Displaying publications 1 - 20 of 80 in total

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  1. Chang G, Chan CW, Hartman M
    Asian Pac J Cancer Prev, 2011;12(6):1635-9.
    PMID: 22126512
    Breast cancer is the most common cancer in Singaporean women and the rate of increase in incidence is one of the highest in the world. In view of the significant contribution of delayed presentation to the disease burden in South East Asia, we reviewed the incidence of late presentation of breast cancer and the contributing factors in Singapore. Disease presentation was analysed using studies based on the Singapore Cancer Registry 2004-2008 and with data from women with breast cancer at the National University Hospital (NUH) in Singapore 1990-2007. Available literature from Singapore on factors contributing to delayed presentation was reviewed and presented here. The overall age-standardized 5-year relative survival for Singaporean women was 70% with only half diagnosed with localized cancer. Of all women diagnosed at NUH close to 20% presented at Stages III and IV. Given the magnitude of the problem of women presenting with more advanced stages of breast cancer, the National University of Singapore has joined a collaborative team with the University of Leeds (UK), the University of Malaya, and University of UAE to set up the UK-SEA-ME Psychosocial-Cultural Cancer Research Network to better understand late presentation.
  2. Yip CH, Buccimazza I, Hartman M, Deo SV, Cheung PS
    World J Surg, 2015 Mar;39(3):686-92.
    PMID: 25398564 DOI: 10.1007/s00268-014-2859-6
    Breast cancer is the most common cancer in women world-wide. Incidence rates in low- and middle-income countries (LMICs) are lower than in high income countries; however, the rates are increasing very rapidly in LMICs due to social changes that increase the risk of breast cancer. Breast cancer mortality rates in LMICs remain high due to late presentation and inadequate access to optimal care. Breast Surgery International brought together a group of breast surgeons from different parts of the world to address strategies for improving outcomes in breast cancer for LMICs at a symposium during International Surgical Week in Helsinki, Finland in August 2013. A key strategy for early detection is public health education and breast awareness. Sociocultural barriers to early detection and treatment need to be addressed. Optimal management of breast cancer requires a multidisciplinary team. Surgical treatment is often the only modality of treatment available in low-resource settings where modified radical mastectomy is the most common operation performed. Chemotherapy and radiotherapy require more resources. Endocrine therapy is available but requires accurate assessment of estrogen receptors status. Targeted therapy with trastuzumab is generally unavailable due to cost. The Breast Health Global Initiative guidelines for the early detection and appropriate treatment of breast cancer in LMICs have been specifically designed to improve breast cancer outcomes in these regions. Closing the cancer divide between rich and poor countries is a moral imperative and there is an urgent need to prevent breast cancer deaths with early detection and optimal access to treatment.
  3. 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.
  4. 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.

  5. Lim JN, Potrata B, Simonella L, Ng CW, Aw TC, Dahlui M, et al.
    BMJ Open, 2015 Dec 21;5(12):e009863.
    PMID: 26692558 DOI: 10.1136/bmjopen-2015-009863
    OBJECTIVE: To explore and compare barriers to early presentation of self-discovered breast cancer in Singapore and Malaysia.

    DESIGN: A qualitative interview study with thematic analysis of transcripts.

    PARTICIPANTS: 67 patients with self-discovered breast symptoms were included in the analysis. Of these, 36% were of Malay ethnicity, 39% were Chinese and 25% Indian, with an average age of 58 years (range 24-82 years). The number of women diagnosed at early stages of cancer almost equalled those at advanced stages. Approximately three-quarters presented with a painless lump, one-quarter experienced a painful lump and 10% had atypical symptoms.

    SETTING: University hospital setting in Singapore and Malaysia.

    RESULTS: Patients revealed barriers to early presentation not previously reported: the poor quality of online website information about breast symptoms, financial issues and the negative influence of relatives in both countries, while perceived poor quality of care and services in state-run hospitals and misdiagnosis by healthcare professionals were reported in Malaysia. The pattern of presentation by ethnicity remained unchanged where more Malay delayed help-seeking and had more advanced cancer compared to Chinese and Indian patients.

    CONCLUSIONS: There are few differences in the pattern of presentation and in the reported barriers to seek medical care after symptom discovery between Singapore and Malaysia despite their differing economic status. Strategies to reduce delayed presentation are: a need to improve knowledge of disease, symptoms and causes, quality of care and services, and quality of online information; and addressing fear of diagnosis, treatment and hospitalisation, with more effort focused on the Malay ethnic group. Training is needed to avoid missed diagnoses and other factors contributing to delay among health professionals.

  6. 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.
  7. 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.

  8. Miao H, Hartman M, Bhoo-Pathy N, Lee SC, Taib NA, Tan EY, et al.
    PLoS One, 2014;9(4):e93755.
    PMID: 24695692 DOI: 10.1371/journal.pone.0093755
    BACKGROUND: In Asia, up to 25% of breast cancer patients present with distant metastases at diagnosis. Given the heterogeneous survival probabilities of de novo metastatic breast cancer, individual outcome prediction is challenging. The aim of the study is to identify existing prognostic models for patients with de novo metastatic breast cancer and validate them in Asia.
    MATERIALS AND METHODS: We performed a systematic review to identify prediction models for metastatic breast cancer. Models were validated in 642 women with de novo metastatic breast cancer registered between 2000 and 2010 in the Singapore Malaysia Hospital Based Breast Cancer Registry. Survival curves for low, intermediate and high-risk groups according to each prognostic score were compared by log-rank test and discrimination of the models was assessed by concordance statistic (C-statistic).
    RESULTS: We identified 16 prediction models, seven of which were for patients with brain metastases only. Performance status, estrogen receptor status, metastatic site(s) and disease-free interval were the most common predictors. We were able to validate nine prediction models. The capacity of the models to discriminate between poor and good survivors varied from poor to fair with C-statistics ranging from 0.50 (95% CI, 0.48-0.53) to 0.63 (95% CI, 0.60-0.66).
    CONCLUSION: The discriminatory performance of existing prediction models for de novo metastatic breast cancer in Asia is modest. Development of an Asian-specific prediction model is needed to improve prognostication and guide decision making.
  9. Phuah SY, Lee SY, Kang P, Kang IN, Yoon SY, Thong MK, et al.
    PLoS One, 2013;8(8):e73638.
    PMID: 23977390 DOI: 10.1371/journal.pone.0073638
    The partner and localizer of breast cancer 2 (PALB2) is responsible for facilitating BRCA2-mediated DNA repair by serving as a bridging molecule, acting as the physical and functional link between the breast cancer 1 (BRCA1) and breast cancer 2 (BRCA2) proteins. Truncating mutations in the PALB2 gene are rare but are thought to be associated with increased risks of developing breast cancer in various populations.
  10. Bhoo-Pathy N, Yip CH, Hartman M, Saxena N, Taib NA, Ho GF, et al.
    Eur J Cancer, 2012 May;48(7):982-9.
    PMID: 22366561 DOI: 10.1016/j.ejca.2012.01.034
    Adjuvant! Online is a free web-based tool which predicts 10-year breast cancer outcomes and the efficacy of adjuvant therapy in patients with breast cancer. As its prognostic performance has only been validated in high income Caucasian populations, we validated the model in a middle income Asian setting.
  11. Bhoo-Pathy N, Yip CH, Hartman M, Uiterwaal CS, Devi BC, Peeters PH, et al.
    Eur J Cancer, 2013 Feb;49(3):703-9.
    PMID: 23040889 DOI: 10.1016/j.ejca.2012.09.014
    The incidence and mortality of breast cancer continues to rise rapidly in Asian countries. However, most of our current knowledge on breast cancer has been generated in Western populations. As the socio-economic profile, life style and culture of Asian and Western women are substantially different, and genetic backgrounds vary to some extent, we need to answer the question on whether to 'adopt' or 'adapt' Western knowledge before applying it in the Asian setting. It is generally accepted that breast cancer risk factors, which have mainly been studied in Western populations are similar worldwide. However, the presence of gene-environment or gene-gene interactions may alter their importance as causal factors across populations. Diagnostic and prognostic study findings, including breast cancer prediction rules, are increasingly shown to be 'setting specific' and must therefore be validated in Asian women before implementing them in clinical care in Asia. Interventional research findings from Caucasian patients may not be applicable in patients in Asia due to differences in tumour biology/profiles, metabolism of drugs and also health beliefs which can influence treatment acceptance and adherence. While breast cancer research in Asia is warranted in all domains of medical research, it is felt that for Asian breast cancer patients, needs are highest for diagnostic and prognostic studies. International clinical trials meanwhile need to include breast cancer patients from various Asian settings to provide an insight into the effectiveness of new treatment modalities in this part of the world.
  12. Bhoo-Pathy N, Hartman M, Yip CH, Saxena N, Taib NA, Lim SE, et al.
    PLoS One, 2012;7(2):e30995.
    PMID: 22363531 DOI: 10.1371/journal.pone.0030995
    The burden of breast cancer in Asia is escalating. We evaluated the impact of ethnicity on survival after breast cancer in the multi-ethnic region of South East Asia.
  13. Saxena N, Hartman M, Yip CH, Bhoo-Pathy N, Khin LW, Taib NA, et al.
    PLoS One, 2012;7(9):e45809.
    PMID: 23029254 DOI: 10.1371/journal.pone.0045809
    Lymph node ratio (LNR, i.e. the ratio of the number of positive nodes to the total number of nodes excised) is reported to be superior to the absolute number of nodes involved (pN stage) in classifying patients at high versus low risk of death following breast cancer. The added prognostic value of LNR over pN in addition to other prognostic factors has never been assessed.
  14. Bhoo-Pathy N, Yip CH, Taib NA, Hartman M, Saxena N, Iau P, et al.
    Breast, 2011 Apr;20 Suppl 2:S75-80.
    PMID: 21316967 DOI: 10.1016/j.breast.2011.01.015
    Two hospital-based breast cancer databases (University Malaya Medical Center, Malaysia [n = 1513] and National University Hospital, Singapore [n = 2545]) were merged into a regional registry of breast cancer patients diagnosed between 1990 and 2007. A review of the data found 51% of patients diagnosed before the age of 50 years. and 72% percent of the women were Chinese followed by Malays (16%), Indians (8%), and other races (4%). Median tumor size at presentation was 26 mm and about 25% of patients presented with TNM stage III or IV disease. Most tumors were of ductal histology (87%). Fifty-seven percent of tumors were estrogen receptor positive and 40% were poorly differentiated. Of those patients who had surgery, 70% had mastectomy while 30% had breast conserving surgery. Overall, chemotherapy was administered to 56% of patients and hormonal treatment to 60%. Five-year overall survival was 82.5% in patients with TNM stage 0 to stage II cancer, and 30.2% in those with later stages.
  15. Bhoo-Pathy N, Verkooijen HM, Tan EY, Miao H, Taib NA, Brand JS, et al.
    Sci Rep, 2015;5:16252.
    PMID: 26536962 DOI: 10.1038/srep16252
    Up to 25% of breast cancer patients in Asia present with de novo metastatic disease. We examined the survival trends of Asian patients with metastatic breast cancer over fifteen years. The impact of changes in patient's demography, tumor characteristics, tumor burden, and treatment on survival trend were examined. Patients with de novo metastatic breast cancer from three hospitals in Malaysia and Singapore (N = 856) were grouped by year of diagnosis: 1996-2000, 2001-2005 and 2006-2010. Step-wise multivariable Poisson regression was used to estimate the contribution of above-mentioned factors on the survival trend. Proportions of patients presenting with metastatic breast cancer were 10% in 1996-2000, 7% in 2001-2005, and 9% in 2006-2010. Patients in 2006-2010 were significantly older, appeared to have higher disease burden, and received more chemotherapy, endocrine therapy, and surgery of primary tumor. The three-year relative survival in the above periods were 20·6% (95% CI: 13·9%-28·2%), 28·8% (95% CI: 23·4%-34·2%), and 33·6% (95% CI: 28·8%-38·5%), respectively. Adjustment for treatment considerably attenuated the relative excess risk of mortality in recent years, compared to other factors. Substantial improvements in survival were observed in patients with de novo metastatic breast cancer in this study.
  16. Wong HS, Subramaniam S, Alias Z, Taib NA, Ho GF, Ng CH, et al.
    Medicine (Baltimore), 2015 Feb;94(8):e593.
    PMID: 25715267 DOI: 10.1097/MD.0000000000000593
    Web-based prognostication tools may provide a simple and economically feasible option to aid prognostication and selection of chemotherapy in early breast cancers. We validated PREDICT, a free online breast cancer prognostication and treatment benefit tool, in a resource-limited setting. All 1480 patients who underwent complete surgical treatment for stages I to III breast cancer from 1998 to 2006 were identified from the prospective breast cancer registry of University Malaya Medical Centre, Kuala Lumpur, Malaysia. Calibration was evaluated by comparing the model-predicted overall survival (OS) with patients' actual OS. Model discrimination was tested using receiver-operating characteristic (ROC) analysis. Median age at diagnosis was 50 years. The median tumor size at presentation was 3 cm and 54% of patients had lymph node-negative disease. About 55% of women had estrogen receptor-positive breast cancer. Overall, the model-predicted 5 and 10-year OS was 86.3% and 77.5%, respectively, whereas the observed 5 and 10-year OS was 87.6% (difference: -1.3%) and 74.2% (difference: 3.3%), respectively; P values for goodness-of-fit test were 0.18 and 0.12, respectively. The program was accurate in most subgroups of patients, but significantly overestimated survival in patients aged <40 years, and in those receiving neoadjuvant chemotherapy. PREDICT performed well in terms of discrimination; areas under ROC curve were 0.78 (95% confidence interval [CI]: 0.74-0.81) and 0.73 (95% CI: 0.68-0.78) for 5 and 10-year OS, respectively. Based on its accurate performance in this study, PREDICT may be clinically useful in prognosticating women with breast cancer and personalizing breast cancer treatment in resource-limited settings.
  17. Saxena N, Hartman M, Bhoo-Pathy N, Lim JN, Aw TC, Iau P, et al.
    World J Surg, 2012 Dec;36(12):2838-46.
    PMID: 22926282 DOI: 10.1007/s00268-012-1746-2
    There are large differences in socio-economic growth within the region of South East Asia, leading to sharp contrasts in health-systems development between countries. This study compares breast cancer presentation and outcome between patients from a high income country (Singapore) and a middle income country (Malaysia) in South East Asia.
  18. Ho PJ, Lau HSH, Ho WK, Wong FY, Yang Q, Tan KW, et al.
    Sci Rep, 2020 01 16;10(1):503.
    PMID: 31949192 DOI: 10.1038/s41598-019-57341-7
    Incidence of breast cancer is rising rapidly in Asia. Some breast cancer risk factors are modifiable. We examined the impact of known breast cancer risk factors, including body mass index (BMI), reproductive and hormonal risk factors, and breast density on the incidence of breast cancer, in Singapore. The study population was a population-based prospective trial of screening mammography - Singapore Breast Cancer Screening Project. Population attributable risk and absolute risks of breast cancer due to various risk factors were calculated. Among 28,130 women, 474 women (1.7%) developed breast cancer. The population attributable risk was highest for ethnicity (49.4%) and lowest for family history of breast cancer (3.8%). The proportion of breast cancers that is attributable to modifiable risk factor BMI was 16.2%. The proportion of breast cancers that is attributable to reproductive risk factors were low; 9.2% for age at menarche and 4.2% for number of live births. Up to 45.9% of all breast cancers could be avoided if all women had breast density <12% and BMI <25 kg/m2. Notably, sixty percent of women with the lowest risk based on non-modifiable risk factors will never reach the risk level recommended for mammography screening. A combination of easily assessable breast cancer risk factors can help to identify women at high risk of developing breast cancer for targeted screening. A large number of high-risk women could benefit from risk-reduction and risk stratification strategies.
  19. Miao H, Hartman M, Verkooijen HM, Taib NA, Wong HS, Subramaniam S, et al.
    BMC Cancer, 2016 10 21;16(1):820.
    PMID: 27769212
    BACKGROUND: CancerMath is a set of web-based prognostic tools which predict nodal status and survival up to 15 years after diagnosis of breast cancer. This study validated its performance in a Southeast Asian setting.

    METHODS: Using Singapore Malaysia Hospital-Based Breast Cancer Registry, clinical information was retrieved from 7064 stage I to III breast cancer patients who were diagnosed between 1990 and 2011 and underwent surgery. Predicted and observed probabilities of positive nodes and survival were compared for each subgroup. Calibration was assessed by plotting observed value against predicted value for each decile of the predicted value. Discrimination was evaluated by area under a receiver operating characteristic curve (AUC) with 95 % confidence interval (CI).

    RESULTS: The median predicted probability of positive lymph nodes is 40.6 % which was lower than the observed 43.6 % (95 % CI, 42.5 %-44.8 %). The calibration plot showed underestimation for most of the groups. The AUC was 0.71 (95 % CI, 0.70-0.72). Cancermath predicted and observed overall survival probabilities were 87.3 % vs 83.4 % at 5 years after diagnosis and 75.3 % vs 70.4 % at 10 years after diagnosis. The difference was smaller for patients from Singapore, patients diagnosed more recently and patients with favorable tumor characteristics. Calibration plot also illustrated overprediction of survival for patients with poor prognosis. The AUC for 5-year and 10-year overall survival was 0.77 (95 % CI: 0.75-0.79) and 0.74 (95 % CI: 0.71-0.76).

    CONCLUSIONS: The discrimination and calibration of CancerMath were modest. The results suggest that clinical application of CancerMath should be limited to patients with better prognostic profile.

  20. Mariapun S, Ho WK, Eriksson M, Tai MC, Mohd Taib NA, Yip CH, et al.
    Breast Cancer Res Treat, 2023 Sep;201(2):237-245.
    PMID: 37338730 DOI: 10.1007/s10549-023-06984-2
    PURPOSE: Mammographic density (MD), after accounting for age and body mass index (BMI), is a strong heritable risk factor for breast cancer. Genome-wide association studies (GWAS) have identified 64 SNPs in 55 independent loci associated with MD in women of European ancestry. Their associations with MD in Asian women, however, are largely unknown.

    METHOD: Using linear regression adjusting for age, BMI, and ancestry-informative principal components, we evaluated the associations of previously reported MD-associated SNPs with MD in a multi-ethnic cohort of Asian ancestry. Area and volumetric mammographic densities were determined using STRATUS (N = 2450) and Volpara™ (N = 2257). We also assessed the associations of these SNPs with breast cancer risk in an Asian population of 14,570 cases and 80,870 controls.

    RESULTS: Of the 61 SNPs available in our data, 21 were associated with MD at a nominal threshold of P value  0.05, 29 variants showed consistent directions of association as those previously reported. We found that nine of the 21 MD-associated SNPs in this study were also associated with breast cancer risk in Asian women (P 

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