Pregnane X Receptor (PXR) is involved in human
cancer, either by directly affecting
carcinogenesis or by inducing drug-drug interactions and
chemotherapy resistance. The clinical significance of PXR expression in invasive
breast carcinoma was evaluated in the present study. PXR
protein expression was assessed immunohistochemically on
formalin fixed
paraffin-embedded breast invasive
carcinoma tissue sections, obtained from 148 patients, and was correlated with clinicopathological parameters, molecular phenotypes,
tumor cells' proliferative capacity, and overall disease-free patients' survival. Additionally, the expression of PXR was examined on human
breast carcinoma cell lines of different histological grade, hormonal status, and metastatic potential. PXR positivity was noted in 79 (53.4%) and high PXR expression in 48 (32.4%), out of 148
breast carcinoma cases. High PXR expression was positively associated with nuclear grade (p = 0.0112) and histological grade of differentiation (p = 0.0305), as well as with
tumor cells' proliferative capacity (p = 0.0051), and negatively with
luminal A subtype (p = 0.0295). Associations between high PXR expression,
estrogen, and
progesterone receptor negative status were also recorded (p = 0.0314 and p = 0.0208, respectively). High PXR expression was associated with shorter overall patients' survival times (log-rank test, p = 0.0009). In multivariate analysis, high PXR expression was identified as an independent prognostic factor of overall patients' survival (Cox-regression analysis, p = 0.0082). PXR expression alterations were also noted in
breast cancer cell lines of different hormonal status. The present data supported evidence that PXR was related to a more aggressive invasive
breast carcinoma phenotype, being a strong and independent poor prognosticator.