A Decade of Change: Systemic Treatment Patterns in Clinically Small HER2-Positive Node-Negative Breast Cancer in the Netherlands: A Population-Based Study.

PURPOSE: The optimal systemic treatment strategy for clinically non metastatic small (cT1N0) node-negative HER2-positive breast cancer remains debated. Insights in temporal changes in treatment strategies, including the timing of sentinel lymph node biopsy (SLNB), choice of chemotherapy regimen, and the adoption of the paclitaxel-trastuzumab (Tolaney) regimen. METHODS: Patients diagnosed with primary cT1N0 HER2-positive breast cancer between 2012 and 2022 were identified from the nationwide Netherlands Cancer Registry. Trends in the use, timing, and type of systemic chemo-targeted therapy, as well as the timing and outcomes of SLNB, were analyzed. RESULTS: A total of 6,184 patients were included. Overall, 73.9% received systemic chemo-targeted therapy, with higher use in cT1c tumors compared to cT1a/b. Neoadjuvant administration increased markedly from 2.1% in 2012 to 62.6% in 2022 (p < 0.001). Use of the Tolaney regimen increased to 71.2% of chemo-targeted therapy treatments in 2022, and 62.2% of it was administered in the neoadjuvant setting. Considerable variation over time was observed in the timing of SLNB; postneoadjuvant SLNB became more common, it was performed in 48.8% of patients in 2022. The rate of macrometastatic nodal disease after neoadjuvant Tolaney regimen was 1.4%, and a pathological complete response was observed in 43.3% of the patients. CONCLUSIONS: Systemic treatment patterns for cT1N0 HER2-positive breast cancer changed substantially over the past decade, with an increased use of neoadjuvant therapy and especially the Tolaney regimen. Despite these changes, considerable lack of consensus remains, particularly regarding SLNB timing. Further data are needed to guide optimal sequencing of systemic therapy and axillary staging.