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1.
Breast Cancer Res Treat ; 177(3): 723-733, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31302855

RESUMO

BACKGROUND: In healthy BRCA1/2 mutation carriers, bilateral risk-reducing mastectomy (BRRM) strongly reduces the risk of developing breast cancer (BC); however, no clear survival benefit of BRRM over BC surveillance has been reported yet. METHODS: In this Dutch multicenter cohort study, we used multivariable Cox models with BRRM as a time-dependent covariable to estimate the associations between BRRM and the overall and BC-specific mortality rates, separately for BRCA1 and BRCA2 mutation carriers. RESULTS: During a mean follow-up of 10.3 years, 722 out of 1712 BRCA1 (42%) and 406 out of 1145 BRCA2 (35%) mutation carriers underwent BRRM. For BRCA1 mutation carriers, we observed 52 deaths (20 from BC) in the surveillance group, and 10 deaths (one from BC) after BRRM. The hazard ratios were 0.40 (95% CI 0.20-0.90) for overall mortality and 0.06 (95% CI 0.01-0.46) for BC-specific mortality. BC-specific survival at age 65 was 93% for surveillance and 99.7% for BRRM. For BRCA2 mutation carriers, we observed 29 deaths (7 from BC) in the surveillance group, and 4 deaths (no BC) after BRRM. The hazard ratio for overall mortality was 0.45 (95% CI 0.15-1.36). BC-specific survival at age 65 was 98% for surveillance and 100% for BRRM. CONCLUSION: BRRM was associated with lower mortality than surveillance for BRCA1 mutation carriers, but for BRCA2 mutation carriers, BRRM may lead to similar BC-specific survival as surveillance. Our findings support a more individualized counseling based on BRCA mutation type.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/etiologia , Neoplasias da Mama/prevenção & controle , Heterozigoto , Mutação , Mastectomia Profilática , Neoplasias da Mama/mortalidade , Neoplasias da Mama/cirurgia , Feminino , Mutação em Linhagem Germinativa , Humanos , Mortalidade , Países Baixos/epidemiologia , Prognóstico , Mastectomia Profilática/métodos , Vigilância em Saúde Pública , Comportamento de Redução do Risco
2.
Nat Commun ; 9(1): 3739, 2018 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-30228269

RESUMO

During the last decade, the emerging field of molecular fluorescence imaging has led to the development of tumor-specific fluorescent tracers and an increase in early-phase clinical trials without having consensus on a standard methodology for evaluating an optical tracer. By combining multiple complementary state-of-the-art clinical optical imaging techniques, we propose a novel analytical framework for the clinical translation and evaluation of tumor-targeted fluorescent tracers for molecular fluorescence imaging which can be used for a range of tumor types and with different optical tracers. Here we report the implementation of this analytical framework and demonstrate the tumor-specific targeting of escalating doses of the near-infrared fluorescent tracer bevacizumab-800CW on a macroscopic and microscopic level. We subsequently demonstrate an 88% increase in the intraoperative detection rate of tumor-involved margins in primary breast cancer patients, indicating the clinical feasibility and support of future studies to evaluate the definitive clinical impact of fluorescence-guided surgery.


Assuntos
Benchmarking , Neoplasias da Mama/diagnóstico por imagem , Corantes Fluorescentes/administração & dosagem , Imagem Molecular/métodos , Cirurgia Assistida por Computador/métodos , Idoso , Ácidos Alcanossulfônicos/administração & dosagem , Ácidos Alcanossulfônicos/química , Animais , Bevacizumab/administração & dosagem , Bevacizumab/química , Neoplasias da Mama/cirurgia , Linhagem Celular Tumoral , Estudos de Viabilidade , Feminino , Corantes Fluorescentes/química , Humanos , Indóis/administração & dosagem , Indóis/química , Margens de Excisão , Mastectomia/métodos , Pessoa de Meia-Idade , Imagem Óptica/métodos
3.
Eur J Surg Oncol ; 44(11): 1708-1713, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30005963

RESUMO

PURPOSE: Around 15%-30% of patients receiving breast-conserving surgery (BCS) for invasive breast carcinoma or ductal carcinoma in situ (DCIS) need a reoperation due to tumor-positive margins at final histopathology. Currently available intraoperative surgical margin assessment modalities all have specific limitations. Therefore, we aimed to assess the feasibility and accuracy of micro-computed tomography (micro-CT) as a novel method for intraoperative margin assessment in BCS. METHODS: Lumpectomy specimens from 30 consecutive patients diagnosed with invasive breast cancer or DCIS were imaged using a micro-CT. Margin status was assessed on micro-CT images by two investigators who were blinded to the final histopathological margin status. The micro-CT margin status was compared with the histopathological margin status. RESULTS: The margin status could be assessed by micro-CT in 29 out of 30 patients. Of these, nine patients had a positive tumor margin and 20 a negative tumor margin at final histopathology. Margin status evaluation by micro-CT took always less than 15 min. The margin status in 25 patients was correctly predicted by micro-CT. There were four false-negative predictions. The accuracy, sensitivity, specificity, positive predictive value and negative predictive value of micro-CT in margin status prediction were 86%, 56%, 100%, 100% and 83%, respectively. With micro-CT, the positive margin rate could potentially have been reduced from 31% to 14%. CONCLUSIONS: Whole lumpectomy specimen micro-CT scanning is a promising technique for intraoperative margin assessment in BCS. Intraoperative quick feedback on the margin status could potentially lead to a reduction in the number of reoperations.


Assuntos
Carcinoma de Mama in situ/diagnóstico por imagem , Carcinoma de Mama in situ/cirurgia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Margens de Excisão , Mastectomia Segmentar , Microtomografia por Raio-X , Idoso , Carcinoma de Mama in situ/patologia , Neoplasias da Mama/patologia , Estudos de Viabilidade , Feminino , Humanos , Cuidados Intraoperatórios , Pessoa de Meia-Idade , Invasividade Neoplásica , Valor Preditivo dos Testes , Sensibilidade e Especificidade
4.
Crit Rev Oncol Hematol ; 123: 83-94, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29482783

RESUMO

Sentinel lymph node biopsy (SLNB) is the standard of care for axillary staging in clinically node-negative (cN0) breast cancer patients without neoadjuvant chemotherapy (NAC). The application of SLNB in patients receiving NAC has also been explored. Evidence supports its use after NAC in pretreatment cN0 patients. Nonetheless, its routine use in all the pretreatment node-positive patients who become cN0 after NAC is unjustified due to the unacceptably high false-negative rate, which can be improved in a subset of patients. Axillary surgery omission in selected patients with a low risk of ALN metastasis has gained more and more research interest because the SLNs are tumor-free in more than 70% of all patients. To avoid drawbacks of conventional mapping methods, novel techniques for SLN detection have been developed and shown to be highly accurate in patients with early breast cancer. This article reviews the progress in SLNB in patients with breast cancer.


Assuntos
Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela/tendências , Axila/patologia , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Biópsia de Linfonodo Sentinela/métodos
5.
J Cancer Educ ; 33(5): 1110-1114, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-28374229

RESUMO

Over the past 5 years, cancer has replaced coronary heart disease as the leading cause of death in the Netherlands. It is thus paramount that medical doctors acquire a knowledge of cancer, since most of them will face many patients with cancer. Studies, however, have indicated that there is a deficit in knowledge of oncology among medical students, which may be due not only to the content but also to the structure of the curriculum. In this study, we compared students' knowledge acquisition in four different undergraduate medical programs. Further, we investigated possible factors that might influence students' knowledge growth as related to oncology. The participants comprised 1440 medical students distributed over four universities in the Netherlands. To measure students' knowledge of oncology, we used their progress test results from 2007 to 2013. The progress test consists of 200 multiple-choice questions; this test is taken simultaneously four times a year by all students. All questions regarding oncology were selected. We first compared the growth of knowledge of oncology using mixed models. Then, we interviewed the oncology coordinator of each university to arrive at a better insight of each curriculum. Two schools showed similar patterns of knowledge growth, with a slight decrease in the growth rate for one of them in year 6. The third school had a faster initial growth with a faster decrease over time compared to other medical schools. The fourth school showed a steep decrease in knowledge growth during years 5 and 6. The interviews showed that the two higher-scoring schools had a more focused semester on oncology, whereas in the others, oncology was scattered throughout the curriculum. Furthermore, the absence of a pre-internship training program seemed to hinder knowledge growth in one school. Our findings suggest that curricula have an influence on students' knowledge acquisition. A focused semester on oncology and a pre-internship preparatory training program are likely to have a positive impact on students' progress in terms of knowledge of oncology.


Assuntos
Currículo/normas , Educação de Graduação em Medicina/normas , Conhecimentos, Atitudes e Prática em Saúde , Oncologia/educação , Neoplasias/prevenção & controle , Faculdades de Medicina/normas , Estudantes de Medicina/estatística & dados numéricos , Humanos , Inquéritos e Questionários
6.
J Cancer Educ ; 33(4): 922-925, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-28194581

RESUMO

Starting in 2009, cancer has been the leading cause of death in the Netherlands. Oncology is therefore an important part of the medical curriculum in undergraduate education. It is crucial that medical students know about cancer, since doctors will encounter many cases of oncology. We have compared the influence that teaching oncology has when spread over a 3-year curriculum versus concentrated in one semester. The participants comprised 525 medical students from one medical school with comprehensive integrated curricula. Of those, 436 followed the massed curriculum, with oncology concentrated in one semester. The remaining 89 students followed a spaced-out curriculum, in which oncology was spread out over 3 years. To measure students' knowledge, we used their progress test results from 2009 to 2012. All questions about oncology were categorized and selected. Because of our unbalanced sample and missing data and to reduce the chances for a type II error, we compared the growth of oncology questions using mixed effect models. A cubic growth model with an unstructured covariance matrix fitted our data best. At the start, students in the spaced-out curriculum scored higher on oncology questions. The initial growth was faster for the spaced-out curriculum students, whereas the acceleration over time was slower compared to the massed curriculum students. At the end of the growth curve, the knowledge of the massed curriculum students increased faster. In the last test, the massed curriculum students outperformed those in the spaced-out curriculum. The way students acquired and applied their knowledge was similar in both curricula. It seems, however, that students benefitted more from massed than spaced-out education, which may be due to the comprehensive integrated teaching involved.


Assuntos
Currículo/normas , Educação de Graduação em Medicina/normas , Conhecimentos, Atitudes e Prática em Saúde , Oncologia/educação , Neoplasias/prevenção & controle , Estudantes de Medicina/estatística & dados numéricos , Humanos
7.
Clin Cancer Res ; 23(11): 2730-2741, 2017 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-28119364

RESUMO

Purpose: To provide proof of principle of safety, breast tumor-specific uptake, and positive tumor margin assessment of the systemically administered near-infrared fluorescent tracer bevacizumab-IRDye800CW targeting VEGF-A in patients with breast cancer.Experimental Design: Twenty patients with primary invasive breast cancer eligible for primary surgery received 4.5 mg bevacizumab-IRDye800CW as intravenous bolus injection. Safety aspects were assessed as well as tracer uptake and tumor delineation during surgery and ex vivo in surgical specimens using an optical imaging system. Ex vivo multiplexed histopathology analyses were performed for evaluation of biodistribution of tracer uptake and coregistration of tumor tissue and healthy tissue.Results: None of the patients experienced adverse events. Tracer levels in primary tumor tissue were higher compared with those in the tumor margin (P < 0.05) and healthy tissue (P < 0.0001). VEGF-A tumor levels also correlated with tracer levels (r = 0.63, P < 0.0002). All but one tumor showed specific tracer uptake. Two of 20 surgically excised lumps contained microscopic positive margins detected ex vivo by fluorescent macro- and microscopy and confirmed at the cellular level.Conclusions: Our study shows that systemic administration of the bevacizumab-IRDye800CW tracer is safe for breast cancer guidance and confirms tumor and tumor margin uptake as evaluated by a systematic validation methodology. The findings are a step toward a phase II dose-finding study aimed at in vivo margin assessment and point to a novel drug assessment tool that provides a detailed picture of drug distribution in the tumor tissue. Clin Cancer Res; 23(11); 2730-41. ©2016 AACR.


Assuntos
Benzenossulfonatos/administração & dosagem , Bevacizumab/administração & dosagem , Neoplasias da Mama Masculina/tratamento farmacológico , Neoplasias da Mama/tratamento farmacológico , Indóis/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Benzenossulfonatos/efeitos adversos , Bevacizumab/efeitos adversos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama Masculina/diagnóstico , Neoplasias da Mama Masculina/diagnóstico por imagem , Neoplasias da Mama Masculina/patologia , Linhagem Celular Tumoral , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/patologia , Estudos de Viabilidade , Feminino , Humanos , Indóis/efeitos adversos , Masculino , Imagem Óptica , Tomografia por Emissão de Pósitrons , Distribuição Tecidual/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/genética
8.
Cancer Res ; 77(3): 623-631, 2017 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-27879266

RESUMO

In vivo tumor labeling with fluorescent agents may assist endoscopic and surgical guidance for cancer therapy as well as create opportunities to directly observe cancer biology in patients. However, malignant and nonmalignant tissues are usually distinguished on fluorescence images by applying empirically determined fluorescence intensity thresholds. Here, we report the development of fSTREAM, a set of analytic methods designed to streamline the analysis of surgically excised breast tissues by collecting and statistically processing hybrid multiscale fluorescence, color, and histology readouts toward precision fluorescence imaging. fSTREAM addresses core questions of how to relate fluorescence intensity to tumor tissue and how to quantitatively assign a normalized threshold that sufficiently differentiates tumor tissue from healthy tissue. Using fSTREAM we assessed human breast tumors stained in vivo with fluorescent bevacizumab at microdose levels. Showing that detection of such levels is achievable, we validated fSTREAM for high-resolution mapping of the spatial pattern of labeled antibody and its relation to the underlying cancer pathophysiology and tumor border on a per patient basis. We demonstrated a 98% sensitivity and 79% specificity when using labeled bevacizumab to outline the tumor mass. Overall, our results illustrate a quantitative approach to relate fluorescence signals to malignant tissues and improve the theranostic application of fluorescence molecular imaging. Cancer Res; 77(3); 623-31. ©2016 AACR.


Assuntos
Bevacizumab/farmacocinética , Neoplasias da Mama/diagnóstico por imagem , Interpretação de Imagem Assistida por Computador/métodos , Imagem Molecular/métodos , Imagem Óptica/métodos , Idoso , Antineoplásicos/farmacocinética , Benzenossulfonatos/farmacocinética , Feminino , Corantes Fluorescentes/farmacocinética , Humanos , Indóis/farmacocinética , Pessoa de Meia-Idade
11.
J Clin Oncol ; 33(23): 2553-62, 2015 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-26150446

RESUMO

PURPOSE: Recommendations for treating patients who carry a BRCA1/2 gene are mainly based on cumulative lifetime risks (CLTRs) of breast cancer determined from retrospective cohorts. These risks vary widely (27% to 88%), and it is important to understand why. We analyzed the effects of methods of risk estimation and bias correction and of population factors on CLTRs in this retrospective clinical cohort of BRCA1/2 carriers. PATIENTS AND METHODS: The following methods to estimate the breast cancer risk of BRCA1/2 carriers were identified from the literature: Kaplan-Meier, frailty, and modified segregation analyses with bias correction consisting of including or excluding index patients combined with including or excluding first-degree relatives (FDRs) or different conditional likelihoods. These were applied to clinical data of BRCA1/2 families derived from our family cancer clinic for whom a simulation was also performed to evaluate the methods. CLTRs and 95% CIs were estimated and compared with the reference CLTRs. RESULTS: CLTRs ranged from 35% to 83% for BRCA1 and 41% to 86% for BRCA2 carriers at age 70 years width of 95% CIs: 10% to 35% and 13% to 46%, respectively). Relative bias varied from -38% to +16%. Bias correction with inclusion of index patients and untested FDRs gave the smallest bias: +2% (SD, 2%) in BRCA1 and +0.9% (SD, 3.6%) in BRCA2. CONCLUSION: Much of the variation in breast cancer CLTRs in retrospective clinical BRCA1/2 cohorts is due to the bias-correction method, whereas a smaller part is due to population differences. Kaplan-Meier analyses with bias correction that includes index patients and a proportion of untested FDRs provide suitable CLTRs for carriers counseled in the clinic.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/genética , Heterozigoto , Mutação , Adulto , Idoso , Feminino , Predisposição Genética para Doença , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Variações Dependentes do Observador , Estudos Retrospectivos , Medição de Risco
12.
Ned Tijdschr Geneeskd ; 159: A8662, 2015.
Artigo em Holandês | MEDLINE | ID: mdl-25784067

RESUMO

We describe a 49-year-old woman who presented to the surgeon with recurring complaints of her right nipple, such as redness, pain, swelling and purulent discharge from the areolar margin. The diagnosis 'Zuska's disease' should be distinguished from breast cancer, Paget's and Mondor's disease. Treatment is surgical with a microdochectomy.


Assuntos
Abscesso/diagnóstico , Doenças Mamárias/diagnóstico , Fístula/diagnóstico , Mamilos/patologia , Abscesso/cirurgia , Doenças Mamárias/cirurgia , Feminino , Fístula/cirurgia , Humanos , Pessoa de Meia-Idade
13.
Maturitas ; 78(4): 252-7, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24894332

RESUMO

DNA-testing for BRCA1 and BRCA2 has become incorporated in the diagnostic procedure of patients with breast and/or ovarian cancer. Since 1994 an immense amount of information has been gathered on mutation spectra, mutation risk assessment, cancer risks for mutation carriers, factors that modify these risks, unclassified DNA variants, surveillance strategies and preventive options. For the patient and family the main determinator still is whether a mutation is found or not. When a pathogenic mutation is detected in an index case, relatives can opt for pre-symptomatic DNA testing. However in the vast majority no mutation, or only unclear mutations are detectable yet. This means that a hereditary cause cannot be excluded, but pre-symptomatic DNA-testing is still unavailable for relatives. Surveillance for both index cases and relatives is based of the family history of cancer. Next generation genetic testing may help to elucidate genetic causes in these families.


Assuntos
Proteína BRCA2/genética , Genes BRCA1 , Genes BRCA2 , Testes Genéticos , Mutação , Neoplasias Ovarianas/genética , Neoplasias da Mama/genética , Feminino , Predisposição Genética para Doença , Humanos
15.
Maturitas ; 77(2): 180-4, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24268650

RESUMO

INTRODUCTION: Strategies in case of high risk of breast cancer in BRCA1/2 mutation carriers are either intensive breast cancer screening or risk-reducing mastectomy (RRM). Both options have a high physical and psychosexual impact. The aim of this study is to investigate who chooses when to undergo RRM. METHODS: BRCA1/2 mutation carriers have been prospectively registered at the family cancer clinic between 1994 and 2011. Analyses were performed to assess the relation between characteristics of the BRCA1/2 mutation carriers and an earlier decision for RRM. RESULTS: A cumulative percentage of 35.6% of all women chose to undergo RRM within the first five years after disclosure of DNA test results. Women needed less time to choose for RRM measured from the first visit, if they were younger than 50 years of age (hazard ratio (HR)=2.67, 95% confidence interval (CI)=1.30-5.48) or had a mother who had had breast cancer (HR=1.51 95% CI=1.04-2.18). Also, women needed less time to choose for RRM in case of a previous breast cancer (HR=2.25, 95% CI=1.55-3.27). After a previous unilateral therapeutic mastectomy as a treatment for breast cancer, women needed less time to choose for RRM of the contralateral breast (HR=2.69, 95% CI=1.29-5.62) compared to women who had had breast-conserving therapy. CONCLUSION: BRCA1/2 mutation carriers aged under 50, having a mother with breast cancer, who had previous unilateral breast cancer and previous unilateral therapeutic mastectomy chose more often and earlier for RRM.


Assuntos
Neoplasias da Mama/psicologia , Genes BRCA1 , Genes BRCA2 , Mastectomia/psicologia , Neoplasias da Mama/genética , Feminino , Humanos , Pessoa de Meia-Idade , Comportamento de Redução do Risco , Fatores de Tempo
16.
J Nucl Med ; 54(7): 1014-8, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23651946

RESUMO

UNLABELLED: Vascular endothelial growth factor (VEGF)-A is overexpressed in most malignant and premalignant breast lesions. VEGF-A can be visualized noninvasively with PET imaging and using the tracer (89)Zr-labeled bevacizumab. In this clinical feasibility study, we assessed whether VEGF-A in primary breast cancer can be visualized by (89)Zr-bevacizumab PET. METHODS: Before surgery, breast cancer patients underwent a PET/CT scan of the breasts and axillary regions 4 d after intravenous administration of 37 MBq of (89)Zr-bevacizumab per 5 mg. PET images were compared with standard imaging modalities. (89)Zr-bevacizumab uptake was quantified as the maximum standardized uptake value (SUV max). VEGF-A levels in tumor and normal breast tissues were assessed with enzyme-linked immunosorbent assay. Data are presented as mean ± SD. RESULTS: Twenty-five of 26 breast tumors (mean size ± SD, 25.1 ± 19.8 mm; range, 4-80 mm) in 23 patients were visualized. SUV max was higher in tumors (1.85 ± 1.22; range, 0.52-5.64) than in normal breasts (0.59 ± 0.37; range, 0.27-1.69; P < 0.001). The only tumor not detected on PET was 10 mm in diameter. Lymph node metastases were present in 10 axillary regions; 4 could be detected with PET (SUV max, 2.66 ± 2.03; range, 1.32-5.68). VEGF-A levels in the 17 assessable tumors were higher than in normal breast tissue in all cases (VEGF-A/mg protein, 184 ± 169 pg vs. 10 ± 21 pg; P = 0.001), whereas (89)Zr-bevacizumab tumor uptake correlated with VEGF-A tumor levels (r = 0.49). CONCLUSION: VEGF-A in primary breast cancer can be visualized by means of (89)Zr-bevacizumab PET.


Assuntos
Anticorpos Monoclonais Humanizados/farmacocinética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/diagnóstico por imagem , Tomografia por Emissão de Pósitrons/métodos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Adulto , Idoso , Bevacizumab , Neoplasias da Mama/metabolismo , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Imagem Molecular/métodos , Radioisótopos , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Zircônio
17.
Breast ; 22(5): 773-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23462681

RESUMO

BACKGROUND: Breast-conserving therapy, consisting of lumpectomy and adjuvant radiotherapy, is considered standard treatment for early-stage breast cancer. One of the most important risk factors of local recurrence is the presence of positive surgical margins following lumpectomy. We aimed to develop and validate a predictive model (nomogram) to predict for positive margins following the first attempt at lumpectomy as a preoperative tool for clinical decision-making. METHODS: Patients with clinical T1-2N0-1Mx-0 histology-proven invasive breast carcinoma who underwent BCT throughout the North-East region of The Netherlands between June 2008 and July 2009 were selected from the Netherlands Cancer Registry (n = 1185). Results from multivariate logistic regression analyses served as the basis for development of the nomogram. Nomogram calibration and discrimination were assessed graphically and by calculation of a concordance index, respectively. Nomogram performance was validated on an external independent dataset (n = 331) from the University Medical Center Groningen. RESULTS: The final multivariate regression model included clinical, radiological, and pathological variables. Concordance indices were calculated of 0.70 (95% CI: 0.66-0.74) and 0.69 (95% CI: 0.63-0.76) for the modeling and the validation group, respectively. Calibration of the model was considered adequate in both groups. A nomogram was developed as a graphical representation of the model. Moreover, a web-based application (http://www.breastconservation.com) was build to facilitate the use of our nomogram in a clinical setting. CONCLUSION: We developed and validated a nomogram that enables estimation of the preoperative risk of positive margins in breast-conserving surgery. Our nomogram provides a valuable tool for identifying high-risk patients who might benefit from preoperative MRI and/or oncoplastic surgery.


Assuntos
Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma/patologia , Carcinoma/terapia , Mastectomia Segmentar , Recidiva Local de Neoplasia/patologia , Nomogramas , Adulto , Idoso , Neoplasias da Mama/complicações , Calcinose/complicações , Carcinoma/complicações , Técnicas de Apoio para a Decisão , Feminino , Humanos , Internet , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasia Residual , Período Pré-Operatório , Radioterapia Adjuvante
18.
Crit Care Med ; 38(7): 1598-601, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20495451

RESUMO

OBJECTIVES: To illustrate the importance of recognizing symptoms of severe hypercortisolism in the intensive care unit and key emergency measures to reduce this extreme hypercortisolism. DESIGN: Case report. SETTING: Intensive care unit in a university hospital. PATIENT: A 55-yr-old woman was admitted to the intensive care unit with multiorgan failure after perforation of the sigmoid. Recent-onset hypertension, spontaneous hypokalemia, and diabetes mellitus suggested severe Cushing's syndrome as the underlying disease. Markedly increased serum cortisol (5900 nmol/L) and adrenocorticotropic hormone (302 ng/L) levels were found, highly suggestive for ectopic adrenocorticotropic hormone secretion. Imaging studies failed to unequivocally establish a solitary source of ectopic adrenocorticotropic hormone secretion. The deteriorating condition of the patient urged rapid intervention. INTERVENTIONS: Etomidate was infused continuously to reduce endogenous adrenal cortisol secretion. Subsequently, a rescue bilateral adrenalectomy was undertaken. MEASUREMENTS AND RESULTS: Etomidate effectively reduced the cortisol level. Serial blood samples were obtained during the bilateral adrenalectomy. Plasma adrenocorticotropic hormone markedly decreased immediately after resection of the right adrenal gland. Histopathological examination revealed a tumor of the right adrenal gland identified as a pheochromocytoma and hyperplasia of the left adrenal gland, but no signs of malignancy. The patient recovered slowly. CONCLUSION: This case illustrates that severe hypercortisolism is a medical emergency and that specific and prompt combined medical and surgical intervention can be life-saving.


Assuntos
Síndrome de Cushing/terapia , Neoplasias das Glândulas Suprarrenais/complicações , Adrenalectomia , Hormônio Adrenocorticotrópico/sangue , Colo Sigmoide , Síndrome de Cushing/complicações , Etomidato/uso terapêutico , Feminino , Humanos , Hidrocortisona/sangue , Unidades de Terapia Intensiva , Perfuração Intestinal/complicações , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/etiologia , Feocromocitoma/complicações , Doenças do Colo Sigmoide/complicações
19.
Breast Cancer Res Treat ; 124(3): 643-51, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-20204502

RESUMO

Accurate estimations of lifetime risks of breast and ovarian cancer are crucial for counselling women from BRCA1/2 families. We therefore determined breast and ovarian cancer penetrance in BRCA1/2 mutation families in the northern Netherlands and compared them with the incidence of cancers in the general population in this region. We identified 1188 female mutation carriers and first-degree female relatives in 185 families with a pathogenic BRCA1 or BRCA2 mutation. The occurrence of breast cancer, contralateral breast cancer and ovarian cancer was recorded. The cumulative incidence of breast cancer by age 70 was 71.4% (95% CI 67.2-82.4%) in BRCA1 and 87.5% (82.4-92.6%) in BRCA2 mutation carriers. For ovarian cancer at age 70, it was 58.9% (53.5-64.3%) in BRCA1 and 34.5% (25.0-44.0%) in BRCA2 mutation carriers. For breast cancer we saw a rise of 24.2% in the cumulative incidence in the seventh decade for BRCA2 mutation carriers versus 6.3% for BRCA1. For ovarian cancer the rise in the seventh decade was 17.3% for BRCA1 mutation carriers and 15.1% for BRCA2. The 10-year risk for contralateral breast cancer was 34.2% (29.4-39.0%) in BRCA1 families and 29.2% (22.9-35.5%) in BRCA2. We show that the incidence of breast and ovarian cancer in BRCA2 mutation carriers and of ovarian cancer in BRCA1 mutation carriers is still high after 60 years. This may justify intensive breast screening as well as oophorectomy even after age 60. The risk of contralateral breast cancer rises approximately 3% per year, which may affect preventive choices.


Assuntos
Proteína BRCA1/genética , Proteína BRCA2/genética , Neoplasias da Mama/genética , Mutação , Recidiva Local de Neoplasia , Neoplasias Ovarianas/genética , Penetrância , Adulto , Fatores Etários , Idoso , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/prevenção & controle , Análise Mutacional de DNA , Feminino , Aconselhamento Genético , Predisposição Genética para Doença , Humanos , Incidência , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Países Baixos/epidemiologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/prevenção & controle , Linhagem , Fenótipo , Sistema de Registros , Medição de Risco , Fatores de Risco , Fatores de Tempo , Adulto Jovem
20.
Psychol Health ; 25(9): 1023-40, 2010 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-20204948

RESUMO

This prospective study examines the cognitive and behavioural mediators of the relation between personal control and the initial response to a breast cancer diagnosis as well as subsequent psychological adjustment. A total of 143 patients participated immediately after diagnosis (T1), after surgery (T2) and 2 months after the end of treatment (T3), of whom 92 also completed a questionnaire pre-diagnosis (T0). The buffering effect of personal control on psychological distress shortly after diagnosis was mediated by cancer-specific cognitions, i.e. threat appraisal and coping self-efficacy. Moreover, a strong sense of personal control predicted lower levels of anxiety 2 months after the end of treatment, but was unrelated to distress at T3. The adaptive effect on anxiety was mediated by threat appraisal and active engagement in social life after surgery, but not by active patient participation or coping self-efficacy. These results confirm and explain the adaptive effect of control. Apparently, women with a low sense of control appraise cancer and their personal coping skills more negatively, which makes them vulnerable to distress in response to diagnosis. Furthermore, women with a strong sense of control might regulate anxiety by remaining engaged in social life.


Assuntos
Adaptação Psicológica , Neoplasias da Mama/psicologia , Controle Interno-Externo , Adulto , Idoso , Feminino , Humanos , Pessoa de Meia-Idade , Países Baixos , Estudos Prospectivos , Inquéritos e Questionários
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