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Treatment paradigms in advanced hormone receptor (HR)-positive breast cancer were substantially transformed with cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) approval. The addition of these drugs to endocrine treatment profoundly improved progression-free and overall survival. Additionally, other important endpoints, such as the response rate, time to chemotherapy, and a delay in quality of life deterioration, were positively impacted by CDK4/6 inhibitors' addition to the treatment of advanced HR-positive breast cancer. This review article will summarize current knowledge on CDK4/6 inhibitors in clinical practice for advanced HR-positive metastatic breast cancer, as well as describe recent efforts to more precisely characterize mechanisms of sensitivity and resistance to these drugs, both on the molecular and clinical characterization level.
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PURPOSE: To monitor oncologists' perspective on cancer pain management. METHODS: An anonymized survey was conducted in two waves. First, over a convenience sample of oncologists known to be particularly concerned with the management of pain. Second, using a random sample of oncologists. RESULTS: In total, 73 and 82 oncologists participated in the first and second wave, respectively. Many oncologists reported to have good knowledge of analgesic drugs (95.9%), the mechanism of action of opioids (79.5%), and good skills to manage opioid-related bowel dysfunction (76.7%). Appropriate adjustment of background medication to manage breakthrough pain was reported by 95.5% of oncologists. Additionally, 87.7% (68.3% in the second wave, p = 0.035) of oncologists reported suitable opioid titration practices, and 90.4% reported to use co-adjuvant medications for neuropathic pain confidently. On the other hand, just 9.6% of oncologists participated in multidisciplinary pain management teams, and merely 30.3 and 27.1% reported to routinely collaborate with the Pain Clinics or involve other staff, respectively. Only 26.4% of the oncologists of the second wave gave priority to pain pathophysiology to decide therapies, and up to 75.6% reported difficulties in treating neuropathic pain. Significantly less oncologists of the second wave (82.9 vs. 94.5%, p = 0.001) used opioid rotation routinely. CONCLUSIONS: Unlike in previous surveys, medical oncologists reported in general good knowledge and few perceived limitations and barriers for pain management. However, multi-disciplinary management and collaboration with other specialists are still uncommon. Oncologists' commitment to optimize pain management seems important to improve and maintain good practices.
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Analgésicos Opioides/uso terapéutico , Actitud del Personal de Salud , Conocimientos, Actitudes y Práctica en Salud , Neoplasias/complicaciones , Oncólogos/psicología , Dolor/tratamiento farmacológico , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adulto , Anciano , Analgésicos/uso terapéutico , Prescripciones de Medicamentos/estadística & datos numéricos , Humanos , Oncología Médica , Persona de Mediana Edad , Dolor/etiología , Manejo del Dolor , Encuestas y CuestionariosRESUMEN
PURPOSE: The Spanish Society of Medical Oncology (SEOM) has conducted a study on the access to oncologic drugs across the 17 Spanish Regions with the aim of identifying potential heterogeneities and making proposals for eliminating the barriers identified at the different levels. METHODS: An Expert Panel made up of medical oncologists designed a survey on certain indications approved for 11 drugs in the approach of breast cancer, melanoma, lung cancer, prostate cancer and support treatment. This survey was sent to 144 National Health System (NHS) hospitals. RESULTS: 77 hospitals answered the survey. The information modules analysed were: scope of the Commission that establishes binding decisions related to drug access; conditions, stages and periods of drug application, approval and administration processes; barriers to accessing drugs. CONCLUSIONS: The study shows variability in drug access. The SEOM makes proposals addressed to reducing the differences identified and homogenizing drug access conditions.
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Antineoplásicos/uso terapéutico , Accesibilidad a los Servicios de Salud , Disparidades en Atención de Salud , Oncología Médica , Neoplasias/tratamiento farmacológico , Sociedades Médicas , Humanos , Encuestas y CuestionariosRESUMEN
La infección persistente por ciertos tipos de alto riesgo oncogénico de virus papiloma humano (VPHAR) es el principal factor de riesgo para el desarrollo de cáncer de cuello uterino y sus lesiones precursoras. Los VPHAR inducen alteraciones moleculares durante todo el proceso de carcinogénesis cervical, que provocan la acumulación de errores genéticos, con la consecuente inestabilidad genética y transformación maligna. Estas alteraciones son producidas por la acción directa de las oncoproteínas virales E6 y E7 sobre las principales proteínas celulares supresoras de tumor, p53 y pRb, respectivamente, y pueden ser monitoreadas durante el surgimiento de la lesión neoplásica, mediante el uso de biomarcadores. En este artículo se revisan las últimas tendencias sobre el uso del estudio inmunocitoquímico, como una prueba complementaria a la citología y a la detección y tipificación de VPHAR en la evaluación de la expresión de biomarcadores como la proteína inhibidora de la proliferación celular p16INK4a, marcador único o combinada con otros biomarcadores, que puedan contribuir eficazmente en la detección de las pacientes con mayor riesgo a desarrollar neoplasia del cuello uterino asociada a la infección por VPHAR, durante la pesquisa de cáncer de cuello uterino de rutina y en el manejo clínico adecuado y oportuno.
Persistent infection with certain types of high oncogenic risk human papillomavirus (HR-HPV) is the main risk factor for developing cervical cancer and its precursor lesions. HR-HPV induces molecular changes during cervical carcinogenesis, causing the accumulation of genetic anomalies, with subsequent genetic instability and malignant transformation. These alterations are produced by the direct action of the E6 and E7 viral oncoproteins on principal tumor cell suppressor proteins, p53 and pRb, respectively, and can be monitored during growth of the neoplastic lesion using biomarkers. In this paper we review the latest trends on the use of immunocytochemistry as a complementary test to cytology and HR-HPV detection and typing in evaluating expression of biomarkers such as the p16INK4a cell proliferation inhibitor protein, as a single marker or combined with other biomarkers, which can contribute effectively to the detection of patients with increased risk of developing cervical neoplasia associated with HR-HPV infection during routine screening for cervical cancer and in appropriate clinical management.
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Humanos , Adulto , Femenino , Adulto Joven , Biomarcadores Farmacológicos/análisis , Biomarcadores Farmacológicos/sangre , Células Epiteliales/química , Neoplasias del Cuello Uterino/diagnóstico , Neoplasias del Cuello Uterino/etiología , Neoplasias del Cuello Uterino/patología , Papiloma/etiología , Papiloma/química , Papiloma/sangre , Análisis Químico de la Sangre , Hematología , Inmunohistoquímica , Oncología MédicaRESUMEN
PURPOSE: Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) -negative breast cancer. PATIENTS AND METHODS: Patients were randomly assigned to first- or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). RESULTS: In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand- foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). CONCLUSION: Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores de Tumor/análisis , Neoplasias de la Mama/tratamiento farmacológico , Receptor ErbB-2/análisis , Administración Oral , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Bencenosulfonatos/administración & dosificación , Brasil , Neoplasias de la Mama/química , Neoplasias de la Mama/enzimología , Neoplasias de la Mama/patología , Capecitabina , Desoxicitidina/administración & dosificación , Desoxicitidina/análogos & derivados , Supervivencia sin Enfermedad , Método Doble Ciego , Esquema de Medicación , Europa (Continente) , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/análogos & derivados , Humanos , Estimación de Kaplan-Meier , Persona de Mediana Edad , Invasividad Neoplásica , Niacinamida/análogos & derivados , Compuestos de Fenilurea , Modelos de Riesgos Proporcionales , Inhibidores de Proteínas Quinasas/administración & dosificación , Piridinas/administración & dosificación , Sorafenib , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study was (a) to evaluate the association between cigarette smoking and the prevalence of distal colorectal polyps and adenocarcinoma and (b) to analyse genetic alterations representing different molecular pathways of the colorectal carcinogenesis. METHODS: A total of 623 asymptomatic male (mean age: 53 years; 50-65) car factory workers were included. Information on smoking habits and other lifestyle factors were collected followed by a 60 cm colonoscopy. APC and KRAS mutations and microsatellite status were determined in colorectal lesions (colorectal carcinoma (CRC), hyperplastic (HP) and adenomatous polyps (AP)). Data were analysed using unconditional multiple logistic regression models. RESULTS: Smokers had a higher prevalence of AP (OR 2.1; 95% CI 1.2-3.6; p<0.05) and HP (OR 5.4; 95% CI 2.6- 11.1; p<0.05). No differences in CRC were observed. There was a dose-response relationship with the number of cigarettes smoked. The risk of developing AP or HP decreased after smoking cessation, even among heavy smokers (≥20 packs/year). KRAS mutations were more prevalent among smokers AP (OR 5.6; 95% CI 1.6-20.4; p=0.007). There was a trend of positive association with APC mutations (OR 3.5; 95% CI 0.9-4.4; p=0.096). APC and KRAS mutations were found in 36% and 61% of the HP of smokers, but were absent in non-smokers (p=0.89 and 0.78, respectively). There were no differences in MSI between smokers and non-smokers. CONCLUSIONS: Cigarette smoking is associated with a higher risk of developing both HP and AP and a higher prevalence of mutations in APC and KRAS.
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Genes APC , Pólipos Intestinales/genética , Mutación , Proteínas Proto-Oncogénicas/genética , Fumar/efectos adversos , Proteínas ras/genética , Adenocarcinoma/epidemiología , Adenocarcinoma/genética , Pólipos Adenomatosos/epidemiología , Pólipos Adenomatosos/genética , Anciano , Neoplasias Colorrectales/epidemiología , Neoplasias Colorrectales/genética , Estudios Transversales , Análisis Mutacional de ADN , Humanos , Pólipos Intestinales/epidemiología , Masculino , Repeticiones de Microsatélite/genética , Persona de Mediana Edad , Prevalencia , Proteínas Proto-Oncogénicas p21(ras) , Fumar/epidemiología , Fumar/genéticaRESUMEN
Identifying breast cancers with HER2 overexpression or amplification is critical as these usually imply the use of HER2-targeted therapies. DNA (amplification) and protein (overexpression) HER2 abnormalities usually occur simultaneously and both in situ hybridisation and immunohistochemistry may be accurate methods for the evaluation of these abnormalities. However, recent studies, including those conducted by the Association for Quality Assurance of the Spanish Society of Pathology, as well as the experience of a number of HER2 testing National Reference Centres have suggested the existence of serious reproducibility issues with both techniques. To address this issue, a joint committee from the Spanish Society of Pathology (SEAP) and the Spanish Society of Medical Oncology (SEOM) was established to review the HER2 testing guidelines. Consensus recommendations are based not only on the panellists' experience, but also on previous consensus guidelines from several countries, including the USA, the UK and Canada. These guidelines include the minimal requirements that pathology departments should fulfil in order to guarantee proper HER2 testing in breast cancer. Pathology laboratories not fulfilling these standards should make an effort to meet them and, until then, are highly encouraged to submit to reference laboratories breast cancer samples for which HER2 determination has clinical implications for the patients.
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Neoplasias de la Mama/genética , Carcinoma Ductal de Mama/genética , ADN de Neoplasias/análisis , Genes erbB-2 , Inmunohistoquímica/métodos , Hibridación in Situ/métodos , Servicio de Patología en Hospital/normas , Manejo de Especímenes/métodos , Algoritmos , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales Humanizados , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/patología , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Femenino , Control de Formularios y Registros/normas , Humanos , Inmunohistoquímica/normas , Hibridación in Situ/normas , Estudios Multicéntricos como Asunto , Servicio de Patología en Hospital/organización & administración , Servicio de Patología en Hospital/estadística & datos numéricos , Garantía de la Calidad de Atención de Salud/organización & administración , Juego de Reactivos para Diagnóstico , Reproducibilidad de los Resultados , España , Manejo de Especímenes/normas , TrastuzumabRESUMEN
Many important studies have changed the perspective from which breast cancer is approached, and they may change what have to date been the standards applicable to the diagnosis and treatment of breast cancer. In 2007, just over 200 oncologists from all over Spain met in Cordoba in order to review the latest evidence related to breast cancer and reach a consensus on the most important aspects of its diagnosis and treatment in different clinical situations: neoadjuvance, adjuvance and advanced disease. In view of these important changes, opinions on some specific aspects may be varied and all are justified. This document represents a review of the current state of the evidence.
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Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Terapia Neoadyuvante , Quimioterapia Adyuvante , Femenino , Humanos , Guías de Práctica Clínica como Asunto , Radioterapia , EspañaRESUMEN
INTRODUCTION: To investigate the value of baseline serum levels of VEGF, bFGF, endostatin and their ratio as predictive factors of response to endocrine therapy in patients with metastatic breast cancer (MBC) and positive ER treated with letrozole after tamoxifen failure. MATERIALS AND METHOD: The serum levels of endostatin, VEGF and bFGF were determined in postmenopausal patients with progressing MBC from serum samples obtained before initiation of letrozole. The relation between serum angiogenic factor levels and TTP was investigated. RESULTS: Seventy-six patients (45.2%) presented a high endostatin level (> 24.6 ng/ml), 40% low bFGF levels (0 pg/ml) and 50.4% low VEGF (=/< 187 ng/ml). With a median follow-up of 22 months, the median TTP was 12.3 months. Median TTP was worse in patients with high endostatin concentration as well as in the low bFGF group, but was not affected when VEGF was considered. When the two factors were combined, the median TTP of patients with endostatin > 24.6 ng/ml and bFGF equal 0 pg/ml was 9.5 months versus 19.5 months in patients with endostatin =/< 24.6 ng/ml and bFGF > 0 pg/ml. CONCLUSIONS: The baseline levels of bFGF and endostatin are predictive factors of efficacy in patients with MBC treated with letrozole and can select groups with different TTP.