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Published on: February 21, 2014

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

Chiara Ghimenti1, Maurizia Mello-Grand, Enrico Grosso

  • 1Cancer Genomics Laboratory, Fondazione Edo ed Elvo Tempia Valenta, Biella;

Experimental and Therapeutic Medicine
|February 15, 2013
PubMed

Insights

Genetic variations in the aromatase gene (CYP19A1) do not predict response to anastrozole in breast cancer patients. Further research into other epigenetic factors is needed to understand treatment resistance to aromatase inhibitors.

Area of Science:

  • Oncology
  • Pharmacogenomics
  • Molecular Biology

Background:

  • Aromatase inhibitors (AIs) like anastrozole are standard for hormone-dependent breast cancer.
  • Treatment resistance occurs in ~20% of patients, with unpredictable sensitivity.
  • Genetic variations (polymorphisms) in the aromatase gene (CYP19A1) may influence AI response.

Purpose of the Study:

  • To investigate the association of rs6493497 and rs7176005 polymorphisms in the CYP19A1 gene with anastrozole response in postmenopausal breast cancer.
  • To examine the relationship between these polymorphisms, aromatase mRNA expression, and treatment outcomes.
  • To explore potential correlations between specific miRNAs, aromatase expression, and AI sensitivity.

Main Methods:

  • Genotyping for CYP19A1 polymorphisms (rs6493497, rs7176005) in 37 postmenopausal breast cancer patients.
  • Measurement of aromatase mRNA expression before and after neoadjuvant anastrozole therapy.
  • Computational analysis of five miRNAs predicted to target aromatase.

Main Results:

  • No association was found between the analyzed polymorphisms and response to anastrozole or changes in aromatase mRNA expression.
  • Polymorphic samples resistant to anastrozole showed no change or decreased aromatase expression, while responsive polymorphic samples showed increased expression.
  • No statistically significant correlation was observed between miRNA expression and aromatase mRNA levels or treatment response.

Conclusions:

  • The studied CYP19A1 polymorphisms (rs6493497, rs7176005) do not appear to be involved in regulating aromatase activity or predicting response to anastrozole.
  • Other epigenetic mechanisms likely play a role in the regulation of aromatase protein expression and subsequent response to AIs.
  • Further investigation into non-genetic factors is warranted to understand and overcome anastrozole resistance in breast cancer treatment.
Keywords:
aromatase inhibitorsaromatase targeting microRNAsbreast neoplasmsgenetic polymorphismintrinsic resistance

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