Displaying publications 1 - 20 of 79 in total

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  1. Evidence for the Higgs Boson Decay to a Z Boson and a Photon at the LHC
    Aad G, Abbott B, Abeling K, Abicht NJ, Abidi SH, Aboulhorma A, et al.
    Phys Rev Lett, 2024 Jan 12;132(2):021803.
    PMID: 38277607 DOI: 10.1103/PhysRevLett.132.021803
    The first evidence for the Higgs boson decay to a Z boson and a photon is presented, with a statistical significance of 3.4 standard deviations. The result is derived from a combined analysis of the searches performed by the ATLAS and CMS Collaborations with proton-proton collision datasets collected at the CERN Large Hadron Collider (LHC) from 2015 to 2018. These correspond to integrated luminosities of around 140  fb^{-1} for each experiment, at a center-of-mass energy of 13 TeV. The measured signal yield is 2.2±0.7 times the standard model prediction, and agrees with the theoretical expectation within 1.9 standard deviations.
  2. First Evidence for cos2β>0 and Resolution of the Cabibbo-Kobayashi-Maskawa Quark-Mixing Unitarity Triangle Ambiguity
    Adachi I, Adye T, Ahmed H, Ahn JK, Aihara H, Akar S, et al.
    Phys Rev Lett, 2018 Dec 28;121(26):261801.
    PMID: 30636113 DOI: 10.1103/PhysRevLett.121.261801
    We present first evidence that the cosine of the CP-violating weak phase 2β is positive, and hence exclude trigonometric multifold solutions of the Cabibbo-Kobayashi-Maskawa (CKM) Unitarity Triangle using a time-dependent Dalitz plot analysis of B^{0}→D^{(*)}h^{0} with D→K_{S}^{0}π^{+}π^{-} decays, where h^{0}∈{π^{0},η,ω} denotes a light unflavored and neutral hadron. The measurement is performed combining the final data sets of the BABAR and Belle experiments collected at the ϒ(4S) resonance at the asymmetric-energy B factories PEP-II at SLAC and KEKB at KEK, respectively. The data samples contain (471±3)×10^{6}BB[over ¯] pairs recorded by the BABAR detector and (772±11)×10^{6}BB[over ¯] pairs recorded by the Belle detector. The results of the measurement are sin2β=0.80±0.14(stat)±0.06(syst)±0.03(model) and cos2β=0.91±0.22(stat)±0.09(syst)±0.07(model). The result for the direct measurement of the angle β of the CKM Unitarity Triangle is β=[22.5±4.4(stat)±1.2(syst)±0.6(model)]°. The measurement assumes no direct CP violation in B^{0}→D^{(*)}h^{0} decays. The quoted model uncertainties are due to the composition of the D^{0}→K_{S}^{0}π^{+}π^{-} decay amplitude model, which is newly established by performing a Dalitz plot amplitude analysis using a high-statistics e^{+}e^{-}→cc[over ¯] data sample. CP violation is observed in B^{0}→D^{(*)}h^{0} decays at the level of 5.1 standard deviations. The significance for cos2β>0 is 3.7 standard deviations. The trigonometric multifold solution π/2-β=(68.1±0.7)° is excluded at the level of 7.3 standard deviations. The measurement resolves an ambiguity in the determination of the apex of the CKM Unitarity Triangle.
  3. Fulltext Breast cancer risk variants at 6q25 display different phenotype associations and regulate ESR1, RMND1 and CCDC170
    Dunning AM, Michailidou K, Kuchenbaecker KB, Thompson D, French JD, Beesley J, et al.
    Nat Genet, 2016 Apr;48(4):374-86.
    PMID: 26928228 DOI: 10.1038/ng.3521
    We analyzed 3,872 common genetic variants across the ESR1 locus (encoding estrogen receptor α) in 118,816 subjects from three international consortia. We found evidence for at least five independent causal variants, each associated with different phenotype sets, including estrogen receptor (ER(+) or ER(-)) and human ERBB2 (HER2(+) or HER2(-)) tumor subtypes, mammographic density and tumor grade. The best candidate causal variants for ER(-) tumors lie in four separate enhancer elements, and their risk alleles reduce expression of ESR1, RMND1 and CCDC170, whereas the risk alleles of the strongest candidates for the remaining independent causal variant disrupt a silencer element and putatively increase ESR1 and RMND1 expression.
  4. Fulltext Genome-Wide Meta-Analyses of Breast, Ovarian, and Prostate Cancer Association Studies Identify Multiple New Susceptibility Loci Shared by at Least Two Cancer Types
    Kar SP, Beesley J, Amin Al Olama A, Michailidou K, Tyrer J, Kote-Jarai Z, et al.
    Cancer Discov, 2016 Sep;6(9):1052-67.
    PMID: 27432226 DOI: 10.1158/2159-8290.CD-15-1227
    Breast, ovarian, and prostate cancers are hormone-related and may have a shared genetic basis, but this has not been investigated systematically by genome-wide association (GWA) studies. Meta-analyses combining the largest GWA meta-analysis data sets for these cancers totaling 112,349 cases and 116,421 controls of European ancestry, all together and in pairs, identified at P < 10(-8) seven new cross-cancer loci: three associated with susceptibility to all three cancers (rs17041869/2q13/BCL2L11; rs7937840/11q12/INCENP; rs1469713/19p13/GATAD2A), two breast and ovarian cancer risk loci (rs200182588/9q31/SMC2; rs8037137/15q26/RCCD1), and two breast and prostate cancer risk loci (rs5013329/1p34/NSUN4; rs9375701/6q23/L3MBTL3). Index variants in five additional regions previously associated with only one cancer also showed clear association with a second cancer type. Cell-type-specific expression quantitative trait locus and enhancer-gene interaction annotations suggested target genes with potential cross-cancer roles at the new loci. Pathway analysis revealed significant enrichment of death receptor signaling genes near loci with P < 10(-5) in the three-cancer meta-analysis.

    SIGNIFICANCE: We demonstrate that combining large-scale GWA meta-analysis findings across cancer types can identify completely new risk loci common to breast, ovarian, and prostate cancers. We show that the identification of such cross-cancer risk loci has the potential to shed new light on the shared biology underlying these hormone-related cancers. Cancer Discov; 6(9); 1052-67. ©2016 AACR.This article is highlighted in the In This Issue feature, p. 932.

  5. Fulltext Fine-mapping identifies two additional breast cancer susceptibility loci at 9q31.2
    Orr N, Dudbridge F, Dryden N, Maguire S, Novo D, Perrakis E, et al.
    Hum Mol Genet, 2015 May 15;24(10):2966-84.
    PMID: 25652398 DOI: 10.1093/hmg/ddv035
    We recently identified a novel susceptibility variant, rs865686, for estrogen-receptor positive breast cancer at 9q31.2. Here, we report a fine-mapping analysis of the 9q31.2 susceptibility locus using 43 160 cases and 42 600 controls of European ancestry ascertained from 52 studies and a further 5795 cases and 6624 controls of Asian ancestry from nine studies. Single nucleotide polymorphism (SNP) rs676256 was most strongly associated with risk in Europeans (odds ratios [OR] = 0.90 [0.88-0.92]; P-value = 1.58 × 10(-25)). This SNP is one of a cluster of highly correlated variants, including rs865686, that spans ∼14.5 kb. We identified two additional independent association signals demarcated by SNPs rs10816625 (OR = 1.12 [1.08-1.17]; P-value = 7.89 × 10(-09)) and rs13294895 (OR = 1.09 [1.06-1.12]; P-value = 2.97 × 10(-11)). SNP rs10816625, but not rs13294895, was also associated with risk of breast cancer in Asian individuals (OR = 1.12 [1.06-1.18]; P-value = 2.77 × 10(-05)). Functional genomic annotation using data derived from breast cancer cell-line models indicates that these SNPs localise to putative enhancer elements that bind known drivers of hormone-dependent breast cancer, including ER-α, FOXA1 and GATA-3. In vitro analyses indicate that rs10816625 and rs13294895 have allele-specific effects on enhancer activity and suggest chromatin interactions with the KLF4 gene locus. These results demonstrate the power of dense genotyping in large studies to identify independent susceptibility variants. Analysis of associations using subjects with different ancestry, combined with bioinformatic and genomic characterisation, can provide strong evidence for the likely causative alleles and their functional basis.
  6. Observation of ϒ(2S)→γη_{b}(1S) Decay
    Fulsom BG, Pedlar TK, Adachi I, Aihara H, Al Said S, Asner DM, et al.
    Phys Rev Lett, 2018 Dec 07;121(23):232001.
    PMID: 30576207 DOI: 10.1103/PhysRevLett.121.232001
    We report the observation of ϒ(2S)→γη_{b}(1S) decay based on an analysis of the inclusive photon spectrum of 24.7  fb^{-1} of e^{+}e^{-} collisions at the ϒ(2S) center-of-mass energy collected with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We measure a branching fraction of B[ϒ(2S)→γη_{b}(1S)]=(6.1_{-0.7-0.6}^{+0.6+0.9})×10^{-4} and derive an η_{b}(1S) mass of 9394.8_{-3.1-2.7}^{+2.7+4.5}  MeV/c^{2}, where the uncertainties are statistical and systematic, respectively. The significance of our measurement is greater than 7 standard deviations, constituting the first observation of this decay mode.
  7. First Measurements of Absolute Branching Fractions of the Ξ_{c}^{0} Baryon at Belle
    Li YB, Shen CP, Yuan CZ, Adachi I, Aihara H, Al Said S, et al.
    Phys Rev Lett, 2019 Mar 01;122(8):082001.
    PMID: 30932568 DOI: 10.1103/PhysRevLett.122.082001
    We present the first measurements of absolute branching fractions of Ξ_{c}^{0} decays into Ξ^{-}π^{+}, ΛK^{-}π^{+}, and pK^{-}K^{-}π^{+} final states. The measurements are made using a dataset comprising (772±11)×10^{6} BB[over ¯] pairs collected at the ϒ(4S) resonance with the Belle detector at the KEKB e^{+}e^{-} collider. We first measure the absolute branching fraction for B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0} using a missing-mass technique; the result is B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})=(9.51±2.10±0.88)×10^{-4}. We subsequently measure the product branching fractions B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→Ξ^{-}π^{+}), B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→ΛK^{-}π^{+}), and B(B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0})B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+}) with improved precision. Dividing these product branching fractions by the result for B^{-}→Λ[over ¯]_{c}^{-}Ξ_{c}^{0} yields the following branching fractions: B(Ξ_{c}^{0}→Ξ^{-}π^{+})=(1.80±0.50±0.14)%, B(Ξ_{c}^{0}→ΛK^{-}π^{+})=(1.17±0.37±0.09)%, and B(Ξ_{c}^{0}→pK^{-}K^{-}π^{+})=(0.58±0.23±0.05)%. For the above branching fractions, the first uncertainties are statistical and the second are systematic. Our result for B(Ξ_{c}^{0}→Ξ^{-}π^{+}) can be combined with Ξ_{c}^{0} branching fractions measured relative to Ξ_{c}^{0}→Ξ^{-}π^{+} to yield other absolute Ξ_{c}^{0} branching fractions.
  8. Search for a Light CP-odd Higgs Boson and Low-Mass Dark Matter at the Belle Experiment
    Seong IS, Vahsen SE, Adachi I, Aihara H, Al Said S, Asner DM, et al.
    Phys Rev Lett, 2019 Jan 11;122(1):011801.
    PMID: 31012694 DOI: 10.1103/PhysRevLett.122.011801
    We report on the first Belle search for a light CP-odd Higgs boson, A^{0}, that decays into low mass dark matter, χ, in final states with a single photon and missing energy. We search for events produced via the dipion transition ϒ(2S)→ϒ(1S)π^{+}π^{-}, followed by the on-shell process ϒ(1S)→γA^{0} with A^{0}→χχ, or by the off-shell process ϒ(1S)→γχχ. Utilizing a data sample of 157.3×10^{6} ϒ(2S) decays, we find no evidence for a signal. We set limits on the branching fractions of such processes in the mass ranges M_{A^{0}}<8.97  GeV/c^{2} and M_{χ}<4.44  GeV/c^{2}. We then use the limits on the off-shell process to set competitive limits on WIMP-nucleon scattering in the WIMP mass range below 5  GeV/c^{2}.
  9. Observation of ϒ(4S)→η^{'}ϒ(1S)
    Guido E, Mussa R, Tamponi U, Aihara H, Al Said S, Asner DM, et al.
    Phys Rev Lett, 2018 Aug 10;121(6):062001.
    PMID: 30141661 DOI: 10.1103/PhysRevLett.121.062001
    We report the first observation of the hadronic transition ϒ(4S)→η^{'}ϒ(1S), using 496  fb^{-1} data collected at the ϒ(4S) resonance with the Belle detector at the KEKB asymmetric-energy e^{+}e^{-} collider. We reconstruct the η^{'} meson through its decays to ρ^{0}γ and to π^{+}π^{-}η, with η→γγ. We measure B(ϒ(4S)→η^{'}ϒ(1S))=[3.43±0.88(stat)±0.21(syst)]×10^{-5}, with a significance of 5.7σ.
  10. Observation of Transverse Λ/Λ[over ¯] Hyperon Polarization in e^{+}e^{-} Annihilation at Belle
    Guan Y, Vossen A, Adachi I, Adamczyk K, Ahn JK, Aihara H, et al.
    Phys Rev Lett, 2019 Feb 01;122(4):042001.
    PMID: 30768311 DOI: 10.1103/PhysRevLett.122.042001
    We report the first observation of the spontaneous polarization of Λ and Λ[over ¯] hyperons transverse to the production plane in e^{+}e^{-} annihilation, which is attributed to the effect arising from a polarizing fragmentation function. For inclusive Λ/Λ[over ¯] production, we also report results with subtracted feed-down contributions from Σ^{0} and charm. This measurement uses a dataset of 800.4  fb^{-1} collected by the Belle experiment at or near a center-of-mass energy of 10.58 GeV. We observe a significant polarization that rises with the fractional energy carried by the Λ/Λ[over ¯] hyperon.
  11. Fulltext Fine scale mapping of the 17q22 breast cancer locus using dense SNPs, genotyped within the Collaborative Oncological Gene-Environment Study (COGs)
    Darabi H, Beesley J, Droit A, Kar S, Nord S, Moradi Marjaneh M, et al.
    Sci Rep, 2016 Sep 07;6:32512.
    PMID: 27600471 DOI: 10.1038/srep32512
    Genome-wide association studies have found SNPs at 17q22 to be associated with breast cancer risk. To identify potential causal variants related to breast cancer risk, we performed a high resolution fine-mapping analysis that involved genotyping 517 SNPs using a custom Illumina iSelect array (iCOGS) followed by imputation of genotypes for 3,134 SNPs in more than 89,000 participants of European ancestry from the Breast Cancer Association Consortium (BCAC). We identified 28 highly correlated common variants, in a 53 Kb region spanning two introns of the STXBP4 gene, that are strong candidates for driving breast cancer risk (lead SNP rs2787486 (OR = 0.92; CI 0.90-0.94; P = 8.96 × 10(-15))) and are correlated with two previously reported risk-associated variants at this locus, SNPs rs6504950 (OR = 0.94, P = 2.04 × 10(-09), r(2) = 0.73 with lead SNP) and rs1156287 (OR = 0.93, P = 3.41 × 10(-11), r(2) = 0.83 with lead SNP). Analyses indicate only one causal SNP in the region and several enhancer elements targeting STXBP4 are located within the 53 kb association signal. Expression studies in breast tumor tissues found SNP rs2787486 to be associated with increased STXBP4 expression, suggesting this may be a target gene of this locus.
  12. Fulltext Germline breast cancer susceptibility genes, tumor characteristics, and survival
    Ho PJ, Khng AJ, Loh HW, Ho WK, Yip CH, Mohd-Taib NA, et al.
    Genome Med, 2021 Dec 02;13(1):185.
    PMID: 34857041 DOI: 10.1186/s13073-021-00978-9
    BACKGROUND: Mutations in certain genes are known to increase breast cancer risk. We study the relevance of rare protein-truncating variants (PTVs) that may result in loss-of-function in breast cancer susceptibility genes on tumor characteristics and survival in 8852 breast cancer patients of Asian descent.

    METHODS: Gene panel sequencing was performed for 34 known or suspected breast cancer predisposition genes, of which nine genes (ATM, BRCA1, BRCA2, CHEK2, PALB2, BARD1, RAD51C, RAD51D, and TP53) were associated with breast cancer risk. Associations between PTV carriership in one or more genes and tumor characteristics were examined using multinomial logistic regression. Ten-year overall survival was estimated using Cox regression models in 6477 breast cancer patients after excluding older patients (≥75years) and stage 0 and IV disease.

    RESULTS: PTV9genes carriership (n = 690) was significantly associated (p < 0.001) with more aggressive tumor characteristics including high grade (poorly vs well-differentiated, odds ratio [95% confidence interval] 3.48 [2.35-5.17], moderately vs well-differentiated 2.33 [1.56-3.49]), as well as luminal B [HER-] and triple-negative subtypes (vs luminal A 2.15 [1.58-2.92] and 2.85 [2.17-3.73], respectively), adjusted for age at diagnosis, study, and ethnicity. Associations with grade and luminal B [HER2-] subtype remained significant after excluding BRCA1/2 carriers. PTV25genes carriership (n = 289, excluding carriers of the nine genes associated with breast cancer) was not associated with tumor characteristics. However, PTV25genes carriership, but not PTV9genes carriership, was suggested to be associated with worse 10-year overall survival (hazard ratio [CI] 1.63 [1.16-2.28]).

    CONCLUSIONS: PTV9genes carriership is associated with more aggressive tumors. Variants in other genes might be associated with the survival of breast cancer patients. The finding that PTV carriership is not just associated with higher breast cancer risk, but also more severe and fatal forms of the disease, suggests that genetic testing has the potential to provide additional health information and help healthy individuals make screening decisions.

  13. Fulltext Establishment of Wolbachia Strain wAlbB in Malaysian Populations of Aedes aegypti for Dengue Control
    Nazni WA, Hoffmann AA, NoorAfizah A, Cheong YL, Mancini MV, Golding N, et al.
    Curr Biol, 2019 Dec 16;29(24):4241-4248.e5.
    PMID: 31761702 DOI: 10.1016/j.cub.2019.11.007
    Dengue has enormous health impacts globally. A novel approach to decrease dengue incidence involves the introduction of Wolbachia endosymbionts that block dengue virus transmission into populations of the primary vector mosquito, Aedes aegypti. The wMel Wolbachia strain has previously been trialed in open releases of Ae. aegypti; however, the wAlbB strain has been shown to maintain higher density than wMel at high larval rearing temperatures. Releases of Ae. aegypti mosquitoes carrying wAlbB were carried out in 6 diverse sites in greater Kuala Lumpur, Malaysia, with high endemic dengue transmission. The strain was successfully established and maintained at very high population frequency at some sites or persisted with additional releases following fluctuations at other sites. Based on passive case monitoring, reduced human dengue incidence was observed in the release sites when compared to control sites. The wAlbB strain of Wolbachia provides a promising option as a tool for dengue control, particularly in very hot climates.
  14. Fulltext Gut microbiome of helminth-infected indigenous Malaysians is context dependent
    Tee MZ, Er YX, Easton AV, Yap NJ, Lee IL, Devlin J, et al.
    Microbiome, 2022 Dec 07;10(1):214.
    PMID: 36476263 DOI: 10.1186/s40168-022-01385-x
    BACKGROUND: While microbiomes in industrialized societies are well characterized, indigenous populations with traditional lifestyles have microbiomes that are more akin to those of ancient humans. However, metagenomic data in these populations remains scarce, and the association with soil-transmitted helminth infection status is unclear. Here, we sequenced 650 metagenomes of indigenous Malaysians from five villages with different prevalence of helminth infections.

    RESULTS: Individuals from villages with higher prevalences of helminth infections have more unmapped reads and greater microbial diversity. Microbial community diversity and composition were most strongly associated with different villages and the effects of helminth infection status on the microbiome varies by village. Longitudinal changes in the microbiome in response to albendazole anthelmintic treatment were observed in both helminth infected and uninfected individuals. Inference of bacterial population replication rates from origin of replication analysis identified specific replicating taxa associated with helminth infection.

    CONCLUSIONS: Our results indicate that helminth effects on the microbiota were highly dependent on context, and effects of albendazole on the microbiota can be confounding for the interpretation of deworming studies. Furthermore, a substantial quantity of the microbiome remains unannotated, and this large dataset from an indigenous population associated with helminth infections is a valuable resource for future studies. Video Abstract.

  15. Fulltext Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer
    Im SA, Gennari A, Park YH, Kim JH, Jiang ZF, Gupta S, et al.
    ESMO Open, 2023 Jun;8(3):101541.
    PMID: 37178669 DOI: 10.1016/j.esmoop.2023.101541
    The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, staging and treatment of patients with metastatic breast cancer (MBC) was published in 2021. A special, hybrid guidelines meeting was convened by ESMO and the Korean Society of Medical Oncology (KSMO) in collaboration with nine other Asian national oncology societies in May 2022 in order to adapt the ESMO 2021 guidelines to take into account the differences associated with the treatment of MBC in Asia. These guidelines represent the consensus opinions reached by a panel of Asian experts in the treatment of patients with MBC representing the oncological societies of China (CSCO), India (ISMPO), Indonesia (ISHMO), Japan (JSMO), Korea (KSMO), Malaysia (MOS), the Philippines (PSMO), Singapore (SSO), Taiwan (TOS) and Thailand (TSCO). The voting was based on the best available scientific evidence and was independent of drug access or practice restrictions in the different Asian countries. The latter were discussed when appropriate. The aim of these guidelines is to provide guidance for the harmonisation of the management of patients with MBC across the different regions of Asia, drawing from data provided by global and Asian trials whilst at the same time integrating the differences in genetics, demographics and scientific evidence, together with restricted access to certain therapeutic strategies.
  16. Fulltext Outcome after neoadjuvant chemotherapy in Asian breast cancer patients
    Lim LY, Miao H, Lim JS, Lee SC, Bhoo-Pathy N, Yip CH, et al.
    Cancer Med, 2017 Jan;6(1):173-185.
    PMID: 28000426 DOI: 10.1002/cam4.985
    We aim to identify clinicopathologic predictors for response to neoadjuvant chemotherapy and to evaluate the prognostic value of pathologic complete response (pCR) on survival in Asia. This study included 915 breast cancer patients who underwent neoadjuvant chemotherapy at five public hospitals in Singapore and Malaysia. pCR following neoadjuvant chemotherapy was defined as 1) no residual invasive tumor cells in the breast (ypT0/is) and 2) no residual invasive tumor cells in the breast and axillary lymph nodes (ypT0/is ypN0). Association between pCR and clinicopathologic characteristics and treatment were evaluated using chi-square test and multivariable logistic regression. Kaplan-Meier analysis and log-rank test, stratified by other prognostic factors, were conducted to compare overall survival between patients who achieved pCR and patients who did not. Overall, 4.4% of nonmetastatic patients received neoadjuvant chemotherapy. The median age of preoperatively treated patients was 50 years. pCR rates were 18.1% (pCR ypT0/is) and 14.4% (pCR ypT0/is ypN0), respectively. pCR rate was the highest among women who had higher grade, smaller size, estrogen receptor negative, human epidermal growth factor receptor 2-positive disease or receiving taxane-based neoadjuvant chemotherapy. Patients who achieved pCR had better overall survival than those who did not. In subgroup analysis, the survival advantage was only significant among women with estrogen receptor-negative tumors. Patients with poor prognostic profile are more likely to achieve pCR and particularly when receiving taxane-containing chemotherapy. pCR is a significant prognostic factor for overall survival especially in estrogen receptor-negative breast cancers.
  17. Prognostic role of adjuvant radiotherapy in triple-negative breast cancer: A historical cohort study
    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.
  18. Detection of Schistosoma spindale ova and associated risk factors among Malaysian cattle through coprological survey
    Tan TK, Low VL, Lee SC, Panchadcharam C, Tay ST, Ngui R, et al.
    Jpn. J. Vet. Res., 2015 May;63(2):63-71.
    PMID: 26164875
    The present study was conducted to determine the occurrence of Schistosoma spindale ova and its associated risk factors in Malaysian cattle through a coprological survey. A total of 266 rectal fecal samples were collected from six farms in Peninsular Malaysia. The overall infection rate of S. spindale was 6% (16 of 266). Schistosoma spindale infection was observed in two farms, with a prevalence of 5.4% and 51.9%, respectively. This trematode was more likely to co-occur with other gastro-intestinal parasites (i.e., Dicrocoelium spp., Paramphistomum spp., strongyle, Eimeria spp. and Entamoeba spp.). Chi-square analysis revealed that female cattle are less likely to get S. spindale infection as compared to male cattle (OR = 0.3; 95% CI = 0.08-1.06; p < 0.05), and cattle weighing lower than 200 kg, were significantly at higher risk than those higher than 200 kg (OR = 5; 95% CI = 1.07-24.79; p < 0.05) to the infection. Multivariate analysis confirmed that among the cattle in Malaysia, the age (cattle with two year old and higher: OR = 21; 95% CI = 2.48-179.44; p < 0.05) and weight (weighing 200 kg and lower: OR = 17; 95% CI = 3.38-87.19; p < 0.05) were risk factors for S. spindale infection among Malaysian cattle.
  19. Fulltext A randomized phase II trial evaluating the addition of low dose, short course sunitinib to docetaxel in advanced solid tumours
    Ang YLE, Ho GF, Soo RA, Sundar R, Tan SH, Yong WP, et al.
    BMC Cancer, 2020 Nov 17;20(1):1118.
    PMID: 33203399 DOI: 10.1186/s12885-020-07616-4
    BACKGROUND: We previously reported that low-dose, short-course sunitinib prior to neoadjuvant doxorubicin-cyclophosphamide (AC) normalised tumour vasculature and improved perfusion, but resulted in neutropenia and delayed subsequent cycles in breast cancer patients. This study combined sunitinib with docetaxel, which has an earlier neutrophil nadir than AC.

    METHODS: Patients with advanced solid cancers were randomized 1:1 to 3-weekly docetaxel 75 mg/m2, with or without sunitinib 12.5 mg daily for 7 days prior to docetaxel, stratified by primary tumour site. Primary endpoints were objective-response (ORR:CR + PR) and clinical-benefit rate (CBR:CR + PR + SD); secondary endpoints were toxicity and progression-free-survival (PFS).

    RESULTS: We enrolled 68 patients from 2 study sites; 33 received docetaxel-sunitinib and 35 docetaxel alone, with 33 breast, 25 lung and 10 patients with other cancers. There was no difference in ORR (30.3% vs 28.6%, p = 0.432, odds-ratio [OR] 1.10, 95% CI 0.38-3.18); CBR was lower in the docetaxel-sunitinib arm (48.5% vs 71.4%, p = 0.027 OR 0.37, 95% CI 0.14-1.01). Median PFS was shorter in the docetaxel-sunitinib arm (2.9 vs 4.9 months, hazard-ratio [HR] 2.00, 95% CI 1.15-3.48, p = 0.014) overall, as well as in breast (4.2 vs 5.6 months, p = 0.048) and other cancers (2.0 vs 5.3 months, p = 0.009), but not in lung cancers (2.9 vs 4.1 months, p = 0.597). Median OS was similar in both arms overall (9.9 vs 10.5 months, HR 0.92, 95% CI 0.51-1.67, p = 0.789), and in the breast (18.9 vs 25.8 months, p = 0.354), lung (7.0 vs 6.7 months, p = 0.970) and other cancers (4.5 vs 8.8 months, p = 0.449) subgroups. Grade 3/4 haematological toxicities were lower with docetaxel-sunitinib (18.2% vs 34.3%, p = 0.132), attributed to greater discretionary use of prophylactic G-CSF (90.9% vs 63.0%, p = 0.024). Grade 3/4 non-haematological toxicities were similar (12.1% vs 14.3%, p = 0.792).

    CONCLUSIONS: The addition of sunitinib to docetaxel was well-tolerated but did not improve outcomes. The possible negative impact in metastatic breast cancer patients is contrary to results of adding sunitinib to neoadjuvant AC. These negative results suggest that the intermittent administration of sunitinib in the current dose and schedule with docetaxel in advanced solid tumours, particularly breast cancers, is not beneficial.

    TRIAL REGISTRATION: The study was registered ( NCT01803503 ) prospectively on clinicaltrials.gov on 4th March 2013.

  20. Fulltext Genotype-guided versus traditional clinical dosing of warfarin in patients of Asian ancestry: a randomized controlled trial
    Syn NL, Wong AL, Lee SC, Teoh HL, Yip JWL, Seet RC, et al.
    BMC Med, 2018 07 10;16(1):104.
    PMID: 29986700 DOI: 10.1186/s12916-018-1093-8
    BACKGROUND: Genotype-guided warfarin dosing has been shown in some randomized trials to improve anticoagulation outcomes in individuals of European ancestry, yet its utility in Asian patients remains unresolved.

    METHODS: An open-label, non-inferiority, 1:1 randomized trial was conducted at three academic hospitals in South East Asia, involving 322 ethnically diverse patients newly indicated for warfarin (NCT00700895). Clinical follow-up was 90 days. The primary efficacy measure was the number of dose titrations within the first 2 weeks of therapy, with a mean non-inferiority margin of 0.5 over the first 14 days of therapy.

    RESULTS: Among 322 randomized patients, 269 were evaluable for the primary endpoint. Compared with traditional dosing, the genotype-guided group required fewer dose titrations during the first 2 weeks (1.77 vs. 2.93, difference -1.16, 90% CI -1.48 to -0.84, P 

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