Impact of Resection Margin Width on Local Control and Prognostic Factors in HER2-enriched and Triple-negative Breast Cancer in the Modern Systemic Treatment Era

Background/Aim: The optimal management of close resection margins after breast-conserving surgery (BCS) remains controversial, particularly in hormone receptor-negative (HR−) breast cancer, which has a relatively high risk of local recurrence (LR). This study evaluated the association between resection margin width and LR and identified high-risk factors among patients with close margins. Patients and Methods: We retrospectively reviewed 842 patients with HR− breast cancer who underwent BCS followed by adjuvant radiotherapy between 2010 and 2020. Resection margins were categorized as clear (≥2 mm) or close (<2 mm). The cumulative incidence of LR was analyzed using competing-risk methods, and disease-free survival (DFS) was also evaluated. Results: The 10-year cumulative incidences of LR were 4.5% in patients with clear margins and 4.9% in those with close margins, with no significant difference between the groups (p=0.359). In contrast, the 10-year disease-free survival was significantly lower in patients with close margins than in those with clear margins (87.7% vs. 92.2%; p=0.008), and close margins remained independently associated with worse DFS in multivariable analysis (hazard ratio=1.85, 95% confidence interval=1.13–3.05; p=0.015). In the multivariable analysis of patients with close margins who were treated with a tumor bed boost of 0 to 10 Gy, the presence of an extensive intraductal component (p<0.001), a Ki-67 proliferation index ≥15% (p=0.012), and the omission of HER2-targeted therapy or chemotherapy (p=0.010) were significantly associated with an increased cumulative incidence of LR. Conclusion: Close margins were not associated with a significantly increased risk of LR in patients with HR− breast cancer treated with contemporary adjuvant therapy, although they were associated with worse DFS. Patients with close margins and additional adverse factors may represent a subgroup in whom intensified local treatment, including a higher tumor bed boost dose, warrants further investigation.