Garcia-Casado et al. BMC Cancer 2010, 10:36 http://www.biomedcentral.com/1471-2407/10/36 Page 7 of 11 Figure 1 Kaplan Meier plot showing the progression-free survival with regard the radiological response to letrozole at 4th month (RR4M) of the induction therapy. a slight decrease in Cys264 allozyme activity. They also demonstrated that the mechanism by which non-synon- ymous SNPs affect the enzymatic activity is a conse- quence of an alteration in the enzyme protein level [32]. In the same study, these authors reported that these var- iants had no significant differences in their affinity to the aromatase inhibitors letrozole and exemestane [32]. Interestingly, the polymorphism rs700519 has also been reported as a prognostic factor in a Chinese study, mainly in a subgroup of premenopausal women [28], but not in the Caucasian population [27]. In addition, it is impor- tant to note the differences between these two popula- tions regarding the minor allele frequency of rs700519, being only 3.2% for the Caucasian population (1,257 patients) [27], in comparison with 15.1% in the Asian Cohort (1,136 patients) [28]. In our series, the genetic variants of this polymorphism were underrepresented and not found in any of the cases. The third study evaluated the efficacy of treatment with letrozole in advanced hormone receptor-positive BC patients with respect to two polymorphisms located at the 3’-UTR (rs10046 and rs4646) and one in intron 2 [rs727479 (G/T)] of the CYP19A1 [29]. The authors found that genetic variants of rs4646 were associated with a greater efficacy of letrozole in terms of time to progression. Hence, patients with the variant genotype (AC/AA) had a three times greater time to progression than the patients with the reference genotype (CC). Furthermore, these authors reported that the frequency of the variant alleles for rs4646 was significantly higher in the responder (61%) than in the non-responder group of patients (40%) [29]. These observations clearly differ from those reported in our series, the genotypic variants of rs4646 being more frequently represented in the non- responder group to letrozole after 4 months of induc- tion therapy (48% vs. 26%). In this regard, there are two