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1.
Nature ; 578(7796): 615-620, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31959985

RESUMO

Single-cell analyses have revealed extensive heterogeneity between and within human tumours1-4, but complex single-cell phenotypes and their spatial context are not at present reflected in the histological stratification that is the foundation of many clinical decisions. Here we use imaging mass cytometry5 to simultaneously quantify 35 biomarkers, resulting in 720 high-dimensional pathology images of tumour tissue from 352 patients with breast cancer, with long-term survival data available for 281 patients. Spatially resolved, single-cell analysis identified the phenotypes of tumour and stromal single cells, their organization and their heterogeneity, and enabled the cellular architecture of breast cancer tissue to be characterized on the basis of cellular composition and tissue organization. Our analysis reveals multicellular features of the tumour microenvironment and novel subgroups of breast cancer that are associated with distinct clinical outcomes. Thus, spatially resolved, single-cell analysis can characterize intratumour phenotypic heterogeneity in a disease-relevant manner, with the potential to inform patient-specific diagnosis.


Assuntos
Neoplasias da Mama/patologia , Imagem Molecular , Análise de Célula Única , Biomarcadores Tumorais/análise , Neoplasias da Mama/classificação , Neoplasias da Mama/diagnóstico , Humanos , Estimativa de Kaplan-Meier , Fenótipo , Modelos de Riscos Proporcionais , Taxa de Sobrevida , Microambiente Tumoral
2.
Ann Surg Oncol ; 31(1): 344-355, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37903951

RESUMO

BACKGROUND: Tailored axillary surgery (TAS) is a novel surgical concept for clinical node-positive breast cancer. It consists of the removal of the sentinel lymph nodes (LNs), as well as palpably suspicious nodes. The TAS technique can be utilized in both the upfront and neoadjuvant chemotherapy (NACT) setting. This study assessed whether/how imaging-guided localization (IGL) influenced TAS. PATIENTS AND METHODS: This was a prospective observational cohort study preplanned in the randomized phase-III OPBC-03/TAXIS trial. IGL was performed at the surgeon's discretion for targeted removal of LNs during TAS. Immediate back-up axillary lymph node dissection (ALND) followed TAS according to TAXIS randomization. RESULTS: Five-hundred patients were included from 44 breast centers in six countries, 151 (30.2%) of whom underwent NACT. IGL was performed in 84.4% of all patients, with significant variation by country (77.6-100%, p < 0.001). No difference in the median number of removed (5 vs. 4, p = 0.3) and positive (2 vs. 2, p = 0.6) LNs by use of IGL was noted. The number of LNs removed during TAS with IGL remained stable over time (p = 0.8), but decreased significantly without IGL, from six (IQR 4-6) in 2019 to four (IQR 3-4) in 2022 (p = 0.015). An ALND was performed in 249 patients, removing another 12 (IQR 9-17) LNs, in which a median number of 1 (IQR 0-4) was positive. There was no significant difference in residual nodal disease after TAS with or without IGL (68.0% vs. 57.6%, p = 0.2). CONCLUSIONS: IGL did not significantly change either the performance of TAS or the volume of residual nodal tumor burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03513614.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela/métodos , Estudos Prospectivos , Metástase Linfática/patologia , Excisão de Linfonodo/métodos , Terapia Neoadjuvante , Axila/patologia , Linfonodos/cirurgia , Linfonodos/patologia
3.
J Mammary Gland Biol Neoplasia ; 28(1): 26, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-38066300

RESUMO

Metastasis is the leading cause of cancer-related deaths of breast cancer patients. Some cancer cells in a tumour go through successive steps, referred to as the metastatic cascade, and give rise to metastases at a distant site. We know that the plasticity and heterogeneity of cancer cells play critical roles in metastasis but the precise underlying molecular mechanisms remain elusive. Here we aimed to identify molecular mechanisms of metastasis during colonization, one of the most important yet poorly understood steps of the cascade. We performed single-cell RNA-Seq (scRNA-Seq) on tumours and matched lung macrometastases of patient-derived xenografts of breast cancer. After correcting for confounding factors such as the cell cycle and the percentage of detected genes (PDG), we identified cells in three states in both tumours and metastases. Gene-set enrichment analysis revealed biological processes specific to proliferation and invasion in two states. Our findings suggest that these states are a balance between epithelial-to-mesenchymal (EMT) and mesenchymal-to-epithelial transitions (MET) traits that results in so-called partial EMT phenotypes. Analysis of the top differentially expressed genes (DEGs) between these cell states revealed a common set of partial EMT transcription factors (TFs) controlling gene expression, including ZNF750, OVOL2, TP63, TFAP2C and HEY2. Our data suggest that the TFs related to EMT delineate different cell states in tumours and metastases. The results highlight the marked interpatient heterogeneity of breast cancer but identify common features of single cells from five models of metastatic breast cancer.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Transição Epitelial-Mesenquimal/genética , Linhagem Celular Tumoral , Fatores de Transcrição , Análise de Célula Única , Proteínas Supressoras de Tumor
4.
Ann Surg ; 278(5): e981-e987, 2023 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36727743

RESUMO

OBJECTIVE: To assess the discrepancy between perioperative complications, prospectively recorded during a cohort study versus retrospectively from health records. BACKGROUND: Perioperative adverse events are relevant for patient outcome, but incomplete reporting is common. METHODS: Two physicians independently recorded all intraoperative adverse events according to ClassIntra and all postoperative complications according to the Clavien-Dindo classification based on all available health records. These retrospective assessments were compared with the number and severity of those prospectively assessed in the same patients during their inclusion in 1 center of a prospective multicenter cohort study. RESULTS: Interrater agreement between both physicians for retrospective recording was high [intraclass correlation coefficient: 0.89 (95% CI, 0.86, 0.91) for intraoperative and 0.88 (95% CI, 0.85, 0.90) for postoperative complications]. In 320 patients, the incidence rate was higher retrospectively than prospectively for any intraoperative complication (incidence rate ratio: 1.79; 95% CI, 1.50, 2.13) and for any postoperative complication (incidence rate ratio: 2.21; 95% CI, 1.90, 2.56). In 71 patients, the severity of the most severe intraoperative complication was higher in the retrospective than in the prospective data collection, whereas in 69 the grading was lower. In 106 patients, the severity of the most severe postoperative complication was higher in the retrospective than in the prospective data collection, whereas in 19 the grading was lower. CONCLUSIONS: There is a noticeable discrepancy in the number and severity of reported perioperative complications between these 2 data collection methods. On the basis of the double-blinded assessment of 2 independent raters, our study renders prospective underreporting more likely than retrospective overreporting.


Assuntos
Complicações Intraoperatórias , Complicações Pós-Operatórias , Humanos , Estudos Retrospectivos , Estudos de Coortes , Estudos Prospectivos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Complicações Intraoperatórias/epidemiologia
5.
Mol Biol Rep ; 50(8): 7133-7139, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37389703

RESUMO

BACKGROUND: Cylindroma of the breast is a rare benign neoplasm. Since its first description in 2001, 20 cases have been reported in the literature. METHODS AND RESULTS: We report another case of this rare tumor in a 60-year-old woman with demonstration of the underlying molecular alteration. Histologically, the tumor showed the typical "jigsaw" pattern of a dual population of cells with a triple-negative phenotype. The pathognomonic mutation of the CYLD gene mutation was detected by whole exome sequencing. Cylindromas show morphological overlap with the solid-basaloid variant of adenoid cystic carcinoma, which renders this differential diagnosis difficult. However, distinction of these two lesions is of outmost importance, since cylindromas, in contrast to solid-basaloid variant of adenoid cystic carcinoma, behave in an entirely benign fashion. CONCLUSIONS: Careful evaluation of morphological features such as mitotic figures and cellular atypia is crucial in the diagnostic work-up of triple-negative breast lesions. It is important to keep cylindroma in mind as a pitfall and possible differential diagnosis for the solid-basaloid variant of adenoid cystic carcinoma. Molecular detection of CYLD gene mutation is helpful in cases with ambiguous histology. With this case report, we aim to contribute to a better understanding of mammary cylindroma and facilitate the diagnosis of this rare entity.


Assuntos
Carcinoma Adenoide Cístico , Humanos , Mama/patologia , Carcinoma Adenoide Cístico/diagnóstico por imagem , Carcinoma Adenoide Cístico/genética , Enzima Desubiquitinante CYLD/genética , Diagnóstico Diferencial , Mutação/genética , Fenótipo , Feminino , Pessoa de Meia-Idade
6.
World J Surg Oncol ; 21(1): 40, 2023 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-36755294

RESUMO

INTRODUCTION: Contralateral axillary lymph node metastasis (CALNM) in breast cancer (BC) is considered a distant metastasis, marking stage 4cancer. Therefore, it is generally treated as an incurable disease. However, in clinical practice, staging and treatment remain controversial due to a paucity of data, and the St. Gallen 2021 consensus panel recommended a curative approach in patients with oligometastatic disease. Aberrant lymph node (LN) drainage following previous surgery or radiotherapy is common. Therefore, CALNM may be considered a regional event rather than systemic disease, and a re-sentinel procedure aided by lymphoscintigraphy permits adequate regional staging. CASE REPORT: Here, we report a 37-year-old patient with Lynch syndrome who presented with CALNM in an ipsilateral relapse of a moderately differentiated invasive ductal BC (ER 90%, PR 30%, HER2 negative, Ki-67 25%, microsatellite stable), 3 years after the initial diagnosis. Lymphoscintigraphy detected a positive sentinel LN in the contralateral axilla despite no sign of LN involvement or distant metastases on FDG PET/CT or MRI. The patient underwent bilateral mastectomy with sentinel node dissection, surgical reconstruction with histological confirmation of the CALNM, left axillary dissection, adjuvant chemotherapy, and anti-hormone therapy. In addition to her regular BC follow-up visits, the patient will undergo annual colonoscopy, gastroscopy, abdominal, and vaginal ultrasound screening. In January 2023, the patient was free of progression for 23 months after initiation of treatment for recurrent BC and CALNM. CONCLUSION: This case highlights the value of delayed lymphoscintigraphy and the contribution of sentinel procedure for local control in the setting of recurrent BC. Aberrant lymph node drainage following previous surgery may be the underlying cause of CALNM. We propose that CALNM without evidence of systemic metastasis should be considered a regional event in recurrent BC, and thus, a curative approach can be pursued. The next AJCC BC staging should clarify the role of CALNM in recurrent BC to allow for the development of specific treatment guidelines.


Assuntos
Neoplasias da Mama , Neoplasias Colorretais Hereditárias sem Polipose , Humanos , Feminino , Adulto , Neoplasias da Mama/patologia , Metástase Linfática/patologia , Biópsia de Linfonodo Sentinela/métodos , Mastectomia , Neoplasias Colorretais Hereditárias sem Polipose/cirurgia , Neoplasias Colorretais Hereditárias sem Polipose/patologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/cirurgia , Excisão de Linfonodo , Linfonodos/cirurgia , Linfonodos/patologia , Recidiva , Axila/patologia
7.
World J Surg Oncol ; 21(1): 176, 2023 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-37287038

RESUMO

BACKGROUND: The Choosing Wisely initiative recommended the omission of routine sentinel lymph node biopsy (SLNB) in patients ≥ 70 years of age, with clinically node-negative, early stage, hormone receptor (HR) positive and human epidermal growth factor receptor 2 (Her2) negative breast cancer in August 2016. Here, we assess the adherence to this recommendation in a Swiss university hospital. METHODS: We conducted a retrospective single center cohort study from a prospectively maintained database. Patients ≥ 18 years of age with node-negative breast cancer were treated between 05/2011 and 03/2022. The primary outcome was the percentage of patients in the Choosing Wisely target group who underwent SLNB before and after the initiative went live. Statistical significance was tested using chi-squared test for categorical and Wilcoxon rank-sum tests for continuous variables. RESULTS: In total, 586 patients met the inclusion criteria with a median follow-up of 2.7 years. Of these, 163 were ≥ 70 years of age and 79 were eligible for treatment according to the Choosing Wisely recommendations. There was a trend toward a higher rate of SLNB (92.7% vs. 75.0%, p = 0.07) after the Choosing Wisely recommendations were published. In patients ≥ 70 years with invasive disease, fewer received adjuvant radiotherapy after omission of SLNB (6.2% vs. 64.0%, p < 0.001), without differences concerning adjuvant systemic therapy. Both short-term and long-term complication rates after SLNB were low, without differences between elderly patients and those < 70 years. CONCLUSIONS: Choosing Wisely recommendations did not result in a decreased use of SLNB in the elderly at a Swiss university hospital.


Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Humanos , Idoso , Feminino , Biópsia de Linfonodo Sentinela , Neoplasias da Mama/patologia , Excisão de Linfonodo , Estudos Retrospectivos , Estudos de Coortes , Suíça/epidemiologia , Hospitais , Axila/patologia , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Linfonodos/patologia
8.
Lancet Oncol ; 22(1): e18-e28, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33387500

RESUMO

Primary systemic therapy is increasingly used in the treatment of patients with early-stage breast cancer, but few guidelines specifically address optimal locoregional therapies. Therefore, we established an international consortium to discuss clinical evidence and to provide expert advice on technical management of patients with early-stage breast cancer. The steering committee prepared six working packages to address all major clinical questions from diagnosis to surgery. During a consensus meeting that included members from European scientific oncology societies, clinical trial groups, and patient advocates, statements were discussed and voted on. A consensus was reached in 42% of statements, a majority in 38%, and no decision in 21%. Based on these findings, the panel developed clinical guidance recommendations and a toolbox to overcome many clinical and technical requirements associated with the diagnosis, response assessment, surgical planning, and surgery of patients with early-stage breast cancer. This guidance could convince clinicians and patients of the major clinical advancements purported by primary systemic therapy, the use of less extensive and more targeted surgery to improve the lives of patients with breast cancer.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/terapia , Mastectomia Segmentar/normas , Oncologia/normas , Terapia Neoadjuvante/normas , Antineoplásicos/efeitos adversos , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Tomada de Decisão Clínica , Consenso , Técnica Delphi , Feminino , Humanos , Mastectomia Segmentar/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Resultado do Tratamento
9.
Br J Cancer ; 125(1): 23-27, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33762721

RESUMO

Circulating tumour cell (CTC) clusters have been proposed to be major players in the metastatic spread of breast cancer, particularly during advanced disease stages. Yet, it is unclear whether or not they manifest in early breast cancer, as their occurrence in patients with metastasis-free primary disease has not been thoroughly evaluated. In this study, exploiting nanostructured titanium oxide-coated slides for shear-free CTC identification, we detect clustered CTCs in the curative setting of multiple patients with early breast cancer prior to surgical treatment, highlighting their presence already at early disease stages. These results spotlight an important aspect of metastasis biology and the possibility to intervene with anti-cluster therapeutics already during the early manifestation of breast cancer.


Assuntos
Neoplasias da Mama/patologia , Células Neoplásicas Circulantes/patologia , Titânio/química , Neoplasias da Mama/cirurgia , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Humanos , Nanoestruturas , Metástase Neoplásica , Estadiamento de Neoplasias
10.
Oncology ; 99(6): 359-364, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33735903

RESUMO

BACKGROUND: Neoadjuvant chemotherapy (NAC) is increasingly used to treat node-positive (N+) breast cancer. Predictors of nodal pathological complete response (pCR) in Asian women are poorly described and there is variety in the management of the axilla after NAC. We evaluated predictors of nodal pCR and axillary management in a cohort of Asian N+ patients. METHODS: Consecutive biopsy-proven N+ breast cancer patients treated with NAC were identified from the Shanghai Ruijin Hospital in China. Axillary lymph node dissection was performed on all patients, irrespective of the nodal response to NAC. RESULTS: A total of 323 patients were included. Nodal pCR was achieved in 105 patients (33%), 15% of HR+/HER2- tumors, 38% of HR+/HER2+ tumors, 49% of HR-/HER2+ tumors, and 42% of HR-/HER2-tumors (p < 0.001). Factors associated with nodal pCR were (1) receptor status (HR+/HER2- [referent]: OR 3.42, 95% CI 1.43-8.16, p = 0.006 for HR+/HER2+; OR 4.19, 95% CI 1.85-9.50, p = 0.001 for HR-/HER2+; and OR 2.94, 95% CI 1.11-7.74, p = 0.029 for HR-/HER2-), (2) breast pCR (no pCR [referent]: OR 15.22, 95% CI 6.29-36.79, p < 0.001), and (3) absence of lymphovascular invasion (LVI [referent]: OR 9.04, 95% CI 2.09-39.18, p = 0.003). CONCLUSION: This study confirmed expected predictors of nodal pCR in Asian women and the benefit of NAC in downstaging the axilla independently of ethnicity.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Excisão de Linfonodo/métodos , Adulto , Axila , Neoplasias da Mama/genética , China/etnologia , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2/genética , Estudos Retrospectivos , Resultado do Tratamento
11.
Lancet Oncol ; 21(8): e375-e385, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32758475

RESUMO

The aims of the Oncoplastic Breast Consortium initiative were to identify important knowledge gaps in the field of oncoplastic breast-conserving surgery and nipple-sparing or skin-sparing mastectomy with immediate breast reconstruction, and to recommend appropriate research strategies to address these gaps. A total of 212 surgeons and 26 patient advocates from 55 countries prioritised the 15 most important knowledge gaps from a list of 38 in two electronic Delphi rounds. An interdisciplinary panel of the Oncoplastic Breast Consortium consisting of 63 stakeholders from 20 countries obtained consensus during an in-person meeting to select seven of these 15 knowledge gaps as research priorities. Three key recommendations emerged from the meeting. First, the effect of oncoplastic breast-conserving surgery on quality of life and the optimal type and timing of reconstruction after nipple-sparing or skin-sparing mastectomy with planned radiotherapy should be addressed by prospective cohort studies at an international level. Second, the role of adjunctive mesh and the positioning of implants during implant-based breast reconstruction should ideally be investigated by randomised controlled trials of pragmatic design. Finally, the BREAST-Q questionnaire is a suitable tool to assess primary outcomes in these studies, but other metrics to measure patient-reported outcomes should be systematically evaluated and quality indicators of surgical morbidity should be further assessed.


Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia , Feminino , Humanos
12.
Breast Cancer Res Treat ; 177(3): 581-589, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31267330

RESUMO

PURPOSE: Myeloperoxidase (MPO) is an enzyme secreted by neutrophil granulocytes as a result of phagocytosis during inflammation. In colorectal cancer, tumour infiltration by MPO expressing cells has been shown to be independently associated with a favourable prognosis. In this study, we explored the role of MPO-positive cell infiltration and its prognostic significance in invasive breast cancer. METHODS: We performed immunohistochemical staining for MPO on multiple tissue microarrays comprising a total of 928 human breast cancer samples with detailed clinical-pathological annotation and outcome data. RESULTS: MPO-positive cell infiltration (≥ 5 cells/tissue punch) was found in 150 (16%) of the 928 evaluable breast cancer cases. In univariate survival analyses, infiltration by MPO-positive cells was associated with a significantly better overall survival (p < 0.001). In subset univariate analyses, the infiltration by MPO-positive cells was associated with significantly better overall survival in the Luminal B/HER2-negative subtype (p = 0.005), the HER2 enriched subtype (p = 0.011), and the Triple Negative subtype (p < 0.001). In multivariate analysis, MPO expression proved to be an independent prognostic factor for improved overall survival (p < 0.001). CONCLUSIONS: This is the first study to show that infiltration of MPO-positive cells is an independent prognostic biomarker for improved overall survival in human breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Infiltração de Neutrófilos , Neutrófilos/enzimologia , Neutrófilos/patologia , Peroxidase/metabolismo , Idoso , Biomarcadores Tumorais , Neoplasias da Mama/mortalidade , Feminino , Seguimentos , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Peroxidase/genética , Prognóstico , Estudos Retrospectivos
14.
Ann Surg Oncol ; 26(9): 2759-2767, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31115853

RESUMO

BACKGROUND: The BREAST-Q is a patient-reported outcome measure to evaluate satisfaction and health-related quality of life (HRQOL) after breast surgery. The aim of this study is to test the acceptability, reliability, and validity of the most recently developed BREAST-Q module for breast-conserving therapy (BCT) in a prospective clinical cohort. METHODS: The BREAST-Q BCT module was translated into German according to international guidelines. A total of 253 women with primary breast cancer undergoing BCT were recruited preoperatively. This study evaluated the BREAST-Q BCT subscales by using psychometric methods including acceptability, reliability, and validity. To examine construct validity, convergent and discriminant validity were determined by testing the instrument's scales against the EORTC C30 and BR23 as reference questionnaires. RESULTS: Acceptability was supported by a high follow-up rate (90%) and low frequency of missing data (< 10%) in all but three scales. Scale reliability was supported by high Cronbach's alpha coefficients (> 0.86) and item-total correlations (range of means, 0.33-0.89). Validity was shown by convergent and divergent correlations. The hypotheses of relationships between the scales of the BREAST-Q and the EORTC QLQ C30 BR23 revealed moderate to high correlations. CONCLUSIONS: The BREAST-Q BCT module proved to be an accepted, reliable, and valid questionnaire for the assessment of HRQOL and patient satisfaction after BCT in breast cancer patients. It can be recommended as a possible standard PROM for individual clinical analysis, quality assessment, and future trials.


Assuntos
Neoplasias da Mama/psicologia , Mastectomia Segmentar/psicologia , Medidas de Resultados Relatados pelo Paciente , Satisfação do Paciente , Qualidade de Vida/psicologia , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
16.
BMC Cancer ; 19(1): 41, 2019 Jan 08.
Artigo em Inglês | MEDLINE | ID: mdl-30621641

RESUMO

BACKGROUND: The Rearranged during Transfection (RET) protein is overexpressed in a subset of Estrogen Receptor (ER) positive breast cancer, with both signalling pathways functionally interacting. This cross-talk plays a pivotal role in the resistance of breast cancer cells to anti-endocrine therapies, and RET expression is assumed to correlate with poor prognosis based on findings in small patient cohorts. The aim of our study was to investigate the impact of RET expression on patient outcome in human breast cancer. METHODS: We performed an immunohistochemical analysis of RET protein expression on a tissue microarray encompassing 990 breast cancer patients and correlated its expression with clinicopathological parameters and survival data. RESULTS: Expression of RET was detected in 409 out of 990 cases (41.3%). RET and ER expression significantly correlated (p < 0.0001). The Luminal B HER2-positive subtype showed the highest expression rate (48.9%). In univariate and multivariate survival analyses, RET expression had no impact on overall survival. CONCLUSION: We confirmed the co-expression of RET and ER, but we did not find RET expression to be an independent prognostic factor in human breast cancer. Clinical trials with newly developed RET inhibitors are needed to evaluate if RET inhibition has a beneficial impact on patient survival in ER positive breast cancer.


Assuntos
Neoplasias da Mama/genética , Receptor alfa de Estrogênio/genética , Prognóstico , Proteínas Proto-Oncogênicas c-ret/genética , Adulto , Idoso , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Transdução de Sinais/genética , Tamoxifeno/administração & dosagem
17.
World J Surg ; 43(10): 2420-2425, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31292675

RESUMO

BACKGROUND: Long-duration surgery requires repeated administration of antimicrobial prophylaxis (amp). Amp "redosing" reduces incidence of surgical site infections (SSI) but is frequently omitted. Clinical relevance of redosing timing needs to be investigated. Here, we evaluated the effects of compliance with amp redosing and its timing on SSI incidence in prolonged duration surgery. METHODS: Data from >9000 patients undergoing visceral, trauma, or vascular surgery with elective or emergency treatment in two tertiary referral Swiss hospitals were analyzed. All patients had to receive amp preoperatively and redosing, if indicated. Antibiotics used were cefuroxime (1.5 or 3 g, if weight >80 kg), or cefuroxime and metronidazole (1.5 and 0.5 g, or 3 and 1 g doses, if weight >80 kg). Alternatively, in cases of known or suspected allergies, vancomycin (1 g), gentamicin (4 mg/Kg), and metronidazole or clindamycin (300 mg) with or without ciprofloxacin (400 mg) were used. Association of defined parameters, including wound class, ASA scores, and duration of operation, with SSI incidence was explored. RESULTS: In the whole cohort, SSI incidence significantly correlated with duration of surgery (ρ = 0.73, p = 0.031). In 593 patients undergoing >240 min long interventions, duration of surgery was the only parameter significantly (p < 0.001) associated with increased SSI risk, whereas wound class, ASA scores, treatment areas, and emergency versus elective hospital entry were not. Redosing significantly reduced SSI incidence as shown by multivariate analysis (OR 0.60, 95% CI 0.37-0.96, p = 0.034), but exact timing had no significant impact. CONCLUSIONS: Long-duration surgery associates with higher SSI incidence. Irrespective of its exact timing, amp redosing significantly decreases SSI risk.


Assuntos
Antibioticoprofilaxia , Infecção da Ferida Cirúrgica/prevenção & controle , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Duração da Cirurgia , Infecção da Ferida Cirúrgica/epidemiologia
18.
Breast Cancer Res Treat ; 172(3): 523-537, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30182349

RESUMO

PURPOSE: Indications for nipple-sparing mastectomy (NSM) have broadened to include the risk reducing setting and locally advanced tumors, which resulted in a dramatic increase in the use of NSM. The Oncoplastic Breast Consortium consensus conference on NSM and immediate reconstruction was held to address a variety of questions in clinical practice and research based on published evidence and expert panel opinion. METHODS: The panel consisted of 44 breast surgeons from 14 countries across four continents with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate. Panelists presented evidence summaries relating to each topic for debate during the in-person consensus conference. The iterative process in question development, voting, and wording of the recommendations followed the modified Delphi methodology. RESULTS: Consensus recommendations were reached in 35, majority recommendations in 24, and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference. CONCLUSIONS: In case of conflicting or missing evidence to guide treatment, the consensus conference revealed substantial disagreement in expert panel opinion, which, among others, supports the need for a randomized trial to evaluate the safest and most efficacious reconstruction techniques.


Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia/métodos , Mastectomia Subcutânea/métodos , Consenso , Feminino , Humanos , Mastectomia Subcutânea/efeitos adversos , Necrose , Mamilos/patologia , Retalhos Cirúrgicos/patologia
19.
World J Surg ; 42(12): 3888-3896, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-29978247

RESUMO

BACKGROUND: Surgical site infections (SSI) are a major cause of morbidity and mortality in surgical patients. Postoperative and total hospital length of stay (LOS) are known to be prolonged by the occurrence of SSI. Preoperative LOS may increase the risk of SSI. This study aims at identifying the associations of pre- and postoperative LOS in hospital and intensive care with the occurrence of SSI. METHODS: This observational cohort study includes general, orthopedic trauma and vascular surgery patients at two tertiary referral centers in Switzerland between February 2013 and August 2015. The outcome of interest was the 30-day SSI rate. RESULTS: We included 4596 patients, 234 of whom (5.1%) experienced SSI. Being admitted at least 1 day before surgery compared to same-day surgery was associated with a significant increase in the odds of SSI in univariate analysis (OR 1.65, 95% CI 1.25-2.21, p < 0.001). More than 1 day compared to 1 day of preoperative hospital stay did not further increase the odds of SSI (OR 1.08, 95% CI 0.77-1.50, p = 0.658). Preoperative admission to an intensive care unit (ICU) increased the odds of SSI as compared to hospital admission outside of an ICU (OR 2.19, 95% CI 0.89-4.59, p = 0.057). Adjusting for potential confounders in multivariable analysis weakened the effects of both preoperative admission to hospital (OR 1.38, 95% CI 0.99-1.93, p = 0.061) and to the ICU (OR 1.89, 95% CI 0.73-4.24, p = 0.149). CONCLUSION: There was no significant independent association between preoperative length of stay and risk of SSI while SSI and postoperative LOS were significantly associated.


Assuntos
Tempo de Internação/estatística & dados numéricos , Período Pós-Operatório , Período Pré-Operatório , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Suíça/epidemiologia , Centros de Atenção Terciária
20.
Breast Cancer Res Treat ; 165(1): 139-149, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28578506

RESUMO

PURPOSE: To obtain consensus recommendations for the standardization of oncoplastic breast conserving surgery (OPS) from an international panel of experts in breast surgery including delegates from the German, Austrian and Swiss societies of senology. METHODS: A total of 52 questions were addressed by electronic voting. The panel's recommendations were put into context with current evidence and the report was circled in an iterative open email process until consensus was obtained. RESULTS: The panelists considered OPS safe and effective for improving aesthetic outcomes and broadening the indication for breast conserving surgery (BCS) towards larger tumors. A slim majority believed that OPS reduces the rate of positive margins; however, there was consensus that OPS is associated with an increased risk of complications compared to conventional BCS. The panel strongly endorsed patient-reported outcomes measurement, and recommended selected scales of the Breast-Q™-Breast Conserving Therapy Module for that purpose. The Clough bi-level classification was recommended for standard use in clinical practice for indicating, planning and performing OPS, and the Hoffmann classification for surgical reports and billing purposes. Mastopexy and reduction mammoplasty were the only two recognized OPS procedure categories supported by a majority of the panel. Finally, the experts unanimously supported the statement that every OPS procedure should be tailored to each individual patient. CONCLUSIONS: When implemented into clinical practice, the panel recommendations may improve safety and effectiveness of OPS. The attendees agreed that there is a need for prospective multicenter studies to optimize patient selection and for standardized criteria to qualify and accredit OPS training centers.


Assuntos
Neoplasias da Mama/cirurgia , Medicina Baseada em Evidências/normas , Mastectomia Segmentar/normas , Neoplasias da Mama/patologia , Consenso , Feminino , Humanos , Cooperação Internacional , Mastectomia Segmentar/efeitos adversos , Mastectomia Segmentar/métodos , Resultado do Tratamento
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