BACKGROUND: Currently, there is no consensus on whether to administer adjuvant radiotherapy after surgery for early stage breast cancer with one to three axillary lymph node metastases (pN1). For this group of patients, the NCCN guidelines from 2008 to 2012 changed from “consider” to “strongly consider” chemotherapy followed by radiotherapy to the chest wall and supraclavicular region. Previous findings suggest that factors associated with local recurrence after surgery in this group of patients include patient age, primary tumor size and quadrant, pathologic grade, hormone receptors, vascular invasion, and number and proportion of lymph node metastases. Since breast cancer is a highly heterogeneous group of tumors, there is an urgent need for new indicators reflecting the intrinsic biological properties of tumor cells to be incorporated into the prediction system of local recurrence. Objective: To explore the relationship between molecular subtypes of pN1 early-stage breast cancer and postoperative local/regional recurrence, to investigate the predictive value of molecular typing for local/regional recurrence of pN1 early-stage breast cancer, and to improve the indications for postoperative adjuvant radiotherapy in this group of patients by combining clinical and pathological features. Materials and methods: A retrospective analysis of breast cancer patients treated at the Cancer Control Center of Sun Yat-sen University from January 1998 to December 2009. A total of 679 patients were entered into this study. The median age at diagnosis was 48 years; 270 cases had pT1 stage and 409 cases had pT2 stage. There were 153 patients who underwent standard radical surgery, 508 patients who underwent modified radical surgery, and 18 patients who underwent breast-conserving surgery. 75 patients received postoperative adjuvant radiotherapy. Based on immunohistochemical results, patients were classified into four subtypes: luminal A [ER(+) or PR(+) and HER-2(-)], luminal B [ER(+) or PR(+) and HER-2(+)], HER-2 overexpressing [ER(-) and PR(-) and HER-2(+)] and basal cell-like [ER(-) and PR(-) and HER-2(+)]. (-) and HER-2(-)]. RESULTS: The median follow-up time was 64 months. The 5-year and 10-year local recurrence-free survival rates for the whole group were 90.3% and 84.9%, respectively; the 5-year and 10-year tumor-free survival rates were 82.8% and 72.5%, respectively; and the 5-year and 10-year overall survival rates were 90.1% and 80.5%, respectively. 134 cases had tumor recurrence, of which 71 cases were local/regional recurrence. The most common sites of recurrence were chest wall and supraclavicular lymph node area. In the whole group of 679 patients, luminal A type accounted for 47.1% (320/679), luminal B type accounted for 25.5% (173/679), HER-2 overexpression type accounted for 8.4% (57/679), and basal cell-like type accounted for 11.0% (75/679). Univariate analysis of the whole group revealed a higher risk of local recurrence in the basal cell-like type compared with the luminal A type, with 5-year LRFS of 93.4% versus 86.6%, respectively (P=0.036), and age ≤35 years and pT2 stage lesions were unfavorable prognostic factors affecting LRFS. Further, in a univariate analysis of 604 patients without postoperative radiotherapy, the risk of local recurrence was higher in HER-2 overexpressing and basal cell-like types compared with luminal A. The 5-year LRFS was 93.5% versus 81.1% and 86.9%, respectively (P=0.044 and P=0.040), and age ≤35 years, pT2 stage lesions and 2 to 3 axillary lymph nodes metastasis were unfavorable prognostic factors affecting LRFS. Multifactorial analysis of the group without postoperative radiotherapy showed that HER-2 overexpression and basal cell-like type, age ≤35 years, pT2 stage lesions and 2-3 axillary lymph node metastases were independent adverse prognostic factors for survival without local recurrence. Further subgroup analysis revealed that 5-year LRFS was 97.7%, 94.7%, and 85.2% for patients with 0, 1, and 2 to 4 risk factors, respectively; and 10-year LRFS was 95.8%, 89.5%, and 76.4%, respectively, with statistically significant differences between the three groups (χ2=17.96, P0.001). The study concluded that for patients with postoperative pN1 early-stage breast cancer, approximate molecular typing based on immunohistochemical markers could better differentiate the risk of local recurrence among patients, and HER-2 overexpression type or basal cell-like type, age ≤35 years, pT2 stage primary tumor and 2-3 axillary lymph node metastases were independent poor prognostic factors for local/regional recurrence, and those with 2 to 4 risk factors should Consider postoperative adjuvant radiotherapy.