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1.
Int J Mol Sci ; 24(23)2023 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-38069096

RESUMO

Breast cancer is one of the most prevalent tumors among women. Its prognosis and treatment outcomes depend on factors related to tumor cell biology. However, recent studies have revealed the critical role of the tumor microenvironment (TME) in the development, progression, and treatment response of breast cancer. In this review, we explore the different components of the TME and their relevance as prognostic and predictive biomarkers in breast cancer. In addition, techniques for assessing the tumor microenvironment, such as immunohistochemistry or gene expression profiling, and their clinical utility in therapeutic decision-making are examined. Finally, therapeutic strategies targeting the TME are reviewed, highlighting their potential clinical benefits. Overall, this review emphasizes the importance of the TME in breast cancer and its potential as a clinical tool for better patient stratification and the design of personalized therapies.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Prognóstico , Microambiente Tumoral/genética , Perfilação da Expressão Gênica , Biomarcadores Tumorais/genética
2.
Int J Mol Sci ; 24(10)2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37239834

RESUMO

By the end of 2020, there were more than 8 million women alive who had received a breast cancer diagnosis in the previous 5 years, making it the most prevalent neoplasia in the world. About 70% of breast-cancer cases present positivity for estrogen and/or progesterone receptors and a lack of HER-2 overexpression. Endocrine therapy has traditionally been the standard of care for ER-positive and HER-2-negative metastatic breast cancer. In the last 8 years, the advent of CDK4/6 inhibitors has shown that adding them to endocrine therapy doubles PFS. As a result, this combination has become the gold standard in this setting. Three CDK4/6 inhibitors have been approved by the EMA and the FDA: abemaciclib, palbociclib, and ribociclib. They all have the same indications, and it is at each physician's discretion to choose one or the other. The aim of our study was to perform a comparative efficacy analysis of the three CDK4/6i using real-world data. We selected patients diagnosed with endocrine-receptor-positive and HER2-negative breast cancer who were treated with all three CDK4/6i as first-line therapy at a reference center. After 42 months of retrospective follow up, abemaciclib was associated with a significant benefit in terms of progression-free survival in endocrine-resistant patients and in the population without visceral involvement. In our real-world cohort, we found no other statistically significant differences among the three CDK4/6 inhibitors.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Estudos Retrospectivos , Quinase 4 Dependente de Ciclina , Inibidores de Proteínas Quinases/farmacologia , Quinase 6 Dependente de Ciclina , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
3.
Nutrients ; 15(2)2023 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-36678163

RESUMO

The NOA (Oncological Nutrition in Andalusia) project analyses the degree of integration and areas of improvement in implementing nutritional support in the care plans of cancer patients in Andalusia. The aim was to analyse nutritional interventions for better care of cancer patients and for the improvement of the management of malnutrition in cancer. A prospective evaluation of the implementation of two areas of improvement in nutrition was conducted in three hospitals. Data were collected from each hospital over a six-month period using an online platform. A standardised care plan was designed for hospitals in Andalusia, in which proposed improvements were devised and prioritised, selecting nutritional screening in oncology services and the participation of the Nutrition Support Team (NST) on the tumour boards, as well as the assessment of the patients presented at these sessions. Our results indicated an increase in the number of medical records with nutritional evaluation results six months later, regardless of the type of tumour or hospitalisation; and there was greater participation of the NST on the tumour boards, mainly for head and neck and oesophagogastric cases. Solutions for improvement have been pinpointed and implemented that have positively impacted the nutritional care plan in the course of oncological disease.


Assuntos
Desnutrição , Neoplasias , Humanos , Avaliação Nutricional , Estado Nutricional , Apoio Nutricional/métodos , Desnutrição/prevenção & controle , Desnutrição/diagnóstico , Neoplasias/complicações , Neoplasias/terapia
4.
Breast ; 62: 75-83, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35131646

RESUMO

BACKGROUND: The phase IIIb CompLEEment-1 study evaluated ribociclib plus letrozole in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC). Outcomes were investigated in the following subgroups: central nervous system (CNS) metastases, prior chemotherapy for advanced disease, Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2, and visceral metastases plus prior chemotherapy for advanced disease or ECOG PS 2. PATIENTS AND METHODS: Patients with HR+, HER2- ABC without prior hormonal treatment for advanced disease received oral ribociclib (600 mg once daily, 3 weeks on/1 week off) plus letrozole (2.5 mg once daily, continuous). Primary endpoint was safety/tolerability, assessed via occurrence of adverse events (AEs); key secondary endpoints included time to progression (TTP), overall response rate, and clinical benefit rate. RESULTS: 51 patients had CNS metastases, 194 received prior chemotherapy for advanced disease, 112 had ECOG PS 2, 146 had visceral metastases plus prior chemotherapy, and 77 had visceral metastases plus ECOG PS 2. Safety results were consistent with those in the overall CompLEEment-1 population; no new safety concerns were identified. The AE profile was manageable with low rates of discontinuations due to AEs. TTP in patients with CNS metastases was consistent with the overall study population and shorter for other patient subgroups. Each patient subgroup achieved meaningful clinical benefit from treatment, consistent with the overall population. CONCLUSION: These findings confirm the clinical benefit of ribociclib plus endocrine therapy in high-risk patient subgroups of clinical interest commonly underrepresented in clinical trials.


Assuntos
Neoplasias da Mama , Aminopiridinas , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/patologia , Feminino , Hormônios/uso terapêutico , Humanos , Letrozol , Purinas , Receptor ErbB-2/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
5.
Breast ; 66: 77-84, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36206609

RESUMO

BACKGROUND: Breast cancer is the most common malignancy and the second leading cause of cancer-related mortality in Spanish women. Ribociclib in combination with endocrine therapy (ET) has shown superiority in prolonging survival in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) advanced breast cancer (ABC) vs. ET alone. METHODS: CompLEEment-1 is a single-arm, open-label phase 3b trial evaluating ribociclib plus letrozole in a broad population of patients with HR+, HER2- ABC. The primary endpoints were safety and tolerability. Here we report data for Spanish patients enrolled in CompLEEment-1. RESULTS: A total of 526 patients were evaluated (median follow-up: 26.97 months). Baseline characteristics showed a diverse population with a median age of 54 years. At study entry, 56.5% of patients had visceral metastases and 8.7% had received prior chemotherapy for advanced disease. Rates of all-grade and Grade ≥3 adverse events (AEs) were 99.0% and 76.2%, respectively; 21.3% of patients experienced a serious AE, and 15.8% of AEs led to treatment discontinuation. AEs of special interest of neutropenia, increased alanine aminotransferase, increased aspartate aminotransferase and QTcF prolongation occurred in 77.8%, 14.8%, 11.4% and 4.0% of patients, respectively. Patients aged >70 years experienced increased rates of all-grade and Grade ≥3 neutropenia and anemia. Efficacy results were consistent with the global study. CONCLUSIONS: Results from Spanish patients enrolled in CompLEEment-1 are consistent with global data showing efficacy and a manageable safety profile for ribociclib plus letrozole treatment in patients with HR+, HER2- ABC, including populations of interest (NCT02941926). TRIAL REGISTRATION: ClinicalTrials.gov NCT02941926.


Assuntos
Neoplasias da Mama , Neutropenia , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/patologia , Letrozol , Receptor ErbB-2/metabolismo , Aminopiridinas/efeitos adversos , Inibidores da Aromatase/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Neutropenia/etiologia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos
6.
Nutr Hosp ; 38(4): 758-764, 2021 Jul 29.
Artigo em Espanhol | MEDLINE | ID: mdl-33703912

RESUMO

INTRODUCTION: Introduction: malnutrition in cancer patients can lead to a reduction in patient quality of life, increased morbidity and mortality, and associated healthcare costs. Objective: to analyze nutritional interventions in the different phases of the oncological process, integrating the needs of patients and those of healthcare professionals. Material and methods: "Design Thinking" techniques were used to address the analysis of the current situation and identify key aspects. Thirteen professionals from 8 public health centers (endocrinology and nutrition, medical and radiotherapy oncology, primary care (PC), nursing and dietetics) participated in the study. Results: nutritional screening is not carried out in a systematic way in the different phases of the oncological process, and there is no universal consensus on the protocols for action and nutritional intervention. A wide compliance with the pathways and referral times of the selected processes has been observed. In the therapeutic phase, there is the possibility of consulting the Clinical Nutrition and Dietetics Unit (UNCYD) and 75 % have specific referral protocols. The nurse case manager is present in all hospitals and in PC. Patient access to the center psychologist was possible in 87 % of the hospitals. Participation of the UNCYD in Tumor Committees was low (only in 25 % of the centers). In all centers there is some kind of collaboration and support by patient associations and the School of Patients, especially in the therapeutic and the control and follow-up phases. Conclusions: variations are observed between the different hospitals and areas in Andalusia, both in terms of means and structures and in activities and procedures. Key points have been selected and prioritized to improve nutritional care in oncology.


INTRODUCCIÓN: Introducción: la desnutrición en los pacientes oncológicos puede conllevar una reducción de la calidad de vida del paciente y un aumento de la morbimortalidad y de los costes sanitarios asociados. Objetivos: analizar las intervenciones nutricionales en las diferentes fases del proceso oncológico, integrando las necesidades de los pacientes y las de los profesionales sanitarios. Material y métodos: se utilizaron técnicas de Design Thinking para abordar el análisis de la situación actual e identificar los aspectos clave. Participaron 13 profesionales de 8 centros sanitarios (endocrinología y nutrición, oncología médica y radioterápica, atención primaria (AP), enfermería y dietética) públicos de Andalucía. Resultados: no se realiza cribado nutricional de forma sistemática en las diferentes fases del proceso oncológico, y no existe consenso universal en los protocolos de actuación e intervención nutricional. Existe un cumplimiento generalizado de los circuitos y tiempos de derivación de los procesos seleccionados. En la fase terapéutica se dispone de la posibilidad de consultar a la Unidad de Nutrición Clínica y Dietética (UNCYD) y el 75 % disponen de protocolos específicos de derivación. La enfermera gestora de casos está presente en todos los hospitales y en AP. El acceso del paciente al psicólogo del centro era posible en el 87 % de los hospitales. Escasa participación de la UNCYD en los Comités de Tumores (solo en el 25 % de los centros). En todos los centros existe algún tipo de colaboración y apoyo de las asociaciones de pacientes y de la Escuela de Pacientes, especialmente en las fases terapéuticas y de control y seguimiento. Conclusiones: se observan variaciones entre los diferentes hospitales y territorios de Andalucía, tanto en la disposición de medios y estructuras como en las actividades y procedimientos. Se han seleccionado y priorizado puntos clave para mejorar la atención nutricional en oncología.


Assuntos
Neoplasias/dietoterapia , Terapia Nutricional/normas , Humanos , Desnutrição/dietoterapia , Desnutrição/epidemiologia , Desnutrição/etiologia , Neoplasias/epidemiologia , Terapia Nutricional/métodos , Terapia Nutricional/estatística & dados numéricos , Qualidade de Vida/psicologia , Encaminhamento e Consulta/tendências , Espanha/epidemiologia
7.
Cell Oncol (Dordr) ; 42(1): 1-12, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30361825

RESUMO

BACKGROUND: Current therapeutic strategies that are used to combat breast cancer vary widely and largely depend on its clinicopathological features, including tumor subtype, size, stage, lymph node involvement, the presence of hormone receptors and/or HER2, as well as the degree of proliferative activity. Recent work has focused on improving our knowledge on the molecular mechanisms that underlie this complex disease. Most of the human genome is transcribed into RNAs that do not encode proteins. These noncoding RNAs may act as mediators in the regulation of gene expression. Based on their size and function, noncoding RNAs are classified into small noncoding RNAs (sncRNAs) and long noncoding RNAs (lncRNAs). LncRNAs have been found to play key roles in relevant biological processes, including breast cancer. As such, lncRNAs have been proposed as diagnostic and prognostic biomarkers, as predictive biomarkers and as putative therapeutic targets. CONCLUSIONS: In this review, we discuss the potential application of lncRNAs for the monitoring and treatment of breast cancer. We conclude that lncRNAs play important roles in the pathophysiology of this disease and may serve as putative therapeutic targets. As such, tumor-specific lncRNAs may be instrumental for improving current breast cancer clinical practices.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Terapia de Alvo Molecular , RNA Longo não Codificante/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Resistencia a Medicamentos Antineoplásicos , Feminino , Humanos , RNA Longo não Codificante/metabolismo
8.
J Drug Assess ; 8(1): 62-69, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31069129

RESUMO

Objective: The aim of this survey conducted by 20 leading Spanish oncologists was to analyze the concurrence between Spanish clinical practice and the recently published definition of the optimal sequence for the systemic treatment of metastatic breast cancer (MBC) according to patient profiles. Methods: A self-administered questionnaire was developed, divided into five sections comprising 34 specific questions related to sequential treatments, plus three additional general questions. Respondents were asked to justify negative answers. Participants were recruited randomly by invitation out of a total of 619 oncologists. The questionnaire was sent and collected via e-mail between October 2015 and May 2016. A total of 191 completed questionnaires were received. Results: Overall, 70% of oncologists would keep the three patient profiles exactly as proposed (hormone receptor-positive and HER2-negative, HER2-positive, and triple negative breast cancer). Affirmative answers to questions regarding treatment sequences for these patient profiles (1-34) ranged from 77.8-99.5%, with an average of 90.9% of oncologists being in agreement with the recommended sequential treatments. The lowest degree of consensus was observed for endocrine treatments in pre-menopausal women and for chemotherapy options in hormone-resistant patients, whilst the highest degree of consensus was reached for targeted therapies in HER2-positive patients and for endocrine therapy in post-menopausal women. In their comments, participants revealed a number of economic constraints that prevented them from implementing some of the best treatment options. Conclusions: In conclusion, despite the complexity of MBC treatment, there is general agreement on the optimal treatment sequences.

9.
J Clin Oncol ; 31(20): 2593-9, 2013 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-23733779

RESUMO

PURPOSE: Adding taxanes to anthracycline-based adjuvant therapy improves survival outcomes of patients with node-positive breast cancer (BC). Currently, however, most patients with BC are node negative at diagnosis. The only pure node-negative study (Spanish Breast Cancer Research Group 9805) reported so far showed a docetaxel benefit but significant toxicity. Here we tested the efficacy and safety of weekly paclitaxel (wP) in node-negative patients, which is yet to be established. PATIENTS AND METHODS: Patients with BC having T1-T3/N0 tumors and at least one high-risk factor for recurrence (according to St. Gallen 1998 criteria) were eligible. After primary surgery, 1,925 patients were randomly assigned to receive fluorouracil, doxorubicin, and cyclophosphamide (FAC) × 6 or FAC × 4 followed by wP × 8 (FAC-wP). The primary end point was disease-free survival (DFS) after a median follow-up of 5 years. Secondary end points included toxicity and overall survival. RESULTS: After a median follow-up of 63.3 months, 93% and 90.3% of patients receiving FAC-wP or FAC regimens, respectively, remained disease free (hazard ratio [HR], 0.73; 95% CI, 0.54 to 0.99; log-rank P = .04). Thirty-one patients receiving FAC-wP versus 40 patients receiving FAC died (one and seven from cardiovascular diseases, respectively; HR, 0.79; 95% CI, 0.49 to 1.26; log-rank P = .31). The most relevant grade 3 and 4 adverse events in the FAC-wP versus the FAC arm were febrile neutropenia (2.7% v 3.6%), fatigue (7.9% v 3.4%), and sensory neuropathy (5.5% v 0%). CONCLUSION: For patients with high-risk node-negative BC, the adjuvant FAC-wP regimen was associated with a small but significant improvement in DFS compared with FAC therapy, in addition to manageable toxicity, especially regarding long-term cardiac effects.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/mortalidade , Recidiva Local de Neoplasia/mortalidade , Paclitaxel/administração & dosagem , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Intervalos de Confiança , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Intervalo Livre de Doença , Relação Dose-Resposta a Droga , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Linfonodos/patologia , Mastectomia/métodos , Dose Máxima Tolerável , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Paclitaxel/efeitos adversos , Modelos de Riscos Proporcionais , Medição de Risco , Análise de Sobrevida , Resultado do Tratamento
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