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  1. Al-Amin M, Eltayeb NM, Hossain CF, Khairuddean M, Fazalul Rahiman SS, Salhimi SM
    Planta Med., 2020 Apr;86(6):387-394.
    PMID: 32168546 DOI: 10.1055/a-1129-7026
    Zingiber montanum rhizomes are traditionally used for the treatment of numerous human ailments. The present study was carried out to investigate the inhibitory activity of the crude extract, chromatographic fractions, and purified compounds from Z. montanum rhizomes on the migration of MDA-MB-231 cells. The effect of the extract on cell migration was investigated by a scratch assay, which showed significant inhibition in a concentration-dependent manner. Vacuum liquid chromatography on silica gel afforded four fractions (Frs. 1 - 4), which were tested on cell migration in the scratch assay. Frs. 1 and 2 showed the most significant inhibition of MDA-MB-231 cell migration. The effect of the most potent fraction (Fr. 2) was further confirmed in a transwell migration assay. The study of Frs. 1 and 2 by gelatin zymography showed significant inhibition of MMP-9 enzyme activity. Chromatographic separation of Frs. 1 and 2 afforded buddledone A (1: ), zerumbone (2: ), (2E,9E)-6-methoxy-2,9-humuradien-8-one (3: ), zerumbone epoxide (4: ), stigmasterol (5: ), and daucosterol (6: ). In a cell viability assay, compounds 1:  - 4: inhibited the viability of MDA-MB-231 cells in a concentration-dependent manner. The study of buddledone A (1: ) and zerumbone epoxide (4: ) on cell migration revealed that 4: significantly inhibited the migration of MDA-MB-231 cells in both scratch and transwell migration assays. The results of the present study may lead to further molecular studies behind the inhibitory activity of zerumbone epoxide (4: ) on cell migration and support the traditional use of Z. montanum rhizomes for the treatment of cancer.
    Matched MeSH terms: Breast Neoplasms*
  2. Assi N, Rinaldi S, Viallon V, Dashti SG, Dossus L, Fournier A, et al.
    Int. J. Cancer, 2020 02 01;146(3):759-768.
    PMID: 30968961 DOI: 10.1002/ijc.32324
    Alcohol consumption is associated with higher risk of breast cancer (BC); however, the biological mechanisms underlying this association are not fully elucidated, particularly the extent to which this relationship is mediated by sex hormone levels. Circulating concentrations of estradiol, testosterone, their free fractions and sex-hormone binding globulin (SHBG), were examined in 430 incident BC cases and 645 matched controls among alcohol-consuming postmenopausal women nested within the European Prospective Investigation into Cancer and Nutrition. Mediation analysis was applied to assess whether individual hormone levels mediated the relationship between alcohol intake and BC risk. An alcohol-related hormonal signature, obtained by partial least square (PLS) regression, was evaluated as a potential mediator. Total (TE), natural direct and natural indirect effects (NIE) were estimated. Alcohol intake was positively associated with overall BC risk and specifically with estrogen receptor-positive tumors with respectively TE = 1.17(95%CI: 1.01,1.35) and 1.36(1.08,1.70) for a 1-standard deviation (1-SD) increase of intake. There was no evidence of mediation by sex steroids or SHBG separately except for a weak indirect effect through free estradiol where NIE = 1.03(1.00,1.06). However, an alcohol-related hormonal signature negatively associated with SHBG and positively with estradiol and testosterone was associated with BC risk (odds ratio [OR] = 1.25 [1.07,1.47]) for a 1-SD higher PLS score, and had a statistically significant NIE accounting for a mediated proportion of 24%. There was limited evidence of mediation of the alcohol-BC association by individual sex hormones. However, a hormonal signature, reflecting lower levels of SHBG and higher levels of sex steroids, mediated a substantial proportion of the association.
    Matched MeSH terms: Breast Neoplasms/etiology; Breast Neoplasms/epidemiology*
  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 breast cancer, further studies are warranted.
    Matched MeSH terms: Breast Neoplasms/diagnosis*; Breast Neoplasms/mortality; Breast Neoplasms/pathology
  4. Papadimitriou N, Dimou N, Tsilidis KK, Banbury B, Martin RM, Lewis SJ, et al.
    Nat Commun, 2020 01 30;11(1):597.
    PMID: 32001714 DOI: 10.1038/s41467-020-14389-8
    Physical activity has been associated with lower risks of breast and colorectal cancer in epidemiological studies; however, it is unknown if these associations are causal or confounded. In two-sample Mendelian randomisation analyses, using summary genetic data from the UK Biobank and GWA consortia, we found that a one standard deviation increment in average acceleration was associated with lower risks of breast cancer (odds ratio [OR]: 0.51, 95% confidence interval [CI]: 0.27 to 0.98, P-value = 0.04) and colorectal cancer (OR: 0.66, 95% CI: 0.48 to 0.90, P-value = 0.01). We found similar magnitude inverse associations for estrogen positive (ER+ve) breast cancer and for colon cancer. Our results support a potentially causal relationship between higher physical activity levels and lower risks of breast cancer and colorectal cancer. Based on these data, the promotion of physical activity is probably an effective strategy in the primary prevention of these commonly diagnosed cancers.
    Matched MeSH terms: Breast Neoplasms/genetics*
  5. Fachal L, Aschard H, Beesley J, Barnes DR, Allen J, Kar S, et al.
    Nat. Genet., 2020 01;52(1):56-73.
    PMID: 31911677 DOI: 10.1038/s41588-019-0537-1
    Genome-wide association studies have identified breast cancer risk variants in over 150 genomic regions, but the mechanisms underlying risk remain largely unknown. These regions were explored by combining association analysis with in silico genomic feature annotations. We defined 205 independent risk-associated signals with the set of credible causal variants in each one. In parallel, we used a Bayesian approach (PAINTOR) that combines genetic association, linkage disequilibrium and enriched genomic features to determine variants with high posterior probabilities of being causal. Potentially causal variants were significantly over-represented in active gene regulatory regions and transcription factor binding sites. We applied our INQUSIT pipeline for prioritizing genes as targets of those potentially causal variants, using gene expression (expression quantitative trait loci), chromatin interaction and functional annotations. Known cancer drivers, transcription factors and genes in the developmental, apoptosis, immune system and DNA integrity checkpoint gene ontology pathways were over-represented among the highest-confidence target genes.
    Matched MeSH terms: Breast Neoplasms/genetics*
  6. Jabbarzadeh Kaboli P, Afzalipour Khoshkbejari M, Mohammadi M, Abiri A, Mokhtarian R, Vazifemand R, et al.
    Biomed. Pharmacother., 2020 Jan;121:109635.
    PMID: 31739165 DOI: 10.1016/j.biopha.2019.109635
    Breast cancer is the most common type of cancer among women. Therefore, discovery of new and effective drugs with fewer side effects is necessary to treat it. Sulforaphane (SFN) is an organosulfur compound obtained from cruciferous plants, such as broccoli and mustard, and it has the potential to treat breast cancer. Hence, it is vital to find out how SFN targets certain genes and cellular pathways in treating breast cancer. In this review, molecular targets and cellular pathways of SFN are described. Studies have shown SFN inhibits cell proliferation, causes apoptosis, stops cell cycle and has anti-oxidant activities. Increasing reactive oxygen species (ROS) produces oxidative stress, activates inflammatory transcription factors, and these result in inflammation leading to cancer. Increasing anti-oxidant potential of cells and discovering new targets to reduce ROS creation reduces oxidative stress and it eventually reduces cancer risks. In short, SFN effectively affects histone deacetylases involved in chromatin remodeling, gene expression, and Nrf2 anti-oxidant signaling. This review points to the potential of SFN to treat breast cancer as well as the importance of other new cruciferous compounds, derived from and isolated from mustard, to target Keap1 and Akt, two key regulators of cellular homeostasis.
    Matched MeSH terms: Breast Neoplasms/drug therapy*
  7. Hanis TM, Yaacob NM, Hairon SM, Abdullah S, Nordin N, Abdullah NH, et al.
    BMC Public Health, 2019 Dec 30;19(1):1754.
    PMID: 31888561 DOI: 10.1186/s12889-019-8113-2
    BACKGROUND: Measurement of breast cancer burden and identification of its influencing factors help in the development of public health policy and strategy against the disease. This study aimed to examine the variability of the excess mortality of female breast cancer patients in the North East Region of Peninsular Malaysia.

    METHODS: This retrospective cohort study was conducted using breast cancer data from the Kelantan Cancer Registry between 2007 and 2011, and Kelantan general population mortality data. The breast cancer cases were followed up for 5 years until 2016. Out of 598 cases, 549 cases met the study criteria and were included in the analysis. Modelling of excess mortality was conducted using Poisson regression.

    RESULTS: Excess mortality of breast cancer varied according to age group (50 years old and below vs above 50 years old, Adj. EHR: 1.47; 95% CI: 1.31, 4.09; P = 0.004), ethnicity (Malay vs non-Malay, Adj. EHR: 2.31; 95% CI: 1.11, 1.96; P = 0.008), and stage (stage III and IV vs. stage I and II, Adj. EHR: 5.75; 95% CI: 4.24, 7.81; P 

    Matched MeSH terms: Breast Neoplasms/mortality*; Breast Neoplasms/therapy
  8. Liew AC, Peh KK, Tan BS, Zhao W, Tangiisuran B
    Support Care Cancer, 2019 Dec;27(12):4515-4524.
    PMID: 30911917 DOI: 10.1007/s00520-019-04724-1
    PURPOSE: This observational study aimed to compare the outcome and health-related quality of life (HRQOL) amongst breast cancer patients using Chinese herbal medicine (CHM) and those not using CHM during chemotherapy.

    METHODS: A prospective, non-randomised longitudinal study was conducted in two government integrated hospitals over an 8-month period. Early-stage breast cancer patients who were (1) either already using complementary and alternative medicine (CAM) or not and (2) who were on a regime of 5-fluorouracil, epirubicin, and cyclophosphamide were included in the study. Patients who agreed to receive CHM were assigned to receive individualised CHM prescriptions deemed suitable for the individual at a particular time. Those who were not willing to take Chinese herbal medicines (CHM) were assigned to the non-CHM control group. Blood profile and chemotherapy-induced AE were recorded whilst HRQOL assessment was done using the EORTC QLQ-C30 questionnaire on first, third, and sixth cycles.

    RESULTS: Forty-seven patients [32 female vs. 1 male, p = 0.31; mean year of age: 52.2(SD = 7.6), p = 0.28)}] were recruited during the study period. Demographics of both groups were comparable. Fifty percent of respondents reported using some kind of CAM before chemotherapy. Diet supplements (40.6%) were the most common CAM used by the respondents. The study showed that patients using CHM had significantly less fatigue (p = 0.012), nausea (p = 0.04), and anorexia (p = 0.005) during chemotherapy. There were no significant differences in patients' HRQOL (p = 0.79). There were no AEs reported during the study.

    CONCLUSION: The use of CHM as an adjunct treatment with conventional chemotherapy have been shown to reduce fatigue, nausea, and anorexia in breast cancer patients but did not reduce chemotherapy-associated hematologic toxicity. The sample size of this study was not powered to assess the significance of HRQOL between two groups of patients.

    Matched MeSH terms: Breast Neoplasms/drug therapy*; Breast Neoplasms/pathology
  9. Chaudhry GE, Jan R, Naveed Zafar M, Mohammad H, Muhammad TST
    Asian Pac. J. Cancer Prev., 2019 Dec 01;20(12):3555-3562.
    PMID: 31870094 DOI: 10.31557/APJCP.2019.20.12.3555
    OBJECTIVE: Breast cancer is the most frequently diagnosed cancer worldwide. The main objective of the present study was to evaluate the cytotoxic effects and mechanism of cell death induced by the extract and fractions of Vitex rotundifolia (leaves) in breast cancer cell line, T-47D.

    METHODS: The cytotoxicity activity was measured using MTS assay. The mode of cell death was analysed by early (phosphatidylserine externalization) and late apoptosis (DNA fragmentation). The caspases 8, 9, 3/7 and apoptotic proteins bax, bcl-2 study were done by western blot and ELISA method.

    RESULTS: The methanol extract was found to inhibit 50% growth of T-47D cells at the concentration of 79.43µg/ml respectively after 72hr. From seven fractions, fraction F1, F2 and F3 produced cytotoxicity effects in T-47D cell line with IC50 (72hr) < 30µg/ml. The results obtained by Annexin V/PI apoptosis detection assay and TUNEL assay suggest that active fractions of  Vitex rotundifolia induced early and late apoptosis (DNA fragmentation) in T-47D cell line. Moreover, western blot analysis and Caspase GloTM luminescent assay demonstrated that fractions F2 and F3 triggered apoptotic cell death via activation of caspases -8, -9 and -3/7 and up-regulation of  Bax and down-regulation of Bcl-2 protein.  Furthermore, chemical profiling confirms the presence of potential metabolites (vitexicarpin) in fractions of Vitex rotundifolia.

    CONCLUSION: Thus, the present study suggests the remarkable potential of active metabolites in fractions of Vitex rotundifolia as future cancer therapeutic agent for the treatment of breast cancer.
    .

    Matched MeSH terms: Breast Neoplasms/drug therapy*; Breast Neoplasms/pathology
  10. Sharma D, Kumar S, Narasimhan B, Ramasamy K, Lim SM, Shah SAA, et al.
    BMC Chem, 2019 Dec;13(1):46.
    PMID: 31384794 DOI: 10.1186/s13065-019-0564-0
    To combat the antimicrobial and anticancer drug resistance by pathogens and cancerous cells, efforts has been made to study the pharmacological activities of newly synthesized N-(4-(4-bromophenyl)thiazol-2-yl)-2-chloroacetamide derivatives. The molecular structures of the synthesized derivatives were confirmed by their physicochemical properties and spectroanalytical data (NMR, IR and elemental). The synthesized compounds were evaluated for their in vitro antimicrobial activity against bacterial (Gram positive and Gram negative) and fungal species using turbidimetric method and anticancer activity against oestrogen receptor positive human breast adenocarcinoma cancer cell line (MCF7) by Sulforhodamine B (SRB) assay. Molecular docking studies were carried out to study the binding mode of active compounds with receptor using Schrodinger v11.5. The antimicrobial activity results revealed that compounds d1, d2 and d3 have promising antimicrobial activity. Anticancer screening results indicated that compounds d6 and d7 were found to be the most active ones against breast cancer cell line. Furthermore, the molecular docking study demonstrated that compounds d1, d2, d3, d6 and d7 displayed good docking score within binding pocket of the selected PDB ID (1JIJ, 4WMZ and 3ERT) and has the potential to be used as lead compounds for rational drug designing.
    Matched MeSH terms: Breast Neoplasms
  11. Mohamad Hanif EA
    Mol. Biol. Rep., 2019 Dec;46(6):6617-6624.
    PMID: 31552595 DOI: 10.1007/s11033-019-05079-w
    FEC chemo-resistance in triple negative breast cancer (TNBC) remains a challenge. Therefore it is crucial to determine the right treatment regime by understanding molecular mechanisms of driver regulators involved in the progression of TNBCs. This study aims to understand SETD1A mechanisms in TNBC development in two TNBC cell lines. SETD1A was transiently transfected in MDA-MB-468 (FEC good prognosis) and Hs578T (FEC poor prognosis). Regulation of potential targets miR205, EMT marker ZEB1 and LRG1 and proliferative marker Ki-67 were tested by RqPCR to elucidate SETD1A interactions. This study displayed significant recovery of miR205 with SETD1A depletion and reduction of ZEB1 in MDA-MB-468. However, ZEB1 remained unchanged in Hs578T indicating ZEB1 regulation may be outcompeted by other mechanisms associated with aggressive cell line characteristics and the expression of endogenous ZEB1 was relatively high in Hs578T. Elevation of LRG1 and declined Ki-67 were observed by SETD1A knocked down. Enhanced expression was observed by LRG1 in Hs578T and not in MDA-MB-468 suggesting LRG1 contributed to distinct poor FEC outcome in TNBCs. The underlying mechanism of SETD1A in miR205/ZEB1/Ki-67/LRG1 axis needs further evaluation. Whether abrogation of the pathway is indeed associated with transcriptional or post-transcriptional activation in TNBC cell lines models, clearly validation in clinical samples is warranted to achieve its prognostic and therapeutic values in TNBCs.
    Matched MeSH terms: Triple Negative Breast Neoplasms/genetics*
  12. Mohamad NE, Abu N, Yeap SK, Alitheen NB
    Integr Cancer Ther, 2019 11 23;18:1534735419880258.
    PMID: 31752555 DOI: 10.1177/1534735419880258
    Background: This study aimed to evaluate the antitumor enhancing effect of bromelain consumption on 4T1-challenged mice treated with cisplatin. Methods: Mice challenged with 4T1 triple-negative breast cancer cells received water, bromelain, cisplatin, or bromelain + cisplatin treatment for 28 days. Tumor size was measured, and lung metastasis was evaluated by clonogenic assay. Expression of tumor inflammatory genes of the harvested tumor was quantified by polymerase chain reaction array and ELISA (enzyme-linked immunosorbent assay). Results: All treatments significantly reduced the size of tumor and lung metastasis, with combination treatment showing the best effect. Also, bromelain alone and combination treatment showed downregulation of the expression of tumor inflammatory genes (Gremlin [GREM1], interleukin 1β [IL-1β], interleukin-4 [IL-4], nuclear factor κB subunit 1 [NFκB1], and prostaglandin-endoperoxide synthase 2 [PTGS2]), tumor nitric oxide level, and serum IL-1β, and IL-4 levels. On the other hand, cisplatin treatment increased the expression of selected inflammatory markers. Conclusion: This study suggests that bromelain treatment could potentiate the antitumor effect of cisplatin on triple-negative breast cancer 4T1 cells through modulating the tumor environmental inflammation.
    Matched MeSH terms: Breast Neoplasms/drug therapy*; Breast Neoplasms/metabolism
  13. Thakur V, Kutty RV
    J. Exp. Clin. Cancer Res., 2019 Oct 28;38(1):430.
    PMID: 31661003 DOI: 10.1186/s13046-019-1443-1
    Triple-negative breast cancer (TNBC) is the most complex and aggressive type of breast cancer encountered world widely in women. Absence of hormonal receptors on breast cancer cells necessitates the chemotherapy as the only treatment regime. High propensity to metastasize and relapse in addition to poor prognosis and survival motivated the oncologist, nano-medical scientist to develop novel and efficient nanotherapies to solve such a big TNBC challenge. Recently, the focus for enhanced availability, targeted cellular uptake with minimal toxicity is achieved by nano-carriers. These smart nano-carriers carrying all the necessary arsenals (drugs, tracking probe, and ligand) designed in such a way that specifically targets the TNBC cells at site. Articulating the targeted delivery system with multifunctional molecules for high specificity, tracking, diagnosis, and treatment emerged as theranostic approach. In this review, in addition to classical treatment modalities, recent advances in nanotheranostics for early and effective diagnostic and treatment is discussed. This review highlighted the recently FDA approved immunotherapy and all the ongoing clinical trials for TNBC, in addition to nanoparticle assisted immunotherapy. Futuristic but realistic advancements in artificial intelligence (AI) and machine learning not only improve early diagnosis but also assist clinicians for their workup in TNBC. The novel concept of Nanoparticles induced endothelial leakiness (NanoEL) as a way of tumor invasion is also discussed in addition to classical EPR effect. This review intends to provide basic insight and understanding of the novel nano-therapeutic modalities in TNBC diagnosis and treatment and to sensitize the readers for continue designing the novel nanomedicine. This is the first time that designing nanoparticles with stoichiometric definable number of antibodies per nanoparticle now represents the next level of precision by design in nanomedicine.
    Matched MeSH terms: Triple Negative Breast Neoplasms/pathology; Triple Negative Breast Neoplasms/therapy*
  14. Mutazah R, Hamid HA, Mazila Ramli AN, Fasihi Mohd Aluwi MF, Yusoff MM
    Food Chem. Toxicol., 2019 Oct 15.
    PMID: 31626839 DOI: 10.1016/j.fct.2019.110869
    Clinacanthus nutans has attracted Malaysian public interest due to its high medicinal value in the prevention of cancer. Currently, the specific compound or compounds giving rise to the anticancer potential of C. nutans has not been investigated thoroughly. The extraction was carried out by MeOH at room temperature using the powdered bark of C. nutans, while chromatography was carried out on a silica gel RP-18 column using the crude methanolic extract. Six fractions collected from column chromatography were evaluated by MTT assay against two breast cancer cell lines: MDA-MB-231 and MCF-7. Amongst the fractions, A12 and A17 were shown to exhibit the highest activity. Two sulphur-containing compounds, viz., entadamide C (1) and clinamide D (2), were isolated from these fractions. Molecular docking simulation studies revealed that entadamide C and clinamide D could bind favourably to the caspase-3 binding site with the binding energy of -4.28 kcal/mol and -4.84 kcal/mol, respectively. This study provides empirical evidence for the presence of sulphur-containing compounds in the leaves of C. nutans that displayed anticancer effects which explains its ethnomedicinal application against breast cancer. The docking simulation study showed that both compounds could serve as important templates for future drug design and development.
    Matched MeSH terms: Breast Neoplasms
  15. Loh HY, Norman BP, Lai KS, Rahman NMANA, Alitheen NBM, Osman MA
    Int J Mol Sci, 2019 Oct 06;20(19).
    PMID: 31590453 DOI: 10.3390/ijms20194940
    MicroRNAs (miRNAs) are small non-coding RNA molecules which function as critical post-transcriptional gene regulators of various biological functions. Generally, miRNAs negatively regulate gene expression by binding to their selective messenger RNAs (mRNAs), thereby leading to either mRNA degradation or translational repression, depending on the degree of complementarity with target mRNA sequences. Aberrant expression of these miRNAs has been linked etiologically with various human diseases including breast cancer. Different cellular pathways of breast cancer development such as cell proliferation, apoptotic response, metastasis, cancer recurrence and chemoresistance are regulated by either the oncogenic miRNA (oncomiR) or tumor suppressor miRNA (tsmiR). In this review, we highlight the current state of research into miRNA involved in breast cancer, with particular attention to articles published between the years 2000 to 2019, using detailed searches of the databases PubMed, Google Scholar, and Scopus. The post-transcriptional gene regulatory roles of various dysregulated miRNAs in breast cancer and their potential as therapeutic targets are also discussed.
    Matched MeSH terms: Breast Neoplasms/genetics*
  16. Chan JY, Ahmad Kayani AB, Md Ali MA, Kok CK, Ramdzan Buyong M, Hoe SLL, et al.
    Electrophoresis, 2019 10;40(20):2728-2735.
    PMID: 31219180 DOI: 10.1002/elps.201800442
    This paper presents the development and experimental analysis of a curved microelectrode platform for the DEP deformation of breast cancer cells (MDA-MB-231). The platform is composed of arrays of curved DEP microelectrodes which are patterned onto a glass slide and samples containing MDA-MB-231 cells are pipetted onto the platform's surface. Finite element method is utilised to characterise the electric field gradient and DEP field. The performance of the system is assessed with MDA-MB-231 cells in a low conductivity 1% DMEM suspending medium. We applied sinusoidal wave AC potential at peak to peak voltages of 2, 5, and 10 Vpp at both 10 kHz and 50 MHz. We observed cell blebbing and cell shrinkage and analyzed the percentage of shrinkage of the cells. The experiments demonstrated higher percentage of cell shrinkage when cells are exposed to higher frequency and peak to peak voltage electric field.
    Matched MeSH terms: Breast Neoplasms/pathology*
  17. Yang Y, Shu X, Shu XO, Bolla MK, Kweon SS, Cai Q, et al.
    EBioMedicine, 2019 Oct;48:203-211.
    PMID: 31629678 DOI: 10.1016/j.ebiom.2019.09.006
    BACKGROUND: We previously conducted a systematic field synopsis of 1059 breast cancer candidate gene studies and investigated 279 genetic variants, 51 of which showed associations. The major limitation of this work was the small sample size, even pooling data from all 1059 studies. Thereafter, genome-wide association studies (GWAS) have accumulated data for hundreds of thousands of subjects. It's necessary to re-evaluate these variants in large GWAS datasets.

    METHODS: Of these 279 variants, data were obtained for 228 from GWAS conducted within the Asian Breast Cancer Consortium (24,206 cases and 24,775 controls) and the Breast Cancer Association Consortium (122,977 cases and 105,974 controls of European ancestry). Meta-analyses were conducted to combine the results from these two datasets.

    FINDINGS: Of those 228 variants, an association was observed for 12 variants in 10 genes at a Bonferroni-corrected threshold of P breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health.

    Matched MeSH terms: Breast Neoplasms/genetics*; Breast Neoplasms/epidemiology*
  18. Global Burden of Disease Cancer Collaboration, Fitzmaurice C, Abate D, Abbasi N, Abbastabar H, Abd-Allah F, et al.
    JAMA Oncol, 2019 Sep 27.
    PMID: 31560378 DOI: 10.1001/jamaoncol.2019.2996
    Importance: Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data.

    Objective: To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning.

    Evidence Review: We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence.

    Findings: In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs).

    Conclusions and Relevance: The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.
    Matched MeSH terms: Breast Neoplasms
  19. Dinesh BJ, Hayati F, Azizan N, Abdul Rashid NF
    BMJ Case Rep, 2019 Sep 18;12(9).
    PMID: 31537599 DOI: 10.1136/bcr-2019-231516
    Florid papillomatosis (FP) of the nipple, or nipple adenoma, is a rare breast tumour, affecting middle-aged group population. A 46-year-old woman presented to us with a cauliflower-like FP of the right nipple with no blood stained discharge or breast lump. FP can be mistaken clinically for Paget's disease and occasionally misinterpreted as invasive ductal or intraductal carcinoma. Extensive intervention, correct diagnosis and prompt treatment are essential. Any breast pathology requires triple assessment including FP of the nipple. Once the diagnosis of ductal carcinoma is excluded, simple complete excision can be undertaken. This is to ensure complete obliteration of disease recurrence and preservation of cosmetic result. We discuss the pathology and psychosocial aspects of FP.
    Matched MeSH terms: Breast Neoplasms/pathology*; Breast Neoplasms/surgery*
  20. Lah ZMANH, Ahmad SAA, Zaini MS, Kamarudin MA
    J Pharm Biomed Anal, 2019 Sep 10;174:608-617.
    PMID: 31265987 DOI: 10.1016/j.jpba.2019.06.024
    A facile electrochemical sandwich immunosensor for the detection of a breast cancer biomarker, the human epidermal growth factor receptor 2 (HER2), was designed, using lead sulfide quantum dots-conjugated secondary HER2 antibody (Ab2-PbS QDs) as a label. Using Ab2-PbS QDs in the development of electrochemical immunoassays leads to many advantages such as straightforward synthesis and well-defined stripping signal of Pb(II) through acid dissolution, which in turn yields better sensing performance for the sandwiched immunosensor. In the bioconjugation of PbS QDs, the available amine and hydroxyl groups from secondary anti-HER2 and capped PbS QDs were bound covalently together via carbonyldiimidazole (CDI) acting as a linker. In order to quantify the biomarker, SWV signal was obtained, where the Pb2+ ions after acid dissolution in HCl was detected. The plated mercury film SPCE was also detected in situ. Under optimal conditions, HER2 was detected in a linear range from 1-100 ng/mL with a limit of detection of 0.28 ng/mL. The measures of satisfactory recoveries were 91.3% to 104.3% for the spiked samples, displaying high selectivity. Therefore, this method can be applied to determine HER2 in human serum.
    Matched MeSH terms: Breast Neoplasms/blood
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