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1.
J Med Genet ; 2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33811135

RESUMO

BACKGROUND: Rare protein-truncating variants (PTVs) in partner and localiser of BRCA2 (PALB2) confer increased risk to breast cancer, but relatively few studies have reported the prevalence in South-East Asian populations. Here, we describe the prevalence of rare variants in PALB2 in a population-based study of 7840 breast cancer cases and 7928 healthy Chinese, Malay and Indian women from Malaysia and Singapore, and describe the functional impact of germline missense variants identified in this population. METHODS: Mutation testing was performed on germline DNA (n=15 768) using targeted sequencing panels. The functional impact of missense variants was tested in mouse embryonic stem cell based functional assays. RESULTS: PTVs in PALB2 were found in 0.73% of breast cancer patients and 0.14% of healthy individuals (OR=5.44; 95% CI 2.85 to 10.39, p<0.0001). In contrast, rare missense variants in PALB2 were not associated with increased risk of breast cancer. Whereas PTVs were associated with later stage of presentation and higher-grade tumours, no significant association was observed with missense variants in PALB2. However, two novel rare missense variants (p.L1027R and p.G1043V) produced unstable proteins and resulted in a decrease in homologous recombination-mediated repair of DNA double-strand breaks. CONCLUSION: Despite genetic and lifestyle differences between Asian and other populations, the population prevalence of PALB2 PTVs and associated relative risk of breast cancer, are similar to those reported in European populations.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33768416

RESUMO

BACKGROUND: A breast cancer polygenic risk score (PRS) comprising 313 common variants reliably predicts disease risk. We examined possible relationships between genetic variation, regulation, and expression to clarify the molecular alterations associated with these variants. METHODS: Genome-wide methylomic variation was quantified (MethylationEPIC) in Asian breast cancer patients (1152 buffy coats from peripheral whole blood). DNA methylation (DNAm) quantitative trait loci (mQTL) mapping was performed for 235 of the 313 variants with minor allele frequencies > 5%. Stability of identified mQTLs (p < 5e-8) across lifetime was examined using a public mQTL database. Identified mQTLs were also mapped to expression quantitative trait loci (eQTLs) in the Genotype-Tissue Expression Project and the eQTLGen Consortium. RESULTS: Breast cancer PRS was not associated with DNAm. A higher proportion of significant cis-mQTLs were observed. Of 822 significant cis-mQTLs (179 unique variants) identified in our dataset, 141 (59 unique variants) were significant (p < 5e-8) in a public mQTL database. Eighty-six percent (121/141) of the matched mQTLs were consistent at multiple time points (birth, childhood, adolescence, pregnancy, middle age, post-diagnosis, or treatment). Ninety-three variants associated with DNAm were also cis-eQTLs (35 variants not genome-wide significant). Multiple loci in the breast cancer PRS are associated with DNAm, contributing to the polygenic nature of the disease. These mQTLs are mostly stable over time. CONCLUSIONS: Consistent results from DNAm and expression data may reveal new candidate genes not previously associated with breast cancer.

4.
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
5.
World J Clin Oncol ; 11(5): 283-293, 2020 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-32728531

RESUMO

BACKGROUND: Invasive lobular carcinomas (ILC) form 5%-10% of breast cancer and rarely show overexpression of human epidermal growth factor receptor 2 (HER2). AIM: To describe the prevalence and prognostic factors of HER2 positive (HER2+) ILC in an Asian population. METHODS: A retrospective review of patients with ILC seen between January 1985 and March 2018 at various SingHealth medical institutions was conducted. Demographic and clinical data were collected from medical records. We examined clinicopathological characteristics and survival in relation to HER2 status. RESULTS: A total of 864 patients were included. Prevalence of HER2 positivity was 10.1% (87 patients). Compared with HER2 negative (HER2-) ILC, HER2+ ILC was associated with a higher proportion of estrogen receptor negative (24.4% vs 5.9%, P < 0.001), progesterone receptor negative (PR-) (40.2% vs 24%, P = 0.002) and grade 3 tumours (Grade 3, 29.0% vs 10.2%, P < 0.001). Overall survival rate was poorer in patients with HER2+ compared to HER2- ILC (56.7% vs 72.9% alive at 10 years; hazard ratio 1.87, 95% confidence interval: 1.21-2.90, P = 0.004). Based on multivariate analysis, negative prognostic factors for overall survival included HER2 positivity, PR negativity, older age, Indian ethnicity and higher tumour stage. CONCLUSION: Prevalence of HER2+ ILC was 10.1%. HER2+ ILC was more likely to have poorer prognostic features such as estrogen receptor negative, PR- and higher tumour grade, and have a poorer survival.

6.
Sci Rep ; 10(1): 1330, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992769

RESUMO

Breast cancer survival has improved with significant progress in treatment and disease management. However, compliance with treatment varies. Treatment guidelines for older patients are unclear. We aim to identify predictors of noncompliance with recommended therapy in a large breast cancer population and assess the impact of noncompliance on survival. Our study included 19,241 non-metastatic female breast cancer patients, of whom 3,158 (16%) died within 10 years post-diagnosis (median survival = 5.8 years). We studied the association between treatment noncompliance and factors with logistic regression, and the impact of treatment noncompliance on survival with a flexible parametric survival model framework. The highest proportion of noncompliance was observed for chemotherapy (18%). Predictors of noncompliance with chemotherapy, radiotherapy and endocrine therapy included age, tumor size, nodal involvement and subtype (except radiotherapy). Factors associated with not receiving surgery included age and subtype. Treatment noncompliance was associated with worse overall survival for surgery (HR: 2.26 [1.80-2.83]), chemotherapy (1.25 [1.11-1.41]), radiotherapy (2.28 [1.94-2.69]) and endocrine therapy (1.70 [1.41-2.04]). Worse survival was similarly observed in older patients for whom guidelines generally do not apply. Our results highlight the importance of following appropriate treatment as recommended by current guidelines. Older patients may benefit from similar recommendations.


Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Ásia/epidemiologia , Neoplasias da Mama/epidemiologia , Terapia Combinada , Gerenciamento Clínico , Feminino , Fidelidade a Diretrizes , Humanos , Pessoa de Meia-Idade , Guias de Prática Clínica como Assunto , Sistema de Registros , Fatores de Risco
7.
Breast Cancer Res Treat ; 177(1): 197-206, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31147984

RESUMO

PURPOSE: This study aimed to identify patterns of relapse after neoadjuvant chemotherapy (NAC) for breast cancer to refine follow-up recommendations. METHODS: Retrospective analysis on 523 breast cancer patients treated with NAC at two public hospitals in Singapore between 2000 and 2014. RESULTS: Majority of patients (71.9%) had locally advanced disease. Median follow-up was 55 months. 5-year recurrence rate was significantly higher in triple negative breast cancer (TNBC) than non-TNBC subtypes (38.4% vs. 29.5%; p = 0.042); 85% of recurrences involved distant sites. Among TNBC and HR (hormone receptor)-/HER2+ subtypes, 97.0% and 95.0% of relapses occurred within 3 years from diagnosis respectively while 10.6% of relapses among HR+ subgroup occurred beyond 5 years. Recurrence risk in high-grade tumours decreased with time. Stage III at diagnosis (hazard ratio = 2.94; p < 0.001), grade 3 tumours (hazard ratio = 2.87; p = 0.018), not achieving pathologic complete response (pCR) (hazard ratio = 8.77; p = 0.003) and not receiving adjuvant radiotherapy (hazard ratio = 3.19; p < 0.001) were independent predictors of inferior recurrence-free survival. Serum CA 15-3 was raised in 49% of patients upon relapse; it correlated with inferior post-relapse survival (median 11 months vs. 22 months; p = 0.019). CONCLUSIONS: While more intensive follow-up during the first 3 years may be required for patients who do not achieve pCR, especially those with TNBC and HR-/HER2+ tumours, the benefit from blood tests such as CA 15-3 appears limited, and the benefit from intensification of surveillance remains to be addressed in prospective studies on high-risk patients.


Assuntos
Neoplasias da Mama/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/etiologia , Quimioterapia Adjuvante , Terapia Combinada , Gerenciamento Clínico , Feminino , Seguimentos , Pesquisas sobre Serviços de Saúde , Humanos , Testes de Função Hepática , Pessoa de Meia-Idade , Gradação de Tumores , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Padrões de Prática Médica , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Resultado do Tratamento , Adulto Jovem
8.
World J Surg ; 43(7): 1737-1745, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31049604

RESUMO

BACKGROUND: Granulomatous mastitis (GM) is an inflammatory breast disease of unknown aetiology. It poses diagnostic and therapeutic challenges with myriad forms of clinical presentation, varying results to treatments and propensity to recur. This study aims to look at clinical and treatment factors that predispose to recurrence of GM. METHODS: We performed a retrospective review of 113 patients in our unit with histologically proven GM from 2006 to 2016. Demographic, clinical, treatment and outcomes data were collected and analysed. RESULTS: Eighty-nine patients were treated with antibiotics (78.8%), 79 (69.9%) with steroids and 23 (20.4%) patients underwent surgery. Twenty (17.7%) patients had recurrence. Patients who presented with inflammatory signs and symptoms had increased odds of having subsequent recurrence: skin changes (1.50), pain (2.00), fistula (4.39) and antibiotic treatment (6.65). Four patients (20%) with recurrence had positive bacterial cultures. All 4 grew Corynebacterium. Patients with Corynebacterium infection had a 2.64 times higher risk of recurrence. Surgery did not preclude recurrence. There was a 70% (7/10) penicillin resistance rate in our patients with positive cultures for Corynebacterium. CONCLUSION: Initial presentation with inflammatory signs and symptoms may confer increased risk of recurrence, warranting closer monitoring. Corynebacterium infection may play a part as a causative factor and risk factor for recurrence. Non-penicillin antibiotics should be considered as first-line antibiotics for patients presenting with inflammatory changes. Further prospective studies with larger patient populations might reveal information on the aetiology of GM and result in the development of a more standardized and effective treatment regimen.


Assuntos
Antibacterianos/uso terapêutico , Infecções por Corynebacterium/tratamento farmacológico , Mastite Granulomatosa/tratamento farmacológico , Mastite Granulomatosa/cirurgia , Esteroides/uso terapêutico , Adulto , Infecções por Corynebacterium/complicações , Feminino , Mastite Granulomatosa/microbiologia , Humanos , Pessoa de Meia-Idade , Resistência às Penicilinas , Recidiva , Estudos Retrospectivos , Singapura , Resultado do Tratamento
9.
J Radiol Case Rep ; 13(10): 1-10, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32184921

RESUMO

We present a case of a 65 year old female with newly diagnosed primary peritoneal serous carcinoma who was found to have indeterminate segmental microcalcifications in the right upper outer quadrant with a mildly enlarged right axillary node on mammogram. There was no associated breast mass on ultrasound. Core biopsy of the right axillary lymph node and right upper outer quadrant breast microcalcifications confirmed the presence of breast metastases at both sites from primary peritoneal serous carcinoma. This case highlights the importance of histopathological correlation of any breast and axillary abnormalities in patient with primary extramammary malignancy. Imaging features of metastatic lesions to the breast are also reviewed.


Assuntos
Doenças Mamárias/diagnóstico por imagem , Neoplasias da Mama/secundário , Calcinose/diagnóstico por imagem , Cistadenocarcinoma Seroso/patologia , Cistadenocarcinoma Seroso/secundário , Neoplasias Peritoneais/patologia , Idoso , Feminino , Humanos , Linfonodos/diagnóstico por imagem , Metástase Linfática , Mamografia
10.
Clin Cancer Res ; 25(8): 2588-2600, 2019 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-30593516

RESUMO

PURPOSE: Trastuzumab-based chemotherapy has shown remarkable clinical benefits for patients with HER2-positive breast cancer. However, treatment regimens involving trastuzumab had little or no effect for a subset of patients. Preliminary studies revealed WW-binding protein 2 (WBP2), an oncogenic transcription coactivator, to be coamplified with HER2 in 36% of HER2-positive breast cancers. We hypothesize that WBP2 regulates and correlates with the response of HER2-positive breast cancer to trastuzumab. EXPERIMENTAL DESIGN: The coexpression of WBP2 and HER2 in breast tumors was validated using IHC. The role and mechanism of WBP2 in regulating breast cancer response to trastuzumab was elucidated using in vitro, patient-derived xenograft and murine xenograft models. A multicenter retrospective study involving 143 patients given neoadjuvant trastuzumab-based chemotherapy was conducted to determine whether WBP2 expression correlates with pathologic complete response (pCR). RESULTS: Elevated expression of WBP2 significantly enhanced breast cancer's response to trastuzumab by augmenting trastuzumab-induced HER2 downregulation and cell-cycle arrest via inhibition of cyclin D expression. High level of WBP2 correlated with better pCR (67.19%) compared with low WBP2 level (26.58%). The highest response was observed in subgroups of patients with high WBP2-expressing tumors also aged below 50 years (77.78%) or were premenopausal in status (73.33%). Retrospectively, WBP2 demonstrated sensitivity of 80% to 81% and specificity of 76.5% to 80% in discriminating between patients showing pCR and non-pCR. CONCLUSIONS: WBP2 expression correlates with the response of HER2-positive breast cancer to trastuzumab-based neoadjuvant chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Regulação Neoplásica da Expressão Gênica , Receptor ErbB-2/genética , Transativadores/genética , Adulto , Idoso , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Amplificação de Genes , Redes Reguladoras de Genes , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Fosforilação , Receptor ErbB-2/metabolismo , Estudos Retrospectivos , Transdução de Sinais/efeitos dos fármacos , Trastuzumab/administração & dosagem , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
11.
Breast Cancer Res Treat ; 171(3): 719-735, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29926297

RESUMO

PURPOSE: The purpose of the study was to improve the understanding of NF1-associated breast cancer, given the increased risk of breast cancer in this tumour predisposition syndrome and the limited data. METHODS: We identified 18 women with NF1 and breast cancer at our institution. Clinical and pathologic characteristics of NF1-associated breast cancers were compared with 7132 breast cancers in patients without NF1 from our institutional database. Next generation sequencing was performed on DNA from blood and breast cancer specimens available. Blood specimens negative for NF1 mutation were subjected to multiplex ligation-dependent probe amplification (MLPA) to identify complete/partial deletions or duplications. Expression of neurofibromin in the NF1-associated breast cancers was evaluated using immunohistochemistry. RESULTS: There was a higher frequency of grade 3 (83.3% vs 45.4%, p = 0.005), oestrogen receptor (ER) negative (66.7% vs 26.3%, p < 0.001) and human epidermal growth factor receptor 2 (HER2)-positive (66.7% vs 23.4%, p < 0.001) tumours among NF1 patients compared to non-NF1 breast cancers. Overall survival was inferior in NF1 patients in multivariable analysis (hazard ratio 2.25, 95% CI 1.11-4.60; p = 0.025). Apart from germline NF1 mutations (11/16; 69%), somatic mutations in TP53 (8/10; 80%), second-hit NF1 (2/10; 20%), KMT2C (4/10; 40%), KMT2D (2/10; 20%), and PIK3CA (2/10; 20%) were observed. Immunohistochemical expression of neurofibromin was seen in the nuclei and/or cytoplasm of all specimens, but without any consistent pattern in the intensity or extent. CONCLUSIONS: This comprehensive series of NF1-associated breast cancers suggests that their aggressive features are related to germline NF1 mutations in cooperation with somatic mutations in TP53, KMT2C and other genes.


Assuntos
Genes da Neurofibromatose 1 , Neurofibromatose 1/diagnóstico , Neurofibromatose 1/genética , Adulto , Idoso , Biomarcadores Tumorais , Análise Mutacional de DNA , Feminino , Amplificação de Genes , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Estadiamento de Neoplasias , Neurofibromatose 1/epidemiologia , Neurofibromatose 1/mortalidade
12.
J Clin Pathol ; 71(2): 125-128, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28751520

RESUMO

AIMS: To validate the Singapore nomogram for outcome prediction in breast phyllodes tumours in a large cohort of Singaporean patients, as previous validation studies were conducted on small numbers of patients. We also investigate the association of fibroadenomas and phyllodes tumours within a subset of our cohort. METHODS: Histological parameters, surgical margin status and clinical follow-up data of 259 women diagnosed with phyllodes tumours were analysed. Patients with concurrent malignant or premalignant disease were excluded from the validation to minimise confounding influences. Biostatistics modelling was performed, and the concordance between predicted and observed survivals was calculated. The association between fibroadenomas and phyllodes tumours was quantified in a subset of the women. RESULTS: Phyllodes tumours with higher number of mitoses, stromal overgrowth and positive surgical margins were found to be associated with greater risk of clinical recurrence. Patients with a higher nomogram score had a significantly higher risk of developing relapse. Forty out of 78 (51.3%) of the subset of phyllodes cases reviewed showed either fibroadenoma-like areas within the phyllodes tumours or concurrent fibroadenomas in the ipsilateral or contralateral breast. CONCLUSIONS: The Singapore nomogram is useful in predicting outcome in breast phyllodes tumours when applied to a large cohort of Singaporean women.


Assuntos
Neoplasias da Mama/diagnóstico , Técnicas de Apoio para a Decisão , Nomogramas , Tumor Filoide/diagnóstico , Adolescente , Adulto , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Fibroadenoma/diagnóstico , Fibroadenoma/mortalidade , Fibroadenoma/patologia , Fibroadenoma/cirurgia , Seguimentos , Humanos , Margens de Excisão , Pessoa de Meia-Idade , Modelos Estatísticos , Tumor Filoide/mortalidade , Tumor Filoide/patologia , Tumor Filoide/cirurgia , Prognóstico , Singapura , Análise de Sobrevida , Adulto Jovem
13.
Int J Surg Case Rep ; 39: 192-195, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28854407

RESUMO

INTRODUCTION: Phyllodes tumours are uncommon fibroepithelial lesions that typically grow up to 4cm in size but 10cm tumours known as giant phyllodes tumours have been described. We present a case report of a 20cm benign phyllodes tumour and a literature review. PRESENTATION OF CASE: A 54 years old lady with an enlarging left breast mass measuring 20cm of 6 months duration presented to our outpatient breast clinic. She also had an incidental right parotid lump. Core biopsy of the left breast mass returned as a cellular fibroepithelial lesion. A mastectomy and axillary lymph node sampling were done and skin cover was obtained from a split skin graft from the thigh. Final histology returned as a benign phyllodes tumour. Her post-operative recovery was uneventful. DISCUSSION: Phyllodes tumours are suspected in middle age women with rapidly enlarging painless breast masses. Though there are some suggestive features on ultrasound and MRI, the key to diagnosis is still histopathology. However, a pre-operative diagnosis may not always be possible as the interpretation of stromal cellularity and degree of atypia needed to differentiate cellular fibroadenoma from a phyllodes tumour is subjective. When a phyllodes tumour is suspected, adequate margins should be taken for optimal outcome. CONCLUSION: Successful management of phyllodes tumour involves obtaining a pre-operative diagnosis via a core biopsy when possible and planning for adequate margins.

14.
J Surg Oncol ; 115(5): 523-537, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28168712

RESUMO

BACKGROUND AND OBJECTIVES: Triple negative breast cancer (TNBC) carries a worse prognosis compared to the other subtypes. There have been conflicting studies that race may impact the prognosis of TNBC patients. We aim to determine the incidence and prognosis of TNBC among the different ethnic races in Singapore, and to determine its associated risk factors for prognosis. METHODS: Patients diagnosed with invasive breast cancer (BC) from 2005 to 2013 at our tertiary institution were included and divided according to race and subtypes. Demographic and clinical information of non-metastatic TNBC patients were analyzed. Log-rank test, univariate and multivariate Cox proportional hazard regression models were used to find associated risk factors related with overall survival (OS) and disease-free survival (DFS). RESULTS: Among 1227 BC patients, 129 (10.5%) had TNBC. TNBC patients had the worst OS (P: 0.0005) and DFS (P: 0.0016) among the subtypes. However, variations in race did not have any difference in OS or DFS among TNBC patients. Axillary lymph node involvement, invasive lobular histology, larger tumor size, and the presence of lymphovascular invasion (LVI) were factors associated with both poor DFS and OS among TNBC patients. CONCLUSIONS: Racial variation did not have any impact on the prognosis of the TNBC.


Assuntos
Grupo com Ancestrais do Continente Asiático , Grupo com Ancestrais do Continente Europeu , Neoplasias de Mama Triplo Negativas/mortalidade , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Mucinoso/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/mortalidade , Carcinoma Lobular/patologia , Carcinoma Lobular/terapia , Quimioterapia Adjuvante , China/etnologia , Feminino , Seguimentos , Humanos , Incidência , Índia/etnologia , Excisão de Linfonodo , Linfonodos/patologia , Malásia/etnologia , Mastectomia , Mastectomia Segmentar , Pessoa de Meia-Idade , Invasividade Neoplásica , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Fatores de Risco , Singapura/epidemiologia , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/terapia
15.
Cancer Med ; 6(1): 173-185, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-28000426

RESUMO

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.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Taxoides/administração & dosagem , Adulto , Idoso , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Malásia , Pessoa de Meia-Idade , Terapia Neoadjuvante , Gradação de Tumores , Prognóstico , Singapura , Análise de Sobrevida , Taxoides/uso terapêutico , Resultado do Tratamento
16.
Int J Surg ; 19: 22-6, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25986061

RESUMO

Adenosquamous carcinoma of the breast (ASBC) is a rare variant of metaplastic breast cancer with both glandular as well as squamous differentiation. Their lack of distinct imaging characteristics, sometimes subtle histological characteristics and overlapping features with other benign lesions pose a diagnostic challenge. Unlike other forms of metaplastic breast cancer, low-grade adenosquamous carcinoma (LGAC) tends to follow an indolent course with favourable prognosis. We reviewed eight cases of LGAC in our institution from June 2005 to March 2014. In six cases, LGAC was only found after excisional biopsy. In our patients, LGAC frequently co-existed with other forms of breast pathology. Two patients had incidental findings of LGAC alongside their primary malignant tumour (adenoid cystic carcinoma and invasive ductal carcinoma in one, four foci between 0.5 and 4.0 mm within a radial sclerosing lesion adjacent to a malignant phyllodes tumour in the other). A further four patients had LGAC within a complex sclerosing lesion. One patient had a focus of LGAC within a fibroadenoma. One had a focus of LGAC within a benign phyllodes tumour. None of the patients had evidence of nodal involvement. A high degree of suspicion is recommended as such lesions tend to be incidental histological findings within benign tumours or within complex sclerosing lesions. Although the risk of nodal and distant metastasis is low, the potential for local recurrence necessitates aggressive local excision with margin clearance. The role of axillary dissection has yet to be defined and routine sentinel node biopsy and axillary clearance may not be necessary in view of rarity of nodal metastasis in literature. Benefit from adjuvant radiotherapy or chemotherapy is not clearly defined. All eight patients in our study have shown no evidence of recurrence after definitive surgery but longer periods of surveillance is required.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Adenoescamoso/patologia , Neoplasias Primárias Múltiplas/patologia , Adulto , Neoplasias da Mama/cirurgia , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Carcinoma Adenoescamoso/cirurgia , Carcinoma Ductal/patologia , Carcinoma Ductal/cirurgia , Quimioterapia Adjuvante , Feminino , Fibroadenoma/patologia , Fibroadenoma/cirurgia , Humanos , Pessoa de Meia-Idade , Gradação de Tumores , Neoplasias Primárias Múltiplas/cirurgia , Tumor Filoide/patologia , Tumor Filoide/cirurgia , Prognóstico , Radioterapia Adjuvante , Biópsia de Linfonodo Sentinela
17.
Langenbecks Arch Surg ; 393(6): 943-8, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18193451

RESUMO

BACKGROUND: Laparoscopic cholecystectomy is an established treatment for almost all gallbladder diseases with bile duct injury rates similar to open cholecystectomy. These laparoscopic skills must be passed on to junior surgeons without compromising patient safety. MATERIALS AND METHODS: We analysed our structured training programme over 6years (May 2000 to May 2006) by following three trainee surgeons during their training and beyond. During this period, 1,000 laparoscopic cholecystectomies were carried out with five consultant surgeons supervising and three new trainees who completed their accreditation in laparoscopic cholecystectomy. RESULTS: There were 694 patients operated on by consultant surgeons (Group 1), 202 by trainee surgeons (Group 2) and 104 by newly trained surgeons (Group 3). There were no differences between the groups in terms of age and gender. However, there was a significant difference in gallbladder disease among the three groups; Group 2 had more gallstone pancreatitis patients (P < 0.019). There were no differences among the three groups in conversion rates, bile duct injury rates, general complication rates or length of stay. However, the duration of operation in Group 2 was significantly longer compared to the other two groups (P < 0.0001). CONCLUSION: This programme is effective in training junior surgeons and does not compromise patient safety.


Assuntos
Colecistectomia Laparoscópica/educação , Cirurgia Geral/educação , Corpo Clínico Hospitalar/educação , Adulto , Idoso , Competência Clínica , Consultores , Currículo , Feminino , Humanos , Tempo de Internação , Masculino , Mentores , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos de Tempo e Movimento , Reino Unido
18.
Ann Acad Med Singap ; 36(8): 631-5, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17767332

RESUMO

INTRODUCTION: Laparoscopic cholecystectomy for acute cholecystitis is associated with higher rate of conversion to laparotomy. The value of several factors that might influence the rate of conversion is analysed. MATERIALS AND METHODS: In a retrospective analysis of a prospective database, the medical records of patients who underwent laparoscopic cholecystectomy from May 1998 to June 2004 were reviewed. Patients who had acute cholecystitis and had undergone interval laparoscopic cholecystectomy were included in this study. RESULTS: Out of 1000 laparoscopic cholecystectomies, 201 were operated on for acute cholecystitis. One hundred and forty-five patients (72.3%) underwent successful laparoscopic cholecystectomy and 56 patients (27.7%) needed conversion to open cholecystectomy. Patient's age (P = 0.031), total white cell count (P = 0.014), total bilirubin (P = 0.002), alkaline phosphatase (P = 0.003) and presence of common bile duct stone (P = 0.001) were found to be independently associated with conversion. CONCLUSION: Laparoscopic cholecystectomy can be performed safely for acute cholecystitis. Predictors of conversion will be helpful when planning the laparoscopic approach and for counselling patients preoperatively.


Assuntos
Colecistectomia Laparoscópica/efeitos adversos , Colecistite Aguda/cirurgia , Adulto , Colecistectomia Laparoscópica/estatística & dados numéricos , Colecistite Aguda/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Estudos Retrospectivos , Fatores de Risco , Singapura
19.
ANZ J Surg ; 75(4): 231-3, 2005 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-15839972

RESUMO

BACKGROUND: Laparoscopic cholecystectomy is a commonly performed procedure in general surgical practice but it also has an inherently steep learning curve. The training of surgeons in this procedure presents a challenge to teaching hospitals, which essentially have to strike a balance between effective training and safety of the patient. The present study aims first to assess the safety of the structured training programme for this procedure at the Department of Surgery, Changi General Hospital, Singapore. Secondly, it seeks to audit the conversion and bile duct injury rates among the laparoscopic cholecystectomies performed by the department, and the factors which influence these. METHODS: Notes of all patients who underwent laparoscopic cholecystectomy in the department over an 18-month period were reviewed retrospectively and the relevant data prospectively collected. Demographics, as well as details of cases of conversion to open operation and of bile duct injury were identified and the reasons for each recorded. RESULTS: A total of 443 patients underwent laparoscopic cholecystectomy in the 18-month period. The most common indication for surgery was biliary colic/dyspepsia (61.4%), followed by cholecystitis, cholangitis, pancreatitis and common bile duct stone. The overall conversion rate was 11.5%. Three hundred and fifty-five patients were operated on by consultant surgeons, while 88 were by registrars who had been through the structured training programme. There was no statistically significant difference found in the conversion rates between these two groups (P = 0.284). Twenty-two of the 268 female (8.2%) patients had conversion to open operation, while 29 of the 175 male patients (16.6%) underwent conversion (P = 0.007). Amongst cases of cholecystitis and cholangitis, the conversion rate for patients operated on within 7 days of onset of symptoms was 35%, while those operated on 8 or more days later had a conversion rate of 29.7% (P = 0.639). There was a solitary case of bile duct injury among the 443 cases, equating to a bile duct injury rate of 0.23%. CONCLUSION: A structured training programme involving stepwise progression of training, with close supervision by consultant surgeons and a built-in system of audit can effectively train junior surgeons in laparoscopic cholecystectomy without exposing patients to undue risks.


Assuntos
Ductos Biliares/lesões , Colecistectomia Laparoscópica/efeitos adversos , Colecistectomia Laparoscópica/educação , Educação de Pós-Graduação em Medicina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais de Ensino , Humanos , Masculino , Auditoria Médica , Pessoa de Meia-Idade , Avaliação de Processos e Resultados em Cuidados de Saúde , Estudos Retrospectivos , Fatores de Risco , Singapura
20.
ANZ J Surg ; 75(12): 1070-2, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16398813

RESUMO

BACKGROUND: Choledocholithiasis, if left untreated, can lead to significant morbidity and mortality. The management of such a problem has progressed tremendously but controversy still exists as to ideal management, laparoscopic exploration or endoscopic retrograde pancreatography with sphincterotomy. The purpose of this study is to evaluate the results of endoscopic retrograde cholangiopancreatography (ERCP) in a surgical unit. METHODS: We performed a retrospective review on 336 patients who underwent ERCP between 1997-2000. RESULTS: We achieved a successful cannulation rate of 98% and stone clearance rate exceeding 90%. Morbidity has been minimal and there was no mortality in our study. CONCLUSION: We conclude that ERCP is an effective and safe surgical alternative for the management of choledocholithiasis.


Assuntos
Colangiopancreatografia Retrógrada Endoscópica , Coledocolitíase/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Colangiopancreatografia Retrógrada Endoscópica/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pancreatite/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos
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