Distant-metastasis-free survival (DMFS) according to serum HER2 ECD level. (A) DMFS according to serum HER2 ECD level [elevated level (>15.2 ng/ml) vs normal level (≤15.2 ng/ml)] in the overall series. Elevated serum HER2 ECD level was an independent prognostic factor [log-rank P < 0.001, adjusted hazard ratio (HR) = 2.5, and 95% CI = 1.5–4.3]. (B–F) Subgroup analyses by tumor size (B), LN status (C), hormone-receptor status (D), tissue HER2 status (E), and anti-HER2 therapy (F). (A–F) Elevated serum HER2 ECD level was significantly prognostic in all subgroups except in those with LN negativity (log-rank P = 0.148, adjusted HR = 1.7, 95% CI = 0.6–5.1) and negative tissue HER2 status (log-rank P = 0.906, adjusted HR = 1.0, 95% CI = 0.1–7.2). All HRs were adjusted according to the following eight variables: tumor size, LN status, tumor grade, lymphovascular invasion, tissue HER2 status, chemotherapy, antihormone therapy, and trastuzumab therapy.