RESUMEN

PURPOSE: Multimodal therapies affect the quality of life (QoL) of patients with primary breast cancer (PBC). The objectives of this prospective study were to explore the changes in QoL from diagnosis to conclusion of adjuvant therapy and to identify predictive factors of QoL. METHODS: Before surgery (t1), before onset of adjuvant treatment (t2) and after completion of adjuvant chemo- or radiotherapy (t3), patients with PBC (n = 759) completed the European Organization for Research and Treatment of Cancer Quality of Life Core Questionnaire, Charlson Comorbidity Index, Patient Health Questionnaire and Perceived Involvement in Care Scales. Predictors of the course of global QoL were estimated using multinomial logistic regression. Effect estimates are odds ratios (OR) and their 95% confidence intervals (CIs). RESULTS: Global QoL improved between t1 and t3, while physical functioning, emotional functioning and fatigue deteriorated. QoL before surgery was more often poor in patients <60 years (OR 2.2, 95% CI 1.5-3.1) and in those with comorbid mental illnesses (OR 8.6, CI 5.4-13.7). Forty-seven percentage reported good global QoL both at t1 and at t3. QoL improved in 28%, worsened in 10% and remained poor in 15%. Compared to patients with consistently good global QoL, a course of improving QoL was more often seen in patients who had received a mastectomy and in those with intense fear of treatment before surgery. A course of decreasing QoL was more often found in patients who were treated with chemotherapy. QoL stayed poor in patients with chemotherapy, mastectomy and intense fear. There was no evidence that radiotherapy, progressive disease or perceived involvement impact the course of QoL. CONCLUSIONS: Younger age and comorbid mental illnesses are associated with poor QoL pre-therapeutically. QoL is more likely to stay or become poor in patients who receive chemotherapy.

Asunto(s)

Neoplasias de la Mama/psicología , Calidad de Vida/psicología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estudios Longitudinales , Persona de Mediana Edad , Estudios Prospectivos , Encuestas y Cuestionarios

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UNLABELLED: Small tumor size (≤5 mm, T1a) carries an excellent prognosis. Controversy exists over the extent of the variety of treatment approaches. We therefore explored the effect of adjuvant systemic therapy (AST) on recurrence free survival (RFS) and overall survival (OAS) for the group of T1a-tumors. METHODS: The multicenter study population included 9625 early breast cancer patients, diagnosed between 1992 and 2008. 5196 patients were T1 (54.0 %) and 325 of these patients (3.4 %) were T1a. RESULTS: Compared to patients with AST RFS and OAS were significantly worse for patients who did not receive AST (RFS: p = 0.001; OAS: p = 0.021). Even N0-T1a-patients (n = 279) significantly profited from AST (RFS: p = 0.001; OAS: p = 0.006). Patients with at least one poor prognostic factor (HR-, HER2+, N1 or G3) without AST also showed a significantly worse outcome (RFS: p = 0.026; OAS: p = 0.024) compared to pT1a-patients with AST. Consensus guidelines state that the prognosis of patients with T1a that are N0 is uncertain even if HER2 is amplified or overexpressed. In our study nodal-negative (N0) T1a-patients (n = 279) without AST showed a significantly worse RFS (p = 0.001), and a significantly worse OAS (p = 0.006) compared to those patients with AST. In multivariate analysis even after adjusting by age, grading, hormonal receptor status, HER2/neu-status and nodal status T1a-patients without AST were associated with a significantly worse RFS resp. OAS compared to patient with AST (RFS: p = 0.002; OAS: p = 0.007). CONCLUSIONS: There is an association between AST and improved RFS or OAS for breast cancer patients with T1a tumors.

Asunto(s)

Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quimioterapia Adyuvante , Adulto , Anciano , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento

RESUMEN

BACKGROUND: The transforming growth factor-beta (TGF- ß) pathway has been implicated in proliferation, migration and invasion of various cancers. Endoglin is a TGF-ß accessory receptor that modulates signalling. We identified Endoglin as an epigenetically silenced tumour-suppressor gene in lung cancer by means of a genome-wide screening approach, then sought to characterise its effect on lung cancer progression. METHODS: Methylation microarray and RNA sequencing were carried out on lung cancer cell lines. Epigenetic silencing of Endoglin was confirmed by methylation and expression analyses. An expression vector and a 20-gene expression panel were used to evaluate Endoglin function. Pyrosequencing was carried out on two independent cohorts comprising 112 and 202 NSCLC cases, respectively, and the impact of Endoglin methylation on overall survival (OS) was evaluated. RESULTS: Methylation in the promoter region resulted in silencing of Endoglin, which could be reactivated by demethylation. Increased invasion coupled with altered EMT marker expression was observed in cell lines with an epithelial-like, but not those with a mesenchymal-like, profile when Endoglin was absent. Methylation was associated with decreased OS in stage I but not in stages II-III disease. CONCLUSIONS: We show that Endoglin is a common target of epigenetic silencing in lung cancer. We reveal a link between Endoglin silencing and EMT progression that might be associated with decreased survival in stage I disease.

Asunto(s)

Antígenos CD/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Silenciador del Gen , Genes Supresores de Tumor , Neoplasias Pulmonares/genética , Receptores de Superficie Celular/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Línea Celular Tumoral , Progresión de la Enfermedad , Regulación hacia Abajo , Endoglina , Estudio de Asociación del Genoma Completo , Humanos , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Metilación , Regiones Promotoras Genéticas , Análisis por Matrices de Proteínas , Análisis de Secuencia de ADN/métodos

RESUMEN

OBJECTIVES: Gender differences in patients presenting with suspected acute coronary syndromes (ACS) have not yet been fully characterized. The aim of this study was to assess gender-related disparities in clinical profiles, biomarkers and diagnoses of patients with suspected ACS. METHODS: This single-centre, prospective cohort study included 377 consecutive patients presenting with suspected ACS to the emergency department. Suspected ACS was defined as a request for conventional troponin T (c-cTnT) measurements on clinical grounds. RESULTS: Women were older than men (p = 0.004), and had a lower prevalence of known coronary artery and peripheral vascular disease (p < 0.05). c-cTnT was positive in 8% of female and in 14% of male patients (p = 0.16), TIMI risk score and cardiac biomarkers including c-cTnT, hs-cTnT, myoglobin, creatine kinase, N-terminal pro-brain natriuretic peptide, myeloid-related protein 8/14 and pregnancy-associated plasma protein A were lower in women (p < 0.05). Women were less frequently diagnosed with ACS (30 vs. 51%), and were not referred for urgent coronary angiography as often as men (p < 0.001). In multivariate analysis, female gender was associated with a lower referral for coronary angiography (HR 0.41, 95% CI 0.23-0.78, p = 0.006). CONCLUSIONS: In patients with suspected ACS, women presented with different biomarker profiles, and were less often diagnosed with ACS and referred to coronary angiography.

Asunto(s)

Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico , Factores Sexuales , Anciano , Biomarcadores/sangre , Angiografía Coronaria , Creatina Quinasa/sangre , Servicio de Urgencia en Hospital , Femenino , Alemania , Humanos , Modelos Logísticos , Masculino , Persona de Mediana Edad , Análisis Multivariante , Mioglobina/sangre , Péptido Natriurético Encefálico/sangre , Dimensión del Dolor/estadística & datos numéricos , Estudios Prospectivos , Troponina T/sangre

RESUMEN

PURPOSE: Inflammatory breast cancer (IBC) represents a rare and aggressive form of cancer with negative prognosis and high rate of recurrence. The purpose of this retrospective multi-center study was to evaluate the effect of IBC on overall and disease-free survival. Furthermore we analyzed the influence of hormone and Her2 receptor expression on inflammatory breast cancer cells on the clinical outcome of patients. METHODS: This retrospective German multi-center study included 11,780 patients with primary breast cancer recruited from 1992 to 2008. In this sub-group analysis we focused on 70 patients with IBC. RESULTS: Despite the relatively small sample size, we could confirm the aggressiveness of inflammatory breast cancer and the different clinical behavior of IBC subtypes. It could be demonstrated that the lack of expression of hormone receptors on tumor cells is associated with a more aggressive clinical course and decreased overall and disease-free survival. Higher incidence of Her2 overexpression, that is typically associated with poor prognostic outcome among women with non-IBC tumors, seems however to have no prognostic significance. CONCLUSIONS: This BRENDA sub-group analysis, on a German cohort of breast cancer patients confirmed the negative outcome of IBC and the different clinical behavior of IBC subtypes. The best management of IBC requires intensive coordination and cooperation between various clinical disciplines involved in the treatment of IBC patients. Moreover there is a need to identify IBC-specific targeted therapies to improve the curing prospects of this subtype of cancer.

Asunto(s)

Neoplasias Inflamatorias de la Mama/diagnóstico , Neoplasias Inflamatorias de la Mama/metabolismo , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Supervivencia sin Enfermedad , Femenino , Alemania/epidemiología , Humanos , Incidencia , Neoplasias Inflamatorias de la Mama/mortalidad , Estimación de Kaplan-Meier , Persona de Mediana Edad , Análisis Multivariante , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Prevalencia , Pronóstico , Modelos de Riesgos Proporcionales , Estudios Retrospectivos

RESUMEN

BACKGROUND: Radiotherapy (RT) is proven to be an important backbone for adjuvant therapy in randomized, controlled trials, but it is unclear if these effects are provable in a daily routine cohort of breast cancer patients. This study sought to answer the following questions in a daily routine cohort of breast cancer patients: 1. Does guideline-adherent RT improve primary breast cancer patient survival? 2. Is breast-conserving surgery (BCS) followed by RT equal to a mastectomy (MA) with regard to outcome parameters? 3. Does adjuvant RT compensate for an incomplete tumor resection (R1)? PATIENTS AND METHODS: In this retrospective, multicenter cohort study, we investigated data from 8935 primary breast cancer patients recruited from 17 participating certified breast cancer centers in Germany between 1992 and 2008. Guideline adherence based on internationally validated guidelines. RESULTS: The patients who received guideline-adherent RT for primary breast cancer were associated with significantly improved survival parameters [recurrence-free survival (RFS): P < 0.001; overall survival (OS): P < 0.001] compared with patients who did not receive guideline-adherent adjuvant RT. Furthermore, the results demonstrated that there were no significant differences in RFS and OS between BCS followed by RT and MA [RFS: P = 0.293; OS: P = 0.104]. Adjuvant RT did not improve the outcome of patients receiving nonguideline-adherent incomplete tumor resection via BCS (R1); these patients showed a significantly impaired RFS [P < 0.001] and OS [P < 0.001] compared with patients who underwent guideline-adherent complete tumor resection via BCS (R0). In addition, non-guideline-adherent RT after MA (overtherapy) did not significantly influence survival [RFS: P = 0.838; OS: P = 0.613]. CONCLUSION: Our study confirms the importance of guideline-adherent adjuvant RT. It shows highly significant associations between RFS or OS and guideline adherent RT. Nevertheless, inadequate (R1-) surgical resection in a daily routine cohort of patients increases the risk of local recurrence and appears not to be compensated by the following RT.

Asunto(s)

Neoplasias de la Mama/radioterapia , Mastectomía Segmentaria , Radioterapia Adyuvante , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/cirugía , Estudios de Cohortes , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Adhesión a Directriz , Humanos , Recurrencia Local de Neoplasia/mortalidad , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento

RESUMEN

BACKGROUND: The prognosis of metastatic breast cancer (MBC) is extremely heterogeneous. Although patients with MBC will uniformly die to their disease, survival may range from a few months to several years. This underscores the importance of defining prognostic factors to develop risk-adopted treatment strategies. Our aim has been to use simple measures to judge a patient's prognosis when metastatic disease is diagnosed. PATIENTS AND METHODS: We retrospectively analyzed 2269 patients from four clinical cancer registries. The prognostic score was calculated from the regression coefficients found in the Cox regression analysis. Based on the score, patients were classified into high-, intermediate-, and low-risk groups. Bootstrapping and time-dependent receiver operating characteristic curves were used for internal validation. Two independent datasets were used for external validation. RESULTS: Metastatic-free interval, localization of metastases, and hormone receptor status were identified as significant prognostic factors in the multivariate analysis. The three prognostic groups showed highly significant differences regarding overall survival from the time of metastasis [intermediate compared with low risk: hazard ratio (HR) 1.76, 95% confidence interval (CI) 1.36-2.27, P < 0.001; high compared with low risk: HR 3.54, 95% CI 2.81-4.45, P < 0.001). The median overall survival in these three groups were 61, 38, and 22 months, respectively. The external validation showed congruent results. CONCLUSIONS: We developed a prognostic score, based on routine parameters easily accessible in daily clinical care. Although major progress has been made, the optimal therapeutic management of the individual patient is still unknown. Besides elaborative molecular classification of tumors, simple clinical measures such as our model may be helpful to further individualize optimal breast cancer care.

Asunto(s)

Neoplasias de la Mama/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Evaluación de Resultado en la Atención de Salud , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/terapia , Supervivencia sin Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Metástasis de la Neoplasia , Análisis de Regresión , Estudios Retrospectivos , Resultado del Tratamiento , Adulto Joven

RESUMEN

Ayurveda is playing a growing part in Europe. Questions regarding the role of religion and spirituality within Ayurveda are discussed widely. Yet, there is little data on the influence of religious and spiritual aspects on its European diffusion. Methods. A survey was conducted with a new questionnaire. It was analysed by calculating frequency variables and testing differences in distributions with the χ (2)-Test. Principal Component Analyses with Varimax Rotation were performed. Results. 140 questionnaires were analysed. Researchers found that individual religious and spiritual backgrounds influence attitudes and expectations towards Ayurveda. Statistical relationships were found between religious/spiritual backgrounds and decisions to offer/access Ayurveda. Accessing Ayurveda did not exclude the simultaneous use of modern medicine and CAM. From the majority's perspective Ayurveda is simultaneously a science, medicine, and a spiritual approach. Conclusion. Ayurveda seems to be able to satisfy the individual needs of therapists and patients, despite worldview differences. Ayurvedic concepts are based on anthropologic assumptions including different levels of existence in healing approaches. Thereby, Ayurveda can be seen in accordance with the prerequisites for a Whole Medical System. As a result of this, intimate and individual therapist-patient relationships can emerge. Larger surveys involving bigger participant numbers with fully validated questionnaires are warranted to support these results.

RESUMEN

Multifocal (MF) and multicentric (MC) breast cancers have been comprehensively studied, and their outcomes have been compared with unifocal (UF) tumors. We attempted to answer the following questions: (1) Does MF/MC presentation influence the outcome concerning BC mortality?, (2) Is there an impact of guideline-adherent adjuvant treatment in these BC subtypes?, and (3)What is the influence of guideline violations concerning surgery (breast-conserving surgery versus mastectomy) on the survival of MF/MC BC patients? Between 1992 and 2008, we retrospectively analyzed 8,935 breast cancer patients from 17 participating breast cancer centers within the BRENDA study group. Of 8,935 breast cancer patients, 7,073 (79.2 %) had UF tumors, 1,398 (15.6 %) had MF tumors, and 464 (5.2 %) had MC tumors. RFS was significantly worse for MF/MC BC patients compared to patients with UF tumors (MF p = 0.007; MC p = 0.019). OAS was significantly worse for MC patients but not for MF patients compared to patients with UF tumors (MF p = 0.321; MC p = 0.001). Guideline adherence was significantly lower in patients with MF (n = 580; 41.5 %) and MC (n = 204; 44.0 %) compared to patients with UF (n = 3,871; 54.7 %) (p < 0.001) tumors. Guideline violations were associated with a highly significant deterioration in survival throughout all subgroups except for MC, with respect to RFS and OAS. For 100 %-guideline-adherent patients, we could not find any significant differences in RFS and OAS after adjusting by nodal status, grade, and tumor size. Furthermore, we could not find any significant differences in RFS and OAS in patients with MF or MC stratified by breast-conserving therapy (BCT lumpectomy and radiation therapy) and mastectomy. There is a strong association between improved RFS and OAS in patients with MF/MZ BC. There are no significant differences in RFS and OAS for patients with breast-conserving therapy or mastectomy.

Asunto(s)

Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/terapia , Terapia Combinada , Femenino , Adhesión a Directriz , Humanos , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Estudios Retrospectivos , Factores de Riesgo , Resultado del Tratamiento , Adulto Joven

RESUMEN

BACKGROUND: Coronary computed tomography angiography (CCTA) provides information regarding lesion morphology and three-dimensional coronary anatomy incremental to coronary angiography. We addressed the question whether preprocedural CCTA bears potential for guiding percutaneous coronary interventions (PCI). METHODS AND RESULTS: Sixty-six coronary lesions attempted with PCI within 6 months of preprocedural CCTA were retrospectively assessed. Lesion parameters from unenhanced computed tomography (CT) for calcium scoring and CCTA were analyzed and compared with PCI complexity. Complex PCI was defined as use of buddy wire, kissing balloon, necessity of high pressure balloons, or rotablator. Complex PCIs were observed in 32 interventions (48%). Median Agatston score and Hounsfield units were higher in lesions with complex as compared to those with non-complex interventions with 130 (interquartile range, 23-276) vs 29 (0-158; P=.01), and 493 (245-631) vs 341 (68-520 Hounsfield Units; P=.04), respectively. Median local plaque volume and plaque mass were higher in complex PCI with 17 (2-39) vs 5 (0-19.5 mm³; P=.007), and 48 (15-99) vs. 16 (1.5-63 mg hydroxyapatite/mm³; P=.03), respectively. Lesions leading to complex PCI were longer [1.8 (1.2-2.8) vs 1.3 (0.8-1.7) cm; P=.03], and had a higher rate of calcified plaques (23% vs 3%; P=.03). There was a significant correlation between CCTA- and angiography-derived local SYNTAX Scores (P<.001); the CCTA-derived score seems to be predictive for failed and complex PCI (area under curve = 0.75 ± 0.13 and 0.66 ± 0.08, respectively). CONCLUSIONS: Preprocedural lesion assessment by CCTA indicates complexity of PCI. In patients with suspected complex coronary anatomy, prior CCTA adds important information for planning PCI.

Asunto(s)

Angioplastia Coronaria con Balón/métodos , Angiografía Coronaria/métodos , Enfermedad Coronaria/terapia , Tomografía Computarizada por Rayos X/métodos , Anciano , Calcinosis/diagnóstico por imagen , Estenosis Coronaria/diagnóstico por imagen , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Persona de Mediana Edad , Placa Aterosclerótica/diagnóstico por imagen , Placa Aterosclerótica/patología , Placa Aterosclerótica/terapia , Curva ROC , Intensificación de Imagen Radiográfica , Radiografía Intervencional/métodos , Estudios Retrospectivos

RESUMEN

AIM OF THE STUDY: Clinical practice guidelines (CPG) are an appropriate method to optimise routine clinical care. Numerous CPGs for the diagnosis and treatment of breast cancer have been developed by national health institutions or medical societies. While a comparison of methodological criteria has been undertaken before, it is unknown whether these CPGs differ in their actual treatment recommendations. METHODS: We included national breast cancer CPGs from the USA, Canada, Australia, the UK, and Germany that satisfy internationally recognised methodological criteria and are in widespread use in daily clinical care. Treatment recommendations for adjuvant invasive breast cancer including surgery, radiation, endocrine therapy, chemotherapy and anti-HER2-therapy were compared. RESULTS: Recommendations for endocrine therapy show discordances regarding optimal usage of ovarian function suppression for premenopausal patients and aromatase inhibitors for postmenopausal patients. However, most other treatment recommendations exhibit a large degree of congruency. This reflects the fact that they rest on the same evidence base, and that many national guidelines are adopted from other guidelines so that well accepted guidelines are cited within other guidelines. CONCLUDING STATEMENT: Considering that the development of guidelines is a very expensive and resource-intensive task the question arises whether the development of national guidelines in numerous countries is worth the effort since the recommendations differ only marginally.

Asunto(s)

Neoplasias de la Mama/terapia , Carcinoma/terapia , Oncología Médica/legislación & jurisprudencia , Oncología Médica/métodos , Guías de Práctica Clínica como Asunto , Antineoplásicos Hormonales/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/patología , Carcinoma/patología , Gobierno Federal , Femenino , Humanos , Internacionalidad , Mastectomía/métodos , Mastectomía/estadística & datos numéricos , Clasificación del Tumor , Inhibidores de Proteínas Quinasas/uso terapéutico , Radioterapia/estadística & datos numéricos , Receptor ErbB-2/antagonistas & inhibidores , Estados Unidos

RESUMEN

Triple-negative breast cancer (TNBC) (ER-/PGR-/erb-2-) constitutes an aggressive subtype in breast cancer because it is accompanied by a significant decrease in overall survival (OAS) and recurrence-free survival (RFS) compared with hormone receptor positive breast cancers. This retrospective cohort study investigates the following issues: (1) Is there an impact of guideline-adherent treatment on RFS and OAS in TNBC? (2) Which adjuvant treatment has the most important impact on RFS and OAS in TNBC? This German retrospective multi-centre cohort study included 3,658 patients with primary breast cancer recruited from 2000 to 2005. The definition of guideline adherence was based on the German national S3 guideline for diagnosis and treatment of breast cancer (2004). A total of 371 patients (10.1%) had TNBC. Compared with HR+/erb-2- breast cancer (P = 0.001; HR = 1.75; 95% CI: 1.27-2.40), the recurrence rate of TNBC was significantly higher (P < 0.001; HR = 2.86; 95% CI: 2.17-3.76). Furthermore, the 5-year RFS and OAS was significantly lower in TNBC (RFS: 74.8% [95% CI: 68.8-80.8%] vs. 86.5% [95% CI: 84.6-88.4%] [log-rank P = 0.0001]) (OAS: 75.8% [95% CI: 69.9-81.8%] vs. 86.0% [95% CI: 84.1-87.9%] [log-rank P = 0.0001]). The most important parameters predicting RFS and OAS in TNBC after receiving guideline-conform chemotherapy are guideline-adherent surgery, radiotherapy, nodal status and grading. Overall, 66.8% TNBC were found with one or more (18%) guideline violations, which subsequently impaired OAS and RFS. The most important impact on OAS and RFS in TNBC patients was because of guideline violations (GV) concerning adjuvant radiotherapy and GV concerning adjuvant chemotherapy. Patients with TNBC primarily have a worse prognosis in terms of RFS and OAS than patients of a primarily non-TNBC phenotype. There is a strong association between guideline-adherent adjuvant treatment and improved survival outcome in TNBC. The outcome significantly decreases with the number of guideline violations.

Asunto(s)

Neoplasias de la Mama/terapia , Carcinoma Ductal de Mama/terapia , Adhesión a Directriz , Recurrencia Local de Neoplasia , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/mortalidad , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidad , Terapia Combinada , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Análisis Multivariante , Guías de Práctica Clínica como Asunto , Modelos de Riesgos Proporcionales , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Estudios Retrospectivos

RESUMEN

Obesity, defined as a body mass index (BMI) ≥30 is an independent risk factor in breast cancer and is correlated with shorter survival and enhanced recurrence rates. The present subgroup analysis of the German BRENDA-cohort aimed to investigate the correlation between BMI, recurrence-free survival (RFS) and adjuvant endocrine therapy. In this subgroup analysis, 4,636 patients were retrospectively examined using multivariate analyses. Overall 3,759 (81.1%) patients had a BMI <30 (non-obese) and 877 (18.9%) a BMI ≥30 (obese). In the group of all 3,896 (84.0%) patients with hormone-receptor-positive (HR+) breast carcinomas a significant reduction in RFS was demonstrated for those who were obese (P = 0.002; HR = 1.45 (95% CI: 1.15-1.83)), also after adjustment for Nottingham Prognostic Index (NPI) (P = 0.028; HR = 1.30 (95% CI: 1.03-1.65)). In hormone-receptor-negative (HR-) patients BMI had no influence on RFS (P = 0.380; HR = 1.20 (95% CI: 0.80-1.81)). Considering menopausal status, a significantly shorter RFS was seen in postmenopausal obese than in non-obese patients (P < 0.001; HR = 1.61 (95% CI: 1.24-2.09)), whereas the premenopausal patient group only showed a trend towards a shorter RFS (P = 0.202; HR = 1.44 (95% CI: 0.82-2.53)). The group of HR+ postmenopausal patients with normal or intermediate weight showed a non-significant statistical trend towards a survival benefit for aromatase inhibitors (AI) compared to tamoxifen (RFS: P = 0.486; HR = 1.29 (95% CI: 0.63-2.62), while obese patients tended to benefit more from tamoxifen (RFS: P = 0.289; HR = 0.65 (95% CI: 0.29-1.45)). In accordance with recently published results we demonstrated a negative effect of a high BMI on outcome in primary breast cancer. Furthermore the efficacy of AI seems dependent on BMI in contrast to tamoxifen. Prospective studies to optimise the therapy of obese breast cancer patients are urgently needed.

Asunto(s)

Antineoplásicos Hormonales/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Obesidad/complicaciones , Tamoxifeno/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Índice de Masa Corporal , Neoplasias de la Mama/metabolismo , Femenino , Humanos , Persona de Mediana Edad , Receptores de Esteroides/metabolismo , Estudios Retrospectivos , Análisis de Supervivencia , Adulto Joven

RESUMEN

One of the most controversial questions in early breast cancer treatment is the need of chemotherapy in patients with estrogen receptor positive disease. Therefore, we analyzed a group of patients with high estrogen receptor (ER) expression to scrutinize the role of chemotherapy in this situation. To gauge the effect of chemotherapy on recurrence free survival (RFS) three treatment modalities were compared: endocrine treatment only, chemoendocrine treatment, and chemotherapy. 3,971 breast cancer patients whose treatment modalities as well as ER level were known, were included in this retrospective analysis. Their level of ER expression was documented as immunoreactive score (IRS). A high ER group was defined as ER IRS ≥ 9; primary endpoint was RFS. RFS was associated with ER, with the best outcome for strong and the worst result for negative expression. Adjusted to Nottingham prognostic index (NPI), RFS did not differ between the treatment cohorts of endocrine treatment and chemoendocrine treatment (P = 0.828) in the high ER group. Patients with chemotherapy alone fared significantly worse (P = 0.003). Even in high risk patients (according to NPI) the chemoendocrine and the endocrine treatment only groups did not differ significantly (HR = 1.15; 95% CI (0.56-2.34), P = 0.709). Omission of endocrine treatment led to significantly worse outcome (P = 0.013). In conclusion, RFS was significantly longer in patients with high ER expression than with weak or no ER expression. In the high expression group, there was no significant difference in RFS between endocrine treatment only and chemoendocrine therapy-even in high risk patients, for whom chemoendocrine treatment is routinely indicated. It seems insufficient for high ER patients to only consider tumor size, nodal status, and grading in order to decide which patient will benefit from adding chemotherapy to endocrine treatment.

Asunto(s)

Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/metabolismo , Detección Precoz del Cáncer , Receptores de Estrógenos/metabolismo , Adulto , Anciano , Antraciclinas/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Cisplatino/uso terapéutico , Estudios de Cohortes , Supervivencia sin Enfermedad , Femenino , Fluorouracilo/uso terapéutico , Humanos , Estimación de Kaplan-Meier , Metotrexato/uso terapéutico , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Taxoides/uso terapéutico , Resultado del Tratamiento

RESUMEN

BACKGROUND: This randomised phase III trial was carried out to compare the efficacy and safety of epirubicin and cyclophosphamide (EC) with epirubicin and docetaxel (Taxotere) (ED) as first-line chemotherapy for metastatic breast cancer. PATIENTS AND METHODS: Patients (n = 240) were randomly assigned to receive either ED (epirubicin 75 mg/m(2) and docetaxel 75 mg/m(2)) or EC (epirubicin 90 mg/m(2) and cyclophosphamide 600 mg/m(2)). The primary end point was objective response rate (ORR). Secondary end points were progression-free survival (PFS), overall survival (OS), and safety. RESULTS: ORR for patients randomly assigned to receive EC and ED were 42% and 47%, respectively (P = 0.63). Median PFS [10.1 versus 10.3 months; hazard ratio (HR) 0.98; log-rank P = 0.38] and OS (19.9 versus 30.0 months; HR 0.663; log-rank P = 0.21) were comparable in both arms. Although grade 3/4 leucopenia occurred more frequently with ED (81% versus 73%; P = 0.01), there were no significant differences in the incidence of febrile neutropenia and grade 3/4 infections. Grade 3/4 non-haematologic toxicity was infrequent in both arms. Congestive heart failure was observed in one patient in each arm. CONCLUSION: In this randomised trial, no differences in the efficacy study end points were observed between the two treatment arms.

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Adulto , Anciano , Ciclofosfamida/administración & dosificación , Progresión de la Enfermedad , Docetaxel , Epirrubicina/administración & dosificación , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Tasa de Supervivencia , Taxoides/administración & dosificación , Resultado del Tratamiento

RESUMEN

BACKGROUND: Combinations of anthracyclines, taxanes and gemcitabine have shown high activity in breast cancer. This trial was designed to evaluate a modified combination regimen as primary chemotherapy. Non-pegylated liposomal doxorubicin (NPLD) was used instead of conventional doxorubicin to improve cardiac safety. Gemcitabine was given 72 h after NPLD and docetaxel as a prolonged infusion over 4 h in order to optimize synergistic effects and accumulation of active metabolites. PATIENTS AND METHODS: Forty-four patients with histologically confirmed stage II or III breast cancer were treated with NPLD (60 mg/m(2)) and docetaxel (75 mg/m(2)) on day 1 and gemcitabine as 4-h infusion (350 mg/m(2)) on day 4. Treatment was repeated every 3 weeks for a maximum of six cycles. All patients received prophylactically recombinant granulocyte colony-stimulating factor. Patients with axillary lymph node involvement after primary chemotherapy received adjuvant treatment with cyclophosphamide, methotrexate and fluorouracil. RESULTS: The clinical response rate was 80%, and complete remissions of the primary tumor occurred in 10 patients (25%). Breast conservation surgery was performed in 19 out of 20 patients (95%) with an initial tumor size of less than 3 cm and in 14 patients (70%) with a tumor size

Asunto(s)

Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Adulto , Neoplasias de la Mama/patología , Neoplasias de la Mama/cirugía , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Docetaxel , Doxorrubicina/administración & dosificación , Femenino , Factor Estimulante de Colonias de Granulocitos , Humanos , Infusiones Intravenosas , Liposomas , Mastectomía Segmentaria , Persona de Mediana Edad , Taxoides/administración & dosificación , Resultado del Tratamiento , Gemcitabina

RESUMEN

The referral of critically ill cancer patients to an intensive care unit (ICU) is a matter of controversial debate. This study was conducted by an interdisciplinary clinical group to evaluate the outcome of ICU treatment in cancer patients according to their characteristics at the time of referral. A retrospective analysis was used to identify relevant subgroups among 189 consecutive cancer patients referred as emergencies to one of four ICUs during a 2-year period. Reasons for ICU referral were pneumonia (29.6%), sepsis (27.0%), fungal infection (11.1%), another infection (9.5%), gastrointestinal emergency (16.9%), treatment-related organ toxicity (6.9%), or other, non-infectious complications (43.9%). Vasopressor support was required in 50.3%, mechanical ventilation in 49.7%, and haemodialysis/-filtration in 26.5% of the patients. Overall, 41.3% died during ICU treatment, 12.2% died after transfer from ICU to a non-ICU ward, and 35.4% were discharged alive. Sepsis, mechanical ventilation, vasopressor support, renal replacement therapy and neutropenia were independent risk factors for fatal outcome, but no single risk factor unequivocally predicted death. All patients with fungal infection who required vasopressor support and either had sepsis (n=13) or needed mechanical ventilation (n=14) died during ICU treatment, while all non-septic patients. who did not require mechanical ventilation, were younger than 74 years of age and had a non-infectious underlying complication (n=29), survived. This analysis may help to early identify relevant subgroups of cancer patients with different prognoses under ICU treatment. A prospective study to confirm the predictive usefulness of this approach is needed. Cancer patients should not be excluded from referral to the intensive care unit in an emergency solely due to their underlying malignant disease or a single unfavourable prognostic factor.

Asunto(s)

Cuidados Críticos , Neoplasias/terapia , Derivación y Consulta/estadística & datos numéricos , Adulto , Anciano , Anciano de 80 o más Años , Enfermedad Crítica , Árboles de Decisión , Urgencias Médicas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Micosis/terapia , Neutropenia/terapia , Evaluación de Programas y Proyectos de Salud , Estudios Retrospectivos , Factores de Riesgo , Sepsis/terapia , Análisis de Supervivencia , Resultado del Tratamiento

RESUMEN

Prediction of outcome and individualization of therapeutic strategies are challenging problems in oncology. Predictive parameters for response to hormonal treatment include the expression of hormone receptor, the extent and location of metastatic spread, disease-free interval, patient age, response to prior hormonal therapy, grading, and more recently, some molecular markers like the expression of HER-2/neu. The use of conventional statistics for prediction of response to hormonal treatment is limited by non-linearities and complex interactions between predictive factors. Modern computational mathematical models like artificial neural networks, entropy-based inductive algorithms or chi(2) interaction detection algorithms can describe these interactions and generate classification models and decision structures. They can be used to predict the clinical outcome for individual patients. In contrast to conventional methods, the level of confidence for the predictions can reach 90% and more. This might be an important step towards further individualization of therapeutic strategies.

Asunto(s)

Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Árboles de Decisión , Redes Neurales de la Computación , Neoplasias de la Mama/patología , Humanos , Metástasis de la Neoplasia , Modelos de Riesgos Proporcionales

RESUMEN

BACKGROUND: In patients with HER2-positive metastatic breast cancer (MBC), combined treatment of herceptin (H) and chemotherapy (CT) improves time to progression, response rates and survival compared with CT alone. MATERIALS AND METHODS: We evaluated the safety and efficacy of weekly Docetaxel combined with weekly H as treatment in HER2 overexpressing MBC. RESULTS: Preliminary toxicity data from 12 patients and 76 cycles of D and 80 cycles of H were analysed. No G3/4 toxicity was observed. The most frequent non-hematologic toxicities were fatigue (2 patients G2, 2 patients G1), dyspepsia (1 patients G2, 3 patients G1), diarrhea (1 patient G2, 3 patients G1), and nausea (1 patient G2, 3 patients G1). Six partial responses have been observed in 12 patients (ORR 50%). CONCLUSIONS: The combination of weekly Docetaxel and Herceptin is well tolerated with significant anti-tumor activity.

Asunto(s)

Anticuerpos Monoclonales/uso terapéutico , Antineoplásicos Fitogénicos/uso terapéutico , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Paclitaxel/análogos & derivados , Paclitaxel/uso terapéutico , Receptor ErbB-2/inmunología , Taxoides , Adolescente , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales Humanizados , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antineoplásicos Fitogénicos/administración & dosificación , Antineoplásicos Fitogénicos/efectos adversos , Neoplasias de la Mama/fisiopatología , Seguridad de Productos para el Consumidor , Docetaxel , Esquema de Medicación , Sinergismo Farmacológico , Femenino , Humanos , Persona de Mediana Edad , Metástasis de la Neoplasia , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Proyectos Piloto , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Trastuzumab

RESUMEN

BACKGROUND: The American College of Cardiology/American Heart Association (ACC/AHA) stenosis morphology classification (MC) stratifies coronary lesions for probability of success and complications after coronary angioplasty (PTCA). Modern computing techniques were used to evaluate the individual predictive value of MC in random PTCA cases. METHODS AND RESULTS: MC was attributed to the target lesions by consensus of 2 observers. The predictive value regarding procedural success (PS) and major adverse cardiac events (MACE) of MC was analyzed by conventional logistic regression analyses and by inductive machine learning models. The study was adequately powered for the methods applied with 325 target lesions of 250 cases. Overall, PS decreased and MACE increased from type A to type C lesions. Regression analysis identified no single factor as predictive. Logistic regression showed an error rate of 42%. Machine learning techniques achieved an individual predictive error of only 10%, which could be further reduced to 2% by addition of parameters. For PS, MC parameters showed a high ranking for building the model. For MACE, variables of the medical history showed more impact. CONCLUSIONS: MC per se cannot individually predict PS or MACE. However, when all MC parameters are integrated together with additional lesion-specific and history variables, a high individual predictive value can be achieved. This technique may be clinically helpful for risk stratification in the catheterization laboratory and improvement of classification systems in interventional cardiology.

Asunto(s)

Angioplastia Coronaria con Balón , Enfermedad Coronaria/terapia , Algoritmos , Angioplastia Coronaria con Balón/efectos adversos , Angioplastia Coronaria con Balón/normas , Angioplastia Coronaria con Balón/estadística & datos numéricos , Femenino , Humanos , Modelos Logísticos , Masculino , Valor Predictivo de las Pruebas , Programas Informáticos , Resultado del Tratamiento