What Is High-risk Breast Cancer With Pathologically Negative Lymph Nodes for Regional Recurrence?

Purpose: This study aimed to identify high-risk factors for regional recurrence in patients with breast cancer with pathologically negative lymph nodes. Methods and Materials: We retrospectively analyzed 3800 patients with stage pT1-pT3 breast cancer and pathologically negative lymph nodes between 2004 and 2012. All patients underwent upfront surgery with curative intent. Adjuvant systemic treatments were administered to most patients (96.7%) based on contemporary guidelines. Results: After a median follow-up of 83 months (range, 7-175 months), the estimated 10-year cumulative incidence rate of regional recurrence was 2.0%. Multivariate competing risk analysis revealed that high histologic grade, positive lymphovascular invasion, and stage pT2-3 were significant risk factors for any regional recurrence. Patients with ≥2 risk factors showed a significantly higher 10-year cumulative incidence rate of any regional recurrence than those with 1 or no risk factors (5.5% vs 1.2%; P < .001). When the number of retrieved lymph nodes was less than 10, the difference in the incidence rate of regional recurrence between patients with ≥2 risk factors and those with 1 or no risk factors was greater (6.6% vs 1.3%, respectively; P < .001). The 10-year disease-free survival was worse in patients with ≥2 risk factors than in those with 1 or no risk factors (84.7% vs 90.0%, respectively; P < .001). Patients with ≥2 risk factors also showed worse 10-year overall survival than did those with 1 or no risk factors (91.3% vs 97.0%, respectively; P < .001). Conclusions: Overall, the cumulative incidence rate of any regional recurrence was low at 10 years. However, patients with ≥2 risk factors showed an increased risk of any regional recurrence and worse disease-free survival, particularly when the number of retrieved lymph nodes was less than 10.