Regulation of aromatase expression in breast cancer treated with anastrozole neoadjuvant therapy

Chiara Ghimenti, Maurizia Mello-Grand, Enrico Grosso, Maria Scatolini, Lea Regolo, Alberto Zambelli, Giovanna Chiorino

Research output: Contribution to journalArticle

Abstract

Aromatase inhibitors (AIs), such as anastrozole, are established in the treatment of hormone-dependent breast cancer. However, ~20% of patients with hormone receptor-positive breast tumors treated with anastrozole do not respond and it remains impossible to accurately predict sensitivity. Since polymorphisms in the aromatase gene may influence the response to inhibitory drugs, we evaluated the presence of rs6493497 and rs7176005 polymorphisms (mapping in the 5'-flanking region of the CYP19A1 gene coding for the aromatase protein) in a cohort of 37 patients with postmenopausal breast cancer who received three-month neoadjuvant treatment with anastrozole. We then investigated any association of the polymorphisms with changes in aromatase mRNA expression change and/or response to treatment. We also analyzed five miRNAs computationally predicted to target aromatase, to observe any association between their expression and sensitivity to anastrozole. Three samples carried the two polymorphisms and the remaining samples were wild-type for both, however, no association with response or with aromatase mRNA basal expression level or expression difference after therapy was observed. Polymorphic samples that were resistant to anastrozole showed no change or decrease in aromatase expression following AI treatment, whereas an increase in expression was observed for the polymorphic responsive samples. No statistically significant correlation was observed between miRNA and aromatase mRNA expression, or with response to anastrozole neoadjuvant treatment. These data indicate that the polymorphisms analyzed are not involved in aromatase activity and that other epigenetic mechanisms may regulate aromatase protein expression.

Original languageEnglish
Pages (from-to)902-906
Number of pages5
JournalExperimental and Therapeutic Medicine
Volume5
Issue number3
DOIs
Publication statusPublished - Mar 2013

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Keywords

  • Aromatase inhibitors
  • Aromatase targeting microRNAs
  • Breast neoplasms
  • Genetic polymorphism
  • Intrinsic resistance

ASJC Scopus subject areas

  • Medicine(all)
  • Cancer Research
  • Immunology and Microbiology (miscellaneous)

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