Characteristics, treatment and survival in de novo and metachronous metastatic breast cancer: a nationwide comparative analysis

PURPOSE: To compare patient characteristics, treatment patterns, and survival between de novo and metachronous metastatic breast cancer (MBC) using nationwide data. METHODS: A total of 2,366 MBC patients (900 de novo, 1,466 metachronous) diagnosed in 2019 were selected from the Netherlands Cancer Registry. Patient- and tumor characteristics and systemic treatment patterns were compared using chi-squared or Fisher's exact tests. Overall survival (OS) was compared using Kaplan-Meier curves and Cox proportional hazard analyses. All analyses were stratified by clinical subtype (HR+/HER2-, HR+/HER2+, HR-/HER2+, HR-/HER2-). For patients with HR+/HER2 - tumors, a sub-analysis examined OS in de novo versus metachronous MBC, stratifying the latter by receipt of prior (neo)adjuvant systemic treatment. RESULTS: De novo MBC patients were younger, had more HER2-positive (22% vs. 11%) and fewer triple-negative tumors (11% vs. 16%). Patients with metachronous MBC more often had CNS metastases and metastases in other localizations than the lymph nodes, bone, visceral organs and CNS. Among HER2 + patients, chemotherapy and targeted therapy were more often administered in de novo versus metachronous MBC. Median OS was longer in de novo MBC for HR+/HER2- tumors (40.8 vs. 30.3 months, aHR 1.27, 95%CI 1.12-1.43) and HR-/HER2 + tumors (51.1 vs. 9.1 months, aHR 1.62, 95%CI 1.03-2.54). In HR+/HER2 - patients, metachronous MBC patients who received prior (neo)adjuvant systemic treatment had worse OS than de novo cases (prior chemotherapy: aHR 1.52, 95%CI 1.29-1.78); prior hormonal therapy only: aHR 1.33, 95%CI 1.10-1.61), whereas those without prior systemic treatment had similar outcomes. CONCLUSION: De novo and metachronous MBC have different tumor biology, treatment patterns, and survival. In metachronous MBC patients, prior (neo)adjuvant systemic treatment was associated with worse survival compared to de novo MBC or patients with metachronous MBC without prior (neo)adjuvant treatment.