Displaying publications 61 - 80 of 180 in total

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  1. Majid HA, Keow LP, Islam T, Su TT, Cantwell M, Taib NA, et al.
    J Acad Nutr Diet, 2018 04;118(4):705-713.
    PMID: 28756991 DOI: 10.1016/j.jand.2017.05.024
    BACKGROUND: Lifestyle factors, such as diet, body weight, and physical activity, are linked to better survival after breast cancer (BC) diagnosis. A high percentage of the Malaysian population is overweight or obese. In addition, studies have shown a disparity in survival among Malaysian women compared with other higher-income countries. The Malaysian Breast Cancer Survivorship Cohort (MyBCC) study aims to study lifestyle factors that affect survival in BC survivors. These are the preliminary findings on the nutritional status of Malaysian BC survivors.

    OBJECTIVE: Our aim was to evaluate the nutritional status of BC survivors at 1 year after diagnosis.

    DESIGN: This was a cross-sectional study of 194 participants from the MyBCC study, recruited within 1 year of their diagnosis. Participants completed a 3-day food diary.

    PARTICIPANTS: Malaysian women (aged 18 years and older) who were newly diagnosed with primary BC, managed at the University Malaya Medical Center, and able to converse either in Malay, English, or Mandarin were included.

    MAIN OUTCOME MEASURES: Dietary intake and prevalence of overweight or obesity among participants 1 year after diagnosis were measured.

    STATISTICAL ANALYSES PERFORMED: Student's t test and analysis of variance or its equivalent nonparametric test were used for association in continuous variables.

    RESULTS: About 66% (n=129) of participants were overweight or obese and >45% (n=86) had high body fat percentage 1 year after diagnosis. The participants' diets were low in fiber (median=8.7 g/day; interquartile range=7.2 g/day) and calcium (median=458 mg/day; interquartile range=252 mg/day). Ethnicity and educational attainment contributed to the differences in dietary intake among participants. Higher saturated fat and lower fiber intake were observed among Malay participants compared with other ethnic groups.

    CONCLUSIONS: Overweight and obesity were highly prevalent among BC survivors and suboptimal dietary intake was observed. Provision of an individualized medical nutrition therapy by a qualified dietitian is crucial as part of comprehensive BC survivorship care.

  2. Tan WM, Ng WL, Ganggayah MD, Hoe VCW, Rahmat K, Zaini HS, et al.
    Health Informatics J, 2023;29(3):14604582231203763.
    PMID: 37740904 DOI: 10.1177/14604582231203763
    Radiology reporting is narrative, and its content depends on the clinician's ability to interpret the images accurately. A tertiary hospital, such as anonymous institute, focuses on writing reports narratively as part of training for medical personnel. Nevertheless, free-text reports make it inconvenient to extract information for clinical audits and data mining. Therefore, we aim to convert unstructured breast radiology reports into structured formats using natural language processing (NLP) algorithm. This study used 327 de-identified breast radiology reports from the anonymous institute. The radiologist identified the significant data elements to be extracted. Our NLP algorithm achieved 97% and 94.9% accuracy in training and testing data, respectively. Henceforth, the structured information was used to build the predictive model for predicting the value of the BIRADS category. The model based on random forest generated the highest accuracy of 92%. Our study not only fulfilled the demands of clinicians by enhancing communication between medical personnel, but it also demonstrated the usefulness of mineable structured data in yielding significant insights.
  3. Bhoo-Pathy N, Balakrishnan N, See MH, Taib NA, Yip CH
    World J Surg, 2016 12;40(12):2913-2921.
    PMID: 27456497 DOI: 10.1007/s00268-016-3658-z
    BACKGROUND: Factors associated with surgery, adjuvant radiotherapy, and chemotherapy and whether there were missed opportunities for treatment in elderly patients were determined in an Asian setting.

    METHODS: All 5616 patients, diagnosed with breast cancer in University Malaya Medical Centre from 1999 to 2013 were included. In 945 elderly patients (aged 65 years and above), multivariable logistic regression was performed to identify factors associated with treatment, following adjustment for age, ethnicity, tumor, and other treatment characteristics. The impact of lack of treatment on survival of the elderly was assessed while accounting for comorbidities.

    RESULTS: One in five elderly patients had comorbidities. Compared to younger patients, the elderly had more favorable tumor characteristics, and received less loco-regional treatment and chemotherapy. Within stage I-IIIa elderly breast cancer patients, 10 % did not receive any surgery. These patients were older, more likely to be Malays, have comorbidities, and bigger tumors. In elderlies with indications for adjuvant radiotherapy, no irradiation (30 %) was associated with increasing age, comorbidity, and the absence of systemic therapy. Hormone therapy was optimal, but only 35 % of elderly women with ER negative tumors received chemotherapy. Compared to elderly women who received adequate treatment, those not receiving surgery (adjusted hazard ratio: 2.30, 95 %CI: 1.10-4.79), or radiotherapy (adjusted hazard ratio: 1.56, 95 %CI: 1.10-2.19), were associated with higher mortality. Less than 25 % of the survival discrepancy between elderly women receiving loco-regional treatment and no treatment were attributed to excess comorbidities in untreated patients.

    CONCLUSION: While the presence of comorbidities significantly influenced loco-regional treatment decisions in the elderly, it was only able to explain the lower survival rates in untreated patients up to a certain extent, suggesting missed opportunities for treatment.

  4. Soo JS, Ng CH, Tan SH, Malik RA, Teh YC, Tan BS, et al.
    Apoptosis, 2015 Oct;20(10):1373-87.
    PMID: 26276035 DOI: 10.1007/s10495-015-1158-5
    Metformin, an AMPK activator, has been reported to improve pathological response to chemotherapy in diabetic breast cancer patients. To date, its mechanism of action in cancer, especially in cancer stem cells (CSCs) have not been fully elucidated. In this study, we demonstrated that metformin, but not other AMPK activators (e.g. AICAR and A-769662), synergizes 5-fluouracil, epirubicin, and cyclophosphamide (FEC) combination chemotherapy in non-stem breast cancer cells and breast cancer stem cells. We show that this occurs through an AMPK-dependent mechanism in parental breast cancer cell lines. In contrast, the synergistic effects of metformin and FEC occurred in an AMPK-independent mechanism in breast CSCs. Further analyses revealed that metformin accelerated glucose consumption and lactate production more severely in the breast CSCs but the production of intracellular ATP was severely hampered, leading to a severe energy crisis and impairs the ability of CSCs to repair FEC-induced DNA damage. Indeed, addition of extracellular ATP completely abrogated the synergistic effects of metformin on FEC sensitivity in breast CSCs. In conclusion, our results suggest that metformin synergizes FEC sensitivity through distinct mechanism in parental breast cancer cell lines and CSCs, thus providing further evidence for the clinical relevance of metformin for the treatment of cancers.
  5. Kwong SC, Jamil AHA, Rhodes A, Taib NA, Chung I
    J Lipid Res, 2019 11;60(11):1807-1817.
    PMID: 31484694 DOI: 10.1194/jlr.M092379
    Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, partly due to the lack of targeted therapy available. Cancer cells heavily reprogram their metabolism and acquire metabolic plasticity to satisfy the high-energy demand due to uncontrolled proliferation. Accumulating evidence shows that deregulated lipid metabolism affects cancer cell survival, and therefore we sought to understand the function of fatty acid binding protein 7 (FABP7), which is expressed predominantly in TNBC tissues. As FABP7 was not detected in the TNBC cell lines tested, Hs578T and MDA-MB-231 cells were transduced with lentiviral particles containing either FABP7 open reading frame or red fluorescent protein. During serum starvation, when lipids were significantly reduced, FABP7 decreased the viability of Hs578T, but not of MDA-MB-231, cells. FABP7-overexpressing Hs578T (Hs-FABP7) cells failed to efficiently utilize other available bioenergetic substrates such as glucose to sustain ATP production, which led to S/G2 phase arrest and cell death. We further showed that this metabolic phenotype was mediated by PPAR-α signaling, despite the lack of fatty acids in culture media, as Hs-FABP7 cells attempted to survive. This study provides imperative evidence of metabolic vulnerabilities driven by FABP7 via PPAR-α signaling.
  6. Burton A, Byrnes G, Stone J, Tamimi RM, Heine J, Vachon C, et al.
    Breast Cancer Res, 2016 12 19;18(1):130.
    PMID: 27993168
    BACKGROUND: Inter-women and intra-women comparisons of mammographic density (MD) are needed in research, clinical and screening applications; however, MD measurements are influenced by mammography modality (screen film/digital) and digital image format (raw/processed). We aimed to examine differences in MD assessed on these image types.

    METHODS: We obtained 1294 pairs of images saved in both raw and processed formats from Hologic and General Electric (GE) direct digital systems and a Fuji computed radiography (CR) system, and 128 screen-film and processed CR-digital pairs from consecutive screening rounds. Four readers performed Cumulus-based MD measurements (n = 3441), with each image pair read by the same reader. Multi-level models of square-root percent MD were fitted, with a random intercept for woman, to estimate processed-raw MD differences.

    RESULTS: Breast area did not differ in processed images compared with that in raw images, but the percent MD was higher, due to a larger dense area (median 28.5 and 25.4 cm2 respectively, mean √dense area difference 0.44 cm (95% CI: 0.36, 0.52)). This difference in √dense area was significant for direct digital systems (Hologic 0.50 cm (95% CI: 0.39, 0.61), GE 0.56 cm (95% CI: 0.42, 0.69)) but not for Fuji CR (0.06 cm (95% CI: -0.10, 0.23)). Additionally, within each system, reader-specific differences varied in magnitude and direction (p 

  7. Ramanujam TM, Ramesh JC, Goh DW, Wong KT, Ariffin WA, Kumar G, et al.
    J Pediatr Surg, 1999 Nov;34(11):1684-6.
    PMID: 10591570
    Here the first case in the literature of both mesenchymal hamartoma and malignant mesenchymoma occurring in a 6-year-old male child, at different times and at different sites in the liver, and also the possible malignant transformation of a mesenchymal hamartoma is reported. The tumor developed from a lesion in the right lobe that was overlooked initially during a left lateral segmentectomy at 18 months of age for a mesenchymal hamartoma. Malignant mesenchymoma is a rare and aggressive tumor. The origin of this tumor is not well understood. There has been no direct support to the hypothesis that malignant mesenchymoma may be the malignant counterpart of mesenchymal hamartoma. The authors provide clinical and histopathologic evidence in our case that suggests the possibility of malignant mesenchymoma arising from a mesenchymal hamartoma. This case emphasizes the need for complete removal of mesenchymal hamartoma and the need for long-term follow-up to detect multifocal lesion or malignant transformation.
  8. Kalafi EY, Nor NAM, Taib NA, Ganggayah MD, Town C, Dhillon SK
    Folia Biol. (Praha), 2019;65(5-6):212-220.
    PMID: 32362304
    Breast cancer survival prediction can have an extreme effect on selection of best treatment protocols. Many approaches such as statistical or machine learning models have been employed to predict the survival prospects of patients, but newer algorithms such as deep learning can be tested with the aim of improving the models and prediction accuracy. In this study, we used machine learning and deep learning approaches to predict breast cancer survival in 4,902 patient records from the University of Malaya Medical Centre Breast Cancer Registry. The results indicated that the multilayer perceptron (MLP), random forest (RF) and decision tree (DT) classifiers could predict survivorship, respectively, with 88.2 %, 83.3 % and 82.5 % accuracy in the tested samples. Support vector machine (SVM) came out to be lower with 80.5 %. In this study, tumour size turned out to be the most important feature for breast cancer survivability prediction. Both deep learning and machine learning methods produce desirable prediction accuracy, but other factors such as parameter configurations and data transformations affect the accuracy of the predictive model.
  9. Mohamad S, Isa NM, Muhammad R, Emran NA, Kitan NM, Kang P, et al.
    PLoS One, 2015;10(1):e0117104.
    PMID: 25629968 DOI: 10.1371/journal.pone.0117104
    CHEK2 is a protein kinase that is involved in cell-cycle checkpoint control after DNA damage. Germline mutations in CHEK2 gene have been associated with increase in breast cancer risk. The aim of this study is to identify the CHEK2 gene germline mutations among high-risk breast cancer patients and its contribution to the multiethnic population in Malaysia. We screened the entire coding region of CHEK2 gene on 59 high-risk breast cancer patients who tested negative for BRCA1/2 germline mutations from UKM Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ). Sequence variants identified were screened further in case-control cohorts consisting of 878 unselected invasive breast cancer patients (180 Malays, 526 Chinese and 172 Indian) and 270 healthy individuals (90 Malays, 90 Chinese and 90 Indian). By screening the entire coding region of the CHEK2 gene, two missense mutations, c.480A>G (p.I160M) and c.538C>T (p.R180C) were identified in two unrelated patients (3.4%). Further screening of these missense mutations on the case-control cohorts unveiled the variant p.I160M in 2/172 (1.1%) Indian cases and 1/90 (1.1%) Indian control, variant p.R180C in 2/526 (0.38%) Chinese cases and 0/90 Chinese control, and in 2/180 (1.1%) of Malay cases and 1/90 (1.1%) of Malay control. The results of this study suggest that CHEK2 mutations are rare among high-risk breast cancer patients and may play a minor contributing role in breast carcinogenesis among Malaysian population.
  10. See MH, Bhoo-Pathy N, Jamaris S, Kiran A, Evans DG, Yip CH, et al.
    World J Surg, 2018 05;42(5):1270-1277.
    PMID: 29124356 DOI: 10.1007/s00268-017-4319-6
    BACKGROUND: The rate of contralateral risk-reducing mastectomy (CRRM) is increasing in the West with controversial evidence of improved survival in early breast cancer patients. Although uptake of CRRM in Asia appears low, the trends may rise, and there is currently an urgent need to provide evidence for informed decision-making in clinical practice. This study aims to determine the risk of contralateral breast cancer (CBC) and its associated factors in an Asian setting.

    METHOD: A total of 2937 newly diagnosed patients with stage I and stage II breast cancer in University Malaya Medical Centre between Jan 1993 to Dec 2012 were included in the study. Multinomial logistic regression analysis allowing death to compete with CBC as a study outcome was used; patients with unilateral breast cancer who were alive were taken as reference. A stepwise backward regression analysis including age at diagnosis, ethnicity, family history of breast cancer, TNM stage, hormonal receptor status, HER2 status, chemotherapy, radiotherapy, and hormone therapy was conducted.

    RESULTS: Fifty women developed CBC, over a median follow-up of 6 years. The 5- and 10-year cumulative risk of contralateral breast cancer was 1.0% (95% CI 0.6-1.4%) and 2.8% (95% CI 2.0-3.6%), respectively. Young age at diagnosis of first cancer, positive family history, and stage I disease were independent predictors of CBC.

    DISCUSSION: The current study suggests that the risk of CBC is very low in a Southeast Asian setting. Any recommendations or practice of CRRM should be reviewed with caution and patients must be counseled appropriately.

  11. 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.

  12. Mohamed E, Abdul-Rahman PS, Doustjalali SR, Chen Y, Lim BK, Omar SZ, et al.
    Electrophoresis, 2008 Jun;29(12):2645-50.
    PMID: 18494030 DOI: 10.1002/elps.200700828
    A 35 kDa glycoprotein whose abundance was previously demonstrated to be enhanced in sera of patients with endometrial adenocarcinoma (n = 12), was isolated from pooled sera of three of the cancer patients using champedak galactose-binding lectin affinity chromatography in the present study. Subjecting it to 2-DE and MS/MS, the glycoprotein was identified as the O-glycosylated fragment of inter-alpha-trypsin inhibitor heavy chain H4 (ITIH4). When compared to control sera (n = 17), expression of the 35 kDa ITIH4 cleavage fragment was demonstrated to be significantly enhanced in sera of patients with breast carcinoma (n = 10), epithelial ovarian carcinoma (n = 10), and germ cell ovarian carcinoma (n = 10) but not in patients with nasopharyngeal carcinoma (n = 13) and osteosarcoma (n = 7). The lectin-based electrophoretic bioanalytical method adopted in the present study may be used to assess the physiological relevance of ITIH4 fragmentation and its correlation with different malignancies, their stages and progression.
  13. Kang P, Mariapun S, Phuah SY, Lim LS, Liu J, Yoon SY, et al.
    Breast Cancer Res Treat, 2010 Nov;124(2):579-84.
    PMID: 20617377 DOI: 10.1007/s10549-010-1018-5
    Early studies of genetic predisposition due to the BRCA1 and BRCA2 genes have focused largely on sequence alterations, but it has now emerged that 4-28% of inherited mutations in the BRCA genes may be due to large genomic rearrangements of these genes. However, to date, there have been relatively few studies of large genomic rearrangements in Asian populations. We have conducted a full sequencing and large genomic rearrangement analysis (using Multiplex Ligation-dependent Probe Amplification, MLPA) of 324 breast cancer patients who were selected from a multi-ethnic hospital-based cohort on the basis of age of onset of breast cancer and/or family history. Three unrelated individuals were found to have large genomic rearrangements: 2 in BRCA1 and 1 in BRCA2, which accounts for 2/24 (8%) of the total mutations detected in BRCA1 and 1/23 (4%) of the mutations in BRCA2 detected in this cohort. Notably, the family history of the individuals with these mutations is largely unremarkable suggesting that family history alone is a poor predictor of mutation status in Asian families. In conclusion, this study in a multi-ethnic (Malay, Chinese, Indian) cohort suggests that large genomic rearrangements are present at a low frequency but should nonetheless be included in the routine testing for BRCA1 and BRCA2.
  14. Lim KK, Yoon SY, Mohd Taib NA, Shabaruddin FH, Dahlui M, Woo YL, et al.
    Appl Health Econ Health Policy, 2018 06;16(3):395-406.
    PMID: 29572724 DOI: 10.1007/s40258-018-0384-8
    OBJECTIVE: Previous studies showed that offering BRCA mutation testing to population subgroups at high risk of harbouring the mutation may be cost effective, yet no evidence is available for low- or middle-income countries (LMIC) and in Asia. We estimated the cost effectiveness of BRCA mutation testing in early-stage breast cancer patients with high pre-test probability of harbouring the mutation in Malaysia, an LMIC in Asia.

    METHODS: We developed a decision analytic model to estimate the lifetime costs and quality-adjusted life-years (QALYs) accrued through BRCA mutation testing or routine clinical surveillance (RCS) for a hypothetical cohort of 1000 early-stage breast cancer patients aged 40 years. In the model, patients would decide whether to accept testing and to undertake risk-reducing mastectomy, oophorectomy, tamoxifen, combinations or neither. We calculated the incremental cost-effectiveness ratio (ICER) from the health system perspective. A series of sensitivity analyses were performed.

    RESULTS: In the base case, testing generated 11.2 QALYs over the lifetime and cost US$4815 per patient whereas RCS generated 11.1 QALYs and cost US$4574 per patient. The ICER of US$2725/QALY was below the cost-effective thresholds. The ICER was sensitive to the discounting of cost, cost of BRCA mutation testing and utility of being risk-free, but the ICERs remained below the thresholds. Probabilistic sensitivity analysis showed that at a threshold of US$9500/QALY, 99.9% of simulations favoured BRCA mutation testing over RCS.

    CONCLUSIONS: Offering BRCA mutation testing to early-stage breast cancer patients identified using a locally-validated risk-assessment tool may be cost effective compared to RCS in Malaysia.

  15. Saunus JM, Quinn MC, Patch AM, Pearson JV, Bailey PJ, Nones K, et al.
    J Pathol, 2015 Nov;237(3):363-78.
    PMID: 26172396 DOI: 10.1002/path.4583
    Treatment options for patients with brain metastases (BMs) have limited efficacy and the mortality rate is virtually 100%. Targeted therapy is critically under-utilized, and our understanding of mechanisms underpinning metastatic outgrowth in the brain is limited. To address these deficiencies, we investigated the genomic and transcriptomic landscapes of 36 BMs from breast, lung, melanoma and oesophageal cancers, using DNA copy-number analysis and exome- and RNA-sequencing. The key findings were as follows. (a) Identification of novel candidates with possible roles in BM development, including the significantly mutated genes DSC2, ST7, PIK3R1 and SMC5, and the DNA repair, ERBB-HER signalling, axon guidance and protein kinase-A signalling pathways. (b) Mutational signature analysis was applied to successfully identify the primary cancer type for two BMs with unknown origins. (c) Actionable genomic alterations were identified in 31/36 BMs (86%); in one case we retrospectively identified ERBB2 amplification representing apparent HER2 status conversion, then confirmed progressive enrichment for HER2-positivity across four consecutive metastatic deposits by IHC and SISH, resulting in the deployment of HER2-targeted therapy for the patient. (d) In the ERBB/HER pathway, ERBB2 expression correlated with ERBB3 (r(2)  = 0.496; p < 0.0001) and HER3 and HER4 were frequently activated in an independent cohort of 167 archival BM from seven primary cancer types: 57.6% and 52.6% of cases were phospho-HER3(Y1222) or phospho-HER4(Y1162) membrane-positive, respectively. The HER3 ligands NRG1/2 were barely detectable by RNAseq, with NRG1 (8p12) genomic loss in 63.6% breast cancer-BMs, suggesting a microenvironmental source of ligand. In summary, this is the first study to characterize the genomic landscapes of BM. The data revealed novel candidates, potential clinical applications for genomic profiling of resectable BMs, and highlighted the possibility of therapeutically targeting HER3, which is broadly over-expressed and activated in BMs, independent of primary site and systemic therapy.
  16. Ching HC, Naidu R, Seong MK, Har YC, Taib NA
    Int J Oncol, 2011 Sep;39(3):621-33.
    PMID: 21687935 DOI: 10.3892/ijo.2011.1081
    Breast cancer is a heterogeneous disease, marked by extensive chromosomal aberrations. In this study, we aimed to explicate the underlying chromosomal copy number (CN) alterations and loss of heterozygosity (LOH) implicated in a cohort of Malaysian hospital-based primary breast carcinoma samples using a single nucleotide polymorphism (SNP) array platform. The analysis was conducted by hybridizing the extracted DNA of 70 primary breast carcinomas and 37 normal peripheral blood samples to the Affymetrix 250K Sty SNP arrays. Locus-specific CN aberrations and LOH were statistically summarized using the binary segmentation algorithm and hidden Markov model. Selected genes from the SNP array analysis were also validated using quantitative real-time PCR. The merging of CN and LOH data fabricated distinctive integrated alteration profiles, which were comprised of finely demarcated minimal sites of aberrations. The most prevalent gains (≥ 30%) were detected at the 8q arm: 8q23.1, 8q23.3, 8q24.11, 8q24.13, 8q24.21, 8q24.22, 8q24.23 and 8q24.3, whilst the most ubiquitous losses (≥ 20%) were noted at the 8p12, 8p21.1, 8p21.2, 8p21.1-p21.2, 8p21.3, 8p22, 8p23.1, 8p23.1‑p23.2, 8p23.3, 17p11.2, 17p12, 17p11.2-p12, 17p13.1 and 17p13.2 regions. Copy-neutral LOH was characterized as the most prevailing LOH event, in which the most frequent distributions (≥ 30%) were revealed at 3p21.31, 5q33.2, 12q24.12, 12q24.12‑q24.13 and 14q23.1. These findings offer compre-hensive genome-wide views on breast cancer genomic changes, where the most recurrent gain, loss and copy-neutral LOH events were harboured within the 8q24.21, 8p21.1 and 14q23.1 loci, respectively. This will facilitate the uncovering of true driver genes pertinent to breast cancer biology and the develop-ment of prospective therapeutics.
  17. Wen WX, Allen J, Lai KN, Mariapun S, Hasan SN, Ng PS, et al.
    J Med Genet, 2018 02;55(2):97-103.
    PMID: 28993434 DOI: 10.1136/jmedgenet-2017-104947
    BACKGROUND: Genetic testing for BRCA1 and BRCA2 is offered typically to selected women based on age of onset and family history of cancer. However, current internationally accepted genetic testing referral guidelines are built mostly on data from cancer genetics clinics in women of European descent. To evaluate the appropriateness of such guidelines in Asians, we have determined the prevalence of germ line variants in an unselected cohort of Asian patients with breast cancer and healthy controls.

    METHODS: Germ line DNA from a hospital-based study of 2575 unselected patients with breast cancer and 2809 healthy controls were subjected to amplicon-based targeted sequencing of exonic and proximal splice site junction regions of BRCA1 and BRCA2 using the Fluidigm Access Array system, with sequencing conducted on a Illumina HiSeq2500 platform. Variant calling was performed with GATK UnifiedGenotyper and were validated by Sanger sequencing.

    RESULTS: Fifty-five (2.1%) BRCA1 and 66 (2.6%) BRCA2 deleterious mutations were identified among patients with breast cancer and five (0.18%) BRCA1 and six (0.21%) BRCA2 mutations among controls. One thousand one hundred and eighty-six (46%) patients and 97 (80%) carriers fulfilled the National Comprehensive Cancer Network guidelines for genetic testing.

    CONCLUSION: Five per cent of unselected Asian patients with breast cancer carry deleterious variants in BRCA1 or BRCA2. While current referral guidelines identified the majority of carriers, one in two patients would be referred for genetic services. Given that such services are largely unavailable in majority of low-resource settings in Asia, our study highlights the need for more efficient guidelines to identify at-risk individuals in Asia.

  18. Tiong V, Rozita AM, Taib NA, Yip CH, Ng CH
    World J Surg, 2014 Sep;38(9):2288-96.
    PMID: 24700093 DOI: 10.1007/s00268-014-2542-y
    Breast cancer is increasingly reported in young premenopausal women in Asia. Adjuvant chemotherapy improves survival; however, it has a unique consequence of ovarian failure in premenopausal patients.
  19. Taib NA, Akmal M, Mohamed I, Yip CH
    Asian Pac J Cancer Prev, 2011;12(2):345-9.
    PMID: 21545192
    BACKGROUND: There is improvement in breast cancer survival in the developed world, but information on breast cancer survival trends in the Asia Pacific region is limited. The aim of the study was to evaluate survival trends and factors that affect survival in Malaysia.

    METHODS: Two prospective groups of 423 and 965 newly diagnosed breast cancer patients in University of Malaya Medical Centre, Kuala Lumpur, Malaysia diagnosed in two time periods ie. 1993 to 1997 and in 1998 to 2002 were studied. Vital status was obtained from the National Registry of Births and Deaths. The overall survival was calculated from the date of diagnosis to the date of death from any cause. The survival differences between the two groups were analysed using the log-rank or Peto-Wilcoxon method. Survival estimates and independent prognostic factors were estimated by the Kaplan-Meier method and multivariate analysis using Cox proportional hazard models. P values less than 0.05 were considered statistically significant. Analyses were performed using SPlus 2000 Professional Release 2.

    RESULTS AND DISCUSSION: Median follow-up for the two groups were 55 months (SD 29.2 months) in the first group and 52 months (SD 24.43) in the second group. There was improvement in 5-year observed survival from 58.4% (CI 0.54-0.63) to 75.7% (CI 0.73-0.79). The improvement in survival was significantly seen in all co-variates (p< 0.05) except for those aged 40 years and below (p= 0.27), tumour size 2 to 5 cm (p=0.11), grade 3 (p=0.32) and patients with Stage IV disease (p= 0.80). Stage of disease, lymph node (LN) involvement, size and grade were identified as independent prognostic factors in cohort one. For the second cohort; stage and LN involvement remained independent factors with the addition of ER status and ethnicity.

    CONCLUSIONS: There was improvement in 5-year observed survival. Besides known prognostic factors, Malay ethnicity was an independent prognostic factor.

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