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. 2010 Feb 9:10:36.
doi: 10.1186/1471-2407-10-36.

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

Zaida Garcia-Casado  1 , Angel Guerrero-Zotano, Antonio Llombart-Cussac, Ana Calatrava, Antonio Fernandez-Serra, Amparo Ruiz-Simon, Joaquin Gavila, Miguel A Climent, Sergio Almenar, Jose Cervera-Deval, Josefina Campos, Carlos Vazquez Albaladejo, Antonio Llombart-Bosch, Vicente Guillem, Jose A Lopez-Guerrero
Affiliations

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

Zaida Garcia-Casado et al. BMC Cancer. .

Abstract

Background: Aromatase (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.

Methods: We 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.

Results: Thirty-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).

Conclusions: Our 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.

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Figures

Figure 1
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.
Figure 2
Figure 2
Kaplan Meier plot showing the progression-free survival with regard the genetic variants of rs4646 in the global series.
Figure 3
Figure 3
Kaplan Meier plot showing the progression-free survival with regard the genetic variants of rs4646 in the no surgery (A) and surgery group of patients (B).
See this image and copyright information in PMC

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