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  1. Rajagopal K, Kalusalingam A, Bharathidasan AR, Sivaprakash A, Shanmugam K, Sundaramoorthy M, et al.
    Molecules, 2023 May 18;28(10).
    PMID: 37241915 DOI: 10.3390/molecules28104175
    Cancer is a condition marked by abnormal cell proliferation that has the potential to invade or indicate other health issues. Human beings are affected by more than 100 different types of cancer. Some cancer promotes rapid cell proliferation, whereas others cause cells to divide and develop more slowly. Some cancers, such as leukemia, produce visible tumors, while others, such as breast cancer, do not. In this work, in silico investigations were carried out to investigate the binding mechanisms of four major analogs, which are marine sesquiterpene, sesquiterpene lactone, heteroaromatic chalcones, and benzothiophene against the target estrogen receptor-α for targeting breast cancer using Schrödinger suite 2021-4. The Glide module handled the molecular docking experiments, the QikProp module handled the ADMET screening, and the Prime MM-GB/SA module determined the binding energy of the ligands. The benzothiophene analog BT_ER_15f (G-score -15.922 Kcal/mol) showed the best binding activity against the target protein estrogen receptor-α when compared with the standard drug tamoxifen which has a docking score of -13.560 Kcal/mol. TRP383 (tryptophan) has the highest interaction time with the ligand, and hence it could act for a long time. Based on in silico investigations, the benzothiophene analog BT_ER_15f significantly binds with the active site of the target protein estrogen receptor-α. Similar to the outcomes of molecular docking, the target and ligand complex interaction motif established a high affinity of lead candidates in a dynamic system. This study shows that estrogen receptor-α targets inhibitors with better potential and low toxicity when compared to the existing market drugs, which can be made from a benzothiophene derivative. It may result in considerable activity and be applied to more research on breast cancer.
    Matched MeSH terms: Receptors, Estrogen/metabolism
  2. Kwan TK, Thambyrajah V
    Med J Malaysia, 1978 Mar;32(3):236-41.
    PMID: 683049
    Matched MeSH terms: Receptors, Estrogen/metabolism*
  3. Kamal DAM, Ibrahim SF, Ugusman A, Mokhtar MH
    Int J Mol Sci, 2022 Nov 25;23(23).
    PMID: 36499085 DOI: 10.3390/ijms232314757
    Reproductive and metabolic anomalies in polycystic ovary syndrome (PCOS) have been associated with the dysregulation of sex steroid receptors. Kelulut honey (KH) has been shown to be beneficial in PCOS-induced rats by regulating folliculogenesis and the oestrus cycle. However, no study has been conducted to evaluate KH's effect on sex steroid receptors in PCOS. Therefore, the current study examined the effects of KH, metformin, or clomiphene alone and in combination on the mRNA expression and protein distribution of androgen receptor (AR), oestrogen receptor α (ERα), oestrogen receptor β (ERβ), and progesterone receptor (PR) in PCOS-induced rats. The study used female Sprague-Dawley rats, which were treated orally with 1 mg/kg/day of letrozole for 21 days to develop PCOS. PCOS-induced rats were then divided and treated orally for 35 days with KH, metformin, clomiphene, KH + metformin, KH+ clomiphene and distilled water. In this study, we observed aberrant AR, ERα, ERβ and PR expression in PCOS-induced rats compared with the normal control rats. The effects of KH treatment were comparable with clomiphene and metformin in normalizing the expression of AR, ERα, and ERβ mRNA. However, KH, clomiphene and metformin did not affect PR mRNA expression and protein distribution. Hence, this study confirms the aberrant expression of sex steroid receptors in PCOS and demonstrates that KH treatment could normalise the sex steroid receptors profile. The findings provide a basis for future clinical trials to utilize KH as a regulator of sex steroid receptors in patients with PCOS.
    Matched MeSH terms: Receptors, Estrogen/metabolism
  4. Adam SA, Kamaruddin KN, Abd Shukor N, Abdullah Suhaimi SN, Ismail F, Md Yasin M
    Am J Case Rep, 2023 Dec 04;24:e941448.
    PMID: 38048289 DOI: 10.12659/AJCR.941448
    BACKGROUND Breast squamous cell carcinoma (SCC) is a subtype of metaplastic breast carcinoma (MBC), which is a rare malignancy and accounts for 0.1% of all invasive breast carcinomas. Guidelines on definitive management and treatment of breast SCC are not well established, given its rarity and diverse immunohistochemistry (IHC) profile, and lack of clinical data. Most cases of breast SCC are triple-negative breast cancer - negative for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2). This case report outlines the clinicopathological profile of a pure breast SCC case with a rare IHC profile; HER2 and ER positive. CASE REPORT A 41-year-old woman presented with a right breast mass that had been growing for 2 months. Biopsy confirmed breast SCC, a rare malignancy with IHC profile as follows: HER2 overexpression, ER positive, and PR negative. She underwent neoadjuvant chemotherapy for 3 months followed by right mastectomy with axillary clearance, adjuvant radiotherapy, and oral tamoxifen therapy. Unfortunately, she did not receive anti-HER2 therapy. She developed early locoregional recurrence at 2 months postoperatively, which was treated with excision of the right chest wall and transverse rectus abdominis musculocutaneous (TRAM) flap. She developed liver and lung metastasis and succumbed to her disease at 15 months post-diagnosis. CONCLUSIONS Breast SCC is a rare and aggressive tumor with heterogeneous clinicopathological features. Available guidelines do not outline the definitive treatment for breast SCC, given its rarity and heterogenous IHC profile, leading to a general lack of clinical data. Hence, due to the challenges in managing this rare condition, treatment modalities need to be individualized.
    Matched MeSH terms: Receptors, Estrogen/metabolism
  5. Yip CH, Rhodes A
    Future Oncol, 2014 Nov;10(14):2293-301.
    PMID: 25471040 DOI: 10.2217/fon.14.110
    Breast cancer is the most common cancer in women worldwide. The majority of breast cancers show overexpression of estrogen receptors (ERs) and progesterone receptors (PRs). The development of drugs to target these hormone receptors, such as tamoxifen, has brought about significant improvement in survival for women with hormone receptor-positive breast cancers. Since information about ER and PR is vital for patient management, quality assurance is important to ensure accurate testing. In recent guidelines, the recommended definition of ER and PR positivity is 1% or more of cells that stain positive. Semiquantitative assessment of ER and PR is important for prognosis and, hence, management. Even with the development of genomic tests, hormone receptor status remains the most significant predictive and prognostic biomarker.
    Matched MeSH terms: Receptors, Estrogen/metabolism*
  6. Devi CR, Tang TS, Corbex M
    Int J Cancer, 2012 Dec 15;131(12):2869-77.
    PMID: 22407763 DOI: 10.1002/ijc.27527
    We determined the incidences of the estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) subtypes among breast cancer cases in Sarawak, Malaysia and their correlation with various risk factors in the three ethnic groups: Chinese, Malay and native. Subtype status was ascertained for 1,034 cases of female breast cancer (93% of all cases diagnosed since 2003), and the age-standardized incidence rates (ASRs) of each subtype were inferred. Case-case comparisons across subtypes were performed for reproductive risk factors. We found 48% luminal A (ER+/PR+/HER2-), 29% triple-negative (ER-/PR-/HER2-), 12% triple-positive (ER+/PR+/HER2+) and 11% HER2-overexpressing (ER-/PR-/HER2+) subtypes, with ASRs of 10.6, 6.0, 2.8 and 2.8 per 100,000, respectively. The proportions of subtypes and ASRs differed significantly by ethnic groups: HER2-positive cases were more frequent in Malays (29%; 95% CI [23;35]) than Chinese (22%; [19;26] and natives (21%; [16;26]); triple-negative cases were less frequent among Chinese (23%; [20;27]) than Malays (33%; [27;39]) and natives (37%; [31;43]). The results of the case-case comparison were in accordance with those observed in western case series. Some uncommon associations, such as between triple-negative subtype and older age at menopause (OR, 1.59; p < 0.05), were found. The triple-negative and HER2+ subtypes predominate in our region, with significant differences among ethnic groups. Our results support the idea that the risk factors for different subtypes vary markedly. Westernized populations are more likely to have factors that increase the risk for the luminal A type, while risk factors for the triple-negative type are more frequent in local populations.
    Matched MeSH terms: Receptors, Estrogen/metabolism
  7. Looi LM, Cheah PL
    Malays J Pathol, 1998 Jun;20(1):19-23.
    PMID: 10879259
    Eighty-six infiltrating ductal carcinoma of breast were studied by the standard avidin-biotin complex immunoperoxidase method on formalin-fixed, paraffin-embedded tissue sections, for oestrogen receptor (ER) protein and c-erbB-2 oncoprotein expression. They were categorized according to the modified Bloom and Richardson criteria into three histological grades. 21% tumours were ER positive while 44% were c-erbB-2 positive. Of ER positive tumours, 33.3% were c-erbB-2 positive whereas the c-erbB-2 positivity rate was much higher (47.1%) in ER negative tumours. Only 16% of c-erbB-2 positive tumours were ER positive while 25% of c-erbB-2 negative tumours were ER positive. This negative relationship between ER and c-erbB-2 expression was statistically significant (Mc Nemar's test, p < 0.005). The ER positivity rate did not vary significantly with histological grade. However, c-erbB-2 overexpression was significantly more prevalent in grade III tumours compared with grade I and II tumours (Chi-square test, p < 0.005). Since the c-erbB-2 oncogene has extensive structural homology to the epidermal growth factor receptor (EGFR) gene, we expect that c-erbB-2 oncoprotein would share functional similarities with EGFR leading to both loss of oestrogen receptor and poor prognosis in breast cancer. Its overexpression can be expected to relate to more aggressive tumour proliferation and may explain its correlation with high histological grade, a known indicator of aggressive cancer behaviour. As there is no indication that ER protein activity contributes to advancement in histological grade, it would appear that cellular dedifferentiation precedes ER loss during malignant transformation. It has been mooted that ER positive breast cancers which also show c-erbB-2 oncoprotein overexpression have a poorer response to hormonal therapy. The use of this parameter in the routine assessment of breast cancer patients may identify subsets of patients for more aggressive therapy.
    Matched MeSH terms: Receptors, Estrogen/metabolism*
  8. 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*
  9. 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*
  10. 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*
  11. Tan GH, Taib NA, Choo WY, Teo SH, Yip CH
    Asian Pac J Cancer Prev, 2009 Jul-Sep;10(3):395-8.
    PMID: 19640180
    INTRODUCTION: Triple negative (TN) breast cancers are defined by a lack of expression of oestrogen, progesterone, and HER2 receptors. They tend to have a higher grade, with a poorer outcome compared to non-TN breast cancers.
    OBJECTIVE: The aim of this study is to determine the incidence of TN breast cancer in an Asian country consisting of Malays, Chinese and Indians, and to determine the factors associated with this type of breast cancer.
    RESULTS: The incidence of TN breast cancer in the University Malaya Medical Center is 17.6%. There is no significant difference amongst the Malays, Chinese and Indians. In bivariate analysis, TN breast cancer was significantly associated with younger age and Grade 3. However, in multivariate analysis using logistic regression, TN breast cancer was only associated with Grade 3.
    CONCLUSION: The incidence of TN breast cancer in our study is similar to other studies, and associated with a higher grade.
    Study site: University Malaya Medical Centre (UMMC)
    Matched MeSH terms: Receptors, Estrogen/metabolism*
  12. Mohd Taib NA, Yip CH, Mohamed I
    Asian Pac J Cancer Prev, 2008 Apr-Jun;9(2):197-202.
    PMID: 18712958
    BACKGROUND: Breast cancer is the commonest cancer amongst Malaysian women but local survival data are scarce. The present study was therefore conducted to assess overall survival and prognostic factors in Malaysian breast cancer patients.

    METHODS: The research sample was a prospective cohort of 413 patients diagnosed with breast cancer in the University of Malaya Medical Centre between 1993 to 1997. Survival data were obtained from the National Registry of Birth and Deaths in December 2000. The clinico-pathological variables studied were age, ethnic group, stage, tumour size, lymph node status, oestrogen receptor status and grade. The data were analysed utilizing Splus statistical software. The important prognostic factors were identified by fitting the Cox's proportional hazard model to the data set. Survival probabilities were estimated using the Kaplan-Meier method and differences were compared by the log-rank test.

    RESULTS: The overall 5-year survival was 59.1%. The Cox's proportional hazard model identified stage, lymph node status, size and grade as factors that correlated with prognosis. Age was not a significant prognostic factor. The Cox regression model by stepwise selection showed stage, nodal status and grade of tumour to be independent prognostic factors, whereas ethnicity, age and ER status were not.

    INTERPRETATION: The overall survival in our centre was low. Recognizing factors that affect prognosis of breast cancer patients in Malaysia may improve delivery of health care to at-risk groups by strategizing interventions as survival depends on early detection and effective treatment.
    Matched MeSH terms: Receptors, Estrogen/metabolism
  13. Poh BH, Jayaram G, Sthaneshwar P, Yip CH
    Malays J Pathol, 2008 Jun;30(1):43-51.
    PMID: 19108411 MyJurnal
    The aim of this study is to assess tissue and serum prostate-specific antigen (PSA) in breast lesions; to compare tissue PSA with serum PSA; to compare tissue PSA in benign and malignant lesions and to compare PSA with known prognostic factors in breast carcinoma. Tissue PSA immunoreactivity in twenty women with breast carcinoma was compared with PSA in twenty-three women with benign breast lesions. Tissue PSA was also compared with known prognostic indicators such as tumour size, axillary nodal status, histological type, histological grade, oestrogen receptor status, progesterone receptor status and c-erbB-2 oncoprotein over-expression. Serum free PSAlevels from these women were measured pre- and post-operatively and an attempt was made to correlate serum PSA with tissue PSA expression. 40% and 43% of malignant and benign breast lesions respectively showed tissue PSA immunoreactivity. No significant difference was observed in the tissue PSA expression between these two groups as also between tissue PSA and known prognostic indicators. As serum PSA levels were below the detection limit (< 0.004 ng/ml) in all except two benign cases, no statistical evaluation was done for the latter. Tissue PSA expression did not correlate with other prognostic markers and detectable serum PSA levels were present in too few cases for statistical analysis. Although no definitive conclusion is possible in this preliminary study regarding the role of PSA in breast disease, it stimulates interest in further research in this direction.
    Matched MeSH terms: Receptors, Estrogen/metabolism
  14. Nesaretnam K, Selvaduray KR, Abdul Razak G, Veerasenan SD, Gomez PA
    Breast Cancer Res, 2010;12(5):R81.
    PMID: 20929592 DOI: 10.1186/bcr2726
    Basic research has indicated that tocotrienols have potent antiproliferative and proapoptotic effects that would be expected to reduce the effect of breast cancer.

    Study site: Hospital Kuala Lumpur
    Matched MeSH terms: Receptors, Estrogen/metabolism
  15. Ameli F, Ghafourina Nassab F, Masir N, Kahtib F
    Asian Pac J Cancer Prev, 2021 Aug 01;22(8):2603-2609.
    PMID: 34452576 DOI: 10.31557/APJCP.2021.22.8.2603
    INTRODUCTION: Breast carcinoma is the most common malignancy and the leading cause of cancer death in women. Matrix metalloproteinase-13 (MMP-13) is a hypothetical prognostic marker in invasive breast cancer. This study aimed to determine MMP-13 expression in benign and malignant breast lesions and to evaluate the correlation between MMP-13 expression and tumor characteristics in invasive ductal carcinoma (IDC).

    MATERIALS AND METHOD: We evaluated cytoplasmic expression of MMP-13 based on staining index using immunohistochemistry (IHC) in epithelial cells, stromal fibroblasts of IDC (n=90) and benign epithelial breast (n=90) lesions. Correlation between IHC and tumor size, lymph node status, distance metastasis, estrogen receptor (ER), progesterone receptor (PR) and Her-2/neu was assessed.

    RESULTS: MMP-13 expression was 45% and 38.8% in malignant epithelial cells and peritumoral fibroblasts, respectively. Only low level of MMP-13 expression was seen in benign breast lesions (8.8% in epithelial component and 2.2% in stromal fibroblasts), while high level of MMP-13 expression was noted in malignant tumors, mainly grade II or III. Cytoplasmic MMP-13 expressions in epithelial tumor cells was correlated significantly with peritumoral fibroblasts. MMP-13 expression was directly correlated with distant metastasis and tumor stage in epithelial tumoral cells and was inversely correlated with progesterone expression in both tumoral and stromal cells.

    CONCLUSION: This study showed that MMP-13 was a moderator for tumor invasion and metastasis and could be an independent predictor of poor prognosis in breast cancer. The role of MMP-13 in predicting the risk of malignant transformation in benign lesions should be further investigated.

    Matched MeSH terms: Receptors, Estrogen/metabolism
  16. Shu X, Long J, Cai Q, Kweon SS, Choi JY, Kubo M, et al.
    Nat Commun, 2020 Mar 05;11(1):1217.
    PMID: 32139696 DOI: 10.1038/s41467-020-15046-w
    Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P 
    Matched MeSH terms: Receptors, Estrogen/metabolism
  17. Li K, Anderson G, Viallon V, Arveux P, Kvaskoff M, Fournier A, et al.
    Breast Cancer Res, 2018 12 03;20(1):147.
    PMID: 30509329 DOI: 10.1186/s13058-018-1073-0
    BACKGROUND: Few published breast cancer (BC) risk prediction models consider the heterogeneity of predictor variables between estrogen-receptor positive (ER+) and negative (ER-) tumors. Using data from two large cohorts, we examined whether modeling this heterogeneity could improve prediction.

    METHODS: We built two models, for ER+ (ModelER+) and ER- tumors (ModelER-), respectively, in 281,330 women (51% postmenopausal at recruitment) from the European Prospective Investigation into Cancer and Nutrition cohort. Discrimination (C-statistic) and calibration (the agreement between predicted and observed tumor risks) were assessed both internally and externally in 82,319 postmenopausal women from the Women's Health Initiative study. We performed decision curve analysis to compare ModelER+ and the Gail model (ModelGail) regarding their applicability in risk assessment for chemoprevention.

    RESULTS: Parity, number of full-term pregnancies, age at first full-term pregnancy and body height were only associated with ER+ tumors. Menopausal status, age at menarche and at menopause, hormone replacement therapy, postmenopausal body mass index, and alcohol intake were homogeneously associated with ER+ and ER- tumors. Internal validation yielded a C-statistic of 0.64 for ModelER+ and 0.59 for ModelER-. External validation reduced the C-statistic of ModelER+ (0.59) and ModelGail (0.57). In external evaluation of calibration, ModelER+ outperformed the ModelGail: the former led to a 9% overestimation of the risk of ER+ tumors, while the latter yielded a 22% underestimation of the overall BC risk. Compared with the treat-all strategy, ModelER+ produced equal or higher net benefits irrespective of the benefit-to-harm ratio of chemoprevention, while ModelGail did not produce higher net benefits unless the benefit-to-harm ratio was below 50. The clinical applicability, i.e. the area defined by the net benefit curve and the treat-all and treat-none strategies, was 12.7 × 10- 6 for ModelER+ and 3.0 × 10- 6 for ModelGail.

    CONCLUSIONS: Modeling heterogeneous epidemiological risk factors might yield little improvement in BC risk prediction. Nevertheless, a model specifically predictive of ER+ tumor risk could be more applicable than an omnibus model in risk assessment for chemoprevention.

    Matched MeSH terms: Receptors, Estrogen/metabolism*
  18. Chajès V, Assi N, Biessy C, Ferrari P, Rinaldi S, Slimani N, et al.
    Ann Oncol, 2017 Nov 01;28(11):2836-2842.
    PMID: 28950350 DOI: 10.1093/annonc/mdx482
    BACKGROUND: Intakes of specific fatty acids have been postulated to impact breast cancer risk but epidemiological data based on dietary questionnaires remain conflicting.

    MATERIALS AND METHODS: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours.

    RESULTS: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor.

    CONCLUSION: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.

    Matched MeSH terms: Receptors, Estrogen/metabolism
  19. Wan Abdul Rahman WF, Fauzi MH, Jaafar H
    Asian Pac J Cancer Prev, 2014;15(19):8441-5.
    PMID: 25339043
    BACKGROUND: Paired-like homeodomain transcription factor 2 (PITX2) is another new marker in breast carcinoma since hypermethylation at P2 promoter of this gene was noted to be associated with poor prognosis. We investigated the expression of PITX2 protein using immunohistochemistry in invasive ductal carcinoma and its association with the established growth receptors such as estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2).

    METHODS: We conducted a cross sectional study using 100 samples of archived formalin-fixed paraffin embedded tissue blocks of invasive ductal carcinoma and stained them with immunohistochemistry for PITX2, ER, PR and HER2. All HER2 with scoring of 2+ were confirmed with chromogenic in-situ hybridization (CISH).

    RESULTS: PITX2 protein was expressed in 53% of invasive ductal carcinoma and lack of PITX2 expression in 47%. Univariate analysis revealed a significant association between PITX2 expression with PR (p=0.001), ER (p=0.006), gland formation (p=0.044) and marginal association with molecular subtypes of breast carcinoma (p=0.051). Combined ER and PR expression with PITX2 was also significantly associated (p=0.003) especially in double positive cases. Multivariate analysis showed the most significant association between PITX2 and PR (RR 4.105, 95% CI 1.765-9.547, p=0.001).

    CONCLUSION: PITX2 is another potential prognostic marker in breast carcinoma adding significant information to established prognostic factors of ER and PR. The expression of PITX2 together with PR may carry a very good prognosis.

    Matched MeSH terms: Receptors, Estrogen/metabolism*
  20. Abdullah AS, Mohammed AS, Rasedee A, Mirghani ME
    Int J Mol Sci, 2015;16(2):3528-36.
    PMID: 25664859 DOI: 10.3390/ijms16023528
    Breast cancer has become a global health issue requiring huge expenditures for care and treatment of patients. There is a need to discover newer cost-effective alternatives for current therapeutic regimes. Mango kernel is a waste product with potential as a source of anti-cancer phytochemicals, especially since it is non-toxic towards normal breast cell lines at concentrations for which it induces cell death in breast cancer cells. In this study, the anti-cancer effect of mango kernel extract was determined on estrogen receptor-positive human breast carcinoma (MCF-7) cells. The MCF-7 cells were cultured and treated with 5, 10 and 50 μg/mL of mango kernel extract for 12 and 24 h. In response to treatment, there were time- and dose-dependent increases in oxidative stress markers and pro-apoptotic factors; Bcl-2-like protein 4 (BAX), p53, cytochrome c and caspases (7, 8 and 9) in the MCF-7 cells treated with the extract. At the same time, there were decreases in pro-survival markers (Bcl-2 and glutathione) as the result of the treatments. The changes induced in the MCF-7 cells by mango kernel extract treatment suggest that the extract can induce cancer cell apoptosis, likely via the activation of oxidative stress. These findings need to be evaluated further to determine whether mango kernel extract can be developed as an anti-breast cancer agent.
    Matched MeSH terms: Receptors, Estrogen/metabolism
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