The Genetic Influence on Aromatase Inhibitors in Breast Cancer

Aromatase inhibitors in breast cancer therapy

Aromatase is an enzyme, made in the fat cells by several genes. It is important in hormone positive cancers since its primary role is to convert hormones (particularly testosterone) to estrogens that then can contribute to cancer growth. In breast cancer, aromatase inhibitors are commonly used as therapeutic targets to block estrogen formation.

Aromatase Genes 1
There are three primary aromatase inhibitor medications:
  • Arimidex (chemical name: anastrozole)
  • Aromasin (chemical name: exemestane)
  • Femara (chemical name: letrozole)

There are numerous nutrients we use that can help inhibit aromatase:

 

Variants (or defects) in the genes that make the enzymes that convert aromatase to estrogen can either up-regulate (make MORE estrogen) or down-regulate (make LESS estrogen) so understanding these defects is helpful.  One risk-associated gene is the CYP19A1; defects on this gene increase the risk of cancer progression.(1) Other variants (rs700519 and rs2069522) are associated with an increased susceptibility to breast cancer.(2) Yet another is associated with an increased estrone/androstenedione ratio and a fourth variant has an association with improved treatment outcomes and increased time to disease progression. The A allele of rs4646, which is positively associated with longer overall survival, is thought to be the result of having lower levels of aromatase, which enables a greater response to aromatase inhibitor therapy.

 

(1)  2006 Nov;15(11):2115-22. Genetic polymorphisms of the CYP19A1 gene and breast cancer survival. Long JR1, Kataoka N, Shu XO, Wen W, Gao YT, Cai Q, Zheng W.

(2)  2015 Feb 13;16(2):4121-35. doi: 10.3390/ijms16024121. Genetic polymorphisms in estrogen-related genes and the risk of breast cancer among Han Chinese women. Sun MY1, Du HY2, Zhu AN3, Liang HY4, de Garibay GR5, Li FX6, Li M7, Yang XX8.