Displaying publications 21 - 40 of 106 in total

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  1. Emaus MJ, Peeters PH, Bakker MF, Overvad K, Tjønneland A, Olsen A, et al.
    Am J Clin Nutr, 2016 Jan;103(1):168-77.
    PMID: 26607934 DOI: 10.3945/ajcn.114.101436
    BACKGROUND: The recent literature indicates that a high vegetable intake and not a high fruit intake could be associated with decreased steroid hormone receptor-negative breast cancer risk.

    OBJECTIVE: This study aimed to investigate the association between vegetable and fruit intake and steroid hormone receptor-defined breast cancer risk.

    DESIGN: A total of 335,054 female participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort were included in this study (mean ± SD age: 50.8 ± 9.8 y). Vegetable and fruit intake was measured by country-specific questionnaires filled out at recruitment between 1992 and 2000 with the use of standardized procedures. Cox proportional hazards models were stratified by age at recruitment and study center and were adjusted for breast cancer risk factors.

    RESULTS: After a median follow-up of 11.5 y (IQR: 10.1-12.3 y), 10,197 incident invasive breast cancers were diagnosed [3479 estrogen and progesterone receptor positive (ER+PR+); 1021 ER and PR negative (ER-PR-)]. Compared with the lowest quintile, the highest quintile of vegetable intake was associated with a lower risk of overall breast cancer (HRquintile 5-quintile 1: 0.87; 95% CI: 0.80, 0.94). Although the inverse association was most apparent for ER-PR- breast cancer (ER-PR-: HRquintile 5-quintile 1: 0.74; 95% CI: 0.57, 0.96; P-trend = 0.03; ER+PR+: HRquintile 5-quintile 1: 0.91; 95% CI: 0.79, 1.05; P-trend = 0.14), the test for heterogeneity by hormone receptor status was not significant (P-heterogeneity = 0.09). Fruit intake was not significantly associated with total and hormone receptor-defined breast cancer risk.

    CONCLUSION: This study supports evidence that a high vegetable intake is associated with lower (mainly hormone receptor-negative) breast cancer risk.

    Matched MeSH terms: Receptors, Estrogen/metabolism*
  2. Teoh KH, Looi LM, Sabaratnam S, Cheah PL, Nazarina AR, Mun KS
    Malays J Pathol, 2011 Jun;33(1):35-42.
    PMID: 21874750 MyJurnal
    Predictive biomarkers such as oestrogen (ER) and progesterone (PR) receptors and c-erbB-2 oncoprotein have become a staple in breast cancer reports in the country as they increasingly play an important role in the treatment and prognosis of women with breast cancers. This study reviews the practice of histopathology reporting of these biomarkers in a Malaysian tertiary hospital setting. Retrospective data on demographic, pathological and biomarker profiles of patients with invasive ductal carcinoma who had undergone mastectomy or lumpectomy with axillary node clearance from 2005 to 2006 were retrieved from the Department of Pathology, Penang Hospital and analysed. The prevalence of ER positivity (55.8%), PR positivity (52.5%), c-erbB-2 oncoprotein overexpression (24%) and triple negativity (ER negative, PR negative, c-erbB-2 negative) (15%) by immunohistochemistry were comparable with other studies. Notably, c-erbB-2 overexpression was equivocal (2+) in 15% of cases. Since about a quarter of equivocal (2+) cases usually show amplification by FISH, a small but certain percentage of patients would miss the benefit of anti-c-erbB-2 antibody therapy if FISH is not performed. New ASCO/CAP guidelines on the quantitation of ER and PR will probably increase the prevalence of ER/PR positivity, invariably leading to significant ramifications on the management of patients as more patients would be deemed eligible for endocrine therapy, as well as categorisation of triple negative breast cancers.
    Matched MeSH terms: Receptors, Estrogen/biosynthesis; Receptors, Estrogen/genetics
  3. Bong PN, Zakaria Z, Muhammad R, Abdullah N, Ibrahim N, Emran NA, et al.
    Malays J Pathol, 2010 Dec;32(2):117-22.
    PMID: 21329183 MyJurnal
    The GATA3 gene is a potential tumour marker and putative tumour suppressor gene in breast cancer. Its expression is associated with better prognosis and disease free survival in breast cancer patients. We aimed to evaluate GATA3 transcriptome expression and mutation in breast carcinomas and correlate its expression with oestrogen receptor (ER), progesterone receptor (PR), lymph node (LN) status, tumour grade and c-erbB-2 expression. Twenty-two breast infiltrating ductal carcinomas and paired normal tissues were used in Branch DNA assay to detect GATA3 mRNA expression. Normalized data for GATA3 mRNA expression were grouped according to the ER, PR and LN status, tumour grade and c-erbB-2 expression of the tumours. Statistical significance was tested using t-test and ANOVA at 95% confidence interval level. Mutational analysis of GATA3 was performed by direct sequencing of the coding regions of GATA3 mRNA. Our findings showed that GATA3 gene were over-expressed and under-expressed by > 2 fold change in 12 and 4 tested samples, respectively. Eighty per cent of ER positive breast carcinomas were GATA3 positive. There was a statistically significant correlation between GATA3 expression and ER at 95% confidence interval level between the study groups. On the contrary, GATA3 expression was not statistically significant with PR, LN, tumour grade and c-erbB-2 expression in our study. In addition, we observed that there was no mutation in mRNA coding region in 16 breast carcinomas that showed GATA3 differential gene expression. Our preliminary results suggested that GATA3 is linked to the ER. This scenario suggests that GATA3 may play a crucial role in oestrogen receptor positive breast cancer patients. Whether GATA3 expression is involved in regulating tumour cell growth in oestrogen responsive breast cancer is a key question that remains to be answered.
    Matched MeSH terms: Receptors, Estrogen/biosynthesis; Receptors, Estrogen/genetics
  4. Pihie AH, Stanslas J, Din LB
    Anticancer Res, 1998 May-Jun;18(3A):1739-43.
    PMID: 9673398
    The antiproliferative activity of a styrylpyrone derivative (SPD) plant extract, was studied in three different human breast cancer cell lines in culture, and was compared with tamoxifen. The number of living cells was evaluated by Methylene Blue staining technique. SPD showed strong antiproliferative activity in estrogen receptor (ER) and progestin receptor (PgR) positive MCF-7 cells (EC50 = 6.30 x 10(-7) M) and receptor-negative MDA-MB-231 (EC50 = 5.62 x 10(-7) M), but it partially inhibited the high progestin receptor positive T47D cells (EC50 = 1.58 x 10(-6) M). Whereas tamoxifen, a nonsteroidal antiestrogen exhibited strong inhibition on MCF-7 cells (EC50 = 1.41 x 10(-6) M) and partial inhibition on T47D cells (EC50 = 2.5 x 10(-6) M), but did not affect the MDA-MB-231 cells in the concentration range 0.1 nM-1 microM (EC50 = 5.01 microM). At the same concentration range SPD and tamoxifen did not inhibit the proliferation of normal human liver cell line CCL 13 and normal bovine kidney MDBK; whereas adriamycin, a common chemotherapy drug for the treatment of advance cancer, caused 95% inhibition at 10(-6) M. Competitive binding studies showed SPD had no ability to inhibit the binding of [3H]estradiol and [3H]progesterone to ER and PgR, respectively but, tamoxifen exhibited affinity for ER. Therefore, it can be concluded that the antiproliferative activity of SPD was selective towards breast cancer cell lines and not mediated by ER or PgR.
    Matched MeSH terms: Receptors, Estrogen/drug effects; Receptors, Estrogen/metabolism
  5. Rivers C, Idris J, Scott H, Rogers M, Lee YB, Gaunt J, et al.
    BMC Biol, 2015 Dec 22;13:111.
    PMID: 26694817 DOI: 10.1186/s12915-015-0220-7
    BACKGROUND: SAFB1 is a RNA binding protein implicated in the regulation of multiple cellular processes such as the regulation of transcription, stress response, DNA repair and RNA processing. To gain further insight into SAFB1 function we used iCLIP and mapped its interaction with RNA on a genome wide level.

    RESULTS: iCLIP analysis found SAFB1 binding was enriched, specifically in exons, ncRNAs, 3' and 5' untranslated regions. SAFB1 was found to recognise a purine-rich GAAGA motif with the highest frequency and it is therefore likely to bind core AGA, GAA, or AAG motifs. Confirmatory RT-PCR experiments showed that the expression of coding and non-coding genes with SAFB1 cross-link sites was altered by SAFB1 knockdown. For example, we found that the isoform-specific expression of neural cell adhesion molecule (NCAM1) and ASTN2 was influenced by SAFB1 and that the processing of miR-19a from the miR-17-92 cluster was regulated by SAFB1. These data suggest SAFB1 may influence alternative splicing and, using an NCAM1 minigene, we showed that SAFB1 knockdown altered the expression of two of the three NCAM1 alternative spliced isoforms. However, when the AGA, GAA, and AAG motifs were mutated, SAFB1 knockdown no longer mediated a decrease in the NCAM1 9-10 alternative spliced form. To further investigate the association of SAFB1 with splicing we used exon array analysis and found SAFB1 knockdown mediated the statistically significant up- and downregulation of alternative exons. Further analysis using RNAmotifs to investigate the frequency of association between the motif pairs (AGA followed by AGA, GAA or AAG) and alternative spliced exons found there was a highly significant correlation with downregulated exons. Together, our data suggest SAFB1 will play an important physiological role in the central nervous system regulating synaptic function. We found that SAFB1 regulates dendritic spine density in hippocampal neurons and hence provide empirical evidence supporting this conclusion.

    CONCLUSIONS: iCLIP showed that SAFB1 has previously uncharacterised specific RNA binding properties that help coordinate the isoform-specific expression of coding and non-coding genes. These genes regulate splicing, axonal and synaptic function, and are associated with neuropsychiatric disease, suggesting that SAFB1 is an important regulator of key neuronal processes.

    Matched MeSH terms: Receptors, Estrogen/genetics*; Receptors, Estrogen/metabolism
  6. Looi LM, Azura WW, Cheah PL, Ng MH
    Pathology, 2001 Aug;33(3):283-6.
    PMID: 11523925
    This investigation was carried out to gain insight into the prevalence of pS2 expression in invasive ductal breast carcinoma in the Malaysian population and its correlation with oestrogen receptor (ER) protein expression and tumour aggressiveness. Seventy consecutive infiltrating ductal breast carcinomas treated with mastectomy and axillary lymph node clearance were investigated, using the standard avidin-biotin complex immunoperoxidase method with microwave antigen retrieval and commercial monoclonal antibodies (Dako), for expression of pS2 and human ER. This was correlated against histological grade (modified Bloom and Richardson) and the presence of axillary lymph node metastasis of these carcinomas. Four (5.7%) were grade 1, 40 (57.1%) grade 2 and 26 (37.1%) grade 3 tumours. A total of 45 (64%) showed histological evidence of axillary lymph node metastasis. Forty (57%) were ER-positive, while 31 (44%) were pS2-positive. There was a statistically significant correlation between pS2 and ER expressions (chi2-test with Yates correction: P<0.005). There was no correlation between pS2 expression and histological grade (P>0.1) and the presence of lymph node metastasis (P>0.1). Our findings support the views that pS2 may be a co-marker of endocrine responsiveness in invasive breast cancer and that it does not influence breast cancer biology in terms of potential for metastatic spread.
    Matched MeSH terms: Receptors, Estrogen/analysis; Receptors, Estrogen/biosynthesis*
  7. Chinigarzadeh A, Muniandy S, Salleh N
    Steroids, 2016 11;115:47-55.
    PMID: 27521800 DOI: 10.1016/j.steroids.2016.08.007
    In this study, effects of estradiol, progesterone and genistein on uterine aquaporin (AQP)-1, 2, 5 and 7 expression were investigated in sex-steroid deficient state which could help to elucidate the mechanisms underlying uterine fluid volume changes that were reported under these hormone and hormone-like compound influences.

    METHODS: Uteri from ovariectomized, female Sprague-Dawley rats receiving seven days estradiol, progesterone or genistein (25, 50 and 100mg/kg/day) were harvested and levels of AQP-1, 2, 5 and 7 proteins and mRNAs were determined by Western blotting and Real-time PCR (qPCR) respectively. Distribution of these proteins in uterus was observed by immunohistochemistry.

    RESULTS: Genistein caused a dose-dependent increase in uterine AQP-1, 2, 5 and 7 protein and mRNA expression, however at the levels lower than following estradiol or progesterone stimulations. Effects of genistein were antagonized by estradiol receptor blocker, ICI 182780. Estradiol caused the highest AQP-2 protein and mRNA expression while progesterone caused the highest AQP-1, 5 and 7 protein and mRNA expression in uterus. AQP-1, 2, 5 and 7 protein were found to be distributed in the myometrium as well as in uterine luminal and glandular epithelia and endometrial blood vessels. In conclusion, the observed effects of estradiol, progesterone and genistein on uterine AQP-1, 2, 5 and 7 expression could help to explain the differences in the amount of fluid accumulated in the uterus under these different conditions.

    Matched MeSH terms: Receptors, Estrogen/antagonists & inhibitors; Receptors, Estrogen/metabolism
  8. Chinigarzadeh A, Karim K, Muniandy S, Salleh N
    J Biochem Mol Toxicol, 2017 Apr;31(4).
    PMID: 27891704 DOI: 10.1002/jbt.21878
    We hypothesized that genistein could affect the chloride (Cl(-) ) and bicarbonate (HCO3(-) ) secretory mechanisms in uterus. Ovariectomized female rats were given estradiol or estradiol plus progesterone with 25, 50, or 100 mg/kg/day genistein. Following completion of the treatment, uterine fluid Cl(-) and HCO3(-) concentrations were determined by in vivo uterine perfusion. Uteri were subjected for molecular biological analysis (Western blot, qPCR, and immunohistochemistry) to detect levels of expression of Cystic Fibrosis transmembrane regulator (CFTR), Cl(-) /HCO3(-) exchanger (SLC26a6), Na(+) /HCO3(-) cotransporter (SLC4a4), and estrogen receptor (ER)-α and β. Coadministration of genistein resulted in decrease in Cl(-) and HCO3(-) concentrations and expression of CFTR, SLC26a6, SLC4a4, and ER-α and ER-β in the uteri of estradiol-treated rats. In estradiol plus progesterone-treated rats, a significant increase in the above parameters were observed following high-dose genistein treatment except for the SLC24a4 level. In conclusion, genistein-induced changes in the uterus could affect the reproductive processes that might result in infertility.
    Matched MeSH terms: Receptors, Estrogen/drug effects; Receptors, Estrogen/genetics
  9. Thent ZC, Froemming GRA, Ismail ABM, Fuad SBSA, Muid S
    Iran J Basic Med Sci, 2020 Sep;23(9):1155-1163.
    PMID: 32963737 DOI: 10.22038/ijbms.2020.45296.10545
    Objectives: Since bisphenol A (BPA) induces bone loss and phytoestrogens enhance the osteoblastogenesis by binding to the non-classical and classical oestrogen receptors, respectively, the present study was aimed to observe the osteoprotective effect of phytoestrogens on BPA-induced osteoblasts in hFOB 1.19 cells.

    Materials and Methods: All groups of hFOB 1.19 cells were induced with 12.5 μg/ml of BPA except the control (Ctrl) group. Meanwhile, treated groups received phytoestrogens; Daidzein (Dz), Genistein (Gt), Equol (Eq) and 17β-oestradiol (Est) in different concentrations for 24 hr duration.

    Results: We found that the protein expression of non-classical oestrogen-related receptor (ERRG) was highly expressed in BPA group, whereas classical oestrogen receptor alpha (ERα) and oestrogen receptor beta (ERβ) were relatively increased with phytoestrogens treatment under BPA exposure. The dense actin cytoskeletal filaments were also observed. qRT-PCR showed up-regulation of mitogen-activated protein kinase 3 (MAPK3) and G protein-coupled receptor 30 (GPR30) expressions; significant down-regulation of ERRG and up-regulation of ERα and ERβ were observed in phytoestrogens-treated cells, which was supported by the increased expressions of oestrogen receptor 1 (ESR1) and oestrogen receptor 2 (ESR2).

    Conclusion: Phytoestrogens improved the deteriorative effect of BPA via down-regulation of ERRG in hFOB 1.19 cells. This study showed that the efficacy of consumption of phytoestrogens in rendering them as potential therapeutic strategy in combating the adverse bone effects of BPA.

    Matched MeSH terms: Receptors, Estrogen
  10. Sharma D, Kumar S, Narasimhan B, Ramasamy K, Lim SM, Shah SAA, et al.
    BMC Chem, 2019 Dec;13(1):46.
    PMID: 31384794 DOI: 10.1186/s13065-019-0564-0
    To combat the antimicrobial and anticancer drug resistance by pathogens and cancerous cells, efforts has been made to study the pharmacological activities of newly synthesized N-(4-(4-bromophenyl)thiazol-2-yl)-2-chloroacetamide derivatives. The molecular structures of the synthesized derivatives were confirmed by their physicochemical properties and spectroanalytical data (NMR, IR and elemental). The synthesized compounds were evaluated for their in vitro antimicrobial activity against bacterial (Gram positive and Gram negative) and fungal species using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. Molecular docking studies were carried out to study the binding mode of active compounds with receptor using Schrodinger v11.5. The antimicrobial activity results revealed that compounds d1, d2 and d3 have promising antimicrobial activity. Anticancer screening results indicated that compounds d6 and d7 were found to be the most active ones against breast cancer cell line. Furthermore, the molecular docking study demonstrated that compounds d1, d2, d3, d6 and d7 displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and has the potential to be used as lead compounds for rational drug designing.
    Matched MeSH terms: Receptors, Estrogen
  11. Abdul Wahab K, Ahmad FB, Din LB, Cheah SH, Mock SL
    Trop Biomed, 2004 Dec;21(2):139-44.
    PMID: 16493406 MyJurnal
    The crude methanol extracts of Gelsemium elegans leaves were assessed for their cytotoxic activity using the microculture 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay for cellular viability. This study utilized two different types of human cancer cell lines, CaOV-3 (human ovarian cancer cells) and MDA-MB-231 (human estrogen receptor negative breast cancer cells), allowing for comparison of toxicity of G. elegans against these two cancer cells lines. Our results showed that the methanol extract of G. elegans exhibited high cytotoxicity against the human ovarian cancer cell line CaOV-3 with an IC50 value of 5microg/ml after 96 h incubation. However, G. elegans displayed discernibly less toxicity against the MDA-MB-231 cells with an IC50 value 40microg/ml after 96 h incubation and this effect was dose- and time-dependent, up to 72h and 20-30 microg/ml. In conclusion, our results demonstrated that G. elegans is potently cytotoxic against the human ovarian cancer cell line CaOV-3 and to a lesser extend towards the human breast carcinoma cancer MDA-MB-231 cells, suggesting that the extract is selective towards CaOV-3 cells and may have a chemotherapeutic role for ovarian cancer treatment in the future.
    Matched MeSH terms: Receptors, Estrogen
  12. Ivyna Bong, P.N., Zubaidah, Z., Rohaizak, M., Naqiyah, I., Noor Hisham, A., Sharifah, N.A., et al.
    Medicine & Health, 2011;6(1):33-40.
    MyJurnal
    The tetraspanin gene, CD151 is involved in various tumour cell progression and metastasis. Its expression is increased in high grade, estrogen receptor negative and c-erbB-2 positive breast cancer. However, the biological function and expression phenotype among different tumour status, estrogen receptor (ER) status, progesterone receptor (PR) status and c-erbB-2 expression in multi-ethnic Malaysian breast cancer patients has not been well investigated. We used quantitative real-time reverse transcriptase polymerase chain reaction (qRT-PCR) to measure the CD151 gene expression in 45 breast cancers. Our preliminary results revealed that CD151 expression is significantly higher in ER positive and PR positive breast cancers at 95% and 99% confidence intervals, respectively. In contrast, there is no significant correlation between CD151 expression and tumour grades or c-erbB-2 status at 95% confidence interval level. Our preliminary findings suggested that CD151 may be involved in the estrogen responsive pathways. CD151 could be a potential prognostic marker and therapeutic target in the treatment of estrogen dependent breast cancer patients.
    Matched MeSH terms: Receptors, Estrogen
  13. Al-Joudi, Fawwaz S., Iskandar Zulkarnain A.
    MyJurnal
    Bcl-2 is an anti-apoptotic protein belonging to a family of proteins that act as regulators of apoptosis in mammalian cells. Bcl-2 expression has previously been reported in normal breast ductal cells and its involvement in the hormonal regulation of hyperplasia and involution was further suggested, and it was thought to be expressed through hormonedependent pathways. Bcl-2 is a cytoplasmic oncoprotein which is highly expressed in human solid tumours. In breast cancer cells, however, Bcl-2 expression is down regulated, the exact mechanism and the effects of which are not clearly defined, as bcl-2 expression appears to be inversely correlated with the presence of p53 mutations. This work aimed at investigating the expression of bcl-2 in invasive ductal carcinoma of the breast utilizing an immunohistochemistry assay as well as studying the clinical correlations of bcl-2. Bcl-2 was detected in 43.7% of 382 invasive ductal carcinoma study cases. Its expression correlated positively, with lower age of patients, higher histological grades, large tumour sizes, estrogen receptor positivity and progesterone receptor negativity. However, the statistical correlations were weak. With the data obtained, it was found that the expression of bcl-2 correlated with unfavourable prognoses. Furthermore, bcl-2 detection alone may not be very helpful in consolidating a clinical diagnosis.







    59-64

    Matched MeSH terms: Receptors, Estrogen
  14. Rozita, A.M., Marniza, S., Mastura, M.Y., Wan Zamaniah, W.I., Yip, C.H., Taib, N.A.
    JUMMEC, 2010;13(1):24-32.
    MyJurnal
    Despite being the major cause of cancer-related death in Malaysian women,local data on patterns of breast cancer relapse and their long term outcomes are still scarce. We conducted a retrospective study on all patients treated for non-metastatic invasive breast cancer in 1999-2000 at the University of Malaya Medical Centre (UMMC), who subsequently developed relapse. We sought to analyse the patterns of relapse, their associated clinicopathological features and the overall survival ratefollowing the relapses. Univariate and multivariate analyses were used to analyse demographics and clinicopathological factors. Survival was analysed using the Kaplan and Meier method and compared by the log rank test. A total of 268 patients with a mean age of 50, were identified for the study. At a median follow-up of 50 months, 73 patients (27.2%) had relapsed. Local, regional and distant relapse rates were 5.5%, 1.9% and 19.8% respectively, whereas, the 5-year survival rates were 61%, 40% and 21% respectively (p < 0.01). Most relapses occurred within the first five years of diagnosis. Patients with long disease-free interval had better survival. The most common distant relapse site was the lungs while bone was the distant relapse site with the best prognosis. Disease stage, nodal status and oestrogen receptor status were found to have correlation with the risk of relapse. We concluded that the survival of patients with relapsed breast cancer was associated with the site(s) of first relapse and the disease free interval and clinicopathological factors can be used to predict the risk of relapse.
    Matched MeSH terms: Receptors, Estrogen
  15. Yaacob NS, Nengsih A, Norazmi MN
    PMID: 23476711 DOI: 10.1155/2013/989841
    Tualang honey (TH) is rich in flavonoids and phenolic acids and has significant anticancer activity against breast cancer cells comparable to the effect of tamoxifen (TAM), in vitro. The current study evaluated the effects of TH when used in combination with TAM on MCF-7 and MDA-MB-231 cells. We observed that TH promoted the anticancer activity of TAM in both the estrogen receptor-(ER-)responsive and ER-nonresponsive human breast cancer cell lines. Flow cytometric analyses indicated accelerated apoptosis especially in MDA-MB-231 cells and with the involvement of caspase-3/7, -8 and -9 activation as shown by fluorescence microscopy. Depolarization of the mitochondrial membrane was also increased in both cell lines when TH was used in combination with TAM compared to TAM treatment alone. TH may therefore be a potential adjuvant to be used with TAM for reducing the dose of TAM, hence, reducing TAM-induced adverse effects.
    Matched MeSH terms: Receptors, Estrogen
  16. Rajaratinam H, Nafi SNM
    Malays J Med Sci, 2019 Sep;26(5):6-20.
    PMID: 31728115 MyJurnal DOI: 10.21315/mjms2019.26.5.2
    Oestrogen receptor (ER)-positive breast cancer is one of the common forms of breast cancer affecting women worldwide. ER-positive breast cancer patients are subjected to anti-oestrogen therapy such as selective oestrogen receptor modulator (SERM) and aromatase inhibitors (AIs). Recently, the emergence of resistance to anti-oestrogen treatment is under intensive focus. The different mechanisms postulated to explain the occurrence of resistance in ER-positive breast cancer treatment include the loss of ER function and the crosstalk between signalling pathways in cancer cells. Recent literature highlighted that the cholesterol biosynthesis pathway acts as a novel mechanism underlying resistance to oestrogen deprivation. The present study aimed to highlight the role of cholesterol biosynthesis in anti-oestrogen treatment resistance, putatively suggesting an alternative plant-based treatment using andrographolide from Andrographis paniculata. The hypolipidaemic effect of andrographolide can be utilised to prevent the resistance in the treatment of ER-positive breast cancer contributed by cholesterol biosynthesis.
    Matched MeSH terms: Receptors, Estrogen
  17. Mdpaiman N, Md Ali SA, Mdzin R, Meor Kamal MZ, Md Amin WA, Nallusamy M, et al.
    PLoS One, 2014;9(2):e89172.
    PMID: 24586570 DOI: 10.1371/journal.pone.0089172
    Breast cancer estrogen receptor (ER) status is one of the strong additional factors in predicting response of patients towards hormonal treatment. The main aim of this study was to assess the morphological characteristics and proliferative activity using MIB-1(Ki-67) of estrogen receptor negative invasive breast ductal carcinoma (NOS type) as well as to correlate these features with clinicopathological data. We also aim to study the expression of c-erbB2 in ER negative breast tumors. High proliferative rate (MIB-1 above 20%) was observed in 63 (63.6%) of 99 ER negative tumors and that these tumors were associated with high expression of c-erbB2 (57.6%). We observed that MIB-1 is a reliable independent prognostic indicator for ER negative infiltrating ductal carcinoma in this study.
    Matched MeSH terms: Receptors, Estrogen/metabolism*
  18. Ng CH, Pathy NB, Taib NA, Mun KS, Rhodes A, Yip CH
    Asian Pac J Cancer Prev, 2012;13(4):1111-3.
    PMID: 22799290
    The ER-/PR+ breast tumor may be the result of a false ER negative result. The aim of this study was to investigate whether there is a difference in patient and tumor characteristics of the ER-/PR+ phenotype in an Asian setting. A total of 2629 breast cancer patients were categorized on the basis of their age, ethnicity, tumor hormonal receptor phenotype, grade and histological type. There were 1230 (46.8%) ER+/PR+, 306 (11.6%) ER+/PR-, 122 (4.6%) ER-/PR+ and 972 (37%) ER-/PR-. ER-/PR+ tumors were 2.5 times more likely to be younger than 50 years at diagnosis (OR: 2.52; 95% CI: 1.72-3.67). Compared to ER+/PR+ tumors, the ER-/ PR+ phenotype was twice more likely to be associated with grade 3 tumors (OR:2.02; 95%CI: 1.00-4.10). In contrast, compared to ER-/PR- tumors, the ER-/PR+ phenotype was 90% less likely to be associated with a grade 3 tumor (OR: 0.12; 95%CI:0.05-0.26), and more likely to have invasive lobular than invasive ductal histology (OR: 3.66; 95%CI: 1.47-9.11). These results show that the ER-/PR+ phenotype occurs in a younger age group and is associated with intermediate histopathological characteristics compared to ER+/PR+ and ER-/PR- tumors. This may imply that it is a distinct entity and not a technical artifact.
    Matched MeSH terms: Receptors, Estrogen/metabolism*
  19. Ng CH, Pathy NB, Taib NA, Teh YC, Mun KS, Amiruddin A, et al.
    Asian Pac J Cancer Prev, 2011;12(11):2943-6.
    PMID: 22393968
    INTRODUCTION: The age standardised incidence rate (ASR) of breast cancer in Malaysia which is a high middle- income country is similar to Indonesia, a low middle-income country. (Globocan 2008) It is however unknown whether the presentation of breast cancer differs between these two countries.

    OBJECTIVE: We compared the stage, age at presentation, and pathological characteristics of breast cancer between two tertiary hospitals in Indonesia and Malaysia; Dharmais Cancer Centre (DCC), which is the national cancer referral centre in Indonesia, and University Malaya Medical Centre (UMMC), which is an academic hospital with established breast oncology services in Kuala Lumpur. One thousand, one hundred and fourteen consecutive women (477 in UMMC: 637 in DCC) who were newly diagnosed with breast cancer between January and December, 2010 were included. Patient's age, TNM stage at presentation, and pathological characteristics were compared. Estrogen receptor (ER) and progesterone receptor (PR) were considered positive if 10% or greater of invasive cell nuclei were stained while HER2 was considered positive with an immunohistochemistry staining intensity of 3+ . Logistic regression analyses were performed to identify differences.
    RESULTS: Median age at diagnosis was 52 years in UMMC and 47 years in DCC, whereby patients in DCC were more likely to be very young at diagnosis (aged < 35 years) compared to their counterparts in UMMC (Odds ratio (OR): 2.09; 95%CI: 1.32-3.31). Approximately one third of patients in UMMC presented with TNM stage III or IV, compared to 63% in DCC. Patients in DCC were three times more likely to present with metastatic breast cancer compared to patients in UMMC (OR: 3.01; 95% CI: 2.02-4.48). The percentage of low grade tumours in DCC was higher than in UMMC (28% vs 11% respectively), and the difference persisted even after multivariate adjustment. Although the frequency of ER and PR positivity appeared to be higher in UMMC (65% and 55% respectively) compared to DCC (48% and 40% respectively), these differences were not statistically significant following adjustment for age, stage, HER2 status and grade. The frequency of HER2 positivity was 45% in DCC compared to 26% in UMMC, and remained significantly higher even after multivariate adjustment (multivariate OR:1.76; 95%CI:1.25-2.47, in DCC compared to UMMC). The proportion of triple negative breast cancer was however similar in the two centres (19% in UMMC vs 21% in DCC).
    CONCLUSION: Indonesian women with breast cancer seem to present at a younger age and at later stages compared to Malaysian women. Their tumors were more likely to be of low grade and HER2 positive, even after adjustment for other factors, while hormone receptor positivity proved similar in the two groups. The higher HER2 positivity rate in Indonesian patients warrants further study.
    Matched MeSH terms: Receptors, Estrogen/analysis
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