Displaying publications 161 - 180 of 210 in total

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  1. Song CV, Yip CH, Mohd Taib NA, See MH, Teoh LY, Monninkhof EM, et al.
    JCO Glob Oncol, 2022 Mar;8:e2100314.
    PMID: 35245099 DOI: 10.1200/GO.21.00314
    PURPOSE: Addressing unwarranted clinical variation in oncology practices is expected to lead to improved cancer outcomes. Particularly, the application and impact of treatment guidelines on breast cancer outcomes are poorly studied in resource-limited settings. We measured adherence to a set of locally developed adjuvant treatment guidelines in a middle-income setting. Importantly, the impact of guidelines adherence on survival following breast cancer was determined.

    METHODS: Data of 3,100 Malaysian women with nonmetastatic breast cancer diagnosed between 2010 and 2017 were analyzed. Adherence to the Malaysian Clinical Practice Guidelines for Management of Breast Cancer second Edition was measured. Outcomes comprised overall survival and event-free survival.

    RESULTS: Guideline adherence for chemotherapy, radiotherapy, hormonal therapy, and targeted therapy were 61.7%, 79.2%, 85.1%, and 26.2%, respectively. Older age was generally associated with lower adherence to guidelines. Compared with patients who were treated according to treatment guidelines, overall survival and event-free survival were substantially lower in patients who were not treated accordingly; hazard ratios for all-cause mortality were 1.69 (95% CI, 1.29 to 2.22), 2.59 (95% CI, 1.76 to 3.81), 3.08 (95% CI, 1.94 to 4.88), and 4.48 (95% CI, 1.98 to 10.13) for chemotherapy, radiotherapy, hormone therapy, and targeted therapy, respectively. Study inferences remain unchanged following sensitivity analyses.

    CONCLUSION: Our study findings appear to suggest that adherence to treatment guidelines that have been adapted for resource-limited settings may still provide effective guidance in improving breast cancer outcomes.

  2. Pan JW, Zabidi MMA, Ng PS, Meng MY, Hasan SN, Sandey B, et al.
    Nat Commun, 2020 Dec 22;11(1):6433.
    PMID: 33353943 DOI: 10.1038/s41467-020-20173-5
    Molecular profiling of breast cancer has enabled the development of more robust molecular prognostic signatures and therapeutic options for breast cancer patients. However, non-Caucasian populations remain understudied. Here, we present the mutational, transcriptional, and copy number profiles of 560 Malaysian breast tumours and a comparative analysis of breast cancers arising in Asian and Caucasian women. Compared to breast tumours in Caucasian women, we show an increased prevalence of HER2-enriched molecular subtypes and higher prevalence of TP53 somatic mutations in ER+ Asian breast tumours. We also observe elevated immune scores in Asian breast tumours, suggesting potential clinical response to immune checkpoint inhibitors. Whilst HER2-subtype and enriched immune score are associated with improved survival, presence of TP53 somatic mutations is associated with poorer survival in ER+ tumours. Taken together, these population differences unveil opportunities to improve the understanding of this disease and lay the foundation for precision medicine in different populations.
  3. 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 
  4. Henry JA, Reyes AM, Ameh E, Yip CH, Nthumba P, Mehes M, et al.
    BMJ Open, 2023 Jan 24;13(1):e062687.
    PMID: 36693687 DOI: 10.1136/bmjopen-2022-062687
    OBJECTIVES: To develop consensus statements regarding the regional-level or district-level distribution of surgical services in low and middle-income countries (LMICs) and prioritisation of service scale-up.

    DESIGN: This work was conducted using a modified Delphi consensus process. Initial statements were developed by the International Standards and Guidelines for Quality Safe Surgery and Anesthesia Working Group of the Global Alliance for Surgical, Obstetric, Trauma and Anesthesia Care (G4 Alliance) and the International Society of Surgery based on previously published literature and clinical expertise. The Guidance on Conducting and REporting DElphi Studies framework was applied.

    SETTING: The Working Group convened in Suva, Fiji for a meeting hosted by the Ministry of Health and Medical Services to develop the initial statements. Local experts were invited to participate. The modified Delphi process was conducted through an electronically administered anonymised survey.

    PARTICIPANTS: Expert LMIC surgeons were nominated for participation in the modified Delphi process based on criteria developed by the Working Group.

    PRIMARY OUTCOME MEASURES: The consensus panel voted on statements regarding the organisation of surgical services, principles for scale-up and prioritisation of scale-up. Statements reached consensus if there was ≥80% agreement among participants.

    RESULTS: Fifty-three nominated experts from 27 LMICs voted on 27 statements in two rounds. Ultimately, 26 statements reached consensus and comprise the current recommendations. The statements covered three major themes: which surgical services should be decentralised or regionalised; how the implementation of these services should be prioritised; and principles to guide LMIC governments and international visiting teams in scaling up safe, accessible and affordable surgical care.

    CONCLUSIONS: These recommendations represent the first step towards the development of international guidelines for the scaling up of surgical services in LMICs. They constitute the best available basis for policymaking, planning and allocation of resources for strengthening surgical systems.

  5. 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 

  6. Lim GC, Aina EN, Cheah SK, Ismail F, Ho GF, Tho LM, et al.
    BMC Cancer, 2014;14:212.
    PMID: 24650245 DOI: 10.1186/1471-2407-14-212
    BACKGROUND: Cancer is the leading cause of deaths in the world. A widening disparity in cancer burden has emerged between high income and low-middle income countries. Closing this cancer divide is an ethical imperative but there is a dearth of data on cancer services from developing countries.
    METHODS: This was a multi-center, retrospective observational cohort study which enrolled women with breast cancer (BC) attending 8 participating cancer centers in Malaysia in 2011. All patients were followed up for 12 months from diagnosis to determine their access to therapies. We assess care performance using measures developed by Quality Oncology Practice Initiative, American Society of Clinical Oncology/National Comprehensive Cancer Network, American College of Surgeons' National Accreditation Program for Breast Centers as well as our local guideline.
    RESULTS: Seven hundred and fifty seven patients were included in the study; they represent about 20% of incident BC in Malaysia. Performance results were mixed. Late presentation was 40%. Access to diagnostic and breast surgery services were timely; the interval from presentation to tissue diagnosis was short (median = 9 days), and all who needed surgery could receive it with only a short wait (median = 11 days). Performance of radiation, chemo and hormonal therapy services showed that about 75 to 80% of patients could access these treatments timely, and those who could not were because they sought alternative treatment or they refused treatment. Access to Trastuzumab was limited to only 19% of eligible patients.
    CONCLUSIONS: These performance results are probably acceptable for a middle income country though far below the 95% or higher adherence rates routinely reported by centres in developed countries. High cost trastuzumab was inaccessible to this population without public funding support.
  7. Moore MA, Manan AA, Chow KY, Cornain SF, Devi CR, Triningsih FX, et al.
    Asian Pac J Cancer Prev, 2010;11 Suppl 2:81-98.
    PMID: 20553070
    Malaysia, Brunei, Singapore, Indonesia, East Timor and the Philippines constitute peninsular and island South-East Asia. For reasons of largely shared ethnicity, with Chinese elements added to the basic Austromalaysian populations, as well as geographical contiguity, they can be usefully grouped together for studies of chronic disease prevalence and underlying risk factors. The fact of problems are shared in common, particularly regarding increasing cancer rates, underlines the necessity for a coordinated approach to research and development of control measures. To provide a knowledge base, the present review of available data for cancer registration, epidemiology and control was conducted. The most prevalent cancer site in males is the lung, followed by the liver, colon or the prostate in the majority of cases, while breast and cervical cancers predominate in most female populations. However, there are interesting differences among the racial groups, particularly regarding the stomach. General tendencies for increase in adenocarcinomas but decrease in squamous cell carcinomas and gastric cancer, point to change in environmental influence over time. Variation in risk factors depends to some extent on the level of economic development but overall the countries of the region face similar challenges in achieving effective cancer control. A major task is persuading the general populace of the efficacy of early detection and clinical treatment.
  8. Bhoo-Pathy N, Verkooijen HM, Wong FY, Pignol JP, Kwong A, Tan EY, et al.
    Int J Cancer, 2015 Nov 15;137(10):2504-12.
    PMID: 26018878 DOI: 10.1002/ijc.29617
    The value of adjuvant radiotherapy in triple-negative breast cancer (TNBC) is currently debated. We assessed the association between adjuvant radiotherapy and survival in a large cohort of Asian women with TNBC. Women diagnosed with TNBC from 2006 to 2011 in five Asian centers (N = 1,138) were included. Survival between patients receiving mastectomy only, breast-conserving therapy (BCT, lumpectomy and adjuvant radiotherapy) and mastectomy with radiotherapy were compared, and adjusted for demography, tumor characteristics and chemotherapy types. Median age at diagnosis was 53 years (range: 23-96 years). Median tumor size at diagnosis was 2.5 cm and most patients had lymph node-negative disease. The majority of patients received adjuvant chemotherapy (n = 861, 76%) comprising predominantly anthracycline-based regimes. In 775 women with T1-2, N0-1, M0 TNBCs, 5-year relative survival ratio (RSR) was highest in patients undergoing mastectomy only (94.7%, 95% CI: 88.8-98.8%), followed by BCT (90.8%, 95% CI: 85.0-94.7%), and mastectomy with radiotherapy (82.3%, 95% CI: 73.4-88.1%). The adjusted risks of mortality between the three groups were not significantly different. In 363 patients with T3-4, N2-3, M0 TNBCs, BCT was associated with highest 5-year RSR (94.1%, 95% CI: 81.3-99.4%), followed by mastectomy with radiotherapy (62.7%, 95% CI: 54.3-70.1%), and mastectomy only (58.6%, 95% CI: 43.5-71.6%). Following multivariable adjustment, BCT and mastectomy with radiotherapy remained significantly associated with lower mortality risk compared to mastectomy only. Overall, adjuvant radiotherapy was associated with higher survival in women aged <40 years, but not in older women. Adjuvant radiotherapy appears to be independently associated with a survival gain in locally advanced as well as in very young TNBC.
  9. 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.
  10. Kang PC, Phuah SY, Sivanandan K, Kang IN, Thirthagiri E, Liu JJ, et al.
    Breast Cancer Res Treat, 2014 Apr;144(3):635-42.
    PMID: 24578176 DOI: 10.1007/s10549-014-2894-x
    Although the breast cancer predisposition genes BRCA1 and BRCA2 were discovered more than 20 years ago, there remains a gap in the availability of genetic counselling and genetic testing in Asian countries because of cost, access and inaccurate reporting of family history of cancer. In order to improve access to testing, we developed a rapid test for recurrent mutations in our Asian populations. In this study, we designed a genotyping assay with 55 BRCA1 and 44 BRCA2 mutations previously identified in Asian studies, and validated this assay in 267 individuals who had previously been tested by full sequencing. We tested the prevalence of these mutations in additional breast cancer cases. Using this genotyping approach, we analysed recurrent mutations in 533 Malaysian breast cancer cases with <10 % a priori risk, and found 1 BRCA1 (0.2 %) and 5 BRCA2 (0.9 %) carriers. Testing in a hospital-based unselected cohort of 532 Singaporean breast cancer cases revealed 6 BRCA1 (1.1 %) and 3 BRCA2 (0.6 %) carriers. Overall, 2 recurrent BRCA1 and 1 BRCA2 mutations in Malays, 3 BRCA1 and 2 BRCA2 mutations in Chinese and 1 BRCA1 mutation in Indians account for 60, 24 and 20 % of carrier families, respectively. By contrast, haplotype analyses suggest that a recurrent BRCA2 mutation (c.262_263delCT) found in 5 unrelated Malay families has at least 3 distinct haplotypes. Taken together, our data suggests that panel testing may help to identify carriers, particularly Asian BRCA2 carriers, who do not present with a priori strong family history characteristics.
  11. Duggan C, Dvaladze A, Rositch AF, Ginsburg O, Yip CH, Horton S, et al.
    Cancer, 2020 05 15;126 Suppl 10:2339-2352.
    PMID: 32348573 DOI: 10.1002/cncr.32891
    BACKGROUND: The Breast Health Global Initiative (BHGI) established a series of resource-stratified, evidence-based guidelines to address breast cancer control in the context of available resources. Here, the authors describe methodologies and health system prerequisites to support the translation and implementation of these guidelines into practice.

    METHODS: In October 2018, the BHGI convened the Sixth Global Summit on Improving Breast Healthcare Through Resource-Stratified Phased Implementation. The purpose of the summit was to define a stepwise methodology (phased implementation) for guiding the translation of resource-appropriate breast cancer control guidelines into real-world practice. Three expert consensus panels developed stepwise, resource-appropriate recommendations for implementing these guidelines in low-income and middle-income countries as well as underserved communities in high-income countries. Each panel focused on 1 of 3 specific aspects of breast cancer care: 1) early detection, 2) treatment, and 3) health system strengthening.

    RESULTS: Key findings from the summit and subsequent article preparation included the identification of phased-implementation prerequisites that were explored during consensus debates. These core issues and concepts are key components for implementing breast health care that consider real-world resource constraints. Communication and engagement across all levels of care is vital to any effectively operating health care system, including effective communication with ministries of health and of finance, to demonstrate needs, outcomes, and cost benefits.

    CONCLUSIONS: Underserved communities at all economic levels require effective strategies to deploy scarce resources to ensure access to timely, effective, and affordable health care. Systematically strategic approaches translating guidelines into practice are needed to build health system capacity to meet the current and anticipated global breast cancer burden.

  12. Subramaniam S, Kong YC, Chinna K, Kimman M, Ho YZ, Saat N, et al.
    Psychooncology, 2018 09;27(9):2172-2179.
    PMID: 29856903 DOI: 10.1002/pon.4787
    OBJECTIVES: Quality of life and psychological well-being are important patient-centered outcomes, which are useful in evaluation of cancer care delivery. However, evidence from low-income and middle-income countries remains scarce. We assessed health-related quality of life (HRQoL) and prevalence of psychological distress (anxiety or depression), as well as their predictors, among cancer survivors in a middle-income setting.

    METHODS: Through the Association of Southeast Asian Nations Costs in Oncology study, 1490 newly diagnosed cancer patients were followed-up in Malaysia for 1 year. Health-related quality of life was assessed by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and EuroQol-5 (EQ-5D) dimension questionnaires at baseline, 3 and 12 months. Psychological distress was assessed by using Hospital Anxiety and Depression Scale. Data were modeled by using general linear and logistic regressions analyses.

    RESULTS: One year after diagnosis, the mean EORTC QLQ-C30 Global Health score of the cancer survivors remained low at 53.0 over 100 (SD 21.4). Fifty-four percent of survivors reported at least moderate levels of anxiety, while 27% had at least moderate levels of depression. Late stage at diagnosis was the strongest predictor of low HRQoL. Increasing age, being married, high-income status, hospital type, presence of comorbidities, and chemotherapy administration were also associated with worse HRQoL. The significant predictors of psychological distress were cancer stage and hospital type.

    CONCLUSION: Cancer survivors in this middle-income setting have persistently impaired HRQoL and high levels of psychological distress. Development of a holistic cancer survivorship program addressing wider aspects of well-being is urgently needed in our settings.

  13. Bhoo-Pathy N, Ng CW, Lim GC, Tamin NSI, Sullivan R, Bhoo-Pathy NT, et al.
    J Oncol Pract, 2019 06;15(6):e537-e546.
    PMID: 31112479 DOI: 10.1200/JOP.18.00619
    BACKGROUND: Financial toxicity negatively affects the well-being of cancer survivors. We examined the incidence, cost drivers, and factors associated with financial toxicity after cancer in an upper-middle-income country with universal health coverage.

    METHODS: Through the Association of Southeast Asian Nations Costs in Oncology study, 1,294 newly diagnosed patients with cancer (Ministry of Health [MOH] hospitals [n = 577], a public university hospital [n = 642], private hospitals [n = 75]) were observed in Malaysia. Cost diaries and questionnaires were used to measure incidence of financial toxicity, encompassing financial catastrophe (FC; out-of-pocket costs ≥ 30% of annual household income), medical impoverishment (decrease in household income from above the national poverty line to below that line after subtraction of cancer-related costs), and economic hardship (inability to make necessary household payments). Predictors of financial toxicity were determined using multivariable analyses.

    RESULTS: One fifth of patients had private health insurance. Incidence of FC at 1 year was 51% (MOH hospitals, 33%; public university hospital, 65%; private hospitals, 72%). Thirty-three percent of households were impoverished at 1 year. Economic hardship was reported by 47% of families. Risk of FC attributed to conventional medical care alone was 18% (MOH hospitals, 5%; public university hospital, 24%; private hospitals, 67%). Inclusion of expenditures on nonmedical goods and services inflated the risk of financial toxicity in public hospitals. Low-income status, type of hospital, and lack of health insurance were strong predictors of FC.

    CONCLUSION: Patients with cancer may not be fully protected against financial hardships, even in settings with universal health coverage. Nonmedical costs also contribute as important drivers of financial toxicity in these settings.

  14. Mosiun JA, See MH, Teoh LY, Danaee M, Lai LL, Ng CH, et al.
    World J Surg, 2023 Jan;47(1):201-208.
    PMID: 36305952 DOI: 10.1007/s00268-022-06753-0
    BACKGROUND: There is a paucity of data on the use of intraoperative radiotherapy (IORT) with low-energy X-rays in Malaysian women with early breast cancer. The aim of this study is to evaluate the clinical, cosmetic, and patient-reported outcomes in low- and high-risk early breast cancer patients treated with breast conserving surgery (BCS) and IORT.

    METHODOLOGY: Patients suitable for BCS who were treated with IORT between January 2016 and June 2019 from three centres were analysed. They were divided into low-risk and high-risk groups based on the risk of recurrence according to the TARGeted Intraoperative radioTherapy (TARGIT) A and B study criteria. Outcomes of interest included local recurrence, wound complications, and radiation toxicity, with a subset analysed for cosmetic and patient-reported outcomes.

    RESULTS: Within a median follow-up of 31 months, there were 104 and 211 patients in the low- and high-risk groups, respectively. No significant difference was observed in local recurrence rates (low-risk, 1.0% vs. high-risk, 1.4%; p = 1.000). Both cohorts exhibited low frequencies of severe wound complications ranging between 1.4 and 1.9%. No major radiation toxicities were reported in either group. In the subgroup analysis, low-risk patients had significantly better mean scores in the subscales of inframammary fold and scar. Based on the BREAST-Q patient-reported outcomes questionnaire, seven out of nine parameters were scored similarly between both groups with no significant difference.

    CONCLUSION: This study showed that the use of IORT in both low- and high-risk early breast cancers is efficacious and safe with low recurrence rates and an acceptable toxicity profile.

  15. Pan JW, Zabidi MMA, Chong BK, Meng MY, Ng PS, Hasan SN, et al.
    Int J Cancer, 2021 May 15;148(10):2489-2501.
    PMID: 33423300 DOI: 10.1002/ijc.33463
    A 30-kb deletion that eliminates the coding region of APOBEC3B (A3B) is >5 times more common in women of Asian descent compared to European descent. This polymorphism creates a chimera with the APOBEC3A (A3A) coding region and A3B 3'UTR, and it is associated with an increased risk for breast cancer in Asian women. Here, we explored the relationship between the A3B deletion polymorphism with tumour characteristics in Asian women. Using whole exome and whole transcriptome sequencing data of 527 breast tumours, we report that germline A3B deletion polymorphism leads to expression of the A3A-B hybrid isoform and increased APOBEC-associated somatic hypermutation. Hypermutated tumours, regardless of A3B germline status, were associated with the Her2 molecular subtype and PIK3CA mutations. Compared to nonhypermutated tumours, hypermutated tumours also had higher neoantigen burden, tumour heterogeneity and immune activation. Taken together, our results suggest that the germline A3B deletion polymorphism, via the A3A-B hybrid isoform, contributes to APOBEC mutagenesis in a significant proportion of Asian breast cancers. In addition, APOBEC somatic hypermutation, regardless of A3B background, may be an important clinical biomarker for Asian breast cancers.
  16. Benitez Fuentes JD, Morgan E, de Luna Aguilar A, Mafra A, Shah R, Giusti F, et al.
    JAMA Oncol, 2024 Jan 01;10(1):71-78.
    PMID: 37943547 DOI: 10.1001/jamaoncol.2023.4837
    IMPORTANCE: Stage at diagnosis is a key prognostic factor for cancer survival.

    OBJECTIVE: To assess the global distribution of breast cancer stage by country, age group, calendar period, and socioeconomic status using population-based data.

    DATA SOURCES: A systematic search of MEDLINE and Web of Science databases and registry websites and gray literature was conducted for articles or reports published between January 1, 2000, and June 20, 2022.

    STUDY SELECTION: Reports on stage at diagnosis for individuals with primary breast cancer (C50) from a population-based cancer registry were included.

    DATA EXTRACTION AND SYNTHESIS: Study characteristics and results of eligible studies were independently extracted by 2 pairs of reviewers (J.D.B.F., A.D.A., A.M., R.S., and F.G.). Stage-specific proportions were extracted and cancer registry data quality and risk of bias were assessed. National pooled estimates were calculated for subnational or annual data sets using a hierarchical rule of the most relevant and high-quality data to avoid duplicates.

    MAIN OUTCOMES AND MEASURES: The proportion of women with breast cancer by (TNM Classification of Malignant Tumors or the Surveillance, Epidemiology, and End Results Program [SEER]) stage group.

    RESULTS: Data were available for 2.4 million women with breast cancer from 81 countries. Globally, the proportion of cases with distant metastatic breast cancer at diagnosis was high in sub-Saharan Africa, ranging from 5.6% to 30.6% and low in North America ranging from 0.0% to 6.0%. The proportion of patients diagnosed with distant metastatic disease decreased over the past 2 decades from around 3.8% to 35.8% (early 2000s) to 3.2% to 11.6% (2015 onwards), yet stabilization or slight increases were also observed. Older age and lower socioeconomic status had the largest proportion of cases diagnosed with distant metastatic stage ranging from 2.0% to 15.7% among the younger to 4.1% to 33.9% among the oldest age group, and from 1.7% to 8.3% in the least disadvantaged groups to 2.8% to 11.4% in the most disadvantaged groups.

    CONCLUSIONS AND RELEVANCE: Effective policy and interventions have resulted in decreased proportions of women diagnosed with metastatic breast cancer at diagnosis in high-income countries, yet inequality persists, which needs to be addressed through increased awareness of breast cancer symptoms and early detection. Improving global coverage and quality of population-based cancer registries, including the collection of standardized stage data, is key to monitoring progress.

  17. Yip CH, Cazap E, Anderson BO, Bright KL, Caleffi M, Cardoso F, et al.
    Breast, 2011 Apr;20 Suppl 2:S12-9.
    PMID: 21388811 DOI: 10.1016/j.breast.2011.02.015
    In middle resource countries (MRCs), cancer control programs are becoming a priority as the pattern of disease shifts from infectious diseases to non-communicable diseases such as breast cancer, the most common cancer among women in MRCs. The Middle Resource Scenarios Working Group of the BHGI 2010 Global Summit met to identify common issues and obstacles to breast cancer detection, diagnosis and treatment in MRCs. They concluded that breast cancer early detection programs continue to be important, should include clinical breast examination (CBE) with or without mammography, and should be coupled with active awareness programs. Mammographic screening is usually opportunistic and early detection programs are often hampered by logistical and financial problems, as well as socio-cultural barriers, despite improved public educational efforts. Although multidisciplinary services for treatment are available, geographical and economic limitations to these services can lead to an inequity in health care access. Without adequate health insurance coverage, limited personal finances can be a significant barrier to care for many patients. Despite the improved availability of services (surgery, pathology, radiology and radiotherapy), quality assurance programs remain a challenge. Better access to anticancer drugs is needed to improve outcomes, as are rehabilitation programs for survivors. Focused and sustained government health care financing in MRCs is needed to improve early detection and treatment of breast cancer.
  18. Love RR, Hossain SM, Hussain MM, Mostafa MG, Laudico AV, Siguan SS, et al.
    Eur J Cancer, 2016 06;60:107-16.
    PMID: 27107325 DOI: 10.1016/j.ejca.2016.03.011
    PURPOSE: In premenopausal women with metastatic hormone receptor-positive breast cancer, hormonal therapy is the first-line therapy. Gonadotropin-releasing hormone analogue + tamoxifen therapies have been found to be more effective. The pattern of recurrence risk over time after primary surgery suggests that peri-operative factors impact recurrence. Secondary analyses of an adjuvant trial suggested that the luteal phase timing of surgical oophorectomy in the menstrual cycle simultaneous with primary breast surgery favourably influenced long-term outcomes.

    METHODS: Two hundred forty-nine premenopausal women with incurable or metastatic hormone receptor-positive breast cancer entered a trial in which they were randomised to historical mid-luteal or mid-follicular phase surgical oophorectomy followed by oral tamoxifen treatment. Kaplan-Meier methods, the log-rank test, and multivariable Cox regression models were used to assess overall and progression-free survival (PFS) in the two randomised groups and by hormone-confirmed menstrual cycle phase.

    RESULTS: Overall survival (OS) and PFS were not demonstrated to be different in the two randomised groups. In a secondary analysis, OS appeared worse in luteal phase surgery patients with progesterone levels <2 ng/ml (anovulatory patients; adjusted hazard ratio 1.46, 95% confidence interval [CI]: 0.89-2.41, p = 0.14) compared with those in luteal phase with progesterone level of 2 ng/ml or higher. Median OS was 2 years (95% CI: 1.7-2.3) and OS at 4 years was 26%.

    CONCLUSIONS: The history-based timing of surgical oophorectomy in the menstrual cycle did not influence outcomes in this trial of metastatic patients. ClinicalTrials.gov number NCT00293540.

    Study site: Bangladesh, The Philippines, China, Nigeria,
    Indonesia, Malaysia, Taiwan, Morocco, and Vietnam
  19. Tan MM, Ho WK, Yoon SY, Mariapun S, Hasan SN, Lee DS, et al.
    PLoS One, 2018;13(9):e0203469.
    PMID: 30216346 DOI: 10.1371/journal.pone.0203469
    BACKGROUND: Breast cancer risk factors have been examined extensively in Western setting and more developed Asian cities/countries. However, there are limited data on developing Asian countries. The purpose of this study was to examine breast cancer risk factors and the change of selected risk factors across birth cohorts in Malaysian women.

    METHODS: An unmatched hospital based case-control study was conducted from October 2002 to December 2016 in Selangor, Malaysia. A total of 3,683 cases and 3,980 controls were included in this study. Unconditional logistic regressions, adjusted for potential confounding factors, were conducted. The breast cancer risk factors were compared across four birth cohorts by ethnicity.

    RESULTS: Ever breastfed, longer breastfeeding duration, a higher soymilk and soy product intake, and a higher level of physical activity were associated with lower risk of breast cancer. Chinese had the lowest breastfeeding rate, shortest breastfeeding duration, lowest parity and highest age of first full term pregnancy.

    CONCLUSIONS: Our study shows that breastfeeding, soy intake and physical activity are modifiable risk factors for breast cancer. With the increasing incidence of breast cancer there is an urgent need to educate the women about lifestyle intervention they can take to reduce their breast cancer risk.

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