A polymorphism at the 3'-UTR region of the aromatase gene defines a subgroup of postmenopausal breast cancer patients with poor response to neoadjuvant letrozole

BMC Cancer

Research Article

Vicente Guillem¹  Amparo Ruiz-Simon¹  Angel Guerrero-Zotano¹  Joaquin Gavila¹  Miguel A Climent¹  Antonio Llombart-Cussac²  Ana Calatrava³  Sergio Almenar³  Antonio Llombart-Bosch⁴  Jose Cervera-Deval⁵  Josefina Campos⁶  Carlos Vazquez Albaladejo⁶  Zaida Garcia-Casado⁷  Antonio Fernandez-Serra⁷  Jose A Lopez-Guerrero⁷ 

[1] Department of Medical Oncology, Fundación Instituto Valenciano de Oncología, Valencia, Spain;Department of Medical Oncology, Hospital Arnau de Villanova, Lleida, Spain;Department of Pathology, Fundación Instituto Valenciano de Oncología, Valencia, Spain;Department of Pathology, University of Valencia, Spain;Department of Radiology, Fundación Instituto Valenciano de Oncología, Valencia, Spain;Department of Surgery, Fundación Instituto Valenciano de Oncología, Valencia, Spain;Laboratory of Molecular Biology, Fundación Instituto Valenciano de Oncología, Valencia, Spain;

关键词: Breast Cancer;    Tamoxifen;    Aromatase Inhibitor;    Letrozole;    Anastrozole;   

DOI  :  10.1186/1471-2407-10-36

 received in 2009-09-03, accepted in 2010-02-09,  发布年份 2010

来源: Springer

【 摘 要 】

BackgroundAromatase (CYP19A1) regulates estrogen biosynthesis. Polymorphisms in CYP19A1 have been related to the pathogenesis of breast cancer (BC). Inhibition of aromatase with letrozole constitutes the best option for treating estrogen-dependent BC in postmenopausal women. We evaluate a series of polymorphisms of CYP19A1 and their effect on response to neoadjuvant letrozole in early BC.MethodsWe analyzed 95 consecutive postmenopausal women with stage II-III ER/PgR [+] BC treated with neoadjuvant letrozole. Response to treatment was measured by radiology at 4th month by World Health Organization (WHO) criteria. Three polymorphisms of CYP19A1, one in exon 7 (rs700519) and two in the 3'-UTR region (rs10046 and rs4646) were evaluated on DNA obtained from peripheral blood.ResultsThirty-five women (36.8%) achieved a radiological response to letrozole. The histopathological and immunohistochemical parameters, including hormonal receptor status, were not associated with the response to letrozole. Only the genetic variants (AC/AA) of the rs4646 polymorphism were associated with poor response to letrozole (p = 0.03). Eighteen patients (18.9%) reported a progression of the disease. Those patients carrying the genetic variants (AC/AA) of rs4646 presented a lower progression-free survival than the patients homozygous for the reference variant (p = 0.0686). This effect was especially significant in the group of elderly patients not operated after letrozole induction (p = 0.009).ConclusionsOur study reveals that the rs4646 polymorphism identifies a subgroup of stage II-III ER/PgR [+] BC patients with poor response to neoadjuvant letrozole and poor prognosis. Testing for the rs4646 polymorphism could be a useful tool in order to orientate the treatment in elderly BC patients.

【 授权许可】

Unknown   
© Garcia-Casado et al; licensee BioMed Central Ltd. 2010. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.