28 117 132 83 67 7 220 153 33 225 58 27 89 7 124 97 74 91 20 246 105 55 232 171 3 0.713 0.641 0.062 0.649 0.758 0.524 0.421 Two-sided test. 2 doi:10.1371/journal.pone.0121535.t003 6 / 13 The CYP19 RS4646 Polymorphism and the Prognosis of Early Breast Cancer Fig 1. Survival curves for the total patients. a. Disease-free survival of the patients grouped CJ-023423 site according to CYP19 rs4646 genotypes. b. Disease-free survival of the patients grouped by CYP19 rs4646 genotypes. c. Disease-free survival of the patients subgrouped according to CYP19 rs4646 genotypes. doi:10.1371/journal.pone.0121535.g001 and patients characteristics while subgrouped into two cohorts, one with CC genotype and the other carrying AC or AA variants. CYP19 polymorphisms and DFS The median follow-up time was 96 months. Overall, there was no significant difference in DFS among patients with these three genotypes . Moreover, no relationship was observed between the patients with wild-type genotype and those carrying AC or AA variants , between CC or AC genotype and AA variant . In premenopausal women, AA genotype tended to be in relation with longer DFS . 7 / 13 The CYP19 RS4646 Polymorphism and the Prognosis of Early Breast Cancer Fig 2. Survival curves for the premenopausal patients. a. Disease-free survival of the premenopausal women stratified by CYP19 rs4646 PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19763871 genotypes. b. Disease-free survival of the premenopausal women grouped according to CYP19 rs4646 genotypes. doi:10.1371/journal.pone.0121535.g002 1 HR P1 0.041 0.261 0.294 0.625 0.154 0.039 0.157 0.013 0.161 0.299 0.560 1.035 1.060 0.938 0.812 0.943 1.163 0.863 0.866 0.909 Data 
were estimated by Cox regression analyses with adjustment for tumor size, lymph nodes involved, ER and PR status, HER-2 status, Body Mass Index, chemotherapy, adjuvant hormone therapy and radiotherapy. doi:10.1371/journal.pone.0121535.t004 8 / 13 The CYP19 RS4646 Polymorphism and the Prognosis of Early Breast Cancer Fig 3. Survival curves for the postmenopausal patients. a. Disease-free survival of the postmenopausal women grouped by CYP19 rs4646 genotypes. b. Disease-free survival of the postmenopausal women stratified by CYP19 rs4646 genotypes. PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19761601 doi:10.1371/journal.pone.0121535.g003 1 HR P1 0.002 0.617 0.029 0.844 0.153 0.560 0.992 0.102 0.650 0.462 2.983 1.055 1.330 0.939 0.669 0.971 1.001 0.646 0.886 0.880 Data were estimated by Cox regression analyses with adjustment for tumor size, lymph nodes involved, ER and PR status, HER-2 status, Body Mass Index, chemotherapy, adjuvant hormone therapy and radiotherapy. doi:10.1371/journal.pone.0121535.t005 9 / 13 The CYP19 RS4646 Polymorphism and the Prognosis of Early Breast Cancer When the patients were divided into two groups, one with AA variant and the other carrying CC or AC genotypes, AA genotype was significantly associated with prolonged DFS . Furthermore, being adjusted by positive lymph nodes, tumor size >5 cm, negative hormone receptor status, HER-2-postive status, chemotherapy, radiation and hormone therapy in multivariate analyses, AA genotype remained an independent prognostic factor for DFS . In postmenopausal women, AA genotype was evident to be in relation with shorter DFS . Moreover, there was significant difference in DFS between the patients with AA variant and those carrying CC or AC genotype . In the Cox proportional hazards model, after adjusting for the patients features, AA variant was explored to be an independent prognostic factor for DFS . Discussion In the present study, w