Displaying publications 161 - 180 of 352 in total

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  1. Dean SJ, Perks CM, Holly JM, Bhoo-Pathy N, Looi LM, Mohammed NA, et al.
    Am J Clin Pathol, 2014 Mar;141(3):323-33.
    PMID: 24515759 DOI: 10.1309/AJCPR11DEAYPTUSL
    OBJECTIVES: To investigate the association between PTEN loss and IGFBP2 expression in a series of triple-negative breast cancers and to relate this expression to basal cytokeratin expression and clinicopathologic features.

    METHODS: One hundred and one formalin-fixed and paraffin-processed triple-negative breast cancer cases from the University of Malaya Medical Centre were tested immunohistochemically for cytokeratins 5/6 and 14, PTEN, and IGFBP2. The resulting slides were scored for proportion and intensity of staining.

    RESULTS: Loss of tumor nuclear and cytoplasmic staining for PTEN occurred in 48.3% of cases and was significantly associated with younger age at diagnosis (47 years compared with 57 years in those without PTEN loss; P = .005). Independent predictors of PTEN loss were late stage at presentation (P = .026), cytokeratin 5/6 positivity (P = .028), and IGFBP2 expression (P = .042). High levels of IGFBP2 expression were seen in 32% of cases; an independent predictor of high levels was cytokeratin 14 negativity (P = .005). PTEN loss and high levels of IGFBP2 expression were associated with poorer survival, but neither of these trends was significant.

    CONCLUSIONS: PTEN loss is a frequent event in triple-negative breast cancers and is significantly associated with younger age at onset of breast cancer, late stage, and IGFBP2 expression.

    Matched MeSH terms: Triple Negative Breast Neoplasms/pathology
  2. Moad AI, Muhammad TS, Oon CE, Tan ML
    Cell Biochem Biophys, 2013 Jul;66(3):567-87.
    PMID: 23300026 DOI: 10.1007/s12013-012-9504-5
    Autophagy is an evolutionarily conserved lysosomal degradation pathway and plays a critical role in the homeostatic process of recycling proteins and organelles. Functional relationships have been described between apoptosis and autophagy. Perturbations in the apoptotic machinery have been reported to induce autophagic cell deaths. Inhibition of autophagy in cancer cells has resulted in cell deaths that manifested hallmarks of apoptosis. However, the molecular relationships and the circumstances of which molecular pathways dictate the choice between apoptosis and autophagy are currently unknown. This study aims to identify specific gene expression of rapamycin-induced autophagy and the effects of rapamycin when the autophagy process is inhibited. In this study, we have demonstrated that rapamycin is capable of inducing autophagy in T-47D breast carcinoma cells. However, when the autophagy process was inhibited by 3-MA, the effects of rapamycin became apoptotic. The Phlda1 gene was found to be up-regulated in both autophagy and apoptosis and silencing this gene was found to reduce both activities, strongly suggests that Phlda1 mediates and positively regulates both autophagy and apoptosis pathways.
    Matched MeSH terms: Breast Neoplasms/pathology*
  3. Ali R, Draman N, Mohd Yusoff SS, Norsa'adah B
    Asian Pac J Cancer Prev, 2020 Oct 01;21(10):2971-2978.
    PMID: 33112556 DOI: 10.31557/APJCP.2020.21.10.2971
    OBJECTIVE: To determine the level of self-efficacy for coping with breast cancer among Malaysian women and its association with socio-demographic and clinical variables.

    MATERIALS AND METHODS: This cross-sectional study involved 168 women diagnosed with breast cancer. The inclusion criteria were age >18 years old, having histologically confirmed breast cancer, and being diagnosed between January 1, 2009 to December 31, 2012. The exclusion criteria were being illiterate and having cognitive impairment. For data collection patients' medical records and the Cancer Behaviour Inventory-Brief (CBI-B) Malay version questionnaire were used. Simple and multiple logistic regression methods were used to analyse the data.

    RESULTS: Patients' mean (SD) age was 51.4 (10.8) years old. Most of the patients were Malays, married, diagnosed at stage 2 breast cancer (41%), and completed their breast cancer treatment. The mean score for self-efficacy for coping with breast cancer was 83.67 (95% CI: 81.87, 85.47). The significant factors positively correlated with self-efficacy for coping with breast cancer were higher educational background and a higher family income. However, factors such as a family history of breast cancer and breast surgery reduced the mean score of self-efficacy for coping with breast cancer.

    CONCLUSION: The mean score of self-efficacy for coping with breast cancer in this study was moderate. Self-efficacy for coping with breast cancer in Hospital Universiti Sains Malaysia was not adequate among sufferers and improvement is needed probably by providing education to these patients.

    Matched MeSH terms: Breast Neoplasms/pathology
  4. Dinesh BJ, Hayati F, Azizan N, Abdul Rashid NF
    BMJ Case Rep, 2019 Sep 18;12(9).
    PMID: 31537599 DOI: 10.1136/bcr-2019-231516
    Florid papillomatosis (FP) of the nipple, or nipple adenoma, is a rare breast tumour, affecting middle-aged group population. A 46-year-old woman presented to us with a cauliflower-like FP of the right nipple with no blood stained discharge or breast lump. FP can be mistaken clinically for Paget's disease and occasionally misinterpreted as invasive ductal or intraductal carcinoma. Extensive intervention, correct diagnosis and prompt treatment are essential. Any breast pathology requires triple assessment including FP of the nipple. Once the diagnosis of ductal carcinoma is excluded, simple complete excision can be undertaken. This is to ensure complete obliteration of disease recurrence and preservation of cosmetic result. We discuss the pathology and psychosocial aspects of FP.
    Matched MeSH terms: Breast Neoplasms/pathology*
  5. Aggarwal T, Wadhwa R, Gupta R, Paudel KR, Collet T, Chellappan DK, et al.
    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/pathology
  6. Kumcu E, Unverdi H, Kaymaz E, Oral O, Turkbey D, Hucmenoglu S
    Malays J Pathol, 2018 Aug;40(2):137-142.
    PMID: 30173230
    INTRODUCTION: Breast cancer is still a serious health problem in 21st century and diagnosis, treatment and prognosis of this malignant disease are subject to many research. While cancer research has been focused on tumour cells primarily, recent studies showed that tumour stroma contribute to carcinogenesis as well as tumour cells. Especially fibroblasts adjacent to epithelial tumour cells are not ordinary fibroblasts and play the critical role. Studies showed that these cancer associated fibroblasts (CAFs) have different genetic profile and protein expression. One of the differently expressed molecules recently found is podoplanin. Podoplanin, utilised as a lymphatic endothelial marker, is found to be expressed in CAFs. The aim of this study is to evaluate the relationship between the stromal expression of podoplanin in invasive breast carcinoma and clinicopathological parameters.

    MATERIALS & METHODS: Podoplanin expression was evaluated immunohistochemically in 153 breast cancers. Tumours with ≥ 10% distinct cytoplasmic podoplanin staining in CAFs were considered as positive.

    RESULTS: In 65.3% of analysed tumours, podoplanin expression was found positive in CAFs. According to our results, podoplanin positive CAFs correlated significantly with tumour size (p= 0.012), tumour grade (p= 0.032) and cerbB2 score (p= 0.032).

    DISCUSSION: Our results suggest that podoplanin expression by CAFs could predict poor patient outcome in breast carcinoma.

    Matched MeSH terms: Breast Neoplasms/pathology*
  7. Balasundram S, Salekan K, Ahmad Shariffuddin FN, Taib NA, Adnan TH
    Asian Pac J Cancer Prev, 2018 Sep 26;19(9):2409-2415.
    PMID: 30255693
    Objective: To gauge surgical outcome in breast cancer patients with particular reference to overall survival and
    recurrence free survival among breast cancer patients in Hospital Sultanah Nora Ismail Batu Pahat, Johor, Malaysia.
    Methods: Patients undergoing ablative breast cancer surgery were identified and clinical records were assessed.
    Inclusion criteria for enrolment were stage I-IV breast malignancy necessitating resection with or without radiotherapy/
    chemotherapy from 2007 to 2013. All individuals had a pre-operative assessment. The post operative assessment period
    ranged from 1 year to 5 years. Survival distributions were analyzed using Kaplan-Meier curves. Results: A total of
    121 patients were included in this study, with an age range of 28-78 years. Some 98% had undergone local excision/
    lumpectomy/ mastectomy with axillary clearance. While 81% of patients underwent chemotherapy, only 69% had
    radiotherapy. Tumours were oestrogen receptor positive in 58% of cases and progesterone receptor positive in 62%.
    Local recurrence was detected in 10%. The mean age at diagnosis was 51.3 + 10.4 years. The overall survival analysis
    was based on 22 deaths among the 121 patients (18.2%). Three-year and five-year survival rates were 87.6% and 78.4%,
    respectively. Analysis of recurrence-free-survival (RFS) was based on 12 events among 121 patients. The Kaplan-Meier
    RFS analysis revealed that in 90% of the patients with recurrence, it occurred within 45 months. The five year RFS
    rate was 84.5%. The median time taken from diagnosis to ablative surgery was 51 days (upper limit of 791 days).
    Only distant metastasis was a significant factor that impacted on both overall survival and recurrence-free survival
    (p<0.001). Conclusion: Overall survival among our breast cancer patients in our facility is comparable to other in
    other tertiary centres in the country. A trend for earlier detection was noted.
    Matched MeSH terms: Breast Neoplasms/pathology*
  8. Wong WJ, Mosiun JA, Hidayati Z, Balkis R, Sharif SZ, Lee D, et al.
    Breast, 2019 Aug;46:136-143.
    PMID: 31176055 DOI: 10.1016/j.breast.2019.05.016
    INTRODUCTION: Breast-conserving surgery (BCS) with radiation therapy is the procedure of choice for early-stage breast cancer. Survival and locoregional recurrence is non-inferior to mastectomy, with superior cosmetic and psycho-social outcomes. Differing health systems have demonstrated a wide variation in the rate of BCS. Little is known about the rate of BCS and factors influencing its practice in middle resource countries. This study aims to examine the BCS rates in Malaysia and to identify factors influencing its uptake.

    METHODOLOGY: This is a multi-centre, cross-sectional study involving the University of Malaya Medical Centre (UMMC), Queen Elizabeth II Hospital (QEH), and Tengku Ampuan Rahimah Hospital (TARH). Patients diagnosed with invasive breast cancer from January 2014 to December 2015 were included, excluding stromal cancers and lymphomas. Univariate and multivariate analyses identified factors influencing BCS.

    RESULTS: A total of 1005 patients were diagnosed with breast cancer in the allocated time frame. Excluding incomplete records and those who did not have surgery, 730 patients were analysed. Overall BCS rate was 32.9%. The BCS rate was highest at QEH (54.1%), followed by UMMC (29.5%), and TARH (17.4%). 16.9% had BCS after neoadjuvant therapy. Factors influencing BCS uptake included age, ethnic group, breast-surgeon led services, AJCC Stage, tumour size, HER-2 expression, and tumour grade.

    CONCLUSIONS: The rate of BCS in Malaysia is low. A wide variation of rate exists among the studied hospitals. Younger age, earlier AJCC stage, and the presence of a Breast sub-specialist surgeon, would make it more likely that the patient has her breast conserved.

    Matched MeSH terms: Breast Neoplasms/pathology
  9. Wong KK, Hussain FA
    PLoS One, 2020;15(6):e0233884.
    PMID: 32484822 DOI: 10.1371/journal.pone.0233884
    Ion channels form an important class of drug targets in malignancies. Transient receptor potential cation channel subfamily M member 4 (TRPM4) plays oncological roles in various solid tumors. Herein, we examined TRPM4 protein expression profile by immunohistochemistry (IHC) in breast cancer cases compared with normal breast ducts, its association with clinico-demographical parameters, and its potential function in breast cancers by Gene Set Enrichment Analysis (GSEA). Data-mining demonstrated that TRPM4 transcript levels were significantly higher in The Cancer Genome Atlas series of breast cancer cases (n = 1,085) compared with normal breast tissues (n = 112) (p = 1.03 x 10-11). Our IHC findings in tissue microarrays showed that TRPM4 protein was overexpressed in breast cancers (n = 83/99 TRPM4+; 83.8%) compared with normal breast ducts (n = 5/10 TRPM4+; 50%) (p = 0.022). Higher TRPM4 expression (median frequency cut-off) was significantly associated with higher lymph node status (N1-N2 vs N0; p = 0.024) and higher stage (IIb-IIIb vs I-IIa; p = 0.005). GSEA evaluation in three independent gene expression profiling (GEP) datasets of breast cancer cases (GSE54002, n = 417; GSE20685, n = 327; GSE23720, n = 197) demonstrated significant association of TRPM4 transcript expression with estrogen response and epithelial-mesenchymal transition (EMT) gene sets (p<0.01 and false discovery rate<0.05). These gene sets were not enriched in GEP datasets of normal breast epithelium cases (GSE10797, n = 5; GSE9574, n = 15; GSE20437, n = 18). In conclusion, TRPM4 protein expression is upregulated in breast cancers associated with worse clinico-demographical parameters, and TRPM4 potentially regulates estrogen receptor signaling and EMT progression in breast cancer.
    Matched MeSH terms: Breast Neoplasms/pathology
  10. 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/pathology*
  11. Fadzli F, Rahmat K, Ramli MT, Rozalli FI, Hooi TK, Fadzli AN, et al.
    Medicine (Baltimore), 2021 Apr 23;100(16):e25297.
    PMID: 33879660 DOI: 10.1097/MD.0000000000025297
    To evaluate the clinical and imaging findings of papillary breast neoplasm and review the pathologic correlation at a tertiary center.Retrospective study of patients diagnosed with benign and malignant papillary lesions between 2008 to 2018. 147 patients were identified with histology diagnosis of papillary lesions. The clinical, imaging, and pathological characteristics were reviewed.Patient cohort included 147 women diagnosed with papillary lesions (mean age at diagnosis 53.8 years) and were divided into 3 histology groups (benign, atypical, and malignant). Common clinical presentations were breast lump (n = 60) and nipple discharge (n = 29), 48 patients were asymptomatic.Only 37 were detected as a mass lesion on mammogram. The presence of mass lesion on mammogram was the most common feature in all 3 papillary lesion groups, and with the presence of asymmetric density, were the 2 mammographic features significantly associated (P 
    Matched MeSH terms: Breast Neoplasms/pathology
  12. Singh VA, Haseeb A, Alkubaisi AA
    Singapore Med J, 2014 Oct;55(10):539-46.
    PMID: 25631896
    INTRODUCTION: Morbidity and mortality from malignant diseases are usually the result of metastasis. The bone is the third most common site of metastasis.

    METHODS: This is a retrospective study of patients with metastatic bone disease who were referred to the Orthopaedic Department of University Malaya Medical Centre, Malaysia, between January 2004 and October 2009.

    RESULTS: A total of 151 patients (51.0% men, 49.0% women) had metastatic bone disease, with the highest incidence at the age range of 50-59 years. The commonest primary cancer was breast (23.3%), followed by lung (21.2%), prostate (9.3%), thyroid (7.3%) and renal cell carcinoma (5.3%); unknown primary cancer was 6.6%. There was long bone involvement in 52.7% of cases, axial bone in 44.5%, and both long and axial bones in 2.8%. The majority (90.1%) were symptomatic, with pain as the commonest symptom. 106 (70.2%) patients had pathological fractures. Neurological deficit was reported in 90.7% of patients, with 41.1% having extraskeletal metastases. 67.8% of the lesions were osteolytic, 24.3% were sclerotic, and 7.9%, mixed. Palliative and therapeutic interventions were undertaken for 62.0% of patients. The mean survival times were: breast 21.0; thyroid 20.7; prostate 20.3; lung 16.0; and unknown primary cancer 32.6 months.

    CONCLUSION: In our study, breast and lung cancers were the commonest primary cancers in metastatic bone disease. Most patients had more than one site of involvement, pain at presentation and pathological fractures. Surgery is beneficial to relieve pain and improve function and neurology. Duration of survival depends on the type of primary cancer and whether systemic metastasis is present.
    Matched MeSH terms: Breast Neoplasms/pathology
  13. Al-Joudi FS, Iskandar ZA, Hasnan J, Rusli J, Kamal Y, Imran AK, et al.
    Singapore Med J, 2007 Jul;48(7):607-14.
    PMID: 17609820
    INTRODUCTION: Survivin is a 16.5-kDa intracellular protein that inhibits apoptosis and regulates cell division, and belongs to the inhibitors of apoptosis gene family. It appears to have an important role in regulating apoptosis at the cell cycle checkpoints. Survivin has been found to have a differential distribution in cancer compared to normal tissue, as it is over-expressed in malignant tumours.
    METHODS: In addition to the demographical analysis of the disease, data from 382 women with invasive ductal carcinoma of the breast were collected from three hospitals in Northeast Malaysia, and analysed for survivin expression by immunohistochemistry.
    RESULTS: Invasive ductal carcinoma of the breast was found to be the most prevalent breast cancer type. Survivin was detected in 260 (68.1 percent) study cases. In addition, significant correlations have been shown between survivin expression on one hand, and tumour size and lymph node involvement on the other hand (p-value is less than 0.05). However, no significant correlations were found with other clinicopathological factors, such as tumour histological grade, tumour side, oestrogen and progesterone receptors. Nuclear expression of survivin was detected in 16.5 percent of the study cases, cytoplasmic expression was detected in 24.1 percent, and 27.5 percent of the cases expressed survivin in both nuclear and cytoplasmic locations simultaneously. The subcellular localisation of survivin was significantly correlated (p is less than 0.001) with the lymph node involvement indicating its value in predicting the aggressiveness of tumour cells, since it increases the resistance to apoptosis and promotes cell proliferation.
    CONCLUSION: This is the fi rst known report on survivin expression in cancer in West Malaysia and Southeast Asia. It emphasises the importance of the detection of survivin in breast cancer to aid in diagnosis, confirm malignancy, and to assess the disease progress and response to therapy.
    Matched MeSH terms: Breast Neoplasms/pathology
  14. Qian F, Wang S, Mitchell J, McGuffog L, Barrowdale D, Leslie G, et al.
    J Natl Cancer Inst, 2019 Apr 01;111(4):350-364.
    PMID: 30312457 DOI: 10.1093/jnci/djy132
    BACKGROUND: BRCA1/2 mutations confer high lifetime risk of breast cancer, although other factors may modify this risk. Whether height or body mass index (BMI) modifies breast cancer risk in BRCA1/2 mutation carriers remains unclear.

    METHODS: We used Mendelian randomization approaches to evaluate the association of height and BMI on breast cancer risk, using data from the Consortium of Investigators of Modifiers of BRCA1/2 with 14 676 BRCA1 and 7912 BRCA2 mutation carriers, including 11 451 cases of breast cancer. We created a height genetic score using 586 height-associated variants and a BMI genetic score using 93 BMI-associated variants. We examined both observed and genetically determined height and BMI with breast cancer risk using weighted Cox models. All statistical tests were two-sided.

    RESULTS: Observed height was positively associated with breast cancer risk (HR = 1.09 per 10 cm increase, 95% confidence interval [CI] = 1.0 to 1.17; P = 1.17). Height genetic score was positively associated with breast cancer, although this was not statistically significant (per 10 cm increase in genetically predicted height, HR = 1.04, 95% CI = 0.93 to 1.17; P = .47). Observed BMI was inversely associated with breast cancer risk (per 5 kg/m2 increase, HR = 0.94, 95% CI = 0.90 to 0.98; P = .007). BMI genetic score was also inversely associated with breast cancer risk (per 5 kg/m2 increase in genetically predicted BMI, HR = 0.87, 95% CI = 0.76 to 0.98; P = .02). BMI was primarily associated with premenopausal breast cancer.

    CONCLUSION: Height is associated with overall breast cancer and BMI is associated with premenopausal breast cancer in BRCA1/2 mutation carriers. Incorporating height and BMI, particularly genetic score, into risk assessment may improve cancer management.

    Matched MeSH terms: Breast Neoplasms/pathology
  15. Razak NA, Abu N, Ho WY, Zamberi NR, Tan SW, Alitheen NB, et al.
    Sci Rep, 2019 Feb 06;9(1):1514.
    PMID: 30728391 DOI: 10.1038/s41598-018-37796-w
    Eupatorin has been reported with in vitro cytotoxic effect on several human cancer cells. However, reports on the mode of action and detail mechanism of eupatorin in vitro in breast cancer disease are limited. Hence, eupatorin's effect on the human breast carcinoma cell line MCF-7 and MDA-MB-231 was investigated. MTT assay showed that eupatorin had cytotoxic effects on MCF-7 and MDA-MB-231 cells but was non-toxic to the normal cells of MCF-10a in a time-dose dependent manner. At 24 h, the eupatorin showed mild cytotoxicity on both MCF-7 and MDA-MB-231 cells with IC50 values higher than 20 μg/mL. After 48 h, eupatorin at 5 μg/mL inhibited the proliferation of MCF-7 and MDA-MB-231 cells by 50% while the IC50 of MCF-10a was significantly (p 
    Matched MeSH terms: Breast Neoplasms/pathology*
  16. Malagobadan S, Ho CS, Nagoor NH
    Cancer Biol Med, 2020 Feb 15;17(1):101-111.
    PMID: 32296579 DOI: 10.20892/j.issn.2095-3941.2019.0010
    Objective: Anoikis is apoptosis that is induced when cells detach from the extracellular matrix and neighboring cells. As anoikis serves as a regulatory barrier, cancer cells often acquire resistance towards anoikis during tumorigenesis to become metastatic. MicroRNAs (miRNAs) are short strand RNA molecules that regulate genes post-transcriptionally by binding to mRNAs and reducing the expression of its target genes. This study aimed to elucidate the role of a novel miRNA, miR-6744-5p, in regulating anoikis in breast cancer and identify its target gene. Methods: An anoikis resistant variant of the luminal A type breast cancer MCF-7 cell line (MCF-7-AR) was generated by selecting and amplifying surviving cells after repeated exposure to growth in suspension. MiRNA microarray analysis identified a list of dysregulated miRNAs from which miR-6744-5p was chosen for overexpression and knockdown studies in MCF-7. Additionally, the miRNA was also overexpressed in a triple-negative breast cancer cell line, MDA-MB-231, to evaluate its ability to impair the metastatic potential of breast cancer cells. Results: This study showed that overexpression and knockdown of miR-6744-5p in MCF-7 increased and decreased anoikis sensitivity, respectively. Similarly, overexpression of miR-6744-5p in MDA-MB-231 increased anoikis and also decreased tumor cell invasion in vitro and in vivo. Furthermore, NAT1 enzyme was identified and validated as the direct target of miR-6744-5p. Conclusions: This study has proven the ability of miR-6744-5p to increase anoikis sensitivity in both luminal A and triple negative breast cancer cell lines, highlighting its therapeutic potential in treating breast cancer.
    Matched MeSH terms: Breast Neoplasms/pathology
  17. 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/pathology
  18. Kong YC, Bhoo-Pathy N, O'Rorke M, Subramaniam S, Bhoo-Pathy NT, See MH, et al.
    Medicine (Baltimore), 2020 Feb;99(6):e19093.
    PMID: 32028433 DOI: 10.1097/MD.0000000000019093
    Percutaneous biopsy in breast cancer has been associated with an increased risk of malignant cell seeding. However, the importance of these observations remains obscure due to lack of corroborating evidence from clinical studies. We determined whether method of biopsy is associated with breast cancer survival. This hospital registry-based cohort study included 3416 non-metastatic breast cancer patients diagnosed from 1993 to 2011 in a tertiary setting. Factors associated with biopsy methods were assessed. Multivariable Cox regression analysis was used to determine the independent prognostic impact of method of biopsy. Overall, 990 patients were diagnosed by core needle biopsy (CNB), 1364 by fine needle aspiration cytology (FNAC), and 1062 by excision biopsy. Excision biopsy was significantly associated with more favorable tumor characteristics. Radiotherapy modified the prognostic impact of biopsy method (Pinteraction breast cancer, further studies are warranted.
    Matched MeSH terms: Breast Neoplasms/pathology
  19. Bohan S, Ramli Hamid MT, Chan WY, Vijayananthan A, Ramli N, Kaur S, et al.
    Sci Rep, 2021 01 08;11(1):129.
    PMID: 33420200 DOI: 10.1038/s41598-020-80124-4
    This study aims to evaluate the diagnostic accuracy of digital breast tomosynthesis-guided vacuum assisted breast biopsy (DBT-VABB) of screening detected suspicious mammographic abnormalities comprising of calcifications, asymmetric densities, architectural distortions and spiculated masses. In this institutionally approved study, a total of 170 (n = 170) DBT-VABB were performed, 153 (90%) were for calcifications, 8 (4.7%) for spiculated mass, 5 (2.9%) for asymmetric density and 4 (2.4%) for architectural distortion. All these lesions were not detected on the corresponding ultrasound. Histopathology results revealed 140 (82.4%) benign, 9 (5.3%) borderline and 21 (12.4%) malignant lesions. The total upgrade rate at surgery was 40% for atypical ductal hyperplasia and 5.9% for ductal carcinoma in-situ. 3.6% discordant benign lesions showed no upgrade. DBT-VABB showed 100% specificity, 91.3% sensitivity and 100% positive predictive value (PPV) for detecting malignant lesions. The negative predictive value (NPV) was 80%. 2 (1.2%) patients had mild complications and 1 (0.6%) had severe pain. Our study showed that DBT-VABB was a safe and reliable method, with high sensitivity, specificity, PPV and NPV in the diagnosis of non-palpable benign and malignant breast lesions. Our data also confirmed the accuracy of DBT-VABB in detecting malignant lesions and we suggest further surgical excision in borderline lesions for a more accurate diagnostic evaluation.
    Matched MeSH terms: Breast Neoplasms/pathology
  20. Tikk K, Sookthai D, Fortner RT, Johnson T, Rinaldi S, Romieu I, et al.
    Breast Cancer Res, 2015 Mar 31;17:49.
    PMID: 25887963 DOI: 10.1186/s13058-015-0563-6
    INTRODUCTION: The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.

    METHODS: We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects.

    RESULTS: We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2=1.35 (95% CI 1.04-1.76), Ptrend=0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (Phet=0.98) or baseline HT use (Phet=0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (Ptrend=0.06 vs Ptrend=0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors<4 years compared to ≥4 years after blood donation (Ptrend=0.01 vs Ptrend=0.63; Phet=0.04) and among nulliparous women compared to parous women (Ptrend=0.03 vs Ptrend=0.15; Phet=0.07).

    CONCLUSIONS: Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.

    Matched MeSH terms: Breast Neoplasms/pathology*
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