ReviewBreast cancer research and treatment2026
Investigating initial patterns of progression on first-line treatment in patients with de novo metastatic breast cancer.
Review in Breast cancer research and treatment, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
purposeDe novo metastatic breast cancer (dnMBC), defined as stage IV disease at initial diagnosis, comprises 6-10% of all metastatic breast cancer cases. Despite therapeutic advances, the unique clinical course of dnMBC remains underexplored, particularly with regard to patterns of first treatment failure and the potential role of metastasis-directed therapy (MDT). This study investigated patterns of treatment failure in patients with dnMBC treated with first line systemic therapy to understand how to better direct local therapies.
methodsA prospective single-institution database was used to examine patient and tumor characteristics, treatment response, and outcome among 326 patients with dnMBC diagnosed between 2011 and 2022. Anatomic site of first disease progression was categorized as occurring at a pre-existing site only (in breast and/or pre-existing metastatic sites only) vs other (including any combination involving a new metastatic site). Progression patterns were analyzed overall and stratified by clinical subtype. Cumulative incidence functions were used to evaluate time to first treatment failure by site and subtype.
resultsAmong the full cohort, progression-free survival at 2 years was 32.7% (95% CI [27.3, 38.0]) and at 5 years, 7.8% (95% CI [4.5, 11.2]). In total, 40.8% experienced first progression at pre-existing sites only, while 46.5% progressed at new sites. The cumulative incidence of first progression at a pre-existing site only at 5 years by clinical subtype was: 45.4% for HR + /HER2-, 43.8% for HR-/HER2 + , 39.3% for HR-/HER2-, and 34.5% for HR + /HER2 +.
conclusionA substantial proportion (approximately 40%) of dnMBC patients experience initial progression at pre-existing sites, highlighting a potential role for locoregional and MDT in delaying progression and extending time on first-line systemic therapy. These findings support further prospective evaluation of MDT in dnMBC, with an emphasis on subtype-specific strategies and quality-of-life outcomes.
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