Displaying publications 81 - 100 of 178 in total

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  1. Fulltext Does a positive family history influence the presentation of breast cancer?
    Yip CH, bt Mohd Taib NA, Lau PC
    Asian Pac J Cancer Prev, 2008 Jan-Mar;9(1):63-5.
    PMID: 18439076
    INTRODUCTION: An important risk factor for developing breast cancer is a positive family history of breast cancer. In Malaysia, there is no population-based breast screening programme, but the clinical practice guidelines suggest increased surveillance for those with a positive family history ie mammography for those 40 years old and above, breast self-examination and clinical breast examination yearly.
    OBJECTIVE: To determine if women with a family history of breast cancer present with earlier stages of disease.
    METHODOLOGY: From Jan 2001 to Dec 2006, 1553 women with breast cancer presenting to the University Malaya, where family history was recorded, were eligible for this study. Women with a first or second degree relative with breast cancer were compared with those who have no family history with regard to their race, age, stage, size and duration of symptoms. The Chi Square test of significance was used for analysis.
    RESULTS: Out of 1553 patients, 252 (16.2%) were found to have a relative with breast cancer out of which 174 (11.2%) had at least one affected first degree relative. There were no significant difference in the incidence of positive family history between the Malays, Chinese and Indians. 20% below the age of 40 years old had a positive family history compared with 12.6% in women with no family history. (p<0.05). There was no significant difference in stage at diagnosis between those with and without family history, ie 24.2% late stages (Stage 3 and 4) in the group with no family history compared with 21.8% in the group with family history. (p>0.05). The mean size in the group with no family history was 4.4 cm compared to 4.1 cm in the group with family history. There was a significant difference in screen-detected cancers in the women with family history, 10.7% compared with 5.1% of screen-detected cancers in the group without a family history. However there was no difference in the duration of symptoms between the 2 groups--25.8% in the women without a family history presented after 1 year of symptoms compared with 22.4% in the group with a family history (p>0.05).
    CONCLUSION: Having a family history of breast cancer does not appear to have much impact on the health-seeking behavior of women. Even though there were more screen detected cancers, these comprised only 10% of the group with family history. Public education should target women at risk ie with family history to encourage these women to present earlier and to undergo screening for breast cancer.
    Matched MeSH terms: Breast Neoplasms/genetics*
  2. Association of CYP2E1, STK15 and XRCC1 Polymorphisms with Risk of Breast Cancer in Malaysian Women
    Chong ET, Goh LP, See EU, Chuah JA, Chua KH, Lee PC
    Asian Pac J Cancer Prev, 2016;17(2):647-53.
    PMID: 26925658
    BACKGROUND: Breast cancer is the most common type of cancer affecting Malaysian women. Recent statistics revealed that the cumulative probability of breast cancer and related deaths in Malaysia is higher than in most of the countries of Southeast Asia. Single nucleotide polymorphisms (SNPs) in CYP2E1 (rs6413432 and rs3813867), STK15 (rs2273535 and rs1047972) and XRCC1 (rs1799782 and rs25487) have been associated with breast cancer risk in a meta-analysis but any link in Southeast Asia, including Malaysia, remained to be determined. Hence, we investigated the relationship between these SNPs and breast cancer risk among Malaysian women in the present case-control study.

    MATERIALS AND METHODS: Genomic DNA was isolated from peripheral blood of 71 breast cancer patients and 260 healthy controls and subjected to polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis.

    RESULTS: Our study showed that the c1/c2 genotype or subjects with at least one c2 allele in CYP2E1 rs3813867 SNP had significantly increased almost 1.8-fold higher breast cancer risk in Malaysian women overall. In addition, the variant Phe allele in STK15 rs2273535 SNP appeared to protect against breast cancer in Malaysian Chinese. No significance association was found between XRCC1 SNPs and breast cancer risk in the population.

    CONCLUSIONS: This study provides additional knowledge on CYP2E1, STK15 and XRCC1 SNP impact of risk of breast cancer, particularly in the Malaysian population. From our findings, we also recommend Malaysian women to perform breast cancer screening before 50 years of age.

    Matched MeSH terms: Breast Neoplasms/genetics*
  3. Fulltext Mutant p53 mediates survival of breast cancer cells
    Lim LY, Vidnovic N, Ellisen LW, Leong CO
    Br. J. Cancer, 2009 Nov 3;101(9):1606-12.
    PMID: 19773755 DOI: 10.1038/sj.bjc.6605335
    p53 is the most commonly mutated tumour-suppressor gene in human cancers. Unlike other tumour-suppressor genes, most p53 cancer mutations are missense mutations within the core domain, leading to the expression of a full-length mutant p53 protein. Accumulating evidence has indicated that p53 cancer mutants not only lose tumour suppression activity but also gain new oncogenic activities to promote tumourigenesis.
    Matched MeSH terms: Breast Neoplasms/genetics
  4. Rapamycin synergizes cisplatin sensitivity in basal-like breast cancer cells through up-regulation of p73
    Wong SW, Tiong KH, Kong WY, Yue YC, Chua CH, Lim JY, et al.
    Breast Cancer Res Treat, 2011 Jul;128(2):301-13.
    PMID: 20686837 DOI: 10.1007/s10549-010-1055-0
    Recent gene expression profiling studies have identified five breast cancer subtypes, of which the basal-like subtype is the most aggressive. Basal-like breast cancer poses serious clinical challenges as there are currently no targeted therapies available to treat it. Although there is increasing evidence that these tumors possess specific sensitivity to cisplatin, its success is often compromised due to its dose-limiting nephrotoxicity and the development of drug resistance. To overcome this limitation, our goal was to maximize the benefits associated with cisplatin therapy through drug combination strategies. Using a validated kinase inhibitor library, we showed that inhibition of the mTOR, TGFβRI, NFκB, PI3K/AKT, and MAPK pathways sensitized basal-like MDA-MB-468 cells to cisplatin treatment. Further analysis demonstrated that the combination of the mTOR inhibitor rapamycin and cisplatin generated significant drug synergism in basal-like MDA-MB-468, MDA-MB-231, and HCC1937 cells but not in luminal-like T47D or MCF-7 cells. We further showed that the synergistic effect of rapamycin plus cisplatin on basal-like breast cancer cells was mediated through the induction of p73. Depletion of endogenous p73 in basal-like cells abolished these synergistic effects. In conclusion, combination therapy with mTOR inhibitors and cisplatin may be a useful therapeutic strategy in the treatment of basal-like breast cancers.
    Matched MeSH terms: Breast Neoplasms/genetics
  5. Fulltext Association of BRCA1- and BRCA2-deficiency with mutation burden, expression of PD-L1/PD-1, immune infiltrates, and T cell-inflamed signature in breast cancer
    Wen WX, Leong CO
    PLoS One, 2019;14(4):e0215381.
    PMID: 31022191 DOI: 10.1371/journal.pone.0215381
    Immune checkpoint inhibitors have demonstrated effective anti-tumour response in cancer types with high mutation burden (e.g. melanoma) and in subset of cancers with features of genomic instability (e.g. mismatch-repair deficiency). One possible explanation for this effect is the increased expression of immune checkpoint molecules and pre-existing adaptive immune response in these cancers. Given that BRCA1 and BRCA2 are integral in maintaining genomic integrity, we hypothesise that the inactivation of these genes may give rise to breast cancers with such immunogenic phenotype. Therefore, using two large series of publicly available breast cancer datasets, namely that from The Cancer Genome Atlas and Wellcome Trust Institute, we sought to investigate the association between BRCA1- and BRCA2-deficiency with features of genomic instability, expression of PD-L1 and PD-1, landscape of inferred tumour-infiltrating immune cells, and T-cell inflamed signature in breast cancers. Here, we report that BRCA1 and BRCA2-deficient breast cancers were associated with features of genomic instability including increased mutation burden. Interestingly, BRCA1-, but not BRCA2-, deficient breast cancers were associated with increased expression of PD-L1 and PD-1, higher abundance of tumour-infiltrating immune cells, and enrichment of T cell-inflamed signature. The differences in immunophenotype between BRCA1- and BRCA2-deficient breast cancers can be attributed, in part, to PTEN gene mutation. Therefore, features of genomic instability such as that mediated by BRCA1- and BRCA2- deficiency in breast cancer were necessary, but not always sufficient, for yielding T cell-inflamed tumour microenvironment, and by extension, predicting clinical benefit from immunotherapy.
    Matched MeSH terms: Breast Neoplasms/genetics*
  6. Gene expression profiling of giant fibroadenomas of the breast
    Yin Lee JP, Thomas AJ, Lum SK, Shamsudin NH, Hii LW, Mai CW, et al.
    Surg Oncol, 2021 Jun;37:101536.
    PMID: 33677364 DOI: 10.1016/j.suronc.2021.101536
    INTRODUCTION: Fibroadenomas of the breast present as two phenotypic variants. The usual variety is 5 cm or less in diameter and there is another large variant called giant fibroadenoma which is greater than 5 cm in diameter. Despite of its large size, it is not malignant. The aim of our study is to determine whether this large variant is different from the usual fibroadenoma in terms of its biological pathways and biomarkers.

    METHODS: mRNA was extracted from 44 fibroadenomas and 36 giant fibroadenomas, and transcriptomic profiling was performed to identify up- and down-regulated genes in the giant fibroadenomas as compared to the fibroadenomas.

    RESULTS: A total of 40 genes were significantly up-regulated and 18 genes were significantly down-regulated in the giant fibroadenomas as compared to the fibroadenomas of the breast. The top 5 up-regulated genes were FN1, IL3, CDC6, FGF8 and BMP8A. The top 5 down-regulated genes were TNR, CDKN2A, COL5A1, THBS4 and BMPR1B. The differentially expressed genes (DEGs) were found to be associated with 5 major canonical pathways involved in cell growth (PI3K-AKT, cell cycle regulation, WNT, and RAS signalling) and immune response (JAK-STAT signalling). Further analyses using 3 supervised learning algorithms identified an 8-gene signature (FN1, CDC6, IL23A, CCNA1, MCM4, FLT1, FGF22 and COL5A1) that could distinguish giant fibroadenomas from fibroadenomas with high predictive accuracy.

    CONCLUSION: Our findings demonstrated that the giant fibroadenomas are biologically distinct to fibroadenomas of the breast with overexpression of genes involved in the regulation of cell growth and immune response.

    Matched MeSH terms: Breast Neoplasms/genetics*
  7. Fulltext miR-200 affects tamoxifen resistance in breast cancer cells through regulation of MYB
    Gao Y, Zhang W, Liu C, Li G
    Sci Rep, 2019 12 11;9(1):18844.
    PMID: 31827114 DOI: 10.1038/s41598-019-54289-6
    Resistance to tamoxifen is a major clinical challenge. Research in recent years has identified epigenetic changes as mediated by dysregulated miRNAs that can possibly play a role in resistance to tamoxifen in breast cancer patients expressing estrogen receptor (ER). We report here elevated levels of EMT markers (vimentin and ZEB1/2) and reduced levels of EMT-regulating miR-200 (miR-200b and miR-200c) in ER-positive breast cancer cells, MCF-7, that were resistant to tamoxifen, in contrast with the naïve parental MCF-7 cells that were sensitive to tamoxifen. Further, we established regulation of c-MYB by miR-200 in our experimental model. C-MYB was up-regulated in tamoxifen resistant cells and its silencing significantly decreased resistance to tamoxifen and the EMT markers. Forced over-expression of miR-200b/c reduced c-MYB whereas reduced expression of miR-200b/c resulted in increased c-MYB We further confirmed the results in other ER-positive breast cancer cells T47D cells where forced over-expression of c-MYB resulted in induction of EMT and significantly increased resistance to tamoxifen. Thus, we identify a novel mechanism of tamoxifen resistance in breast tumor microenvironment that involves miR-200-MYB signaling.
    Matched MeSH terms: Breast Neoplasms/genetics
  8. Fulltext Investigating meta-approaches for reconstructing gene networks in a mammalian cellular context
    Nazri A, Lio P
    PLoS One, 2012;7(1):e28713.
    PMID: 22253694 DOI: 10.1371/journal.pone.0028713
    The output of state-of-the-art reverse-engineering methods for biological networks is often based on the fitting of a mathematical model to the data. Typically, different datasets do not give single consistent network predictions but rather an ensemble of inconsistent networks inferred under the same reverse-engineering method that are only consistent with the specific experimentally measured data. Here, we focus on an alternative approach for combining the information contained within such an ensemble of inconsistent gene networks called meta-analysis, to make more accurate predictions and to estimate the reliability of these predictions. We review two existing meta-analysis approaches; the Fisher transformation combined coefficient test (FTCCT) and Fisher's inverse combined probability test (FICPT); and compare their performance with five well-known methods, ARACNe, Context Likelihood or Relatedness network (CLR), Maximum Relevance Minimum Redundancy (MRNET), Relevance Network (RN) and Bayesian Network (BN). We conducted in-depth numerical ensemble simulations and demonstrated for biological expression data that the meta-analysis approaches consistently outperformed the best gene regulatory network inference (GRNI) methods in the literature. Furthermore, the meta-analysis approaches have a low computational complexity. We conclude that the meta-analysis approaches are a powerful tool for integrating different datasets to give more accurate and reliable predictions for biological networks.
    Matched MeSH terms: Breast Neoplasms/genetics
  9. Fulltext Re-evaluating genetic variants identified in candidate gene studies of breast cancer risk using data from nearly 280,000 women of Asian and European ancestry
    Yang Y, Shu X, Shu XO, Bolla MK, Kweon SS, Cai Q, et al.
    EBioMedicine, 2019 Oct;48:203-211.
    PMID: 31629678 DOI: 10.1016/j.ebiom.2019.09.006
    BACKGROUND: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets.

    METHODS: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets.

    FINDINGS: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health.

    Matched MeSH terms: Breast Neoplasms/genetics*
  10. Fulltext Evaluating genetic variants associated with breast cancer risk in high and moderate-penetrance genes in Asians
    Han MR, Zheng W, Cai Q, Gao YT, Zheng Y, Bolla MK, et al.
    Carcinogenesis, 2017 May 01;38(5):511-518.
    PMID: 28419251 DOI: 10.1093/carcin/bgx010
    Over the past 20 years, high-penetrance pathogenic mutations in genes BRCA1, BRCA2, TP53, PTEN, STK11 and CDH1 and moderate-penetrance mutations in genes CHEK2, ATM, BRIP1, PALB2, RAD51C, RAD50 and NBN have been identified for breast cancer. In this study, we investigated whether there are additional variants in these 13 genes associated with breast cancer among women of Asian ancestry. We analyzed up to 654 single nucleotide polymorphisms (SNPs) from 6269 cases and 6624 controls of Asian descent included in the Breast Cancer Association Consortium (BCAC), and up to 236 SNPs from 5794 cases and 5529 controls included in the Shanghai Breast Cancer Genetics Study (SBCGS). We found three missense variants with minor allele frequency (MAF) <0.05: rs80358978 (Gly2508Ser), rs80359065 (Lys2729Asn) and rs11571653 (Met784Val) in the BRCA2 gene, showing statistically significant associations with breast cancer risk, with P-values of 1.2 × 10-4, 1.0 × 10-3 and 5.0 × 10-3, respectively. In addition, we found four low-frequency variants (rs8176085, rs799923, rs8176173 and rs8176258) in the BRCA1 gene, one common variant in the CHEK2 gene (rs9620817), and one common variant in the PALB2 gene (rs13330119) associated with breast cancer risk at P < 0.01. Our study identified several new risk variants in BRCA1, BRCA2, CHEK2, and PALB2 genes in relation to breast cancer risk in Asian women. These results provide further insights that, in addition to the high/moderate penetrance mutations, other low-penetrance variants in these genes may also contribute to breast cancer risk.
    Matched MeSH terms: Breast Neoplasms/genetics*
  11. Fulltext Fine-scale mapping of 8q24 locus identifies multiple independent risk variants for breast cancer
    Shi J, Zhang Y, Zheng W, Michailidou K, Ghoussaini M, Bolla MK, et al.
    Int J Cancer, 2016 Sep 15;139(6):1303-1317.
    PMID: 27087578 DOI: 10.1002/ijc.30150
    Previous genome-wide association studies among women of European ancestry identified two independent breast cancer susceptibility loci represented by single nucleotide polymorphisms (SNPs) rs13281615 and rs11780156 at 8q24. A fine-mapping study across 2.06 Mb (chr8:127,561,724-129,624,067, hg19) in 55,540 breast cancer cases and 51,168 controls within the Breast Cancer Association Consortium was conducted. Three additional independent association signals in women of European ancestry, represented by rs35961416 (OR = 0.95, 95% CI = 0.93-0.97, conditional p = 5.8 × 10(-6) ), rs7815245 (OR = 0.94, 95% CI = 0.91-0.96, conditional p = 1.1 × 10(-6) ) and rs2033101 (OR = 1.05, 95% CI = 1.02-1.07, conditional p = 1.1 × 10(-4) ) were found. Integrative analysis using functional genomic data from the Roadmap Epigenomics, the Encyclopedia of DNA Elements project, the Cancer Genome Atlas and other public resources implied that SNPs rs7815245 in Signal 3, and rs1121948 in Signal 5 (in linkage disequilibrium with rs11780156, r(2)  = 0.77), were putatively functional variants for two of the five independent association signals. The results highlighted multiple 8q24 variants associated with breast cancer susceptibility in women of European ancestry.
    Matched MeSH terms: Breast Neoplasms/genetics*
  12. Pharmacologic downregulation of protein arginine methyltransferase1 expression by adenosine dialdehyde increases cell senescence in breast cancer
    Singh P, Charles S, Madhavan T, Munusamy-Ramanujam G, Saraswathi NT, Arasu MV, et al.
    Eur J Pharmacol, 2021 Jan 15;891:173697.
    PMID: 33144068 DOI: 10.1016/j.ejphar.2020.173697
    We investigated the role of protein arginine methylation (PAM) in estrogen receptor (ER)-positive breast cancer cells through pharmacological intervention. Tamoxifen (TAM) or adenosine dialdehyde (ADOX), independently, triggered cell cycle arrest and down-regulated PAM, as reduced protein arginine methyltransferase1 (PRMT1) mRNA and asymmetric dimethylarginine (ADMA) levels. Synergistic effect of these compounds elicited potent anti-cancer effect. However, reduction in ADMA was not proportionate with the compound-induced down-regulation of PRMT1 mRNA. We hypothesized that the disproportionate effect is due to the influence of the compounds on other methyltransferases, which catalyze the arginine dimethylation reaction and the diversity in the degree of drug-protein interaction among these methyltransferases. In silico analyses revealed that independently, ADOX or TAM, binds with phosphatidylethanolamine-methyltransferase (PEMT) or betaine homocysteine-methyl transferase (BHMT); and that the binding affinity of ADOX with PEMT or BHMT is prominent than TAM. These observations suggest that in breast cancer, synergistic effect of ADOX + TAM elicits impressive protective function by regulating PAM; and plausibly, restoration of normal enzyme activities of methyltransferases catalyzing arginine dimethylation could have clinical benefits.
    Matched MeSH terms: Breast Neoplasms/genetics
  13. Fulltext Mitochondrial DNA mutations in Malaysian female breast cancer patients
    Omasanggar R, Yu CY, Ang GY, Emran NA, Kitan N, Baghawi A, et al.
    PLoS One, 2020;15(5):e0233461.
    PMID: 32442190 DOI: 10.1371/journal.pone.0233461
    Cancer development has been ascribed with diverse genetic variations which are identified in both mitochondrial and nuclear genomes. Mitochondrial DNA (mtDNA) alterations have been detected in several tumours which include lung, colorectal, renal, pancreatic and breast cancer. Several studies have explored the breast tumour-specific mtDNA alteration mainly in Western population. This study aims to identify mtDNA alterations of 20 breast cancer patients in Malaysia by next generation sequencing analysis. Twenty matched tumours with corresponding normal breast tissues were obtained from female breast cancer patients who underwent mastectomy. Total DNA was extracted from all samples and the entire mtDNA (16.6kb) was amplified using long range PCR amplification. The amplified PCR products were sequenced using mtDNA next-generation sequencing (NGS) on an Illumina Miseq platform. Sequencing involves the entire mtDNA (16.6kb) from all pairs of samples with high-coverage (~ 9,544 reads per base). MtDNA variants were called and annotated using mtDNA-Server, a web server. A total of 18 of 20 patients had at least one somatic mtDNA mutation in their tumour samples. Overall, 65 somatic mutations were identified, with 30 novel mutations. The majority (59%) of the somatic mutations were in the coding region, whereas only 11% of the mutations occurred in the D-loop. Notably, somatic mutations in protein-coding regions were non-synonymous (49%) in which 15.4% of them are potentially deleterious. A total of 753 germline mutations were identified and four of which were novel mutations. Compared to somatic alterations, less than 1% of germline missense mutations are harmful. The findings of this study may enhance the current knowledge of mtDNA alterations in breast cancer. To date, the catalogue of mutations identified in this study is the first evidence of mtDNA alterations in Malaysian female breast cancer patients.
    Matched MeSH terms: Breast Neoplasms/genetics*
  14. Fulltext Macrophage-derived interleukin-1beta promotes human breast cancer cell migration and lymphatic adhesion in vitro
    Storr SJ, Safuan S, Ahmad N, El-Refaee M, Jackson AM, Martin SG
    Cancer Immunol Immunother, 2017 Oct;66(10):1287-1294.
    PMID: 28551814 DOI: 10.1007/s00262-017-2020-0
    Lymphovascular invasion (LVI), encompassing blood and lymphatic vessel invasion, is an important event in tumourigenesis. Macrophages within the tumour microenvironment are linked to the presence of LVI and angiogenesis. This study investigates the role of macrophage-derived, caspase-1-dependent interleukin-1beta (IL-1β) in an in vitro model of LVI. IL-1β significantly augmented the adhesion and transmigration of breast cancer cell lines MCF7 and MDA-MB-231 across endothelial cell barriers. MDA-MB-231 and MCF7 showed a higher percentage of adhesion to lymphatic endothelial cells than blood endothelial cells following endothelial cell IL-1β stimulation (P breast cancer cells and their adhesion to, and transmigration across, blood and lymphatic endothelial cells. Results suggest that IL-1β may play a role in the adhesion to lymphatic endothelial cells in particular.
    Matched MeSH terms: Breast Neoplasms/genetics*
  15. Fulltext The functional ALDH2 polymorphism is associated with breast cancer risk: A pooled analysis from the Breast Cancer Association Consortium
    Ugai T, Milne RL, Ito H, Aronson KJ, Bolla MK, Chan T, et al.
    Mol Genet Genomic Med, 2019 Jun;7(6):e707.
    PMID: 31066241 DOI: 10.1002/mgg3.707
    BACKGROUND: Epidemiological studies consistently indicate that alcohol consumption is an independent risk factor for female breast cancer (BC). Although the aldehyde dehydrogenase 2 (ALDH2) polymorphism (rs671: Glu>Lys) has a strong effect on acetaldehyde metabolism, the association of rs671 with BC risk and its interaction with alcohol intake have not been fully elucidated. We conducted a pooled analysis of 14 case-control studies, with individual data on Asian ancestry women participating in the Breast Cancer Association Consortium.

    METHODS: We included 12,595 invasive BC cases and 12,884 controls for the analysis of rs671 and BC risk, and 2,849 invasive BC cases and 3,680 controls for the analysis of the gene-environment interaction between rs671 and alcohol intake for BC risk. The pooled odds ratios (OR) with 95% confidence intervals (CI) associated with rs671 and its interaction with alcohol intake for BC risk were estimated using logistic regression models.

    RESULTS: The Lys/Lys genotype of rs671 was associated with increased BC risk (OR = 1.16, 95% CI 1.03-1.30, p = 0.014). According to tumor characteristics, the Lys/Lys genotype was associated with estrogen receptor (ER)-positive BC (OR = 1.19, 95% CI 1.05-1.36, p = 0.008), progesterone receptor (PR)-positive BC (OR = 1.19, 95% CI 1.03-1.36, p = 0.015), and human epidermal growth factor receptor 2 (HER2)-negative BC (OR = 1.25, 95% CI 1.05-1.48, p = 0.012). No evidence of a gene-environment interaction was observed between rs671 and alcohol intake (p = 0.537).

    CONCLUSION: This study suggests that the Lys/Lys genotype confers susceptibility to BC risk among women of Asian ancestry, particularly for ER-positive, PR-positive, and HER2-negative tumor types.

    Matched MeSH terms: Breast Neoplasms/genetics*
  16. MicroRNAs as Biomarker for Breast Cancer
    Aggarwal T, Wadhwa R, Gupta R, Paudel KR, Collet T, Chellappan DK, et al.
    Endocr Metab Immune Disord Drug Targets, 2020;20(10):1597-1610.
    PMID: 32342824 DOI: 10.2174/1871530320666200428113051
    Regardless of advances in detection and treatment, breast cancer affects about 1.5 million women all over the world. Since the last decade, genome-wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with the regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause a disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute a large family of non-coding RNAs, which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus to study the role of microRNAs in breast cancer.
    Matched MeSH terms: Breast Neoplasms/genetics
  17. Global Disparities in Breast Cancer Genetics Testing, Counselling and Management
    Yip CH, Evans DG, Agarwal G, Buccimazza I, Kwong A, Morant R, et al.
    World J Surg, 2019 05;43(5):1264-1270.
    PMID: 30610270 DOI: 10.1007/s00268-018-04897-6
    Hereditary breast cancers, mainly due to BRCA1 and BRCA2 mutations, account for only 5-10% of this disease. The threshold for genetic testing is a 10% likelihood of detecting a mutation, as determined by validated models such as BOADICEA and Manchester Scoring System. A 90-95% reduction in breast cancer risk can be achieved with bilateral risk-reducing mastectomy in unaffected BRCA mutation carriers. In patients with BRCA-associated breast cancer, there is a 40% risk of contralateral breast cancer and hence risk-reducing contralateral mastectomy is recommended, which can be performed simultaneously with surgery for unilateral breast cancer. Other options for risk management include surveillance by mammogram and breast magnetic resonance imaging, and chemoprevention with hormonal agents. With the advent of next-generation sequencing and development of multigene panel testing, the cost and time taken for genetic testing have reduced, making it possible for treatment-focused genetic testing. There are also drugs such as the PARP inhibitors that specifically target the BRCA mutation. Risk management multidisciplinary clinics are designed to quantify risk, and offer advice on preventative strategies. However, such services are only possible in high-income settings. In low-resource settings, the prohibitive cost of testing and the lack of genetic counsellors are major barriers to setting up a breast cancer genetics service. Family history is often not well documented because of the stigma associated with cancer. Breast cancer genetics services remain an unmet need in low- and middle-income countries, where the priority is to optimise access to quality treatment.
    Matched MeSH terms: Breast Neoplasms/genetics*
  18. Dysregulation of non-histone molecule miR205 and LRG1 post-transcriptional de-regulation by SETD1A in triple negative breast cancer
    Mohamad Hanif EA
    Mol Biol Rep, 2019 Dec;46(6):6617-6624.
    PMID: 31552595 DOI: 10.1007/s11033-019-05079-w
    FEC chemo-resistance in triple negative breast cancer (TNBC) remains a challenge. Therefore it is crucial to determine the right treatment regime by understanding molecular mechanisms of driver regulators involved in the progression of TNBCs. This study aims to understand SETD1A mechanisms in TNBC development in two TNBC cell lines. SETD1A was transiently transfected in MDA-MB-468 (FEC good prognosis) and Hs578T (FEC poor prognosis). Regulation of potential targets miR205, EMT marker ZEB1 and LRG1 and proliferative marker Ki-67 were tested by RqPCR to elucidate SETD1A interactions. This study displayed significant recovery of miR205 with SETD1A depletion and reduction of ZEB1 in MDA-MB-468. However, ZEB1 remained unchanged in Hs578T indicating ZEB1 regulation may be outcompeted by other mechanisms associated with aggressive cell line characteristics and the expression of endogenous ZEB1 was relatively high in Hs578T. Elevation of LRG1 and declined Ki-67 were observed by SETD1A knocked down. Enhanced expression was observed by LRG1 in Hs578T and not in MDA-MB-468 suggesting LRG1 contributed to distinct poor FEC outcome in TNBCs. The underlying mechanism of SETD1A in miR205/ZEB1/Ki-67/LRG1 axis needs further evaluation. Whether abrogation of the pathway is indeed associated with transcriptional or post-transcriptional activation in TNBC cell lines models, clearly validation in clinical samples is warranted to achieve its prognostic and therapeutic values in TNBCs.
    Matched MeSH terms: Triple Negative Breast Neoplasms/genetics*
  19. Differentially expressed proteins in ER+ MCF7 and ER- MDA- MB-231 human breast cancer cells by RhoGDI-α silencing and overexpression
    Hooshmand S, Ghaderi A, Yusoff K, Thilakavathy K, Rosli R, Mojtahedi Z
    Asian Pac J Cancer Prev, 2014;15(7):3311-7.
    PMID: 24815488
    BACKGROUND: The consequence of Rho GDP dissociation inhibitor alpha (RhoGDIα) activity on migration and invasion of estrogen receptor positive (ER+) and negative (ER-) breast cancer cells has not been studied using the proteomic approach. Changes in expression of RhoGDIα and other proteins interacting directly or indirectly with RhoGDIα in MCF7 and MDA-MB-231, with different metastatic potentials is of particular interest.

    MATERIALS AND METHODS: ER+ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/time- of-flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDIα using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDIα.

    RESULTS: The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDIα in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDIα in MCF7, while only one protein was identified in the upregulation of RhoGDIα in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-α activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells.

    CONCLUSIONS: Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDIα with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration.

    Matched MeSH terms: Breast Neoplasms/genetics*
  20. Fulltext The prevalence and assessment of ErbB2-positive breast cancer in Asia: a literature survey
    Tan YO, Han S, Lu YS, Yip CH, Sunpaweravong P, Jeong J, et al.
    Cancer, 2010 Dec 1;116(23):5348-57.
    PMID: 20715159 DOI: 10.1002/cncr.25476
    Overexpression of the epidermal growth factor receptor-related gene ErbB2 occurs in 18% to 25% of patients with breast cancer in Western countries and is associated with a poor prognosis. The prevalence of ErbB2-positive tumors in Asia is unclear, partly because data are limited. The objective of this review was to summarize the reported prevalence of ErbB2-positive tumors from a large sample of Asian patients and to examine ErbB2 assessment methods in Asia. From searches of MEDLINE, local language journals, and local and international conference proceedings as well as locoregional breast cancer experts' recommendations, the authors selected up to 5 studies each from India, Korea, Malaysia, the Philippines, Singapore, Taiwan, and Thailand that reported ErbB2 results based on assessment with immunohistochemistry (IHC) and/or fluorescence in situ hybridization (FISH). The reported prevalence of ErbB2-positive tumors in 22 studies on 24,671 patients, of whom 14,398 patients were assessed for ErbB2 status, varied widely (range, 6%-65%) as did the assessment methods used. Most studies (n=21) used IHC to assess ErbB2 status, but definitions for positivity varied. When robust assessment methods were used, the median prevalence was 19% based on strong IHC staining (IHC3+; n=9812 patients) and 25% based on FISH (n=681 patients). Data on the prevalence of ErbB2-positive breast cancer in Asia are limited. The current survey indicated that the prevalence in Asia may be similar to that in Western countries; thus, up to 1 in 4 Asian patients with breast cancer potentially could benefit from ErbB2-targeted treatment. A standard, reliable ErbB2 assessment method available to patients across Asia is urgently required.
    Matched MeSH terms: Breast Neoplasms/genetics*
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