RESUMO
OBJECTIVES: We aimed to examine: (1) the long-term association between coping styles and psychological distress, (2) if women diagnosed with breast cancer have a predominant coping style, (3) stability of coping styles, (4) predictors of changes in coping styles, (5) if maladaptive coping adversely impacts disease-free survival (DFS). METHODS: This prospective study included women diagnosed with primary breast cancer during 2006-2009. Patients completed questionnaires for the Norwegian Mini-Mental Adjustment to Cancer scale, which includes positive attitude (PA), helplessness/hopelessness (HH), anxious preoccupation (AP), and avoidance (AV), and the Hospital Anxiety and Depression Scale at diagnosis and 1, 3, and 5 years postdiagnosis. RESULTS: Two hundred and ninety-three of 367 women (79.8%) completed the questionnaires at all time points. Anxiety and depression were moderately to strongly correlated with HH and AP coping styles (r = 0.31 to r = 0.69) at all time points. The predominant coping style was PA (23.4-29.9%). Stability for PA and cognitive AV styles was found at the group level, but not at an individual level. Chemotherapy and comorbidity were predictors for HH, AP, and AV 5 years postdiagnosis (p < 0.05). Maladaptive coping was not associated with DFS. CONCLUSIONS: HH and AP were associated with higher psychological distress at all times. Group level coping remained stable over time for PA and AV. Coping style stability at an individual level was not observed. Having received chemotherapy and experienced adverse events affected coping at 5 years postdiagnosis. Maladaptive coping was not associated with DFS.
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Adaptação Psicológica , Ansiedade/epidemiologia , Neoplasias da Mama/psicologia , Sobreviventes de Câncer/psicologia , Depressão/epidemiologia , Adolescente , Adulto , Idoso , Ansiedade/psicologia , Neoplasias da Mama/complicações , Neoplasias da Mama/epidemiologia , Comorbidade , Feminino , Humanos , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Estudos Prospectivos , Angústia Psicológica , Autoimagem , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Breast cancer is a heterogeneous disease at the clinical and molecular level. In this study we integrate classifications extracted from five different molecular levels in order to identify integrated subtypes. METHODS: Tumor tissue from 425 patients with primary breast cancer from the Oslo2 study was cut and blended, and divided into fractions for DNA, RNA and protein isolation and metabolomics, allowing the acquisition of representative and comparable molecular data. Patients were stratified into groups based on their tumor characteristics from five different molecular levels, using various clustering methods. Finally, all previously identified and newly determined subgroups were combined in a multilevel classification using a "cluster-of-clusters" approach with consensus clustering. RESULTS: Based on DNA copy number data, tumors were categorized into three groups according to the complex arm aberration index. mRNA expression profiles divided tumors into five molecular subgroups according to PAM50 subtyping, and clustering based on microRNA expression revealed four subgroups. Reverse-phase protein array data divided tumors into five subgroups. Hierarchical clustering of tumor metabolic profiles revealed three clusters. Combining DNA copy number and mRNA expression classified tumors into seven clusters based on pathway activity levels, and tumors were classified into ten subtypes using integrative clustering. The final consensus clustering that incorporated all aforementioned subtypes revealed six major groups. Five corresponded well with the mRNA subtypes, while a sixth group resulted from a split of the luminal A subtype; these tumors belonged to distinct microRNA clusters. Gain-of-function studies using MCF-7 cells showed that microRNAs differentially expressed between the luminal A clusters were important for cancer cell survival. These microRNAs were used to validate the split in luminal A tumors in four independent breast cancer cohorts. In two cohorts the microRNAs divided tumors into subgroups with significantly different outcomes, and in another a trend was observed. CONCLUSIONS: The six integrated subtypes identified confirm the heterogeneity of breast cancer and show that finer subdivisions of subtypes are evident. Increasing knowledge of the heterogeneity of the luminal A subtype may add pivotal information to guide therapeutic choices, evidently bringing us closer to improved treatment for this largest subgroup of breast cancer.
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Biomarcadores Tumorais , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Análise por Conglomerados , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/mortalidade , Variações do Número de Cópias de DNA , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Redes e Vias Metabólicas , Metabolômica/métodos , MicroRNAs/genética , Noruega/epidemiologia , Prognóstico , RNA Mensageiro/genéticaRESUMO
BACKGROUND: Recent registry studies on early-stage breast cancer have shown better survival rates when women underwent breast-conserving therapy (BCT) compared with mastectomy (MTX). The aim of this study is to investigate women participating in screening, in all four stages of early breast cancer (T1N0M0, T2N0M0, T1N1M0, and T2N1M0), as to whether there is a survival benefit when women undergo BCT compared to MTX. METHOD: A cohort of 6387 women aged 50-69, with primary-operated breast cancer from January 1998 to December 2009, participating in screening and followed-up until the end of 2010. Life tables were calculated by stages (pT1N0M0, pT2N0M0, pT1N1M0, and pT2N1M0), surgery groups (BCT and MTX), and screening detection (first screening, later screening, or interval cancer). Cox regression was used to calculate hazard ratios (HR) between BCT and MTX in crude and adjusted analyses. RESULTS: In stage T1N1M0, women who underwent MTX had an HR of 2.91 (95% CI 1.30-6.48) for breast cancer death compared to women who underwent BCT, after adjusting for screening detection, years of diagnosis, age at diagnosis, histology, grade, and hormone receptor status. For all other TNM categories of early breast cancer, there was no difference in survival. 10-year breast cancer-specific survival (BCSS) in T1N0M0 was 98% for women undergoing BCT and 96% for women undergoing MTX. 10-year BCSS in T1N1M0 was 97% for women undergoing BCT and 89% for women undergoing MTX. CONCLUSIONS: For women participating in screening, there is a benefit of BCT over MTX in stage T1N1M0. No such effects were observed in the other early stages of breast cancer.
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Neoplasias da Mama/mortalidade , Mastectomia Segmentar/mortalidade , Mastectomia/mortalidade , Sistema de Registros/estatística & dados numéricos , Idoso , Axila , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Prognóstico , Taxa de SobrevidaRESUMO
INTRODUCTION: Hypercoagulability in malignancy increases the risk of thrombosis, but is also involved in cancer progression. Experimental studies suggest that tissue factor (TF) and tissue factor pathway inhibitor (TFPI) are involved in cancer biology as a tumor- promoter and suppressor, respectively, but the clinical significance is less clear. Here, we aimed to investigate the clinical relevance of TF and TFPI genetic and phenotypic diversity in breast cancer. METHODS: The relationship between tumor messenger RNA (mRNA) expression and plasma levels of TF and TFPI (α and ß), tagging single nucleotide polymorphisms (tagSNPs) in F3 (TF) (n=6) and TFPI (n=18), and clinicopathological characteristics and molecular tumor subtypes were explored in 152 treatment naive breast cancer patients. The effect of tumor expressed TF and TFPIα and TFPIß on survival was investigated in a merged breast cancer dataset of 1881 patients. RESULTS: Progesterone receptor negative patients had higher mRNA expression of total TFPI (α+ß) (P=0.021) and TFPIß (P=0.014) in tumors. TF mRNA expression was decreased in grade 3 tumors (P=0.003). In plasma, total TFPI levels were decreased in patients with larger tumors (P=0.013). SNP haplotypes of TFPI, but not TF, were associated with specific clinicopathological characteristics like tumor size (odds ratio (OR) 3.14, P=0.004), triple negativity (OR 2.4, P=0.004), lymph node spread (OR 3.34, P=0.006), and basal-like (OR 2.3, P=0.011) and luminal B (OR 3.5, P=0.005) molecular tumor subtypes. Increased expression levels of TFPIα and TFPIß in breast tumors were associated with better outcome in all tumor subtypes combined (P=0.007 and P=0.005) and in multiple subgroups, including lymph node positive subjects (P=0.006 and P=0.034). CONCLUSIONS: This study indicates that genetic and phenotypic variation of both TFPIα and TFPIß, more than TF, are markers of cancer progression. Together with the previously demonstrated tumor suppressor effects of TFPI, the beneficial effect of tumor expressed TFPI on survival, renders TFPI as a potential anticancer agent, and the clinical significance of TFPI in cancer deserves further investigation.
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Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Expressão Gênica , Lipoproteínas/genética , Lipoproteínas/metabolismo , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Alelos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Feminino , Estudos de Associação Genética , Genótipo , Haplótipos , Humanos , Lipoproteínas/sangue , Pessoa de Meia-Idade , Gradação de Tumores , Metástase Neoplásica , Estadiamento de Neoplasias , Fenótipo , Prognóstico , RNA Mensageiro/genética , Tromboplastina/genética , Tromboplastina/metabolismo , Carga TumoralRESUMO
BACKGROUND: Breast-conserving therapy (BCT) and mastectomy (MTX) has been considered to have a similar long-time survival. However, better survival in women undergoing BCT compared with MTX is found in two recent register studies from the United States. The purpose of this study was to compare survival after BCT and MTX for women with early-stage breast cancer in Norway. METHODS: Women with invasive, early-stage breast cancer (1998-2008) where BCT and MTX were considered as equally beneficial treatments were included for a total of 13,015 women. Surgery was divided in two main cohorts (primary BCT, primary MTX) and five subcohorts. Analyses were stratified into T1N0M0, T2N0M0, T1N1M0, T2N1M0, and age groups (<50, 50-69, ≥70). Overall survival and breast cancer-specific survival (BCSS) were calculated in life tables, hazard ratios by Cox regression, and sensitivity analyses. RESULTS: Five-year BCSS for women who underwent primary BCT or primary MTX was 97 and 88 %, respectively. Women who underwent primary MTX had a hazard ratio of 1.64 (95 % confidence interval 1.43-1.88) for breast cancer death compared with women who underwent primary BCT after adjusting for the year of diagnosis, age at diagnosis, stage, histology, and grade. CONCLUSIONS: Survival was better or equal after breast-conserving therapy than mastectomy in all early stages, surgical subcohorts, and age groups. This advantage could not only be attributed to differences in tumor biology.
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Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Mastectomia , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/secundário , Feminino , Humanos , Estimativa de Kaplan-Meier , Metástase Linfática , Mastectomia Segmentar , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Noruega , Modelos de Riscos Proporcionais , Radioterapia Adjuvante , Sistema de Registros , Reoperação , Taxa de SobrevidaRESUMO
BACKGROUND: The procoagulant state in cancer increases the thrombotic risk, but also supports tumor progression. To investigate the molecular mechanisms controlling cancer and hemostasis, we conducted a case-control study of genotypic and phenotypic variables of the tissue factor (TF) pathway of coagulation in breast cancer. METHODS: 366 breast cancer patients and 307 controls were genotyped for SNPs (n = 41) in the F2, F3 (TF), F5, F7, F10, TFPI and EPCR genes, and assayed for plasma coagulation markers (thrombin generation, activated protein C (APC) resistance, D-dimer, antithrombin, protein C, protein S, and TF pathway inhibitor (TFPI)). Associations with breast cancer were evaluated using logistic regression to obtain odds ratios (ORs) and 95% confidence intervals (CIs), or the chi-square test. RESULTS: Four SNPs in F5 (rs12120605, rs6427202, rs9332542 and rs6427199), one in F10 (rs3093261), and one in EPCR (rs2069948) were associated with breast cancer. EPCR rs2069948 was associated with estrogen receptor (ER) and progesterone receptor (PR) positivity, while the SNPs in F5 appeared to follow hormone receptor negative and triple negative patients. The prothrombotic polymorphisms factor V Leiden (rs6025) and prothrombin G20210A (rs1799963) were not associated with breast cancer. High APC resistance was associated with breast cancer in both factor V Leiden non-carriers (OR 6.5, 95% CI 4.1-10.4) and carriers (OR 38.3, 95% CI 6.2-236.6). The thrombin parameters short lag times (OR 5.8, 95% CI 3.7-9.2), short times to peak thrombin (OR 7.1, 95% CI 4.4-11.3), and high thrombin peak (OR 6.1, 95% CI 3.9-9.5) predicted presence of breast cancer, and high D-dimer also associated with breast cancer (OR 2.0, 95% CI 1.3-3.3). Among the coagulation inhibitors, low levels of antithrombin associated with breast cancer (OR 5.7, 95% CI 3.6-9.0). The increased coagulability was not explained by the breast cancer associated SNPs, and was unaffected by ER, PR and triple negative status. CONCLUSIONS: A procoagulant phenotype was found in the breast cancer patients. Novel associations with SNPs in F5, F10 and EPCR to breast cancer susceptibility were demonstrated, and the SNPs in F5 were confined to hormone receptor negative and triple negative patients. The study supports the importance of developing new therapeutic strategies targeting coagulation processes in cancer.
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Antígenos CD/genética , Coagulação Sanguínea/genética , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Fator V/genética , Fator X/genética , Polimorfismo Genético , Receptores de Superfície Celular/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Receptor de Proteína C Endotelial , Feminino , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Hemostasia , Humanos , Desequilíbrio de Ligação , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Polimorfismo de Nucleotídeo Único , Risco , Transdução de Sinais , Tromboplastina/metabolismoRESUMO
INTRODUCTION: Over-treatment of low-risk early breast cancer patients with adjuvant systemic therapies is an important clinical challenge. Better techniques are required which can be used to distinguish between the large group of patients with no residual disease after surgery and consequently no benefit of adjuvant treatment, from the smaller group with high relapse risk. A better integration of available prognostic factors might contribute to improved prediction of clinical outcome. MATERIAL AND METHODS: The current study included 346 unselected pT1pN0 patients who did not receive adjuvant systemic treatment. In Norway, no patients with this stage were recommended systemic treatment at the time of the study (1995-1998). Histological type, tumour size, grade, vascular invasion (VI), hormone receptor (HR) status, HER2 and Ki67 (cut-off 10%) were analysed. Median follow-up was 86 months for relapse and 101 months for death. RESULTS: Thirty-eight patients experienced relapse, 31 with distant metastasis. Twenty-one patients died of breast cancer. In univariate analysis grade, HER2, HR, VI and Ki67 had impact on clinical outcome (p < 0.005, log rank). In multivariate analysis, only grade 1-2 vs. grade 3, HER2, VI, and Ki67 status were significant for disease free survival, distant disease free survival, and/or breast cancer specific survival. These factors were used in combination, to separate patients into groups based on the number of unfavourable factors present [combined prognostic score (CPS) 0-4]. Close to 2/3 of the patients (61.4%) had no unfavourable factor (CPS0), whilst 18.4% had CPS ≥ 2. Only 3.6% of those with CPS0 developed metastasis (p < 0.001). The outcome was clearly worse for patients with CPS ≥ 2 (p < 0.001), systemic relapse was detected in approximately 40%. CONCLUSIONS: This study indicates that the combined use of grade, VI, HER2 and Ki67 identifies a subgroup of breast cancer patients with a relapse risk that may question the benefit of adjuvant systemic therapy.
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Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Antígeno Ki-67/metabolismo , Receptor ErbB-2/metabolismo , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Quimioterapia Adjuvante , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Análise Multivariada , Gradação de Tumores , Invasividade Neoplásica , Metástase Neoplásica , Recidiva Local de Neoplasia , Radioterapia AdjuvanteRESUMO
BACKGROUND: Studies have revealed variations in breast cancer survival between different counties in Norway. This study describes trends in surgical treatment of ductal carcinoma in situ (DCIS) and breast cancer in Norway, over time and by county. MATERIAL AND METHOD: Information about surgical treatment, age and county for 3,915 women with DCIS and for 54,732 women with breast cancer, diagnosed in the periods 1995-2009 and 1986-2009 respectively, was provided from the incidence database at the Cancer Registry of Norway. RESULTS: In the period 1995-97, 3.0 in 100,000 women with DCIS had breast conserving treatment (BCT), while 5.0 in 100,000 had mastectomy. In 2004-06 the rates were 8.6 and 4.2, respectively. In 1995-97, 18.7 in 100,000 women with breast cancer had BCT, while 77.3 in 100,000 had mastectomy. In 2004-06 the rates were 57.9 and 50.8, respectively. The percentage of women with DCIS or breast cancer who were treated with BCT was lower in 2007-09 in all counties than in 2004-06. For 2007-09 the percentage of women with DCIS who were treated with BCT varied by county from 39% to 75%. For breast cancer the percentage varied from 33% to 67%. INTERPRETATION: The number and percentage of women with DCIS or breast cancer who were treated with BCT increased until 2005, then it fell, and the percentage varied between counties. The reasons for this need to be identified and followed up with regard to the recommendations from the Norwegian Breast Cancer Group.
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Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/cirurgia , Mastectomia Segmentar , Mastectomia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Mastectomia/estatística & dados numéricos , Mastectomia/tendências , Mastectomia Segmentar/estatística & dados numéricos , Mastectomia Segmentar/tendências , Pessoa de Meia-Idade , Noruega/epidemiologia , Sistema de RegistrosRESUMO
INTRODUCTION: The presence of tumor cells in the axillary lymph nodes is the most important prognostic factor in early stage breast cancer. However, the optimal method for sentinel lymph node (SLN) examination is still sought and currently many different protocols are employed. To examine two approaches for tumor cell detection we performed, in sequence, immunomagnetic enrichment and RT-PCR analysis on SLN samples from early stage breast cancer patients. This allowed us to compare findings based on the expression of cell surface proteins with those based on detection of intracellular transcripts. METHODS: Enrichment of EpCAM and Mucin 1 expressing cells from fresh SLN samples was achieved using magnetic beads coated with the appropriate antibodies. All resulting cell fractions were analyzed by RT-PCR using four chosen breast epithelial markers (hMAM, AGR2, SBEM, TFF1). Gene expression was further analyzed using RT-PCR arrays and markers for epithelial to mesenchymal transition (EMT). RESULTS: Both EpCAM and Mucin 1 enriched for the epithelial-marker expressing cells. However, EpCAM-IMS identified epithelial cells in 71 SLNs, whereas only 35 samples were positive with RT-PCR targeting breast epithelial transcripts. Further analysis of EpCAM positive but RT-PCR negative cell fractions showed that they had increased expression of MMPs, repressors of E-cadherin, SPARC and vimentin, all transcripts associated with the process of epithelial to mesenchymal transition. CONCLUSIONS: The EpCAM IMS-assay detected tumor cells with epithelial and mesenchymal-like characteristics, thus proving to be a more robust marker than pure epithelial derived biomarkers. This finding has clinical implications, as most methods for SLN analysis today rely on the detection of epithelial transcripts or proteins.
Assuntos
Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Moléculas de Adesão Celular/metabolismo , Separação Imunomagnética/métodos , Linfonodos/patologia , Axila , Caderinas/genética , Molécula de Adesão da Célula Epitelial , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Feminino , Humanos , Linfonodos/metabolismo , Metástase Linfática/patologia , Mucina-1/metabolismo , Mucinas/genética , Mucoproteínas , Proteínas Oncogênicas , Osteonectina/genética , Proteínas/genética , Reprodutibilidade dos Testes , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Biópsia de Linfonodo Sentinela/métodos , Fator Trefoil-1 , Proteínas Supressoras de Tumor/genética , Vimentina/genéticaRESUMO
OBJECTIVE: The purpose was to investigate whether self-reported health-related quality-of-life (HRQOL) parameters at time of diagnosis and/or 1-year follow-up are prognostic for disease-free survival (DFS) in early-stage breast cancer patients. METHODS: Data from 195 women, diagnosed with early-stage breast cancer, who had filled in the EORTC QLQ-C30 and the Hospital Anxiety and Depression Scale (HADS) at time of diagnosis and 1 year after surgery, were analyzed. RESULTS: After a median follow-up of 8.2 years (range 0.09-9.45), 27 (14.1%) deaths and 22 (11.5%) recurrences were observed. Using Cox multivariate regression analysis, appetite loss reported 1-year following surgery (HR 2.92, 95% CI 1.50-5.66), p=0.002) was significantly predictive for shorter DFS, even after controlling for age and depression. None of the clinical or biological prognostic factors was found to have a confounding effect. CONCLUSION: The findings indicate that loss of appetite probably is of prognostic value in addition to well-recognized clinical and biological data, in early-stage breast cancer.
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Neoplasias da Mama/psicologia , Qualidade de Vida/psicologia , Adulto , Fatores Etários , Idoso , Apetite , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/mortalidade , Depressão/etiologia , Depressão/psicologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Escalas de Graduação Psiquiátrica , Análise de Regressão , Análise de Sobrevida , Adulto JovemRESUMO
BACKGROUND: Several studies have reported an association between breast cancer unit volume and prognosis. We hypothesize that this may be due to inappropriate coping with the recommended guidelines for adjuvant therapy rather than improper breast cancer surgery provided at smaller units. METHODS: A cohort of 1131 patients with operable breast cancer (pT(1-2) and positive axillary lymph nodes, stage II) enrolled between 1984 and 1994 were analyzed. The women had participated in one of three prospective trials on adjuvant endocrine treatment and were enrolled from 50 centers in Norway. The hospitals were categorized into four groups according to the annual number of surgically treated breast cancer patients reported to the national discharge database in 1990. The hospitals were also stratified according to whether they are university or non-university hospitals. To assess the effect of unit size on patient outcome, local recurrence rates and overall survival were compared in women treated at units with different patient volumes. RESULTS: The median time from study enrolment to the end of the study was 10.5 years. Relapse-free survival and overall survival did not differ significantly between the hospital groups based on the surgical workload or between university and non-university hospitals. CONCLUSIONS: Patient volume or teaching status of a hospital did not have any impact on the prognosis of pre- or postmenopausal stage II breast cancer patients included in the adjuvant endocrine trials. Our data support the hypothesis that differences in survival related to patient volume at the treatment units may be explained by inappropriate adjuvant systemic treatment.
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Neoplasias da Mama , Hospitais , Adulto , Idoso , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante/efeitos adversos , Intervalo Livre de Doença , Feminino , Hospitais/estatística & dados numéricos , Hospitais Universitários/estatística & dados numéricos , Humanos , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Noruega , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Análise de SobrevidaRESUMO
BACKGROUND: Estrogen receptor (ER) status and progesterone receptor (PgR) status are strong prognostic and predictive markers in breast carcinomas. Steroid receptors are fragile and optimal handling of both cytological and histological material, including fixation, is crucial. Liquid based material offers the possibility to prepare a number of slides from one lesion and is increasingly being used for immunocytochemistry. It also offers the possibility to prepare several smears and to store these at different temperatures as well as storing residual material in the liquid. MATERIALS AND METHODS: The samples consisted of fine needle aspirate material from 53 breast carcinomas. Direct smears and liquid based preparations were used in parallel for immunocytochemical detection of ER and PgR receptor status. Slides from liquid suspensions were stored at -20°C and -74°C for 3 and 6 months, respectively. Direct smears were fixed primarily in 4% formalin. Liquid based specimens were post-fixed in 4% formalin. All specimens were subjected to microwave-stimulated epitope retrieval. Antibody concentrations were ER 1:150 and PgR 1:200 for both preparation methods. The immunostaining program was identical for both the methods. RESULTS: Liquid based specimens had a statistically non-significant higher percentage of positive cases compared to direct smears. Specimens prepared from liquid suspensions and stored at -20°C and -74°C for 3 and 6 months, respectively, showed a virtually unchanged ER and PgR reactivity (P = 0.002). CONCLUSIONS: Liquid suspensions and liquid based slide preparations seem to offer an optimal pre-fixation and preservation of ER/PgR in breast carcinoma cells. Post-fixation with 4% formalin followed by microwave-stimulated epitope retrieval before immunostaining is recommended. Long-time storage of liquid based specimens at -20°C or -74°C for at least 6 months without significant loss of immunoreactivity is feasible. They may be used as internal positive and negative controls.
RESUMO
The clinical relevance of isolated tumor cell (ITC:
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Neoplasias da Mama/mortalidade , Carcinoma/secundário , Metástase Linfática , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Axila , Medula Óssea/patologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Carcinoma/tratamento farmacológico , Carcinoma/mortalidade , Carcinoma/cirurgia , Quimioterapia Adjuvante , Ciclofosfamida/administração & dosagem , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Excisão de Linfonodo , Metástase Linfática/diagnóstico , Mastectomia , Metotrexato/administração & dosagem , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Hormônio-Dependentes/tratamento farmacológico , Neoplasias Hormônio-Dependentes/patologia , Neoplasias Hormônio-Dependentes/cirurgia , Noruega/epidemiologia , Prognóstico , Tamoxifeno/administração & dosagemRESUMO
BACKGROUND. The influence of physical activity on the development of arm lymphedema (ALE) after breast cancer surgery with axillary node dissection has been debated. We evaluated the development of ALE in two different rehabilitation programs: a no activity restrictions (NAR) in daily living combined with a moderate resistance exercise program and an activity restrictions (AR) program combined with a usual care program. The risk factors associated with the development of ALE 2 years after surgery were also evaluated. MATERIAL AND METHODS. Women (n = 204) with a mean age of 55+/-10 years who had axillary node dissection were randomized into two different rehabilitation programs that lasted for 6 months: NAR (n = 104) or AR (n = 100). The primary outcomes were the difference in arm volume between the affected and control arms (Voldiff, in ml) and the development of ALE. Baseline (before surgery) and follow-up tests were performed 3 months, 6 months, and 2 years after surgery. Data were analyzed using ANCOVA and regression analysis. RESULTS. Voldiff did not differ significantly between the two treatment groups. Arm volume increased significantly over time in both the affected and the control arms. The development of ALE from baseline to 2 years increased significantly in both groups (p < 0.001). The only risk factor for ALE was BMI > 25 kg/m(2). CONCLUSION. Patients that undergo breast cancer surgery with axillary lymph node dissection should be encouraged to maintain physical activity in their daily lives without restrictions and without fear of developing ALE.
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Neoplasias da Mama/cirurgia , Terapia por Exercício , Excisão de Linfonodo/efeitos adversos , Excisão de Linfonodo/reabilitação , Linfedema/prevenção & controle , Mastectomia/reabilitação , Adulto , Idoso , Braço , Axila , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Perna (Membro) , Metástase Linfática , Linfedema/etiologia , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE. Many breast cancer survivors (BCS) suffer from long-term upper limb morbidities after axillary node dissection. The purpose of this five-year follow-up study was to describe changes in long-term upper limb morbidities, physical activity level, and Health-Related Quality of Life (HRQoL) and to find factors that predict HRQoL five years after surgery. PATIENTS AND METHODS. This study included 204 women aged 55+/-10 years who had primary breast cancer surgery with axillary node dissection. The subjects were examined for arm volumes and arm lymphedema, arm pain, sensation of heaviness, shoulder function, physical activity level, and HRQoL, prior to surgery, and six months and five years after surgery. The statistical analyses used included ANOVA for repeated measures and multivariate linear regression. RESULTS. ALE (13%), pain (36%), and sensation of heaviness (21%) in the upper limbs were present five years after surgery. ALE was the only morbidity that continued to increase over time. Several dimensions of HRQoL temporarily declined after surgery, but significantly improved in the period from six months to five years after surgery. The significant predictive factors of HRQoL five years after surgery included HRQoL prior to surgery, physical activity level at leisure time (both prior to and at six months after surgery), and duration of sick leave after surgery (in weeks). CONCLUSIONS. The overall HRQoL improved significantly from baseline to five years, despite the chronic arm pain and increase in ALE. Three independent predictive factors of HRQoL were identified.
Assuntos
Braço/fisiopatologia , Neoplasias da Mama/cirurgia , Excisão de Linfonodo/efeitos adversos , Linfedema/etiologia , Dor/etiologia , Qualidade de Vida , Adulto , Idoso , Análise de Variância , Axila , Neoplasias da Mama/mortalidade , Feminino , Seguimentos , Indicadores Básicos de Saúde , Humanos , Perna (Membro) , Modelos Lineares , Linfedema/epidemiologia , Mastectomia/efeitos adversos , Pessoa de Meia-Idade , Morbidade , Atividade Motora , Dor/epidemiologia , Amplitude de Movimento Articular , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVES: To evaluate concurrent and construct validity for the Simplified Water Displacement Instrument (SWDI), an instrument for measuring arm volumes and arm lymphedema as a result of breast cancer surgery. DESIGN: Validity design. SETTING: Hospital setting. PARTICIPANTS: Women (N=23; mean age, 64+/-11y) were examined 6 years after breast cancer surgery with axillary node dissection. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The SWDI was included for measuring arm volumes to estimate arm lymphedema as a result of breast cancer surgery. A computed tomography (CT) scan was included to examine the cross-sectional areas (CSAs) in square millimeters for the subcutaneous tissue, for the muscle tissue, and for measuring tissue density in Hounsfield units. Magnetic resonance imaging (MRI) with T2-weighted sequences was included to show increased signal intensity in subcutaneous and muscle tissue areas. RESULTS: The affected arm volume measured by the SWDI was significantly correlated to the total CSA of the affected upper limb (R=.904) and also to the CSA of the subcutaneous tissue and muscles tissue (R=.867 and R=.725), respectively (P<.001). The CSA of the subcutaneous tissue for the upper limb was significantly larger compared with the control limb (11%). Tissue density measured in Hounsfield units did not correlate significantly with arm volume (P>.05). The affected arm volume was significantly larger (5%) than the control arm volume (P<.05). Five (22%) women had arm lymphedema defined as a 10% increase in the affected arm volume compared with the control arm volume, and an increased signal intensity was identified in all 5 women on MRI (T2-weighted, kappa=.777, P<.001). CONCLUSIONS: The SWDI showed high concurrent and construct validity as shown with significant correlations between the CSA (CT) of the subcutaneous and muscle areas of the affected limb and the affected arm volume (P>.001). There was a high agreement between those subjects who were diagnosed with arm lymphedema by using the SWDI and the increased signal intensity on MRI, with a kappa value of .777 (P<.001). High construct validity for the SWDI was confirmed for arm lymphedema as a volume increase, but it was not confirmed for lymphedema without an increase in arm volume (swelling). The SWDI is a simple and valid tool for estimating arm volume and arm lymphedema after breast cancer surgery.