Does Surgical Timing After Neoadjuvant Anti‐HER2 Therapy Affect Pathological Complete Response and Survival in HER2‐Positive Breast Cancer? A Multicenter Retrospective Cohort Study

<jats:title>ABSTRACT</jats:title> <jats:sec> <jats:title>Background</jats:title> <jats:p>The optimal timing of surgery after completion of neoadjuvant chemotherapy (NAC) remains uncertain, particularly for patients with HER2‐positive breast cancer receiving targeted therapy.</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>This multicenter retrospective study included 176 patients with early or locally advanced HER2‐positive breast cancer who underwent surgery following neoadjuvant chemotherapy combined with anti‐HER2 therapy between 2010 and 2025. The study was conducted using a previously established multicenter real‐world cohort (Birsin et al. 2025). This dataset has been used in prior analyses focusing on different endpoints; however, the current study addresses a distinct research question evaluating the impact of surgical timing after neoadjuvant therapy. Patients were categorized according to the interval between the last cycle of systemic therapy and surgery into three groups: &lt; 4 weeks, 4–8 weeks, or &gt; 8 weeks. The primary endpoint was pathological complete response (pCR), defined as ypT0/is ypN0. Secondary endpoints were disease‐free survival (DFS) and overall survival (OS).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p> The median interval between completion of NAC and surgery was 8 weeks (range, 3–20 weeks). A pCR was achieved in 49% of patients. In multivariate analysis, hormone receptor negativity (OR = 2.56, <jats:italic>p</jats:italic>  = 0.011), HER2 IHC 3+ status (OR = 0.27, <jats:italic>p</jats:italic>  = 0.018), lower T stage (OR = 0.39, <jats:italic>p</jats:italic>  = 0.026), and dual anti‐HER2 therapy (OR = 2.47, <jats:italic>p</jats:italic>  = 0.021) were independent predictors of pCR; however, surgical timing (&lt; 8 weeks vs. ≥ 8 weeks; &lt; 4 vs. 4–8 weeks; and &lt; 4 vs. &gt; 8 weeks) did not significantly influence pCR ( <jats:italic>p</jats:italic>  = 0.893, <jats:italic>p</jats:italic>  = 0.171, <jats:italic>p</jats:italic>  = 0.187). The estimated 5‐year DFS rates were 87.5%, 83.5%, and 80.8%, and the OS rates were 85.2%, 82.1%, and 89.7% for the &lt; 4‐week, 4–8‐week, and &gt; 8‐week groups, respectively. Neither DFS nor OS differed significantly among the groups (log‐rank <jats:italic>p</jats:italic>  = 0.828 and <jats:italic>p</jats:italic>  = 0.778, respectively). </jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>In patients with early and locally advanced HER2‐positive breast cancer, the interval between completion of neoadjuvant chemotherapy combined with anti‐HER2 therapy and surgery did not affect pCR, DFS, or OS. Moderate delays in surgery beyond 8 weeks did not appear to adversely affect patient outcomes.</jats:p> </jats:sec>