Garcia-Casado et al. BMC Cancer 2010, 10:36 http://www.biomedcentral.com/1471-2407/10/36 Page 8 of 11 Figure 2 Kaplan Meier plot showing the progression-free survival with regard the genetic variants of rs4646 in the global series. main issues that could explain the differences between these two studies. First, and independently of the disease stage, are the criteria for patient selection. Whereas in our series the patients were treated with letrozole as a first line, in the study of Colomer et al. the patients had progressed from a previous treatment with tamoxifen [29]. It is well established that tamoxifen metabolism is influenced by the number of mutant alleles of the gene encoding cytochrome P450 2D6 (CYP2D6), because this enzyme affects the levels of endoxifen, the active tamox- ifen metabolite. Thus, for patients who are wild type for CYP2D6, the 5-year disease-free survival outcomes are similar to or perhaps even superior with tamoxifen than with aromatase inhibitors [39]. Therefore, previous treatment with tamoxifen could have genetically selected a population of patients more sensitive to letrozole. Sec- ondly, in our study we used constitutive DNA obtained from peripheral blood for the genetic analysis, whereas Colomer et al. performed the genetic study on DNA obtained from the fixed and paraffin-embedded tumors [29]. The polymorphism studies performed on tumor samples are subject to genetic alterations that can affect the chromosomal region of the gene under study. In this way, CYP19A1 is located in the 21.2 region of the long arm of chromosome 15 (15q21.2) [40], and this region has been reported to be a frequent target of alle- lic imbalance in advanced breast carcinomas [41], and which could affect the frequency distribution of the alle- lic variants. From our series, 65 women underwent surgery after letrozole induction, being age the only difference observed between the operated and non-operated patients. In fact 77% of patients within the non-surgery group were over 78.3 years. We have demonstrated that genetic variants of rs4646 have prognostic value, espe- cially in this group of patients. Indeed, the 6 women who progressed within the group of non-surgery patients were genetically characterized by the variant rs4646 (AC/AA). In this elderly group of patients the decision for undergoing surgery is not always easy and very often both the patient and the clinician opt for a local control of the tumor maintaining the treatment with letrozole. Hence, in this group of patients, in which the tumor is not removed, is where the rs4646 poly- morphism identifies the women who progressed, indi- cating, and despite the small number the cases included