Long-term outcome for neoadjuvant versus adjuvant chemotherapy in early breast cancer and the prognostic impact of nodal therapy response: A population-based study

Introduction: Although neoadjuvant systemic treatment for non-metastatic breast cancer has gained ground during the past decade, there is no compelling evidence that it improves overall survival compared to primary tumor resection and adjuvant treatment. At the same time, the approach to responders to neoadjuvant treatment in the axilla is evolving. Materials and methods: This is a retrospective analysis of a prospectively collected population-based registry. Patients that received neoadjuvant (n = 2126) or adjuvant chemotherapy (n = 4754) for non-metastatic breast cancer during 2007-2020 in the Stockholm-Gotland region, which comprises 25 % of the entire Swedish population, were included. Overall survival of patients treated preoperatively and postoperatively was compared using inverse probability treatment weighting and landmark analysis. The prognostic impact of change between prechemotherapy clinical to postchemotherapy pathologic nodal stage (cN/pN) in women receiving neoadjuvant treatment was investigated. Results: Median follow-up was 4.93 years. There was no difference in adjusted overall survival between adjuvant (reference) and neoadjuvant treatment in the entire population (HR = 1.38, 95 % CI 0.98-1.93, p = 0.062) or in breast cancer subtypes. Patients converting from positive clinical to negative pathologic nodal stage (cN+/pN0) had improved outcomes compared to cN0/pN0 or patients with pN0 following primary surgery. These patients had a particular disease trajectory, with early peak in risk of death followed by quick and sustained decrease. Conclusion: There was no difference in survival of patients treated with neoadjuvant versus adjuvant systemic therapy for non-metastatic breast cancer. Patients with cN+/pN0 have excellent prognosis and represent potential candidates for de-escalation of local and systemic treatment.