Kwon et al. BMC Cancer 2010, 10:557 http://www.biomedcentral.com/1471-2407/10/557 have evaluated the long-term prognosis according to the hormone receptor and human epidermal growth factor receptor 2 (HER2) statuses because many patients were not examined for estrogen receptor (ER), progesterone receptor (PR), or HER2 status before these tests became widely available. Therefore, some controversy remains regarding treatment decisions for these patients. The features of breast cancer vary among Asian coun- tries, but there is a common tendency of younger age- onset and a large proportion of premenopausal women [5,13]. Some studies have reported higher rates of hormone receptor negative or high-grade breast tumor in Asian populations [14]. However, the ethnic differences asso- ciated with recurrence or mortality remain unclear, espe- cially in node-negative early breast cancer of 1cm or less. The aim of this study was to evaluate the overall prog- nosis of lymph node negative invasive ductal carcinoma of the breast of ≤ 1 cm in size, including microinvasive carcinoma (T1mic) in a Korean population. Moreover, through identification of subgroups of patients with a high risk of recurrence and their characteristics, we set out to determine which subgroup of patients would be candidates for systemic adjuvant therapies. Methods Study population We identified the study population from a prospectively maintained hospital-based cancer registry and collected information from all consecutive women diagnosed as invasive breast carcinoma at Seoul National University Hospital and Seoul National University Bundang Hospital from January 2000 to December 2006. Eligibility criteria included complete surgical resection, histologic diagnosis of invasive ductal carcinoma of 1 cm or less (T1a, T1b), or microinvasive carcinoma (T1mic) and no lymph node metastasis (N0) according to the fifth and sixth editions of the American Joint Committee on Cancer (AJCC) Cancer Staging Manual [15]. Both the fifth and sixth edi- tions were used because T staging did not differ between the two staging systems. Patients with a history of pre- vious malignancy of the breast or other sites and who received neoadjuvant chemotherapy were excluded. Clinical and biological data acquisition Data on patient’s baseline characteristics and symptoms, mammography results, type of operation and axillary lymph node examinations were collected. The type of operation was divided into mastectomy and breast- conserving surgery, and breast-conserving surgery included lumpectomy, quadrantectomy and excision of the primary tumor. Methods of axillary lymph node examination were classified into sentinel lymph node biopsies and axillary lymph node dissections. Page 2 of 8 Pathologic information was obtained by reviewing pathology reports on the following variables: tumor size, histologic subtype, modified Bloom-Richardson histologic grade (tubule formation, nuclear pleomorphism, mitotic counts), extent of intraductal carcinoma, lymphatic inva- sion, venous invasion and tumor border. Immunohisto- chemical data for standard prognostic biomarkers (ER, PR, HER-2, p53 and Ki-67) were also collected. Immuno- histochemical staining was determined from microinva- sive foci in cases of T1mic disease. For ER and PR, cases with 10% or more positive staining were grouped as posi- tive. For HER-2, 3+ staining by immunohistochemistry was considered positive. For Ki-67 status, we grouped the cases with 10% or more positive staining as a positive [16]. A 10% cutoff value was also used for p53 expression. Information about treatment undertaken as an adjuvant therapy was also retrieved. Recurrence free survival (RFS) was calculated as the time from operation to diagnosis of a recurrent disease in the ipsilateral breast, local, regional or distant site. For patients who remained alive and recurrence-free, data were censored at the date of the last follow up. The information of recurrent disease included time of diagnosis, sites of disease (local, regional, systemic), and histologic features of recurrent tumor (ductal carcinoma in situ or invasive ductal carcinoma). Diagnosis of con- tra-lateral breast cancer was not included in the cate- gory of recurrent disease. Overall survival was measured as the time from operation to death. Statistical analysis Pearson’s chi-square test was used to assess differences in clinical and biological characteristics between T stage subgroups. The RFS curves were constructed using the Kaplan-Meier method, and the log-rank test was used for a comparison of the survival curves between sub- groups according to prognostic factors. We also com- pared the five-year cumulative survival rate and investigated the association between the probability of death or recurrence and the clinical and biologic fea- tures. Multivariate analysis was conducted using Cox’s proportional hazard regression model, and our data was shown to satisfy the proportional hazard assumption. A significance level of 0.05 was used for covariate entry. All statistical analyses were performed using SPSS for Windows software, version 15.0 (SPSS Inc., Chicago, IL). The study was approved by an independent review board at the Seoul National University Bundang Hospi- tal and Seoul National University Hospital. Results Clinical and histologic characteristics From January 2000 to December 2006, we identified a total of 3889 women with invasive breast cancer who