In node positive breast cancer patients who are treated with neoadjuvant systemic therapy, axillary staging and treatment is still a topic of debate. This multicenter study will contribute to evidence-based guidelines with regard to the oncologic safety and impact on quality of life of less vs. more invasive axillary staging and treatment strategies.Background: Node positive breast cancer (cN+) patients with an axillary pathologic complete response after neoadjuvant systemic therapy (NST) are not expected to benefit from axillary lymph node dissection (ALND). Therefore, less invasive axillary staging procedures have been introduced to establish response-guided treatment. However, evidence is lacking with regard to their oncologic safety and impact on quality of life (QoL). We hypothesize that if response-guided treatment is given, less invasive staging procedures are non-inferior to standard ALND in terms of oncologic safety, and superior to standard ALND in terms of QoL. Patients and Methods: MINIMAX is a Dutch multicenter registry study that includes patients with cN1-3M0 unilateral invasive breast cancer, who receive NST, followed by axillary staging and treatment according to local protocols. In a retrospective registry of +/- 4000 patients, the primar y endpoint is oncologic safety at 5 and 10 years (disease-free, breast-cancer-specific and overall survival, and axillary recurrence rate). In a prospective multicenter registry, the primar y endpoints are QoL at 1 and 5 years, and we aim to verify the 5-year oncologic safety. With an estimated 5-year disease-free survival of 72.5% and anticipated loss to follow-up of 10%, a sample size of 549 is needed to have 80% power to detect non-infer iority (with a 10% margin) of less invasive staging procedures. Conclusion: In cN+ patients treated with NST, less invasive axillary staging procedures are already implemented globally. Evidence is needed to support the assumed oncologic safety and superior QoL of such procedures. This study will contribute to ...