MyMedR

Predictors of axillary lymph node metastases in breast cancer: is there a role for minimal axillary surgery?

Yip CH, Taib NA, Tan GH, Ng KL, Yoong BK, Choo WY

World J Surg, 2009 Jan;33(1):54-7.

PMID: 18958521 DOI: 10.1007/s00268-008-9782-7

Axillary nodal status is one of the most important prognostic factors in breast cancer. In the present study we used it to determine the predictors of axillary lymph node metastases in breast cancer and to determine if there is a group of patients in whom minimal axillary surgery is indicated.

Impact of breast surgery on survival in women presenting with metastatic breast cancer

Bhoo-Pathy N, Verkooijen HM, Taib NA, Hartman M, Yip CH

Br J Surg, 2011 Nov;98(11):1566-72.

PMID: 21858791 DOI: 10.1002/bjs.7650

Advanced breast cancer is common in less affluent parts of Asia. The impact of breast surgery on survival of women presenting with metastatic breast cancer in this setting was investigated.

Fulltext Trends of breast cancer treatment in Sabah, Malaysia: a problem with lack of awareness

Leong BD, Chuah JA, Kumar VM, Rohamini S, Siti ZS, Yip CH

Singapore Med J, 2009 Aug;50(8):772-6.

PMID: 19710974

Sabah, formerly known as North Borneo, is part of East Malaysia. 52.2 percent of patients with breast cancer in Sabah presented at advanced stages and up to 20.4 percent of patients defaulted proper treatment, opting for traditional therapy. We performed a two-year prospective study looking at the treatment trends of breast cancer in Sabah.

Fulltext Spectrum of very early breast cancer in a setting without organised screening

Bhoo-Pathy N, Subramaniam S, Taib NA, Hartman M, Alias Z, Tan GH, et al.

Br J Cancer, 2014 Apr 29;110(9):2187-94.

PMID: 24736587 DOI: 10.1038/bjc.2014.183

BACKGROUND: Within a setting without organised breast cancer screening, the characteristics and survival of very early breast cancer were determined.

METHODS: All 4930 women diagnosed with breast cancer in University Malaya Medical Center, Malaysia from 1993 to 2011 were included. Factors associated with very early presentation (stage I) at diagnosis were identified. Tumour characteristics, management patterns, and survival of very early breast cancer were described, and where appropriate, compared with other settings.

RESULTS: Proportion of women presenting with stage I breast cancer significantly increased from 15.2% to 25.2% over two decades. Factors associated with very early presentation were Chinese ethnicity, positive family history of breast cancer, and recent period of diagnosis. Within stage I breast cancers, median tumour size at presentation was 1.5 cm. A majority of stage I breast cancer patients received mastectomy, which was associated with older age, Chinese ethnicity, postmenopausal status, and larger tumours. Chemotherapy was administered in 36% of patients. Five-year age-adjusted relative survival for women with stage I breast cancer was 99.1% (95% CI: 97.6-99.6%).

CONCLUSIONS: The proportion of women presenting with very early breast cancer in this setting without organised screening is increasing. These women seem to survive just as well as their counterparts from affluent settings.

Differentiation between benign and malignant breast lesions using quantitative diffusion-weighted sequence on 3 T MRI

Tan SL, Rahmat K, Rozalli FI, Mohd-Shah MN, Aziz YF, Yip CH, et al.

Clin Radiol, 2014 Jan;69(1):63-71.

PMID: 24156797 DOI: 10.1016/j.crad.2013.08.007

To investigate the capability and diagnostic accuracy of diffusion-weighted imaging (DWI) in differentiating benign from malignant breast lesions using 3 T magnetic resonance imaging (MRI).

Improved diagnostic accuracy in differentiating malignant and benign lesions using single-voxel proton MRS of the breast at 3 T MRI

Suppiah S, Rahmat K, Mohd-Shah MN, Azlan CA, Tan LK, Aziz YF, et al.

Clin Radiol, 2013 Sep;68(9):e502-10.

PMID: 23706826 DOI: 10.1016/j.crad.2013.04.002

To investigate the diagnostic accuracy of single-voxel proton magnetic resonance spectroscopy (SV (1)H MRS) by quantifying total choline-containing compounds (tCho) in differentiating malignant from benign lesions, and subsequently, to analyse the relationship of tCho levels in malignant breast lesions with their histopathological subtypes.

Factors affecting estrogen receptor status in a multiracial Asian country: an analysis of 3557 cases

Yip CH, Bhoo-Pathy N, Uiterwaal CS, Taib NA, Tan GH, Mun KS, et al.

Breast, 2011 Apr;20 Suppl 2:S60-4.

PMID: 21349715 DOI: 10.1016/j.breast.2011.02.004

Estrogen receptor (ER) positive rates in breast cancer may be influenced by grade, stage, age and race. This study reviews the ER positive rates over a 15-year period at the University Malaya Medical Centre, Kuala Lumpur, Malaysia. Data on ER status of 3557 patients from 1994 to 2008 was analyzed. ER status was determined by immunohistochemistry with a cut-off point of 10%. ER positivity increased by about 2% for every 5-year cohort, from 54.5% in 1994-1998 to 58.4% in 2004-2008. Ethnicity and grade were significantly associated with ER positivity rates: Malay women were found to have a higher risk of ER negative tumors compared with Chinese women. Grade 1 cancers were nine times more likely to be ER positive compared with grade 3 cancers. In summary, the proportion of ER positive cancers increased with each time period, and ethnicity and grade were independent factors that influenced ER positive rates.

Global Disparities in Breast Cancer Genetics Testing, Counselling and Management

Yip CH, Evans DG, Agarwal G, Buccimazza I, Kwong A, Morant R, et al.

World J Surg, 2019 05;43(5):1264-1270.

PMID: 30610270 DOI: 10.1007/s00268-018-04897-6

Hereditary breast cancers, mainly due to BRCA1 and BRCA2 mutations, account for only 5-10% of this disease. The threshold for genetic testing is a 10% likelihood of detecting a mutation, as determined by validated models such as BOADICEA and Manchester Scoring System. A 90-95% reduction in breast cancer risk can be achieved with bilateral risk-reducing mastectomy in unaffected BRCA mutation carriers. In patients with BRCA-associated breast cancer, there is a 40% risk of contralateral breast cancer and hence risk-reducing contralateral mastectomy is recommended, which can be performed simultaneously with surgery for unilateral breast cancer. Other options for risk management include surveillance by mammogram and breast magnetic resonance imaging, and chemoprevention with hormonal agents. With the advent of next-generation sequencing and development of multigene panel testing, the cost and time taken for genetic testing have reduced, making it possible for treatment-focused genetic testing. There are also drugs such as the PARP inhibitors that specifically target the BRCA mutation. Risk management multidisciplinary clinics are designed to quantify risk, and offer advice on preventative strategies. However, such services are only possible in high-income settings. In low-resource settings, the prohibitive cost of testing and the lack of genetic counsellors are major barriers to setting up a breast cancer genetics service. Family history is often not well documented because of the stigma associated with cancer. Breast cancer genetics services remain an unmet need in low- and middle-income countries, where the priority is to optimise access to quality treatment.

Prediction of lymph node involvement in patients with breast tumors measuring 3-5 cm in a middle-income setting: the role of CancerMath

Pijnappel EN, Bhoo-Pathy N, Suniza J, See MH, Tan GH, Yip CH, et al.

World J Surg, 2014 Dec;38(12):3133-7.

PMID: 25167896 DOI: 10.1007/s00268-014-2752-3

In settings with limited resources, sentinel lymph node biopsy (SNB) is only offered to breast cancer patients with small tumors and a low a priori risk of axillary metastases.

Breast Cancer Outcomes as Defined by the Estrogen Receptor, Progesterone Receptor, and Human Growth Factor Receptor-2 in a Multi-ethnic Asian Country

Subramaniam S, Bhoo-Pathy N, Taib NA, Tan GH, See MH, Jamaris S, et al.

World J Surg, 2015 Oct;39(10):2450-8.

PMID: 26138872 DOI: 10.1007/s00268-015-3133-2

Breast cancer can be divided into four subtypes based on the expressions of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (HER2). Each subtype has different clinicopathological features and outcomes.

Identification of germline alterations in breast cancer predisposition genes among Malaysian breast cancer patients using panel testing

Ng PS, Wen WX, Fadlullah MZ, Yoon SY, Lee SY, Thong MK, et al.

Clin Genet, 2016 10;90(4):315-23.

PMID: 26757417 DOI: 10.1111/cge.12735

Although an association between protein-truncating variants and breast cancer risk has been established for 11 genes, only alterations in BRCA1, BRCA2, TP53 and PALB2 have been reported in Asian populations. Given that the age of onset of breast cancer is lower in Asians, it is estimated that inherited predisposition to breast cancer may be more significant. To determine the potential utility of panel testing, we investigated the prevalence of germline alterations in 11 established and 4 likely breast cancer genes in a cross-sectional hospital-based cohort of 108 moderate to high-risk breast cancer patients using targeted next generation sequencing. Twenty patients (19%) were identified to carry deleterious mutations, of whom 13 (12%) were in the BRCA1 or BRCA2, 6 (6%) were in five other known breast cancer predisposition genes and 1 patient had a mutation in both BRCA2 and BARD1. Our study shows that BRCA1 and BRCA2 account for the majority of genetic predisposition to breast cancer in our cohort of Asian women. Although mutations in other known breast cancer genes are found, the functional significance and breast cancer risk have not yet been determined, thus limiting the clinical utility of panel testing in Asian populations.

Fulltext Breast-conserving surgery versus mastectomy in young women with breast cancer in Asian settings

Sinnadurai S, Kwong A, Hartman M, Tan EY, Bhoo-Pathy NT, Dahlui M, et al.

BJS Open, 2019 02;3(1):48-55.

PMID: 30734015 DOI: 10.1002/bjs5.50111

Background: Mastectomy rates among women with early breast cancer in Asia have traditionally been high. This study assessed trends in the surgical management of young women with early-stage breast cancer in Asian settings. Survival in women treated with breast-conserving surgery (BCS; lumpectomy with adjuvant radiotherapy) and those undergoing mastectomy was compared.

Methods: Young women (aged less than 50 years) newly diagnosed with stage I or II (T1-2 N0-1 M0) breast cancer in four hospitals in Malaysia, Singapore and Hong Kong in 1990-2012 were included. Overall survival (OS) was compared for patients treated by BCS and those who had a mastectomy. Propensity score analysis was used to account for differences in demographic, tumour and treatment characteristics between the groups.

Results: Some 63·5 per cent of 3536 women underwent mastectomy. Over a 15-year period, only a modest increase in rates of BCS was observed. Although BCS was significantly associated with favourable prognostic features, OS was not significantly different for BCS and mastectomy; the 5-year OS rate was 94·9 (95 per cent c.i. 93·5 to 96·3) and 92·9 (91·7 to 94·1) per cent respectively. Inferences remained unchanged following propensity score analysis (hazard ratio for BCS versus mastectomy: 0·81, 95 per cent c.i. 0·64 to 1·03).

Conclusion: The prevalence of young women with breast cancer treated by mastectomy remains high in Asian countries. Patients treated with BCS appear to survive as well as those undergoing mastectomy.

Fulltext Reagent Effects on the Activated Partial Thromboplastin Time Clot Waveform Analysis: A Multi-Centre Study

Wong WH, Tan CW, Abdul Khalid NB, Dalimoenthe NZ, Yip C, Tantanate C, et al.

Diagnostics (Basel), 2023 Jul 22;13(14).

PMID: 37510191 DOI: 10.3390/diagnostics13142447

(1) Background: The activated partial thromboplastin time (APTT)- based clot waveform analysis (CWA) quantitatively extends information obtained from the APTT waveform through its derivatives. However, pre-analytical variables including reagent effects on the CWA parameters are poorly understood and must be standardized as a potential diagnostic assay. (2) Methods: CWA was first analysed with patient samples to understand reagent lot variation in three common APTT reagents: Pathromtin SL, Actin FS, and Actin FSL. A total of 1055 healthy volunteers were also recruited from seven institutions across the Asia-Pacific region and CWA data were collected with the Sysmex CS analysers. (3) Results: CWA parameters varied less than 10% between lots and the linear mixed model analysis showed few site-specific effects within the same reagent group. However, the CWA parameters were significantly different amongst all reagent groups and thus reagent-specific 95% reference intervals could be calculated using the nonparametric method. Post-hoc analysis showed some degree of influence by age and gender with weak correlation to the CWA (r < 0.3). (4) Conclusions: Reagent type significantly affects APTT-based CWA with minimal inter-laboratory variations with the same coagulometer series that allow for data pooling across laboratories with more evidence required for age- and gender-partitioning.

Fulltext Evaluation of BRCA1 and BRCA2 mutations and risk-prediction models in a typical Asian country (Malaysia) with a relatively low incidence of breast cancer

Thirthagiri E, Lee SY, Kang P, Lee DS, Toh GT, Selamat S, et al.

Breast Cancer Res, 2008;10(4):R59.

PMID: 18627636 DOI: 10.1186/bcr2118

The cost of genetic testing and the limited knowledge about the BRCA1 and BRCA2 genes in different ethnic groups has limited its availability in medium- and low-resource countries, including Malaysia. In addition, the applicability of many risk-assessment tools, such as the Manchester Scoring System and BOADICEA (Breast and Ovarian Analysis of Disease Incidence and Carrier Estimation Algorithm) which were developed based on mutation rates observed primarily in Caucasian populations using data from multiplex families, and in populations where the rate of breast cancer is higher, has not been widely tested in Asia or in Asians living elsewhere. Here, we report the results of genetic testing for mutations in the BRCA1 or BRCA2 genes in a series of families with breast cancer in the multi-ethnic population (Malay, Chinese and Indian) of Malaysia.

Fulltext 2q36.3 is associated with prognosis for oestrogen receptor-negative breast cancer patients treated with chemotherapy

Li J, Lindström LS, Foo JN, Rafiq S, Schmidt MK, Pharoah PD, et al.

Nat Commun, 2014 Jun 17;5:4051.

PMID: 24937182 DOI: 10.1038/ncomms5051

Large population-based registry studies have shown that breast cancer prognosis is inherited. Here we analyse single-nucleotide polymorphisms (SNPs) of genes implicated in human immunology and inflammation as candidates for prognostic markers of breast cancer survival involving 1,804 oestrogen receptor (ER)-negative patients treated with chemotherapy (279 events) from 14 European studies in a prior large-scale genotyping experiment, which is part of the Collaborative Oncological Gene-environment Study (COGS) initiative. We carry out replication using Asian COGS samples (n=522, 53 events) and the Prospective Study of Outcomes in Sporadic versus Hereditary breast cancer (POSH) study (n=315, 108 events). Rs4458204_A near CCL20 (2q36.3) is found to be associated with breast cancer-specific death at a genome-wide significant level (n=2,641, 440 events, combined allelic hazard ratio (HR)=1.81 (1.49-2.19); P for trend=1.90 × 10(-9)). Such survival-associated variants can represent ideal targets for tailored therapeutics, and may also enhance our current prognostic prediction capabilities.

Fulltext Common non-synonymous SNPs associated with breast cancer susceptibility: findings from the Breast Cancer Association Consortium

Milne RL, Burwinkel B, Michailidou K, Arias-Perez JI, Zamora MP, Menéndez-Rodríguez P, et al.

Hum Mol Genet, 2014 Nov 15;23(22):6096-111.

PMID: 24943594 DOI: 10.1093/hmg/ddu311

Candidate variant association studies have been largely unsuccessful in identifying common breast cancer susceptibility variants, although most studies have been underpowered to detect associations of a realistic magnitude. We assessed 41 common non-synonymous single-nucleotide polymorphisms (nsSNPs) for which evidence of association with breast cancer risk had been previously reported. Case-control data were combined from 38 studies of white European women (46 450 cases and 42 600 controls) and analyzed using unconditional logistic regression. Strong evidence of association was observed for three nsSNPs: ATXN7-K264R at 3p21 [rs1053338, per allele OR = 1.07, 95% confidence interval (CI) = 1.04-1.10, P = 2.9 × 10(-6)], AKAP9-M463I at 7q21 (rs6964587, OR = 1.05, 95% CI = 1.03-1.07, P = 1.7 × 10(-6)) and NEK10-L513S at 3p24 (rs10510592, OR = 1.10, 95% CI = 1.07-1.12, P = 5.1 × 10(-17)). The first two associations reached genome-wide statistical significance in a combined analysis of available data, including independent data from nine genome-wide association studies (GWASs): for ATXN7-K264R, OR = 1.07 (95% CI = 1.05-1.10, P = 1.0 × 10(-8)); for AKAP9-M463I, OR = 1.05 (95% CI = 1.04-1.07, P = 2.0 × 10(-10)). Further analysis of other common variants in these two regions suggested that intronic SNPs nearby are more strongly associated with disease risk. We have thus identified a novel susceptibility locus at 3p21, and confirmed previous suggestive evidence that rs6964587 at 7q21 is associated with risk. The third locus, rs10510592, is located in an established breast cancer susceptibility region; the association was substantially attenuated after adjustment for the known GWAS hit. Thus, each of the associated nsSNPs is likely to be a marker for another, non-coding, variant causally related to breast cancer risk. Further fine-mapping and functional studies are required to identify the underlying risk-modifying variants and the genes through which they act.

Fulltext Association analysis identifies 65 new breast cancer risk loci

Michailidou K, Lindström S, Dennis J, Beesley J, Hui S, Kar S, et al.

Nature, 2017 Nov 02;551(7678):92-94.

PMID: 29059683 DOI: 10.1038/nature24284

Breast cancer risk is influenced by rare coding variants in susceptibility genes, such as BRCA1, and many common, mostly non-coding variants. However, much of the genetic contribution to breast cancer risk remains unknown. Here we report the results of a genome-wide association study of breast cancer in 122,977 cases and 105,974 controls of European ancestry and 14,068 cases and 13,104 controls of East Asian ancestry. We identified 65 new loci that are associated with overall breast cancer risk at P

Displaying publications 41 - 57 of 57 in total