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1.
Nat Commun ; 11(1): 3833, 2020 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737321

RESUMO

Polygenic risk scores (PRS) have been shown to predict breast cancer risk in European women, but their utility in Asian women is unclear. Here we evaluate the best performing PRSs for European-ancestry women using data from 17,262 breast cancer cases and 17,695 controls of Asian ancestry from 13 case-control studies, and 10,255 Chinese women from a prospective cohort (413 incident breast cancers). Compared to women in the middle quintile of the risk distribution, women in the highest 1% of PRS distribution have a ~2.7-fold risk and women in the lowest 1% of PRS distribution has ~0.4-fold risk of developing breast cancer. There is no evidence of heterogeneity in PRS performance in Chinese, Malay and Indian women. A PRS developed for European-ancestry women is also predictive of breast cancer risk in Asian women and can help in developing risk-stratified screening programmes in Asia.


Assuntos
Neoplasias da Mama/diagnóstico , Neoplasias da Mama/genética , Herança Multifatorial , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Ásia/epidemiologia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/etnologia , Estudos de Casos e Controles , Europa (Continente)/epidemiologia , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Pessoa de Meia-Idade , Razão de Chances , Prognóstico , Risco
2.
Clin Breast Cancer ; 20(5): 371-376, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32605812

RESUMO

Previous reports have suggested that breast cancer is more common among flight attendants than that in the general population. Constant exposure to cosmic radiation and circadian disruption are postulated to be the culprits of the problem. A systematic review was performed by 2 independent reviewers with predefined search strategy, in line with the PRISMA protocol. A total of 43 studies were identified using the preset keywords defined in the study protocol. After excluding irrelevant papers, 12 studies were included for pooled analysis. Ten studies evaluated the breast cancer prevalence in flight attendants, whereas 3 studies evaluated the breast cancer-related deaths. Pooled analysis found that, of the 45,111 flight attendants censored, 1061 (2.35%) had breast cancer. The standardized prevalence ratios were 1.08 (95% confidence interval [CI], 0.37-1.59) and 1.09 (95% Cl, 0.37-1.60), respectively, when compared with the American and European general population. Pooled analysis of the 3 studies on breast cancer mortality found that, of the 44,508 flight attendants censored, 139 (0.32%) had breast cancer-related mortality. Standardized mortality ratios to the American/European general population were 1.8 (95% CI, 0.63-4.25) and 1.3 (95% CI, 0.47-3.15), respectively. A review of the available literature indicates that there is insufficient evidence to suggest an association between cosmic irradiation, circadian disruption, and breast cancer in flight attendants. Breast cancer prevalence and mortality among flight attendants are comparable with that of the general population.

3.
Clin Breast Cancer ; 20(5): 402-407, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32665188

RESUMO

INTRODUCTION: Immediate breast reconstruction offers cosmetic and psychological advantages post-mastectomy. There are various options of reconstruction, and this study aims to evaluate the associated complications. PATIENTS AND METHODS: This is a single-center retrospective study analyzing data from January 1, 2008 to December 31, 2017 for immediate breast reconstruction procedures post-mastectomy performed at an academic breast unit. Procedures included expander and implant insertion, latissimus dorsi, pedicle transverse rectus abdominis musculocutaneous (TRAM), free TRAM, and deep inferior epigastric perforator. Complications and reoperative complications (defined as those requiring a reoperation within the first 30-day period), and associated risk factors were investigated using separate logistic regressions, and odds ratios (ORs) were calculated. RESULTS: A total of 243 post-mastectomy immediate breast reconstruction procedures and complications rates were analyzed. The overall complication rate was 27.6%, comprised mainly of reconstruction-specific complications such as post-TRAM hernia or bulges, fat necrosis, and implant capsular contracture and leakage. The rate of reoperative complications was relatively low at 6.6%. The flap failure rate was similar between expander/implant reconstruction and autologous reconstruction methods at 3.3% and 5.6%, respectively (P = .60). Logistic regression identified significantly higher risks associated with diabetes mellitus (OR, 5.21; P = .022), obesity (OR, 5.80; P = .016), and free pedicle autologous reconstruction (OR, 3.975; P = .046) for reoperative complications. CONCLUSION: Different methods of immediate breast reconstruction post-mastectomy are feasible and safe. However, patient variables and procedure choice should be taken into consideration when counseling patients on reconstructive options, as they are strong predictors for postoperative complications.

4.
Pediatr Res ; 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32634817

RESUMO

BACKGROUND: We investigated whether plasma high-sensitivity cardiac troponin T (hs-cTnT) and circulating heart-associated microRNA (miRs) are increased in children with leukaemias during anthracycline-based chemotherapeutic treatment. METHODS: In vitro human pluripotent stem cell (hPSC)-derived cardiomyocyte model showed that miR-1, miR-133a, miR-208a, miR-208b, and miR-499 are released from cells into culture medium in a time- and dose-dependent manner on doxorubicin exposure. Left ventricular (LV) myocardial deformation and circulating heart-associated miRs and plasma hs-cTnT during and after completion of chemotherapy were determined in 40 children with newly diagnosed acute leukaemia. RESULTS: Significant reduction of LV global longitudinal strain and strain rates were found within 1 week after completion of anthracycline therapy in the induction phase of treatment (all p < 0.05). Hs-cTnT level peaked and miR-1 increased significantly at this time point. Log-transformed hs-cTnT correlated negatively with LV global systolic longitudinal strain (r = -0.38, p < 0.001). Receiver operating characteristic analysis revealed that area under the curve for changes in plasma hs-cTnT from baseline and plasma miR-1 levels in detecting a reduction in ≥20% of global longitudinal strain were respectively 0.62 (95% CI 0.38-0.87) and 0.62 (95% CI 0.40-0.84). CONCLUSION: Plasma hs-cTnT and circulating miR-1 may be useful markers of myocardial damage during chemotherapy in children with leukaemias. IMPACT: Heart-associated miRNAs including miR-1, miR-133a, miR-208a, miR-208b,and miR-499 were increased in the culture medium upon exposure of hPSC-derived cardiomyocytes to doxorubicin.Only miR-1 increased significantly during anthracycline-based therapy in paediatric leukaemic patients.In paediatric leukaemic patients, plasma hs-cTnT and circulating level of miR-1 showed the most significant increase within 1 week after completion of anthracycline therapy in the induction treatment phase.The study provides the first evidence of progressive increase in circulating miR-1 and plasma hs-cTnT levels during the course of anthracycline-based therapy in children with leukaemias, with hs-cTnT level also associated with changes in LV myocardial deformation.

5.
Cancer Treat Res Commun ; 24: 100182, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32534410

RESUMO

AIMS: Breast cancer onset is known to be younger in China when compared to many westernized countries, the reason remains unknown. This study aims to evaluate the clinical and pathological characteristics of young breast cancer in Hong Kong and Shenzhen, China. METHODS: This is a 5-year retrospective review of a prospectively-maintained region-wide database. Patients treated in Hong Kong and Shenzhen between 2013 and 2017 were analysed. RESULTS: 1610 breast cancer patients were identified for analysis, 1108 patients were from Hong Kong and 502 patients were from Shenzhen. Median age of breast cancer onset was 60 years old in Hong Kong (Range 21 - 103), while that in Shenzhen was 46 years old (Range 23 - 85). 59 (5.3%) patients from the Hong Kong cohort were younger than 40 years old at the age of diagnosis (i.e. young breast cancer), comparing to 152 (30.3%) patients from the Shenzhen cohort (p < 0.0001). There were more nulliparity, positive family history and use of exogenous hormones in young breast cancer patients in Hong Kong (p = 0.0043, < 0.0001 and 0.0022). Pathological characteristics were however comparable between the two cohorts, apart from being more triple negative breast cancers in young breast cancer patients in Hong Kong (p = 0.05). CONCLUSION: Age of onset of breast cancer tends to be younger in mainland China than in Hong Kong. Personal and familial risk factors were not significantly different. Environmental factor may play an important role.

6.
Biomolecules ; 10(5)2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32365569

RESUMO

It is well-established that tumor-associated macrophages (TAMs) play an important role in breast cancer development. Accumulating evidence suggested that human cathelicidin antimicrobial protein (CAMP), which is mainly expressed in host defense cells such as macrophages, is crucial not only in combating microorganisms but also promoting tumor growth. Here we report the interaction of CAMP with TAMs in breast cancer. CAMP expression was upregulated in cancer tissues and in the circulation of breast cancer patients. Surgical removal of tumor decreased CAMP peptide serum level. Knockdown of CAMP decreased cell proliferation and migration/invasion ability in breast cancer cells. CAMP expression was altered during macrophage M1/M2 polarization and was expressed predominantly in M2 phenotype. In addition, breast cancer cells co-cultured with macrophages upregulated CAMP expression and also increased cancer cell viability. Xenograft tumors reduced significantly upon CAMP receptor antagonist treatment. Our data implicated that CAMP confers an oncogenic role in breast cancer and plays an important role in the tumor microenvironment between TAMs and breast cancer cells, and blocking the interaction between them would provide a novel therapeutic option for this malignant disease.

7.
Brain Behav Immun ; 88: 88-96, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32305573

RESUMO

Chemotherapy causes various side effects, including cognitive impairment, known as 'chemobrain'. In this study, we determined whether a novel acupuncture mode called electroacupuncture trigeminal nerve stimulation plus body acupuncture (EA/TNS + BA) could produce better outcomes than minimum acupuncture stimulation (MAS) as controls in treating chemobrain and other symptoms in breast cancer patients. In this assessor- and participant-blinded, randomized controlled trial, 93 breast cancer patients under or post chemotherapy were randomly assigned to EA/TNS + BA (n = 46) and MAS (n = 47) for 2 sessions per week over 8 weeks. The Montreal Cognitive Assessment (MoCA) served as the primary outcome. Digit span test was the secondary outcomes for attentional function and working memory. The quality of life and multiple functional assessments were also evaluated. EA/TNS + BA treated group had much better performance than MAS-treated group on reverse digit span test at Week 2 and Week 8, with medium effect sizes of 0.53 and 0.48, respectively, although no significant differences were observed in MoCA score and prevalence of chemobrain between the two groups. EA/TNS + BA also markedly reduced incidences of diarrhoea, poor appetite, headache, anxiety, and irritation, and improved social/family and emotional wellbeing compared to MAS. These results suggest that EA/TNS + BA may have particular benefits in reducing chemotherapy-induced working memory impairment and the incidence of certain digestive, neurological, and distress-related symptoms. It could serve as an effective intervention for breast cancer patients under and post chemotherapy (trial registration: https://www.clinicaltrials.gov: NCT02457039).

8.
Clin Breast Cancer ; 20(3): e244-e250, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32144082

RESUMO

Similar to mastectomy, breast conserving surgery (BCS) is currently the reference standard of surgical treatment of sporadic breast cancer in patients. However, its oncologic safety for BRCA mutation carriers has remained controversial. Thus, we conducted a systematic review to critically evaluate the best evidence from reported studies. A comprehensive search was performed of the Medline, EMBASE, CINAHL, and Cochrane databases using a predefined strategy. The retrieved studies were independently screened and rated for relevance. Data were extracted for qualitative synthesis in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses protocol for systematic reviews. No randomized controlled trial has directly compared BCS and mastectomy for BRCA mutation carriers. Of the 18 studies included in our review, the pooled analysis of overall survival at 5, 10, and 15 years were comparable between BCS and mastectomy (88.7%, 89.0% and 83.6% with BCS and 83%, 86.0%, and 83.2% with mastectomy, respectively). However, the pooled ipsilateral breast cancer recurrence rates at 5, 10, and 15 years were higher in the BCS group (8.2%, 15.5%, and 23%, respectively) than in the mastectomy group (3.4%, 4.9%, and 6.4%, respectively). BCS was associated with a greater rate of ipsilateral breast cancer recurrence in BRCA mutation carriers. However, it was not associated with adverse short- and long-term survival outcomes. BCS should be offered as an option to BRCA mutation carriers with proper preoperative counseling.

9.
Cancer Med ; 9(10): 3305-3309, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32167660

RESUMO

INTRODUCTION: Male breast cancer is uncommon, delay in seeking medical attention often results in late presentation and poor prognosis. METHODS: Retrospective review of a prospectively maintained database was performed. Patients who were still having regular follow-up were contacted for telephone interview. RESULTS: In this study, 56 male breast cancer patients were treated in our center from January 1998 to December 2018, accounting for 0.88% of all breast cancers treated during the same period of time. Median age of onset was 61 years old (Range: 33-95). In this study, 6 (10.7%) patients presented with distant metastasis at the time of diagnosis and received palliative systemic treatment only. And, 50 patients were surgically treated and all had mastectomy. Axillary dissection was performed in 36 (72%) patients, while sentinel node biopsy was performed in 14 (28%) patients. Median tumor size was 23 mm (2-100 mm). A Majority were diagnosed with invasive carcinoma (NOS), while 38 (67.8%) patients were node positive.Here 36 (64.3%) patients were alive at the time of the study, 31 (86.1%) patients responded to the telephone interview. More than 90% of our patients expressed various degrees of embarrassment at the time of breast symptom onset. Similarly, more than 90% of these patients experienced embarrassment while waiting in the breast center with predominant female patients. Most patients (N = 26) were not aware that breast cancer can occur in men prior to the diagnosis. Median duration from symptoms to the first medical consultation was 12.4 months (1-120 months). CONCLUSION: Male breast cancer is rare and patients usually present late, Lack of knowledge, public education, and embarrassment are the important related factors.

10.
Nat Commun ; 11(1): 1217, 2020 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-32139696

RESUMO

Known risk variants explain only a small proportion of breast cancer heritability, particularly in Asian women. To search for additional genetic susceptibility loci for breast cancer, here we perform a meta-analysis of data from genome-wide association studies (GWAS) conducted in Asians (24,206 cases and 24,775 controls) and European descendants (122,977 cases and 105,974 controls). We identified 31 potential novel loci with the lead variant showing an association with breast cancer risk at P < 5 × 10-8. The associations for 10 of these loci were replicated in an independent sample of 16,787 cases and 16,680 controls of Asian women (P < 0.05). In addition, we replicated the associations for 78 of the 166 known risk variants at P < 0.05 in Asians. These findings improve our understanding of breast cancer genetics and etiology and extend previous findings from studies of European descendants to Asian women.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Neoplasias da Mama/genética , Grupo com Ancestrais do Continente Europeu/genética , Loci Gênicos , Predisposição Genética para Doença , Feminino , Humanos , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Receptores Estrogênicos/metabolismo , Fatores de Risco
11.
Breast Cancer ; 27(4): 607-612, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32008216

RESUMO

BACKGROUND: Microdochectomy is the gold-standard for definitive diagnosis for pathological nipple discharge (PND); however, problem of over-treating exists since majority of PND are self-limiting and due to benign causes. Ductoscopy may assist diagnosis, and triage patients for intervention or expectant management. This study aimed to evaluate if ductoscopy could reduce unnecessary microdochectomy but not compromising the diagnosis of malignancy. METHOD: A multicenter, retrospective study was conducted in consecutive patients of PND without a suspected malignancy on routine diagnostic evaluation. Ductoscopy was performed with attempts to remove intraductal lesions if they were found. Microdochectomy was carried out if there were positive intraductal lesions, but failed endoscopic extraction, or failed ductoscopy and persistent PND. Efficacy of ductoscopy was determined by cannulation success rate, number of avoided surgery and number of missed malignancy. RESULTS: In a 3-year period between 2016 and 2018, a total of 223 ductoscopy were performed and 94.2% had successful cannulation. Within such, 59.5% (N = 125) had intraductal mass identified, and 82 microdochectomy were carried out. The final histology showed 15 malignancy, making the overall malignancy rate 6.7%. Ductoscopy successful and negative patients (N = 85, 37.8%) were triaged for surveillance and the malignancy rate is 0% in a median follow-up of 2 years; hence, microdochectomy was avoided. CONCLUSION: PND with non-suspicious conventional imaging and negative ductoscopy have rare malignancy rate which makes subsequent microdochectomy unnecessary. However, intraductal mass in ductoscopy is a predictor for malignancy so definitive histology diagnosis is mandatory.

12.
J Mol Diagn ; 22(4): 544-554, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32068069

RESUMO

Differences in the mutation spectrum across ethnicities suggest the importance of identifying genes in addition to common high penetrant genes to estimate the associated breast cancer risk in China. A total of 1338 high-risk breast cancer patients who tested negative for germline BRCA1, BRCA2, TP53, and PTEN mutations between 2007 and 2017 were selected from the Hong Kong Hereditary Breast Cancer Family Registry. Patient samples were subjected to next-generation DNA sequencing using a multigene panel (Color Genomics). All detected pathogenic variants were validated by bidirectional DNA sequencing. The sequencing data were coanalyzed by a bioinformatics pipeline developed in-house. Sixty-one pathogenic variants (4.6%) were identified in this cohort in 11 cancer predisposition genes. Most carriers (77.1%) had early onset of breast cancer (age <45 years), 32.8% had family members with breast cancer, and 11.5% had triple-negative breast cancer. The most common mutated genes were PALB2 (1.4%), RAD51D (0.8%), and ATM (0.8%). A total of 612 variants of unknown significance were identified in 494 patients, and 87.4% of the variants of unknown significance were missense mutations. Pathogenic variants in cancer predisposition genes beyond BRCA1, BRCA2, TP53, and PTEN were detected in an additional 4.6% of patients using the multigene panel. PALB2 (1.4%) and RAD51D (0.8%) were the most commonly mutated genes in patients who tested mutation negative by a four-gene panel.

13.
Breast Cancer ; 27(3): 456-463, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31916189

RESUMO

BACKGROUND: Dual HER2 blockade with transtuzumab and pertuzumab is known to be associated with improved oncologic outcome, however, its evidence on the impact of surgical decision remains limited. This study aims to evaluate the efficacy of dual HER2 blockade, when compared to single blockade, in improving breast conservation rate in an Asian cohort. METHODS: Retrospective study was performed on a prospectively-maintained database in our tertiary academic-based hospital, including patients with non-metastatic, HER2-positive breast cancer receiving neoadjuvant systemic therapy (NST) between January 2014 and December 2018. RESULTS: 142 patients were analyzed: 75 received Herceptin (H)-based NST and 67 received H + Pertuzumab (P)-based NST. Before NST, 65 patients (45.8%) were eligible for breast conserving therapy (BCT); and this increased to 103 (72.5%) after NST. Thirty-seven out of 75 patients (49.3%) who were deemed not BCT candidate converted to BCT-eligible after NST. More than half of the patients who were BCT-eligible opted for mastectomy. PH-based comparing to H-based NST did not differ significantly in BCT rate (35.5% vs 32.0%, P = 0.72); but there was a trend of increase in conversion to BCT-eligible rate (43.9-52.8%), reducing tumor diameter (40.2-53.1% reduction) and volume (69.5-80.0% reduction). CONCLUSION: The conversion rate from mastectomy to BCT-eligible was more than 50% after dual target therapy, which was slightly higher than single target agent. However the actual BCT rate was not significantly increased, and more than half of the BCT-eligible patients opted for mastectomy.

14.
Int J Cancer ; 146(4): 1042-1051, 2020 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-31396961

RESUMO

Esophageal squamous cell carcinoma (ESCC) occurs with highest frequency in China with over 90% mortality, highlighting the need for early detection and improved treatment strategies. We aimed to identify ESCC cancer predisposition gene(s). Our study included 4,517 individuals. The discovery phase using whole-exome sequencing (WES) included 186 familial ESCC patients from high-risk China. Targeted gene sequencing validation of 598 genes included 3,289 Henan and 1,228 moderate-risk Hong Kong Chinese. A WES approach identified BRCA2 loss-of-function (LOF) mutations in 3.23% (6/186) familial ESCC patients compared to 0.21% (9/4300) in the ExAC East Asians (odds ratio [OR] = 15.89, p = 2.48 × 10-10 ). BRCA2 LOF mutation frequency in the combined Henan cohort has significantly higher prevalence (OR = 10.55, p = 0.0035). Results were independently validated in an ESCC Hong Kong cohort (OR = 10.64, p = 0.022). One Hong Kong pedigree was identified to carry a BRCA2 LOF mutation. BRCA2 inactivation in ESCC was via germline LOF mutations and wild-type somatic allelic loss via loss of heterozygosity. Gene-based association analysis, including LOF mutations and rare deleterious missense variants defined with combined annotation dependent depletion score ≥30, confirmed the genetic predisposition role of BRCA2 (OR = 9.50, p = 3.44 × 10-5 ), and provided new evidence for potential association of ESCC risk with DNA repair genes (POLQ and MSH2), inflammation (TTC39B) and angiogenesis (KDR). Our findings are the first to provide compelling evidence of the role of BRCA2 in ESCC genetic susceptibility in Chinese, suggesting defective homologous recombination is an underlying cause in ESCC pathogenesis, which is amenable to therapeutic options based on synthetic lethality approaches such as targeting BRCA2 with PARP1 inhibitors in ESCC.


Assuntos
Proteína BRCA2/genética , Neoplasias Esofágicas/genética , Carcinoma de Células Escamosas do Esôfago/genética , Genes BRCA2 , Mutação em Linhagem Germinativa , Adulto , Idoso , Grupo com Ancestrais do Continente Asiático/genética , China , Estudos de Coortes , Exoma , Feminino , Predisposição Genética para Doença , Humanos , Perda de Heterozigosidade , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Linhagem , Penetrância
15.
Asian J Surg ; 43(1): 240-243, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31130499

RESUMO

BACKGROUND: Atypical ductal hyperplasia (ADH) is known to be associated with underlying malignant breast conditions. Previous studies have shown that up to 40% of ADH found in core needle biopsy of the breasts had undiagnosed malignant lesions after excision. METHODS: This is a retrospective study on a prospectively maintained database. From 1st January 2005 to 31st December 2014, a total of 262 excision or mastectomy specimens were identified to contain ADH. Clinical, radiological and pathological data were retrieved and analyzed. Correlating factors for the presence of co-existing pre-malignant or malignant conditions were analyzed. Overall survival in patients with or without co-existing malignant breast lesions were evaluated. RESULTS: 95 (36.3%) had co-existing malignant breast lesions within the same specimen. The median age at diagnosis was 49 (Range 17-85). Suspicious breast imaging features (BIRADS 4 or above) and lesions larger than 10 mm on breast imaging were independent risk factor for co-existing malignant pathology (p < 0.001 and 0.005 respectively). After median follow-up interval of 60 months (6-120 months), the overall survival was comparable between the groups of patients having ADH with or without co-existing malignant pathologies (98.2% and 97.9% respectively). CONCLUSION: Co-existing malignant lesions were present in up to 36.3% of the pathology specimens containing ADH, in which its presence could be predicted by pre-operative breast imaging.

16.
Psychooncology ; 29(2): 271-279, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31663187

RESUMO

OBJECTIVE: This longitudinal study mapped distinct trajectories of fear of cancer recurrence (FCR) over 12 months among patients with breast (BC) or colorectal (CRC) cancer, and examined if metacognition, indirectly via attentional bias, intrusive thoughts and avoidance (hallmarks of cognitive attentional syndrome; CAS) predicted FCR trajectory membership. METHODS: Two hundred and seventy BC (n = 163) or CRC (n = 107) patients were assessed at 8-weeks, 3-, 6-, and 12-months postsurgery on a measure of FCR (FCRI-SF). Metacognition (MCQ-30), Intrusive and Avoidant Thoughts (CIES-R) and attentional bias (dot-probe tasks) were assessed at baseline. Latent growth mixture modeling identified FCR trajectories. Fully-adjusted Multinomial Logistic Regression identified whether direct and indirect effects of metacognition through CAS determined FCR trajectory membership. RESULTS: Three distinct FCR trajectories were identified, namely, low-stable (62.4%), high-stable (29.2%), and recovery (8.3%). Negative beliefs about worry, cognitive confidence, and age predicted FCR trajectories (χ2 (6) = 38.31, P<.001). Compared with Low-stable group, Recovery FCR patients held greater Negative beliefs about worry (OR = 1.13, P = .035) and High-stable FCR patients reported poorer Cognitive confidence (OR = 1.12, P = .004). The effect of Negative beliefs about worry was partially mediated by avoidance (ß = .06, 95% CIs 0.03-0.12) and fully mediated by intrusive thoughts (ß = .14, 95% CIs 0.08-0.20). Attentional bias did not predict FCR trajectories. CONCLUSIONS: While most patients experienced low level of FCR, 3 in 10 persistently worried about cancer returning over the first 12-months postsurgery. Modifying metacognitive knowledge to interrupt maladaptive cognitive processing including intrusion and avoidance may be an effective therapeutic intervention for patients at risk of persistent FCR.

17.
EBioMedicine ; 48: 203-211, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31629678

RESUMO

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 < 2·19 × 10-4. The associations for four variants reached P < 5 × 10-8 and have been reported by previous GWAS, including rs6435074 and rs6723097 (CASP8), rs17879961 (CHEK2) and rs2853669 (TERT). The remaining eight variants were rs676387 (HSD17B1), rs762551 (CYP1A2), rs1045485 (CASP8), rs9340799 (ESR1), rs7931342 (CHR11), rs1050450 (GPX1), rs13010627 (CASP10) and rs9344 (CCND1). Further investigating these 10 genes identified associations for two additional variants at P < 5 × 10-8, including rs4793090 (near HSD17B1), and rs9210 (near CYP1A2), which have not been identified by previous GWAS. INTERPRETATION: Though most candidate gene variants were not associated with breast cancer risk, we found 14 variants showing an association. Our findings warrant further functional investigation of these variants. FUND: National Institutes of Health.


Assuntos
Grupo com Ancestrais do Continente Asiático , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Grupo com Ancestrais do Continente Europeu , Predisposição Genética para Doença , Variação Genética , Alelos , Grupo com Ancestrais do Continente Asiático/genética , Caspase 8 , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Genótipo , Humanos , Razão de Chances , Polimorfismo de Nucleotídeo Único , Vigilância da População , Risco
18.
Hepatobiliary Pancreat Dis Int ; 18(5): 452-457, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31474444

RESUMO

BACKGROUND: Survival of patients with breast cancer liver metastasis is very poor. This study aimed to analyze the survival outcome of hepatectomy for this patient population. METHODS: From January 1995 to December 2014, 2522 patients with liver cancer received hepatectomy at our hospital. Twenty-one of them, all female, received the operation for breast cancer liver metastasis. Performance was compared with patients with colorectal liver metastasis treated with hepatectomy after propensity score analysis in a ratio of 1:3. RESULTS: Twenty-one patients received hepatectomy for breast cancer. After propensity score matching, 63 patients who had hepatectomy for colorectal cancer were selected for comparison. There was no significant difference in immediate or short-term outcomes between the two groups of patients in terms of operative time, blood loss and surgical morbidities. All patients with breast cancer had R0 resection. No hospital death occurred. After hepatectomy, the 1-, 3- and 5-year overall survival rates were 100.0%, 58.9% and 58.9% respectively in patients with breast cancer. The 1-, 3- and 5-year overall survival rates were 95.0%, 57.2% and 39.7% respectively in patients with colorectal cancer (P = 0.572). On multivariate analysis, triple negative status was the only independent poor prognostic factor in breast cancer liver metastasis (OR = 6.411; 95% CI: 1.351-30.435; P = 0.019). CONCLUSIONS: Hepatectomy is a safe and effective way of treating breast cancer liver metastasis at experienced centers where multidisciplinary adjuvant treatments are available. It can be considered more frequently as part of the multidisciplinary care for this patient population.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/cirurgia , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , China/etnologia , Neoplasias Colorretais/mortalidade , Feminino , Hepatectomia , Hong Kong/epidemiologia , Humanos , Neoplasias Hepáticas/secundário , Pessoa de Meia-Idade , Pontuação de Propensão , Estudos Retrospectivos , Taxa de Sobrevida , Neoplasias de Mama Triplo Negativas/mortalidade
19.
Surg Oncol ; 31: 46-53, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31536927

RESUMO

Acetylcholine (ACh) was first identified as a classic neuromodulator and transmit signals through two subgroups of receptors, namely muscarinic receptors (mAChRs) and nicotinic receptors (nAChRs). Apart from its well-established physiological role in central nervous system (CNS) and peripheral nervous system (PNS), autonomic nervous system and neuromuscular junction, the widely distributed expression of AChRs in different human organs suggests roles in other biological processes in addition to synaptic transmission. Accumulating evidence revealed that cancer cell processes such as proliferation, apoptosis, angiogenesis and even epithelial-mesenchymal transition (EMT) are mediated by overexpression of AChRs in different kinds of tumors. In breast cancer, α7-nAChR and α9-nAChR were reported to be oncogenic. On the other hand, research on the role of mAChRs in breast cancer tumorgenesis is limited and confined to M3 receptor only. Since AChRs distributed in both CNS and PNS even non-neuronal tissues, there is an urgent need for the development of subtype-specific AChR antagonist which inhibits cancer cell progression with minimal intervention on the normal acetylcholine-regulated system within human body.


Assuntos
Acetilcolina/metabolismo , Neoplasias/patologia , Receptores Colinérgicos/metabolismo , Animais , Transição Epitelial-Mesenquimal , Humanos , Neoplasias/metabolismo , Transdução de Sinais
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