In the group 2, three patients received adjuvance with tamoxifen, 19 tamoxifen and chemotherapy, 4 received chemotherapy only and 5 adjuvant endocrine therapy without tamoxifen. before 48 months showed nuclear location of hPXR isoform 2. This location was associated with the nuclear immunoexpression of RXR-alpha. Conclusion Breast cancer cells can express both variants 1 and 2 of hPXR. Infiltrative carcinomas that recurred showed a nuclear location of both hPXR and RXR-alpha; therefore, the overexpression and the subcellular location changes of hPXR could be considered as a potential new prognostic indicator. Background The human pregnane X receptor (hPXR, also known as SXR) is a member of the NR1I2 subfamily [1]. This receptor presents different isoforms that are differentially activated by a remarkably diverse collection of compounds including both xenobiotics and natural steroids [2]. PXR orthologs show marked differences in their activation profiles between species; ATP (Adenosine-Triphosphate) thus, pregnenolone 16-carbonitrile is an efficacious activator of mouse and rat PXR, but has much less activity on the human and rabbit receptors. Conversely, rifampicin activates the human and rabbit PXR but has no activity on the mouse or rat receptors [3]. PXR is a needed partner of RXRs [4] to form heterodimers that induce transcription from ER6 [5] or IR6 [6] response elements present in steroid-inducible em cytochrome P450 /em ( em CYP /em ) gene promoters [7]. em Cytochrome P450 /em constitutes a multigene family of hemoproteins responsible for the metabolism of numerous xenobiotics, including therapeutic drugs, environmental chemicals and dietary constituents, as well as endogenous compounds such as steroids and bile acids [8]. Kliewer et ATP (Adenosine-Triphosphate) al. [3] demonstrated in mice that the strong activation of PXR evoked by the pregnane compounds seemed to be mediated by em CYP3A /em induction; this effect also appeared in the homologous counterparts of rat, rabbit, and humans [5,6,9,10]. CYP3A and hPXR are mainly expressed in the liver and the intestine, and, to a lesser extent, in kidney and lung [11]; in addition CYP3A enzymes have been found in human breast cancer tissue [12,13]. The tissue distribution and the relative abundance of hPXR mRNA resemble CYP3A expression very closely, suggesting that hPXR may be important not only for induction but also for constitutive expression of these enzymes [11]. Dotzlaw et al. [14] have shown that the level of hPXR mRNA did not differ between breast tumours and their adjacent matched normal breast cells; however, among different breast tumour ATP (Adenosine-Triphosphate) types the manifestation of hPXR mRNA is definitely diverse. This suggests that hPXR is not significantly modified during tumorigenesis but may display changes related to the malignancy phenotype and the degree of differentiation [14]. However, Miki et al. [15] analyzed samples of atypical ductal hyperplasia, ductal carcinoma em in situ /em and invasive ductal carcinoma of the human being breast and they detected the presence of neither hPXR mRNA nor protein in non-neoplastic breast tissues Fn1 suggesting that hPXR is definitely predominantly indicated in carcinoma cells. Several studies ATP (Adenosine-Triphosphate) possess implicated different cytochrome P450 proteins in the mechanisms of resistance to antiestrogens (tamoxifen and toremifene), taxanes and additional anticancer compounds. Therefore, the study of the manifestation and regulatory pathways of P450 in malignancy became an active study field [16,17]; in contrast, studies concerning hPXR are hardly ever found in the literature. Because hPXR is related to the response to different antitumoural treatments, we have investigated the distribution of this orphan receptor and its needed partner RXRs in normal, premalignant, and malignant breast cells. Also, we analysed its relationship with the patient’s clinicopathological data to elucidate whether some variations in the pattern of manifestation of these proteins occurred and whether these variations could be important for prognostic purposes. Methods Individuals and histological samples Breast samples from 99 individuals ATP (Adenosine-Triphosphate) randomly selected and diagnosed from the Pathology Services of the Hospital Prncipe de Asturias and Hospital Virgen de la Victoria were used with the consent of the individuals and permission of the Ethics Committees of Private hospitals. Glandular lesions were classified as follows: 12 instances of benign proliferative diseases (BBDs) including ductal and lobular hyperplasia, apocrine metaplasia, fibroadenoma and fibrocystic.