Features of expression of transforming growth factor beta in estrogen-positive breast cancer

Tomsk National Research Medical Center of the Russian Academy of Sciences, Tomsk, Russia

Topicality . Changes in the activity of growth factors and their receptors play a key role in shaping the response to treatment with anticancer hormonal drugs.

The aim of this work was to study the relationship between the TGFβ1 and TGFβR1 expression and the progression of breast cancer (BC) during tamoxifen therapy.

Material and methods . Our study included 65 patients with primary estrogen-positive breast cancer who received tamoxifen at a standard dose of 20 mg/day as an adjuvant treatment. The age of the patients was 40–79 years. Depending on the effectiveness of the treatment, the patients were divided into two groups: a tamoxifen-sensitive group (no signs of disease progression, N = 55) and a tamoxifen-resistant group (with disease recurrence, N = 10). Genotyping of polymorphic loci (SNPs) TGFβ1 (rs1800470) and TGFβR1 (rs334354) was carried out by real-time PCR. The expression profile of the TGFβ1 and TGFβR1 genes was studied using reverse transcription PCR. The expression levels of TGFβ1 and TGFβR1 were assessed by flow cytometry.

Results . Our genotyping analysis showed that the carriage of mutant variants of the TGFβ1 gene (rs1800470) was associated with sensitivity to hormone therapy (p = 0.019 and p = 0.039; for the genotype and allele, respectively). Disease progression while taking tamoxifen was more often observed in patients with a high level of the TGFβ1 expression in the tumor tissue (p = 0.025). The percentage of cells expressing TGFβR1 was more often observed in tumors responding to the treatment (p = 0.036). A positive correlation between the transcriptional activity of the TGFβ1 and TGFβR1 genes (r = 0.295; p = 0.039) was revealed.

Conclusion . Determining the genetic features and the expression profile of TGFβI and TGFβRI can be essential in evaluating the effectiveness of antitumor treatment with tamoxifen.