Abstract 94P
Background
The PI3K/Akt signaling pathway can be considered as an important regulator of breast cancer stem cells that play critical role in the tumor progression and drug resistance. The purpose of this study was to investigate the PI3K/Akt signaling components and CD326+CD44+CD24-/low cells in relation to tamoxifen treatment in breast cancer patients.
Methods
Flow cytometry was used to evaluate the expression levels of CD326+CD44+CD24-/low, p-Akt473, PTEN, IGFR1 (CD221) and their combinations in fresh frozen breast cancer samples from 59 patients who developed distant metastasis or recurrence during the adjuvant tamoxifen therapy (tamoxifen resistance group – TR) or had responsive to tamoxifen treatment (tamoxifen sensitive group –TS). Genotypes for ESR1 rs2228480, Akt1 rs1130233, PTEN rs11202592, IGFR1 rs2016347 SNPs were analysed by a TaqMan technology. Progression-free survival was used as end-point for survival analyses.
Results
The population of CD326+CD44+CD24-/low cells were significantly associated with tamoxifen resistance (P=0.049). The triple-positive CD326+CD44+CD221+ population was more prevalent in TR patients than in TS group (P=0.041). TR tumors contained the higher percentage of p-Akt473 cells compare to TS (P=0.048). The triple-positive CD326+CD221+p-Akt473+ expression was marginally associated with resistance to tamoxifen (P=0.091). We observed higher frequency of G allele of IGFR1 rs2016347 among patients who did not benefit from tamoxifen treatment compare to tamoxifen sensitive patients (P=0.046). The AA mutant genotypes of ESR1 rs2228480 were more frequent among the TR group than in TS patients (P=0.040). Kaplan–Meier analysis showed a poorer clinical outcome for patients of the mutant genotype of ESR1 rs2228480 (log-rank P=0.043).
Conclusions
Our results suggest that breast cancer patients with high CD326+CD44+CD24-/low and p-Akt473 expression as well as with co-expression of CD221+ cells in tumor tissue were less sensitive to tamoxifen treatment. More detailed assessment of breast cancer stem cells markers and PI3K/Akt signaling components are required to investigate their clinical and prognostic efficacy.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Russian ScientificFoundation, grant #19-75-30016.
Disclosure
All authors have declared no conflicts of interest.