Zhou et al. BMC Cancer 2010, 10:653 http://www.biomedcentral.com/1471-2407/10/653 Follow-up and Study End Points Follow-up started on the day of diagnosis and concluded on the date the patient was last observed or the date of death. The database was frozen for the statistical ana- lyses based on follow-up through 30th April 2008. Com- plete follow-up was achieved for all 458 patients. For this study, the two primary end points were local recurrence and invasive- or general recurrence. Local recurrence was defined as any ipsilateral recurrence (in situ or invasive). In addition, we defined “invasive- or general recurrence” as occurrence of an invasive ipsilat- eral recurrence, general metastasis or breast cancer- specific death, whichever occurred first. All women with an invasive local recurrence were included as cases regard- ing both endpoints. The endpoint “invasive- or general recurrence” was constructed to find patients with a biolo- gically more aggressive disease. Contralateral breast tumors were considered as new primary breast cancers. Statistic analyses Baseline characteristics among patients with different molecular subtypes were compared by Chi-square for categorical variables or analysis of variance for continu- ous variables. Survival and probabilities of local recur- rence and invasive disease among patients with different molecular subtypes were first compared by the Kaplan- Meier method. Cox proportional hazards regression models were used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs), with adjustment for age in the univariate analysis and further, histological grade, type of surgery, tumor size, detection mode and post- operative radiotherapy in the multivariate analysis. Kaplan-Meier curves and Cox proportional hazard mod- els were used to assess the association between molecu- lar subgroup and progression of breast cancer. Data were analyzed using the SAS (SAS Institute, Cary, NC) and R softwares. This study was approved by the Ethics Committee at Uppsala University Hospital (Dnr 2005: 118). In this ret- rospective cohort study we did not have to get an informed consent from the women according to the ethical approval, Dnr 170/95 and 99/422. Results 1. Baseline Characteristics Baseline characteristics according to the molecular sub- type of 392 eligible study participants (66 women did not get enough IHC information) are presented in Table 1. The median follow-up was 122 months (range 3-130). Among the 392 women, 32 (8.2%) were classi- fied as basal-like, 351 (89.5%) as luminal or HER2- positive, and 9 (2.3%) were unclassified. The median age at diagnose was 58 years (range 30-90 years). All basic characteristics, including age, tumor size and grade, Page 3 of 8 were evenly distributed between the basal-like and non basal-like tumors. No women received antiestrogen or chemotherapy after primary surgery. Type of surgery, mastectomy vs. breast conserving surgery (BCS) and postoperative radiotherapy were decided according to local tradition. BCS in Sweden means removing a sector of the breast parenchyma in up to a quadrant of the breast, aiming for a 10 mm free margin. The breast par- enchyma is removed from behind the areola margin to the periphery of the gland. Postoperative radiotherapy was given to 140 of 298 women undergoing BCS. It was generally given at 25 occasions, up to 50 Grey. A small part of these women were included in a Swedish study randomizing between radiotherapy or not after BCS for a primary DCIS [27]. Others were given radiotherapy based on tumor size and histopathological grade. How- ever, at that time, no criteria for radiotherapy regarding size or grade were given in the Swedish National Guidelines. 2. Survival Outcomes 2.1 Local-recurrence Of the 76 women who had a local recurrence, 42 had an in situ recurrence and 34 an invasive recurrence. Med- ian follow-up to local recurrence was 97.5 months (range 3-255). In both the univariate and multivariate models, basal-like DCIS showed a higher risk of local recurrence compared with non basal-like DCIS, hazard ratio (HR), 1.7 (CI 95%: 0.8-3.8) and 1.8 (0.8-4.2) respec- tively (Table 2). However, the difference was not statisti- cally significant. When only looking at women who had BCS, the risk for basal-like DCIS was equally higher (Table 2). Kaplan-Meier analyses were also made for all women and those undergoing BCS separately. The ana- lyses showed a higher risk for basal-like DCIS compared to the non basal-like group but it was not statistically significant. The p-value was 0.08 for all women and 0.26 for women undergoing BCS (Figure 1a). 2.2 Invasive- or general recurrence Forty-seven women developed invasive disease. Forty- four had an invasive local recurrence (of which 10 first had an in situ local recurrence and then an invasive local recurrence). Three women had general metastases as the first event. Eight died from breast cancer, but all of these had had a local recurrence or general metas- tases before death. Median follow-up to an invasive- or general recurrence was 111.5 months (range 3-255). Basal-like DCIS showed a higher risk of invasive- or general recurrence compared with non basal-like DCIS, HR, 2.0 (CI 95%: 0.8-5.0) and 1.9 (0.7-5.1) respectively (Table 2). However, the difference was not statistically significant. When only looking at women who had BCS, the risk for basal-like DCIS was also about doubled, but the risk was not statistically significant higher (Table 2).