testing the addition of adjuvant CDK4/6 inhibitors to standard endocrine therapy have enrolled intermediate-to high-risk populations using various definitions and with heterogeneous results. Results of the recent generation of clinical trials testing systemic therapy for early breast cancer provide an opportunity to learn and improve future trial designs and accelerate progress to innovation for patients.