Kwon et al. BMC Cancer 2010, 10:557 http://www.biomedcentral.com/1471-2407/10/557 On the univariate analysis, age younger than 35 years and hormone receptor negative disease were risk factors of recurrence. The five-year cumulative RFS rate was 90.9% vs. 97.7% in patients ≤35 and >35 years of age (p = 0.002, Figure 1 A). Each of ER and PR status did not show a significant association with recurrence, but negative status of both ER and PR tend to be associated with shorter RFS (p = 0.069). Patients with both ER and PR negative disease showed a five-year cumulative RFS rate of 94.9%; hormone receptor-positive patients showed a rate of 98.4%. Patients with triple negative dis- ease had a significantly lower RFS rate compared to hor- mone receptor-positive and/or HER2-positive patients (p = 0.018, Figure 1 B). HER2 status alone, Ki-67 and p53 status were not prognostic factors of RFS. Whether adjuvant chemotherapy was given was not associated with the development of systemic recurrence (p= 0.422). Cox proportional hazard regression model was con- structed using the variables of age, triple negativity, p53 and Ki-67. The independent prognostic factors of recur- rence were triple negativity (HR 4.93; 95% CI 1.312- 18.519, p = 0.018), and age younger than 35 years (HR 4.91; 95% CI 1.014-23.763, p = 0.048) (Table 3). In the analysis of distant disease-free survival, age younger than 35 (p = 0.029) and negative hormone receptor status (p = 0.011) were the convincing poor Figure 1 Recurrence-free survival by (a) age (b) breast cancer subtype according to HR and HER2 status. Page 5 of 8 Table 3 Multivariate analysis: prognostic value of selected factors on recurrence P value Hazard ratio 95% Confidence interval Triple negative Age (≤35) KI-67 p53 0.018 0.048 0.481 0.819 4.93 4.91 1.67 1.18 1.312 - 18.519 1.014 - 23.763 0.400 - 6.995 0.285 - 4.896 prognostic factors. Univariate analysis on HER2, Ki67, p53 status and multivariate analysis could not be per- formed due to the small number of distant metastasis events. There were twelve patients who experienced recur- rence of disease, and their median RFS time was 29.5 months (range 6.1-121.2 months, Table 4). Four patients were diagnosed as T1micN0M0 initially, two patients were T1a, and six were T1b. Three patients were less than 35 years old. Three of 12 patients developed sys- temic recurrence. All three patients had ER/PR negative disease and developed lung metastases. One patient died during the follow up period. This patient, initially diag- nosed with T1bN0M0 breast cancer with ER-PR- and positive HER2, received quadrantectomy with radiation therapy and adjuvant chemotherapy. At 29.5 months after surgical resection, she developed multiple metas- tases in the lung, skin, and chest wall. She died from breast cancer progression at 40.6 months after surgery. Discussion The results of this study confirmed an excellent short- term prognosis of lymph-node-negative invasive ductal carcinoma of the breast of 1 cm or less in a Korean population. Among 375 patients, only one patient died of breast cancer and only twelve cases of recurrence were reported. The overall five-year cumulative RFS rate was 97%. Univariate and multivariate analyses revealed that triple negative status and age younger than 35 years were significantly associated with shorter RFS. There are a number of studies that focus on the prog- nosis and predictors of recurrence of node-negative early breast cancer. Though many reviews were retro- spective and had small populations, high tumor grade was the most consistent factor associated with poor out- come in these studies [6,17-19]. Chia et al. surveyed 430, a relatively large number of patients with T1a,b breast cancer. They noted that patients with grade 3 tumor had shorter 10-year RFS compared to grade 1, 2 patients (with 74% vs. 82%, p = 0.007) [10]. Age, tumor size, lymphovascular invasion and estrogen receptor negativity were also commonly found to be poor prog- nostic factors [20-23]. In another report, Ki-67 and p53 were considered as significant prognostic factors of sur- vival [24]. More recently, reports have shown that