Inflammatory breast cancer (IBC) is rare, with challenging diagnostics and unfavorable outcomes. Therefore, more molecular insight into IBC is needed. The comprehensive Dutch prospective INFLAME registry related IBC follow-up and treatment to histopathology and molecular analysis. Of consecutive patients, nationwide identified with newly diagnosed IBC, clinicopathological, treatment and outcome data were collected. Histopathology and RNA-sequencing were related to outcome. 125 IBC patients were enrolled. Forty-one (34%) patients had HER2 + , and 31 (25%) had triple-negative IBC. The estimated 3-year OS was 78% in M0 IBC and 29% in M1. PFS was worst in triple-negative IBC (median 7.9 vs 16.3 and 15.8 months in M1 HER2+ and HR + /HER2- IBC). DFS and OS in M0 IBC were better with guideline-concordant trimodal therapy than without (HR 0.15 and 0.15; p = 0.000005 and 0.00038). The unique prospective INFLAME confirms unfavorable IBC characteristics and outcomes. International efforts may support guideline adherence and identify IBC-specific targets.
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