Displaying publications 1 - 20 of 178 in total

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  1. 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*
  2. Yip CH, Taib NA, Choo WY, Rampal S, Thong MK, Teo SH
    World J Surg, 2009 Oct;33(10):2077-81.
    PMID: 19649760 DOI: 10.1007/s00268-009-0146-8
    Mutations in BRCA1 and BRCA2 confer an increased risk to breast and other cancers, but to date there have only been limited numbers of studies of BRCA1- and BRCA2-associated cancers among Asians. Malaysia is a multiracial country with three main races: Malays, Chinese, Indians. We determined whether tumor pathologic features and clinical features differ in patients with and without BRCA mutations in this Asian population.
    Matched MeSH terms: Breast Neoplasms/genetics*
  3. Nesaretnam K, Jin Lim E, Reimann K, Lai LC
    Toxicology, 2000 Oct 26;151(1-3):117-26.
    PMID: 11074306
    Breast cancer is the most common cancer in women worldwide. The growth of breast cancer cells is either hormone-dependent or hormone-independent. Both types are represented in vitro by the estrogen-receptor positive (ER+) MCF-7 and the estrogen-receptor negative (ER-) MDA-MB-231 cell lines, respectively. The pS2 gene is an estrogen-regulated gene and serves as a marker for the ER+ tumours. Carotenoids are pigments with anti-cancer properties besides having pro-vitamin A, antioxidant and free-radical quenching effects. This study was designed firstly, to compare the effect of palm oil carotene concentrate with retinoic acid on the growth of the ER+ MCF-7 and the ER- MDA-MB-231 cells; and secondly to evaluate the effect of the palm oil carotene concentrate on the regulation of pS2 mRNA. The growth experiments were performed with monolayer cells seeded in phenol red free RPMI 1640 culture media and subsequently treated with varying concentrations of either retinoic acid or palm oil carotenoids. The cell numbers were determined at the start of each experiment and then at successive time intervals. The results showed that the palm oil carotene concentrate caused dose-dependent inhibition of estradiol-stimulated growth of MCF-7 cells but did not affect the proliferation of MDA-MB-231 cells. Retinoic acid caused similar, albeit more potent effects, as significant inhibition was observed at lower concentrations than the palm oil carotenoids. In the pS2 gene expression experiment, cell monolayers were treated with the carotene concentrate (10(-6) M), either with or without supplemented estradiol (10(-8) M), and subsequently the RNA was extracted. Northern blotting was performed and the regulation of pS2 mRNA determined using a 32P-labelled pS2 cDNA probe. The results showed that the palm oil carotene concentrate did not affect the expression of pS2 mRNA and are therefore independent of the estrogen-regulated pathway.
    Matched MeSH terms: Breast Neoplasms/genetics*
  4. Hor SY, Lee SC, Wong CI, Lim YW, Lim RC, Wang LZ, et al.
    Pharmacogenomics J, 2008 Apr;8(2):139-46.
    PMID: 17876342
    Previously studied candidate genes have failed to account for inter-individual variability of docetaxel and doxorubicin disposition and effects. We genotyped the transcriptional regulators of CYP3A and ABCB1 in 101 breast cancer patients from 3 Asian ethnic groups, that is, Chinese, Malays and Indians, in correlation with the pharmacokinetics and pharmacodynamics of docetaxel and doxorubicin. While there was no ethnic difference in docetaxel and doxorubicin pharmacokinetics, ethnic difference in docetaxel- (ANOVA, P=0.001) and doxorubicin-induced (ANOVA, P=0.003) leukocyte suppression was observed, with Chinese and Indians experiencing greater degree of docetaxel-induced myelosuppression than Malays (Bonferroni, P=0.002, P=0.042), and Chinese experiencing greater degree of doxorubicin-induced myelosuppression than Malays and Indians (post hoc Bonferroni, P=0.024 and 0.025). Genotyping revealed both PXR and CAR to be well conserved; only a PXR 5'-untranslated region polymorphism (-24381A>C) and a silent CAR variant (Pro180Pro) were found at allele frequencies of 26 and 53%, respectively. Two non-synonymous variants were identified in HNF4alpha (Met49Val and Thr130Ile) at allele frequencies of 55 and 1%, respectively, with the Met49Val variant associated with slower neutrophil recovery in docetaxel-treated patients (ANOVA, P=0.046). Interactions were observed between HNF4alpha Met49Val and CAR Pro180Pro, with patients who were wild type for both variants experiencing least docetaxel-induced neutropenia (ANOVA, P=0.030). No other significant genotypic associations with pharmacokinetics or pharmacodynamics of either drug were found. The PXR-24381A>C variants were significantly more common in Indians compared to Chinese or Malays (32/18/21%, P=0.035) Inter-individual and inter-ethnic variations of docetaxel and doxorubicin pharmacokinetics or pharmacodynamics exist, but genotypic variability of the transcriptional regulators PAR, CAR and HNF4alpha cannot account for this variability.
    Matched MeSH terms: Breast Neoplasms/genetics
  5. Chin FW, Chan SC, Abdul Rahman S, Noor Akmal S, Rosli R
    Breast J, 2016 Jan-Feb;22(1):54-62.
    PMID: 26510986 DOI: 10.1111/tbj.12518
    The cytochrome P450, family 2, subfamily D, polypeptide 6 (CYP2D6) is an enzyme that is predominantly involved in the metabolism of tamoxifen. Genetic polymorphisms of the CYP2D6 gene may contribute to inter-individual variability in tamoxifen metabolism, which leads to the differences in clinical response to tamoxifen among breast cancer patients. In Malaysia, the knowledge on CYP2D6 genetic polymorphisms as well as metabolizer status in Malaysian breast cancer patients remains unknown. Hence, this study aimed to comprehensively identify CYP2D6 genetic polymorphisms among 80 Malaysian breast cancer patients. The genetic polymorphisms of all the 9 exons of CYP2D6 gene were identified using high-resolution melting analysis and confirmed by DNA sequencing. Seven CYP2D6 alleles consisting of CYP2D6*1, CYP2D6*2, CYP2D6*4, CYP2D6*10, CYP2D6*39, CYP2D6*49, and CYP2D6*75 were identified in this study. Among these alleles, CYP2D6*10 is the most common allele in both Malaysian Malay (54.8%) and Chinese (71.4%) breast cancer patients, whereas CYP2D6*4 in Malaysian Indian (28.6%) breast cancer patients. In relation to CYP2D6 genotype, CYP2D6*10/*10 is more frequently observed in both Malaysian Malay (28.9%) and Chinese (57.1%) breast cancer patients, whereas CYP2D6*4/*10 is more frequently observed in Malaysian Indian (42.8%) breast cancer patients. In terms of CYP2D6 phenotype, 61.5% of Malaysian Malay breast cancer patients are predicted as extensive metabolizers in which they are most likely to respond well to tamoxifen therapy. However, 57.1% of Chinese as well as Indian breast cancer patients are predicted as intermediate metabolizers and they are less likely to gain optimal benefit from the tamoxifen therapy. This is the first report of CYP2D6 genetic polymorphisms and phenotypes in Malaysian breast cancer patients for different ethnicities. These data may aid clinicians in selecting an optimal drug therapy for Malaysian breast cancer patients, hence improve the clinical outcome of the patients.
    Matched MeSH terms: Breast Neoplasms/genetics*
  6. Al-Joudi FS, Iskandar ZA, Imran AK
    PMID: 18041310
    This work studied the correlations between survivin, bcl-2 and p53 in infiltrating ductal carcinoma of the breast. A total number of 382 cases were collected from 3 hospitals in northeastern Malaysia. Survivin, bcl-2 and p53 were detected by immunohistochemistry on samples prepared from tissue blocks. Significant correlations were found between tumor histological grades and tumor size and lymph node involvement. Highly significant statistical correlations (p<0.001) were found in expression of the markers under study. It is concluded that such significant correlations may imply that the alterations in the expression take place in a concerted fashion, implying that many of these cases may share common abnormalities.
    Matched MeSH terms: Breast Neoplasms/genetics
  7. Breast Cancer Association Consortium, Dorling L, Carvalho S, Allen J, González-Neira A, Luccarini C, et al.
    N Engl J Med, 2021 02 04;384(5):428-439.
    PMID: 33471991 DOI: 10.1056/NEJMoa1913948
    BACKGROUND: Genetic testing for breast cancer susceptibility is widely used, but for many genes, evidence of an association with breast cancer is weak, underlying risk estimates are imprecise, and reliable subtype-specific risk estimates are lacking.

    METHODS: We used a panel of 34 putative susceptibility genes to perform sequencing on samples from 60,466 women with breast cancer and 53,461 controls. In separate analyses for protein-truncating variants and rare missense variants in these genes, we estimated odds ratios for breast cancer overall and tumor subtypes. We evaluated missense-variant associations according to domain and classification of pathogenicity.

    RESULTS: Protein-truncating variants in 5 genes (ATM, BRCA1, BRCA2, CHEK2, and PALB2) were associated with a risk of breast cancer overall with a P value of less than 0.0001. Protein-truncating variants in 4 other genes (BARD1, RAD51C, RAD51D, and TP53) were associated with a risk of breast cancer overall with a P value of less than 0.05 and a Bayesian false-discovery probability of less than 0.05. For protein-truncating variants in 19 of the remaining 25 genes, the upper limit of the 95% confidence interval of the odds ratio for breast cancer overall was less than 2.0. For protein-truncating variants in ATM and CHEK2, odds ratios were higher for estrogen receptor (ER)-positive disease than for ER-negative disease; for protein-truncating variants in BARD1, BRCA1, BRCA2, PALB2, RAD51C, and RAD51D, odds ratios were higher for ER-negative disease than for ER-positive disease. Rare missense variants (in aggregate) in ATM, CHEK2, and TP53 were associated with a risk of breast cancer overall with a P value of less than 0.001. For BRCA1, BRCA2, and TP53, missense variants (in aggregate) that would be classified as pathogenic according to standard criteria were associated with a risk of breast cancer overall, with the risk being similar to that of protein-truncating variants.

    CONCLUSIONS: The results of this study define the genes that are most clinically useful for inclusion on panels for the prediction of breast cancer risk, as well as provide estimates of the risks associated with protein-truncating variants, to guide genetic counseling. (Funded by European Union Horizon 2020 programs and others.).

    Matched MeSH terms: Breast Neoplasms/genetics*
  8. Razif SM, Sulaiman S, Hanie SS, Aina EN, Rohaizak M, Fuad I, et al.
    Med J Malaysia, 2011 Aug;66(3):220-6.
    PMID: 22111444 MyJurnal
    Breast cancer is the most common cancer among Malaysian women. This study aimed to determine the reproductive for premenopausal breast cancer risk in Kuala Lumpur, Malaysia. A case-control study was conducted in 216 histopathologically confirmed cases of premenopausal breast cancer and 216 community-based controls that were matched by age within a 5-year period and ethnicity. The results of this study showed that premenopausal breast cancer risks were strongly related to parity, number of live births and family history of breast cancer. Premenopausal women with these known reproductive and family history risk factors should take extra measures to undergo appropriate screening method for early detection of breast cancer.
    Matched MeSH terms: Breast Neoplasms/genetics
  9. Al-Joudi FS, Iskandar ZA, Rusli J
    Med J Malaysia, 2008 Jun;63(2):96-9.
    PMID: 18942291
    The p53 gene is a tumour suppressor gene that encodes a 393-amino-acid nuclear DNA-binding phosphoprotein. The significance of p53 detection is that p53 mutation is linked with chemo-resistance and transformation to more aggressive disease in a large number of tumour types and it was confirmed that mutant p53 is involved in neoplastic transformations. In addition, the expression of p53 has been closely correlated with clinicopathological findings. Since breast cancer has been reported as one of the most frequent malignancies in women in Malaysia, the expression of p53 was studied in 382 cases of invasive ductal carcinoma of the breast, obtained from three major hospitals in the North-East States of Malaysia. The study utilized an enzyme immunohistochemistry assay for the detection of p53. It was found that p53 was expressed in 29.6% of all the study cases. Furthermore, its expression was significantly correlated with the age and the clinical grading of the disease. No significant statistical correlations were depicted with lymph node status, tumour size, side of tumour, and expression of estrogen and progesterone receptors. Nevertheless, knowledge of the p53 status may be valuable in making clinical decisions regarding diagnosis, prognosis and therapy.
    Matched MeSH terms: Breast Neoplasms/genetics*
  10. Ho CC, Mun KS, Naidu R
    Malays J Pathol, 2013 Jun;35(1):33-43.
    PMID: 23817393 MyJurnal
    Breast cancer is the most common malignancy in women worldwide. The incidence of breast cancer in Malaysia is lower compared to international statistics, with peak occurrence in the age group between 50 to 59 years of age and mortality rates of 18.6%. Despite current diagnostic and prognostic methods, the outcome for individual subjects remain poor. This is in part due to breast cancers' wide genetic heterogeneity. Various platforms for genetics studies are now employed to determine the identity of these genetic abnormalities, including microarray methods like high density single-nucleotide-polymorphism (SNP) oligonucleotide arrays which combine the power of chromosomal comparative genomic hybridization (cCGH) and loss of heterozygosity (LOH) in the offering of higher-resolution mappings. These platforms and their applications in highlighting the genomic alteration frameworks manifested in breast carcinoma will be discussed.
    Matched MeSH terms: Breast Neoplasms/genetics*
  11. 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: Breast Neoplasms/genetics*
  12. 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: Breast Neoplasms/genetics*
  13. McCart Reed AE, Kalaw E, Nones K, Bettington M, Lim M, Bennett J, et al.
    J Pathol, 2019 02;247(2):214-227.
    PMID: 30350370 DOI: 10.1002/path.5184
    Metaplastic breast carcinoma (MBC) is relatively rare but accounts for a significant proportion of global breast cancer mortality. This group is extremely heterogeneous and by definition exhibits metaplastic change to squamous and/or mesenchymal elements, including spindle, squamous, chondroid, osseous, and rhabdomyoid features. Clinically, patients are more likely to present with large primary tumours (higher stage), distant metastases, and overall, have shorter 5-year survival compared to invasive carcinomas of no special type. The current World Health Organisation (WHO) diagnostic classification for this cancer type is based purely on morphology - the biological basis and clinical relevance of its seven sub-categories are currently unclear. By establishing the Asia-Pacific MBC (AP-MBC) Consortium, we amassed a large series of MBCs (n = 347) and analysed the mutation profile of a subset, expression of 14 breast cancer biomarkers, and clinicopathological correlates, contextualising our findings within the WHO guidelines. The most significant indicators of poor prognosis were large tumour size (T3; p = 0.004), loss of cytokeratin expression (lack of staining with pan-cytokeratin AE1/3 antibody; p = 0.007), EGFR overexpression (p = 0.01), and for 'mixed' MBC, the presence of more than three distinct morphological entities (p = 0.007). Conversely, fewer morphological components and EGFR negativity were favourable indicators. Exome sequencing of 30 cases confirmed enrichment of TP53 and PTEN mutations, and intriguingly, concurrent mutations of TP53, PTEN, and PIK3CA. Mutations in neurofibromatosis-1 (NF1) were also overrepresented [16.7% MBCs compared to ∼5% of breast cancers overall; enrichment p = 0.028; mutation significance p = 0.006 (OncodriveFM)], consistent with published case reports implicating germline NF1 mutations in MBC risk. Taken together, we propose a practically minor but clinically significant modification to the guidelines: all WHO_1 mixed-type tumours should have the number of morphologies present recorded, as a mechanism for refining prognosis, and that EGFR and pan-cytokeratin expression are important prognostic markers. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
    Matched MeSH terms: Breast Neoplasms/genetics*
  14. Al Joudi FS
    Indian J Med Res, 2014 May;139(5):675-85.
    PMID: 25027076
    Human mammaglobin is a member of the uteroglobin proteins family that has recently been tested as a specific marker for breast cancer. While low levels may be seen in normal breast tissue, expression is increased dramatically in breast cancer and is correlated with higher grade. Detection in blood and body fluids is also correlated with cancer metastasis, and its levels with prognosis. This promises to be a useful screen for early detection of breast cancer, especially in high risk individuals. Mammoglobin has also been used for immunotherapeutic targeting of breast cancer cells. However, there are some controversies regarding its diagnostic efficacy and prognostic value, which warrant further study.
    Matched MeSH terms: Breast Neoplasms/genetics
  15. Teh LK, Mohamed NI, Salleh MZ, Rohaizak M, Shahrun NS, Saladina JJ, et al.
    AAPS J, 2012 Mar;14(1):52-9.
    PMID: 22183189 DOI: 10.1208/s12248-011-9313-6
    CYP2D6 plays a major role in the metabolism of tamoxifen, and polymorphism of P-glycoprotein has been associated with resistance of many drug therapies. This study investigates the clinical impact of genetic variants of CYP2D6 and ABCB1 in breast cancer patients treated with tamoxifen. Blood samples from 95 breast cancer patients treated with tamoxifen were collected and genotyped for CYP2D6 and ABCB1 variants using allele-specific PCR method. Recurrence risks were calculated using Kaplan-Meier analysis and compared using the log-rank test. Patients carrying CYP2D6*10/*10 and heterozygous null allele (IM) showed higher risks of developing recurrence and metastasis (OR 13.14; 95% CI 1.57-109.94; P = 0.004) than patients with CYP2D6*1/*1 and *1/*10 genotypes. Patients with homozygous CC genotypes of ABCB1 C3435T showed a shorter time to recurrence. Patients who were CYP2D6 IM and homozygous CC genotype of C3435T have statistically significant higher risks of recurrence (P = 0.002). Similarly, median time to recurrence in these patients was only 12 months (95% CI = 0.79-23.2) compared to those without this combination which was 48 months (95% CI = 14.7-81.2). Patients with CYP2D6 IM and homozygous CC genotype of ABCB1 C3435T have shorter times to recurrence. The results confirmed the findings of previous studies and support FDA recommendation to perform pre-genotyping in patients before the choice of therapy is determined in breast cancer patients.
    Matched MeSH terms: Breast Neoplasms/genetics
  16. 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*
  17. Balraj P, Khoo AS, Volpi L, Tan JA, Nair S, Abdullah H
    Singapore Med J, 2002 Apr;43(4):194-7.
    PMID: 12188064
    Thirty patients with early onset breast cancer or familial breast cancer from Malaysia were analysed for germline mutation in the early onset breast cancer I gene (BRCA1). Direct sequencing of the entire coding region of BRCA1 identified a frameshift mutation, c.5447-5448insC (insC5447) (codon 1776 of exon 21) in a patient aged 32 of the Malay ethnic origin, who had no family history of breast and/or ovarian cancer. Eight polymorphisms (2201C > T, 2430T > C, P871L, E1038G, K1183R, 4427T > C, S1613G and IVS8-57delT) were identified in the samples tested.
    Matched MeSH terms: Breast Neoplasms/genetics*
  18. 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
  19. Tung J, Tew LS, Hsu YM, Khung YL
    Sci Rep, 2017 04 11;7(1):793.
    PMID: 28400564 DOI: 10.1038/s41598-017-00912-3
    Measuring at ~30 nm, a fully customizable holliday junction DNA nanoconstruct, was designed to simultaneously carry three unmodified SiRNA strands for apoptosis gene knockout in cancer cells without any assistance from commercial transfection kits. In brief, a holliday junction structure was intelligently designed to present one arm with a cell targeting aptamer (AS1411) while the remaining three arms to carry different SiRNA strands by means of DNA/RNA duplex for inducing apoptosis in cancer cells. By carrying the three SiRNA strands (AKT, MDM2 and Survivin) into triple negative breast MDA-MB-231 cancer cells, cell number had reduced by up to ~82% within 24 hours solely from one single administration of 32 picomoles. In the immunoblotting studies, up-elevation of phosphorylated p53 was observed for more than 8 hours while the three genes of interest were suppressed by nearly half by the 4-hour mark upon administration. Furthermore, we were able to demonstrate high cell selectivity of the nanoconstruct and did not exhibit usual morphological stress induced from liposomal-based transfection agents. To the best of the authors' knowledge, this system represents the first of its kind in current literature utilizing a short and highly customizable holliday DNA junction to carry SiRNA for apoptosis studies.
    Matched MeSH terms: Triple Negative Breast Neoplasms/genetics*
  20. Dörk T, Peterlongo P, Mannermaa A, Bolla MK, Wang Q, Dennis J, et al.
    Sci Rep, 2019 08 29;9(1):12524.
    PMID: 31467304 DOI: 10.1038/s41598-019-48804-y
    Fanconi anemia (FA) is a genetically heterogeneous disorder with 22 disease-causing genes reported to date. In some FA genes, monoallelic mutations have been found to be associated with breast cancer risk, while the risk associations of others remain unknown. The gene for FA type C, FANCC, has been proposed as a breast cancer susceptibility gene based on epidemiological and sequencing studies. We used the Oncoarray project to genotype two truncating FANCC variants (p.R185X and p.R548X) in 64,760 breast cancer cases and 49,793 controls of European descent. FANCC mutations were observed in 25 cases (14 with p.R185X, 11 with p.R548X) and 26 controls (18 with p.R185X, 8 with p.R548X). There was no evidence of an association with the risk of breast cancer, neither overall (odds ratio 0.77, 95%CI 0.44-1.33, p = 0.4) nor by histology, hormone receptor status, age or family history. We conclude that the breast cancer risk association of these two FANCC variants, if any, is much smaller than for BRCA1, BRCA2 or PALB2 mutations. If this applies to all truncating variants in FANCC it would suggest there are differences between FA genes in their roles on breast cancer risk and demonstrates the merit of large consortia for clarifying risk associations of rare variants.
    Matched MeSH terms: Breast Neoplasms/genetics*
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