Research on aromatase gene (CYP19A1) polymorphisms as a predictor of endocrine therapy effectiveness in breast cancer

Single nucleotide polymorphisms (SNPs) of the CYP19A1 gene have shown the ability to modify its activity, but no association has been established with aromatase inhibitor (AI) efficiency in hormone receptor positive breast cancer (BC).

The study included blood samples from 53 patients (p) with BC and 1 control (male DNA); 22p. (investigational group) were administered an Al and followed up.

Homozygous (hh) -CC and TT -, and heterozygous (hz) - TC - genotypes of the rs10046 SNP were balanced. Response to treatment or progression were not affected (p=0.630) in patients with T allele 1; local relapse occurred significantly more rarely and overall survival (OS) was superior (p=0.046). For rs4646, genotypes were mainly hhGG (57%), with no implication to study parameters (p>0.05). For rs727479 SNP, major genotypes were hhTT (40%) and hzTG (45%). Therapeutic response was better in patients with T allele 2 (p=0.040), T allele 1 was associated with reduced local recurrence (p=0.047) and TT genotype with better OS (p = 0.008). In rs700518 SNP, genotype was mostly hzGA (49%). Local recurrence rates were reduced in the presence of G allele 1 (p=0.047) and GG homozygosity.

At this stage, the study was purely exploratory and hypothesis generating. Genotyping of at least three of the four CYP19A1 SNPs evaluated (except rs4646) may have an impact in clinical practice, providing better criteria for patient selection, prognosis and therapeutic decision in BC.