Garcia-Casado et al. BMC Cancer 2010, 10:36 http://www.biomedcentral.com/1471-2407/10/36 Table 1: Clinical and pathological characteristics of the patients. (Continued) Surgery status No surgery Surgery 30 (32.0) 65 (68.0) *IDC, Infiltrating ductal carcinoma; ILC, Infiltrating lobular carcinoma; Others (Mucinous, tubular and medullar carcinomas). **Hormonal status was considered as ≤ 40% when either estrogen and progesterone receptors were ≤ 40%, and as > 40% when at least one of the receptors were > 40%. CYP19A1 polymorphism analysis A total of three single nucleotide polymorphisms (SNPs) were evaluated: one located in exon 7 (rs700519) and two in the 3’-UTR region of CYP19A1 (rs10046 and rs4646). Polymorphism references, genotypes, gene and chromosome locations, and frequency distribution of observed genotypes in the series are shown in Table 2. In addition, values for Hardy-Weinberg (HW) [33] equi- librium were estimated for each polymorphism and are also listed in Table 2. Both rs10046 and rs4646 were in HW equilibrium; however, for rs700519 this calculation was not possible as no genetic variant (CT, TT) was observed in any of the analyzed cases. Analysis between RR4M and clinical, pathological and genotypic parameters No statistically significant association was found between RR4M and the clinical and pathological para- meters (Table 3). However, an overrepresentation of the genetic variants (AC/AA) of the rs4646 polymorphism was observed in the non-responder group (48.3%) com- pared with the responders (25.7%) (p = 0.03) (Table 3). Clinical, pathological, genotypic parameters and progression free survival (PFS) The median follow-up of the series was of 40.6 months (range: 4.3-113.8 months). A total of 18 patients (18.9%) reported disease progression during this period (Table 1). Among the analyzed parameters, IIIa-IIIb stages and Table 2 CYP19A1 polymorphisms and genotype frequencies Genotype CC CT TT AA AG GG CC AC AA n (%) 89 (100) 0 (0) 0 (0) 23 (24.2) 57 (60.0) 15 (15.8) 57 (60.0) 30 (31.6) 8 (8.4) p* - 0.127 0.397 db-SNP id rs700519 rs10046 rs4646 Page 5 of 11 the non response to letrozole induction therapy were significantly associated with shorter PFS (Table 4; Addi- tional file 1: Supplemental Table S1; Fig. 1). Interest- ingly, those patients carrying the genetic variants (AC/ AA) of rs4646 presented a worse PFS than the patients homozygous for the reference variant (Table 4; Addi- tional file 1: Supplemental Table S1; Fig. 2). Multivariate analysis showed that lymph node involvement [Hazard Ratio (HR) = 4.3 (1.7-11); p = 0.002] and RR4M [HR = 11 (1.5-83); p = 0.012] constituted independent prognos- tic factors for PFS. Clinical, pathological, genotypic parameters and PFS according to the surgery status Sixty-five out of the 95 patients (68%) underwent surgery after letrozole induction therapy and no association was observed between the progression status and surgery (Table 1). In fact, 20% of non-surgery cases progressed, while 18.5% of the surgery group experienced progression events (p = 0.861). In addition, no significant differences in terms of PFS were observed between the non-surgery (74.5%) and surgery (60.4%) groups (p = 0.600). However, when we compared clinical, pathological and genetic parameters between the two groups of patients according to surgery status, we observed that 77% of patients of the non-surgery group were over the median age, compared with 37% of the patients from the surgery group (p = 0.00032). Moreover, rs4646 variant (AC/AA) was overre- presented in the non-surgery group (57%) in contrast to the surgery group (32%) (p = 0.024). Univariate analysis performed for PFS for each group of patients revealed that in the non-surgery group, RR4M and r4646 where associated with a worse prog- nosis (Table 5; Additional file 2: Supplemental Table S2). Indeed, the 6 patients who progressed were geneti- cally characterized by the variant rs4646 (AC/AA) (Fig. 3A). However, in the multivariate analysis only the poly- morphism rs4646 emerged as an independent prognostic factor although it did not reach statistical significance (p = 0.191). Gene location Exon 7 (codon 264) Chromosome position** 49.295.260 3’UTR 3’UTR 49.290.278 49.290.136 *p > 0.05 is consistent with the Hardy-Weinberg equilibrium; ** Sequence of reference NT_010194.16.