Garcia-Casado et al. BMC Cancer 2010, 10:36 http://www.biomedcentral.com/1471-2407/10/36 cases, this reduction in the tumor proliferation rate is only modest and could not be sufficient to determine a resistance to the treatment. As expected, early tumor changes are not limited to proliferation markers, but to other genes directly regulated by ER, including the aro- matase itself [43]. Other, currently ongoing, approaches have used gene expression profiling techniques able to predict response to endocrine therapy, but the results obtained so far are inconsistent [43]. In our series, expression of proliferating marker Ki67 constituted a factor of poor prognosis in the group of patients under- going surgery following letrozole induction therapy, sug- gesting that this marker could identify tumors with a more aggressive behavior. Conclusion We have found that genetic variants of the polymorph- ism rs4646 in the 3’-UTR of CYP19A1 are associated to poor response to letrozole after 4 months induction therapy and to poor outcome of elderly patients without surgery after letrozole administration in postmenopausal women with ER/PgR [+] BC. Although our study would suggest that analysis of rs4646 could improve the clini- cal management of these patients by facilitating a more individualized therapy, further studies based on larger series are necessary to confirm these findings. List of abbreviations 3’-UTR: 3’-untranslated region; CYP19A1: aromatase gene; BC: breast cancer; BCS: breast conserving surgery; CR: complete response; DAB: diamino-benzidine; ER: estrogen recetor; HWE: Hardy-Weinberg equilibrium; IDC: infiltrating ductal carcinoma; ILC: infiltrating lobu- lar carcinoma; PR: partial response; PBS: phosphate-buf- fer saline; PgR: progesterone receptor; PD: progression disease; PFS: progression free survival; RR4M: radiologi- cal response at 4 months; SNPs: single nucleotide poly- morphisms; SD: stable disease; WHO: World Health Organization. Additional file 1: Table S1. Association of clinical, pathological and genotypic parameters with progression free survival (PFS). This table shows the associations of the clinicopathological and genetic parameters with PFS that have not been statistically significant. Click here for file [ http://www.biomedcentral.com/content/supplementary/1471-2407-10- 36-S1.DOC ] Additional file 2: Table S2. Association of clinical, histopathological and genotypic parameters with progression free survival (PFS) according to surgery status. This table shows the associations of the clinicopathological and genetic parameters with PFS that have not been statistically significant according to surgery status. Click here for file [ http://www.biomedcentral.com/content/supplementary/1471-2407-10- 36-S2.DOC ] Page 10 of 11 Acknowledgements We thank Maria Garcia Flores, Tania Mazcuñan and Laura Martinez for their technical assistance. This study has been financed by grants GV0A6/256 from the Conselleria d’Empresa Universitat i Ciència of the Generalitat Valenciana (JALG) and SOLTI 06/01 (ALLC). Author details 1Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. 2Department of Medical Oncology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. 3Department of Medical Oncology, Hospital Arnau de Villanova, Lleida, Spain. 4Department of Pathology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. 5Department of Pathology, University of Valencia, Spain. 6Department of Radiology, Fundación Instituto Valenciano de Oncología, Valencia, Spain. 7Department of Surgery, Fundación Instituto Valenciano de Oncología, Valencia, Spain. Authors’ contributions ZGC carried out the molecular genetic studies, participated in the genetic analysis and drafted the manuscript. AGZ reviewed the clinical records of the patients included in the study and drafted the manuscript. AFS performed the genetic analysis. ALlC, ARS, JG, MAC and VG treated most of the patients included in the study and updated the clinical follow-up. AC, SA and ALlB carried out the histopathological and immunohistochemical analysis. JCD performed the radiological evaluation of the study. JC and CVA performed the trucut biopsies and informed to the patients about the study. JALG conceived of the study, performed the statistical analysis and participated in its design and coordination and helped to draft the manuscript. All authors read and approved the final manuscript. Competing interests The authors declare that they have no competing interests. Received: 3 September 2009 Accepted: 9 February 2010 Published: 9 February 2010 References 1. Simpson ER, Mahendroo MS, Means GD, Kilgore MW, Hinshelwood MM, Graham-Lorence S, Amarneh B, Ito Y, Fisher CR, Michael MD, et al: Aromatase cytochrome P450, the enzyme responsible for estrogen biosynthesis. Endocr Rev 1994, 15(3):342-355. 2. 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