Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 129
Filtrar
Más filtros

Banco de datos
País/Región como asunto
Tipo del documento
Intervalo de año de publicación
1.
J Natl Compr Canc Netw ; 22(5): 331-357, 2024 07.
Artículo en Inglés | MEDLINE | ID: mdl-39019058

RESUMEN

Breast cancer is treated with a multidisciplinary approach involving surgical oncology, radiation oncology, and medical oncology. The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget's disease, Phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of systemic therapy (preoperative and adjuvant) options for nonmetastatic breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.


Asunto(s)
Neoplasias de la Mama , Humanos , Neoplasias de la Mama/terapia , Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/patología , Femenino , Oncología Médica/normas , Oncología Médica/métodos , Terapia Combinada/normas
2.
South Med J ; 117(8): 489-493, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-39094799

RESUMEN

OBJECTIVES: The landscape of the emergency medicine (EM) workforce has undergone significant changes recently, posing challenges for residents who are about to graduate from EM training programs. The objective of this study was to survey graduating residents' perceptions of the recent EM job market. METHODS: We conducted a cross-sectional survey study involving EM residents from programs in New York and New Jersey between August 2021 and November 2021. The survey consisted of 12 multiple-choice questions that focused on graduating EM residents' perceptions of the EM job market, its impact on their job search, and their interest in pursuing fellowship training. RESULTS: During the study period, 436 survey results were collected from 26 EM residency programs. Of the 418 respondents, 233 (56%) expressed their intention to start their job search earlier than their counterparts in previous years, as highlighted by the survey. Among respondents, 141 (76%) postgraduate year (PGY)-2, 139 (79%) PGY-3, and 47 (85%) PGY-4 residents anticipated a challenging job search. Nearly 90% of respondents believed that the coronavirus disease 2019 pandemic would affect both academic and nonacademic medical centers in terms of job openings. A total of 248 (59%) were interested in pursuing a fellowship after residency. Most residents preferred job opportunities on the East and West Coasts of the United States. CONCLUSIONS: The findings highlight the increasing competitiveness and challenges residents face in securing their first job, the declining interest in pursuing fellowships as residents progress in their training, and the geographic preferences for job opportunities.


Asunto(s)
Medicina de Emergencia , Empleo , Internado y Residencia , Humanos , Medicina de Emergencia/educación , Estudios Transversales , Internado y Residencia/estadística & datos numéricos , Internado y Residencia/tendencias , Encuestas y Cuestionarios , Empleo/estadística & datos numéricos , Femenino , Masculino , Selección de Profesión , Adulto , New York , COVID-19/epidemiología , New Jersey , Becas/estadística & datos numéricos , Becas/tendencias
3.
J Natl Compr Canc Netw ; 21(6): 594-608, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-37308117

RESUMEN

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer address all aspects of management for breast cancer. The treatment landscape of metastatic breast cancer is evolving constantly. The therapeutic strategy takes into consideration tumor biology, biomarkers, and other clinical factors. Due to the growing number of treatment options, if one option fails, there is usually another line of therapy available, providing meaningful improvements in survival. This NCCN Guidelines Insights report focuses on recent updates specific to systemic therapy recommendations for patients with stage IV (M1) disease.


Asunto(s)
Neoplasias de la Mama , Humanos , Femenino , Oncología Médica
4.
Mol Carcinog ; 61(3): 359-371, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34856027

RESUMEN

The tumor microenvironment (TME) is an important modulator of response and resistance to endocrine therapy in estrogen receptor alpha (ER) positive breast cancer. Endocrine therapy is highly effective at reducing tumor burden and preventing recurrence in most estrogen receptor alpha (ER) positive breast cancers. Existing drugs work either directly by targeting tumor-cell ER or indirectly by inhibiting estrogen production in stromal cells with aromatase inhibitors (AI). However, many stromal cells also express ER and the direct impact of endocrine therapies on ER + stromal cells remain unclear. In this study, we investigated how neoadjuvant endocrine therapy (NET) directly effects stromal cells by measuring changes in stomal components of the TME that favor tumor progression. We previously defined two major subsets of tumor-associated stromal cells (TASCs): CD146 positive/CDCP1 negative (TASCCD146 ), CD146 negative/CDCP1 positive (TASCCDCP1 ), and generated a differentially expressed genes list associated with each type. Here, we applied the TASC gene list for classification and an algorithm that estimates immune cell abundance (TIMEx) to METABRIC transcriptomic data for ER + breast cancer patients coupled with multiplex imaging and analysis of paired tissue samples pre- and post- NET with the AI exemestane. TASCCDCP1 composition predicted for decreased patient survival in the METABRIC cohort. Exemestane treatment significantly increased expression of TASCCDCP1 and decreased expression of TASCCD146 . The posttreatment shift toward TASCCDCP1 composition correlated with increased macrophage infiltration and increased CD8+ T-cell, B cell, and general stromal components. The effectiveness of NET is currently based solely on the reduction of ER+ breast cancer cells. Here, we show NET displays clear TME effects that promote the expansion of the less favorable TASCCDCP1 population which are correlated with TME remodeling and reshaping immune infiltration supportive of tumor progression. Our findings highlight the need to further understand the role of endocrine therapy on TME remodeling, tumor progression, and patient outcomes.


Asunto(s)
Neoplasias de la Mama , Receptores de Estrógenos , Antígenos de Neoplasias , Inhibidores de la Aromatasa/farmacología , Inhibidores de la Aromatasa/uso terapéutico , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Antígeno CD146 , Moléculas de Adhesión Celular , Receptor alfa de Estrógeno , Femenino , Humanos , Terapia Neoadyuvante , Receptores de Estrógenos/metabolismo , Microambiente Tumoral
5.
J Natl Compr Canc Netw ; 20(6): 691-722, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-35714673

RESUMEN

The therapeutic options for patients with noninvasive or invasive breast cancer are complex and varied. These NCCN Clinical Practice Guidelines for Breast Cancer include recommendations for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, and management of breast cancer during pregnancy. The content featured in this issue focuses on the recommendations for overall management of ductal carcinoma in situ and the workup and locoregional management of early stage invasive breast cancer. For the full version of the NCCN Guidelines for Breast Cancer, visit NCCN.org.


Asunto(s)
Neoplasias de la Mama , Carcinoma Intraductal no Infiltrante , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Carcinoma Intraductal no Infiltrante/terapia , Femenino , Humanos , Oncología Médica
6.
Inorg Chem ; 61(12): 5025-5032, 2022 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-35290060

RESUMEN

Atomic-level understanding of the gate-opening phenomenon in flexible porous materials is an important step toward learning how to control, design, and engineer them for applications such as the separation of gases from complex mixtures. Here, we report such mechanistic insight through an in-depth study of the pressure-induced gate-opening phenomenon in our earlier reported metal-organic framework (MOF) Zn(dps)2(SiF6) (dps = 4,4'-dipyridylsulfide), also called UTSA-300, using isotherm and calorimetry measurements, in situ infrared spectroscopy, and ab initio simulations. UTSA-300 is shown to selectively adsorb acetylene (C2H2) over ethylene (C2H4) and ethane (C2H6) and undergoes an abrupt gate-opening phenomenon, making this framework a highly selective gas separator of this complex mixture. The selective adsorption is confirmed by pressure-dependent in situ infrared spectroscopy, which, for the first time, shows the presence of multiple C2H2 species with varying strengths of bonding. A rare energetic feature at the gate-opening condition of the flexible MOF is observed in our differential heat energies, directly measured by calorimetry, showcasing the importance of this tool in adsorption property exploration of flexible frameworks and offering an energetic benchmark for further energy-based fundamental studies. Based on the agreement of this feature with ab initio-based adsorption energies of C2H2 in the closed-pore structure UTSA-300a ("a" refers to the activated form), this feature is assigned to the weakening of the H-bond C-H···F formed between C2H2 and fluorine of the MOF. Our analysis identifies the weakening of this H-bond, the expansion of the closed-pore MOF upon successive C2H2 coadsorption until its volume is close to that of the open-pore MOF, and the spontaneous gate opening to energetically favor C2H2 adsorption in the open-pore structure as crucial steps in the gate-opening mechanism in this system.

7.
Cancer ; 127(6): 894-904, 2021 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-33231866

RESUMEN

BACKGROUND: Therapeutic options for patients with advanced soft-tissue sarcoma (STS) are limited. The goal of the current phase 2 study was to examine the clinical activity and safety of the combination of gemcitabine plus pazopanib, a multityrosine kinase inhibitor with activity in STS. METHODS: The current randomized, phase 2 trial enrolled patients with advanced nonadipocytic STS who had received prior anthracycline-based therapy. Patients were assigned 1:1 to receive gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 with pazopanib at a dose of 800 mg daily (G+P) or gemcitabine at a dose of 900 mg/m2 on days 1 and 8 and docetaxel at a dose of 100 mg/m2 on day 8 (G+T) every 3 weeks. Crossover was allowed at the time of disease progression. The study used a noncomparative statistical design based on the precision of 95% confidence intervals for reporting the primary endpoints of median progression-free survival (PFS) and rate of grade ≥3 adverse events (AEs) for these 2 regimens based on the intent-to-treat patient population (AEs were graded using version 4.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events). RESULTS: A total of 90 patients were enrolled: 45 patients on each treatment arm. The median PFS was 4.1 months for each arm (P = .3, log-rank test). The best overall response of stable disease or better (complete response + partial response + stable disease) was the same for both treatment arms (64% for both the G+T and G+P arms). The rate of related grade ≥3 AEs was 82% for the G+T arm and 78% for the G+P arm. Related grade ≥3 AEs occurring in ≥10% of patients in the G+T and G+P arms were anemia (36% and 20%, respectively), fatigue (29% and 13%, respectively), thrombocytopenia (53% and 49%, respectively), neutropenia (20% and 49%, respectively), lymphopenia (13% and 11%, respectively), and hypertension (2% and 20%, respectively). CONCLUSIONS: The data from the current study have demonstrated the safety and efficacy of G+P as an alternative to G+T for patients with nonadipocytic STS.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Desoxicitidina/análogos & derivados , Docetaxel/administración & dosificación , Indazoles/administración & dosificación , Pirimidinas/administración & dosificación , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Adulto , Anciano , Anciano de 80 o más Años , Estudios Cruzados , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Docetaxel/efectos adversos , Femenino , Humanos , Indazoles/efectos adversos , Masculino , Persona de Mediana Edad , Pirimidinas/efectos adversos , Neoplasias de los Tejidos Blandos/mortalidad , Sulfonamidas/efectos adversos , Adulto Joven , Gemcitabina
8.
J Natl Compr Canc Netw ; 19(5): 484-493, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-34794122

RESUMEN

The NCCN Guidelines for Breast Cancer include up-to-date guidelines for clinical management of patients with carcinoma in situ, invasive breast cancer, Paget disease, phyllodes tumor, inflammatory breast cancer, male breast cancer, and breast cancer during pregnancy. These guidelines are developed by a multidisciplinary panel of representatives from NCCN Member Institutions with breast cancer-focused expertise in the fields of medical oncology, surgical oncology, radiation oncology, pathology, reconstructive surgery, and patient advocacy. These NCCN Guidelines Insights focus on the most recent updates to recommendations for adjuvant systemic therapy in patients with nonmetastatic, early-stage, hormone receptor-positive, HER2-negative breast cancer.


Asunto(s)
Neoplasias de la Mama , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/terapia , Terapia Combinada , Humanos , Masculino , Oncología Médica
9.
Mol Carcinog ; 59(10): 1129-1139, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-32822091

RESUMEN

For solid tumors, extravasation of cancer cells and their survival in circulation represents a critical stage of the metastatic process that lacks complete understanding. Gaining insight into interactions between circulating tumor cells (CTCs) and other peripheral blood mononuclear cells (PBMCs) may provide valuable prognostic information. The purpose of this study was to use single-cell RNA-sequencing (scRNA-seq) of liquid biopsies from breast cancer patients to begin defining intravascular interactions. We captured CTCs from the peripheral blood of breast cancer patients using size-exclusion membranes followed by scRNA-seq of enriched CTCs and carry-over PBMCs. Transcriptome analysis identified two populations of CTCs: one enriched for transcripts indicative of estrogen responsiveness and increased proliferation and another enriched for transcripts characteristic of reduced proliferation and epithelial-mesenchymal transition (EMT). We applied interactome and pathway analysis to determine interactions between CTCs and other captured cells. Our analysis predicted for enhanced immune evasion in the CTC population with EMT characteristics. In addition, PD-1/PD-L1 pathway activation and T cell exhaustion were predicted in T cells isolated from breast cancer patients compared with normal T cells. We conclude that scRNA-seq of breast cancer CTCs generally stratifies them into two types based on their proliferative and epithelial state and differential potential to interact with PBMCs. Better understanding of CTC subtypes and their intravascular interactions may help design treatments directed against CTCs with high metastatic and immune-evasive competence.


Asunto(s)
Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Transición Epitelial-Mesenquimal , Leucocitos Mononucleares/patología , Células Neoplásicas Circulantes/patología , Neoplasias de la Mama/sangre , Femenino , Humanos , Pronóstico , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Células Tumorales Cultivadas
10.
J Natl Compr Canc Netw ; 18(4): 452-478, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32259783

RESUMEN

Several new systemic therapy options have become available for patients with metastatic breast cancer, which have led to improvements in survival. In addition to patient and clinical factors, the treatment selection primarily depends on the tumor biology (hormone-receptor status and HER2-status). The NCCN Guidelines specific to the workup and treatment of patients with recurrent/stage IV breast cancer are discussed in this article.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Neoplasias de la Mama/etiología , Neoplasias de la Mama/mortalidad , Toma de Decisiones Clínicas , Manejo de la Enfermedad , Susceptibilidad a Enfermedades , Femenino , Humanos , Metástasis de la Neoplasia , Estadificación de Neoplasias , Recurrencia
11.
N Engl J Med ; 375(1): 11-22, 2016 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-27406346

RESUMEN

BACKGROUND: The heterogeneity of breast cancer makes identifying effective therapies challenging. The I-SPY 2 trial, a multicenter, adaptive phase 2 trial of neoadjuvant therapy for high-risk clinical stage II or III breast cancer, evaluated multiple new agents added to standard chemotherapy to assess the effects on rates of pathological complete response (i.e., absence of residual cancer in the breast or lymph nodes at the time of surgery). METHODS: We used adaptive randomization to compare standard neoadjuvant chemotherapy plus the tyrosine kinase inhibitor neratinib with control. Eligible women were categorized according to eight biomarker subtypes on the basis of human epidermal growth factor receptor 2 (HER2) status, hormone-receptor status, and risk according to a 70-gene profile. Neratinib was evaluated against control with regard to 10 biomarker signatures (prospectively defined combinations of subtypes). The primary end point was pathological complete response. Volume changes on serial magnetic resonance imaging were used to assess the likelihood of such a response in each patient. Adaptive assignment to experimental groups within each disease subtype was based on Bayesian probabilities of the superiority of the treatment over control. Enrollment in the experimental group was stopped when the 85% Bayesian predictive probability of success in a confirmatory phase 3 trial of neoadjuvant therapy reached a prespecified threshold for any biomarker signature ("graduation"). Enrollment was stopped for futility if the probability fell to below 10% for every biomarker signature. RESULTS: Neratinib reached the prespecified efficacy threshold with regard to the HER2-positive, hormone-receptor-negative signature. Among patients with HER2-positive, hormone-receptor-negative cancer, the mean estimated rate of pathological complete response was 56% (95% Bayesian probability interval [PI], 37 to 73%) among 115 patients in the neratinib group, as compared with 33% among 78 controls (95% PI, 11 to 54%). The final predictive probability of success in phase 3 testing was 79%. CONCLUSIONS: Neratinib added to standard therapy was highly likely to result in higher rates of pathological complete response than standard chemotherapy with trastuzumab among patients with HER2-positive, hormone-receptor-negative breast cancer. (Funded by QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Quinolinas/administración & dosificación , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Teorema de Bayes , Biomarcadores de Tumor , Neoplasias de la Mama/genética , Neoplasias de la Mama/cirugía , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Quinolinas/efectos adversos , Receptor ErbB-2 , Receptores de Estrógenos , Receptores de Progesterona , Trastuzumab/administración & dosificación
12.
N Engl J Med ; 375(1): 23-34, 2016 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-27406347

RESUMEN

BACKGROUND: The genetic and clinical heterogeneity of breast cancer makes the identification of effective therapies challenging. We designed I-SPY 2, a phase 2, multicenter, adaptively randomized trial to screen multiple experimental regimens in combination with standard neoadjuvant chemotherapy for breast cancer. The goal is to match experimental regimens with responding cancer subtypes. We report results for veliparib, a poly(ADP-ribose) polymerase (PARP) inhibitor, combined with carboplatin. METHODS: In this ongoing trial, women are eligible for participation if they have stage II or III breast cancer with a tumor 2.5 cm or larger in diameter; cancers are categorized into eight biomarker subtypes on the basis of status with regard to human epidermal growth factor receptor 2 (HER2), hormone receptors, and a 70-gene assay. Patients undergo adaptive randomization within each biomarker subtype to receive regimens that have better performance than the standard therapy. Regimens are evaluated within 10 biomarker signatures (i.e., prospectively defined combinations of biomarker subtypes). Veliparib-carboplatin plus standard therapy was considered for HER2-negative tumors and was therefore evaluated in 3 signatures. The primary end point is pathological complete response. Tumor volume changes measured by magnetic resonance imaging during treatment are used to predict whether a patient will have a pathological complete response. Regimens move on from phase 2 if and when they have a high Bayesian predictive probability of success in a subsequent phase 3 neoadjuvant trial within the biomarker signature in which they performed well. RESULTS: With regard to triple-negative breast cancer, veliparib-carboplatin had an 88% predicted probability of success in a phase 3 trial. A total of 72 patients were randomly assigned to receive veliparib-carboplatin, and 44 patients were concurrently assigned to receive control therapy; at the completion of chemotherapy, the estimated rates of pathological complete response in the triple-negative population were 51% (95% Bayesian probability interval [PI], 36 to 66%) in the veliparib-carboplatin group versus 26% (95% PI, 9 to 43%) in the control group. The toxicity of veliparib-carboplatin was greater than that of the control. CONCLUSIONS: The process used in our trial showed that veliparib-carboplatin added to standard therapy resulted in higher rates of pathological complete response than standard therapy alone specifically in triple-negative breast cancer. (Funded by the QuantumLeap Healthcare Collaborative and others; I-SPY 2 TRIAL ClinicalTrials.gov number, NCT01042379.).


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Bencimidazoles/administración & dosificación , Carboplatino/administración & dosificación , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Teorema de Bayes , Bencimidazoles/efectos adversos , Carboplatino/efectos adversos , Femenino , Humanos , Persona de Mediana Edad , Terapia Neoadyuvante , Paclitaxel/administración & dosificación , Paclitaxel/efectos adversos , Inhibidores de Poli(ADP-Ribosa) Polimerasas/administración & dosificación , Inhibidores de Poli(ADP-Ribosa) Polimerasas/efectos adversos , Neoplasias de la Mama Triple Negativas/cirugía
13.
Breast Cancer Res Treat ; 173(1): 37-48, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30267249

RESUMEN

PURPOSE: Male breast cancer (BC) is rare, representing approximately 1% of cancers that occur in men and approximately 1% of all BCs worldwide. Because male BC is rare, not much is known about the disease, and treatment recommendations are typically extrapolated from data available from clinical trials enrolling female BC patients. METHODS: We review the epidemiology, risk factors, prognosis, and the varied molecular and clinicopathologic features that characterize male BC. In addition, we summarize the available data for the use of systemic therapy in the treatment of male BC and explore the ongoing development of targeted therapeutic agents for the treatment of this subgroup of BCs. RESULTS: There are important biological differences between male and female BC. Male BC is almost exclusively hormone receptor positive (+), including the androgen receptor (AR), and is associated with an increased prevalence of BRCA2 germline mutations, especially in men with increased risk for developing high-risk BC. Additional research is warranted to better characterize male BC. To accomplish this, a multi-national consortium approach, such as the International Male Breast Cancer Program, is needed in response to the scarcity of patients. This approach allows the pooling of information from a large number of men with BC and the creation of registries for future therapeutic-focused clinical trials. CONCLUSIONS: Given the unique biology of BC in men, promising new therapeutic targets are currently under investigation, including the use of poly-ADP-ribose polymerase inhibitors or AR-targeted agents either as monotherapy or in combination with other agents.


Asunto(s)
Neoplasias de la Mama Masculina/epidemiología , Neoplasias de la Mama Masculina/terapia , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Neoplasias de la Mama Masculina/etiología , Ensayos Clínicos como Asunto , Epigénesis Genética , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Masculino , Programa de VERF
14.
J Natl Compr Canc Netw ; 17(2): 118-126, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-30787125

RESUMEN

These NCCN Guidelines Insights highlight the updated recommendations for use of multigene assays to guide decisions on adjuvant systemic chemotherapy therapy for women with hormone receptor-positive, HER2-negative early-stage invasive breast cancer. This report summarizes these updates and discusses the rationale behind them.


Asunto(s)
Neoplasias de la Mama/diagnóstico , Neoplasias de la Mama/terapia , Neoplasias de la Mama/etiología , Femenino , Humanos
16.
Breast Cancer Res ; 20(1): 82, 2018 08 02.
Artículo en Inglés | MEDLINE | ID: mdl-30071865

RESUMEN

BACKGROUND: Triple-negative breast cancer (TNBC) remains an aggressive breast cancer subtype with limited treatment options. ENMD-2076 is a small-molecule inhibitor of Aurora and angiogenic kinases with proapoptotic and antiproliferative activity in preclinical models of TNBC. METHODS: This dual-institution, single-arm, two-stage, phase II clinical trial enrolled patients with locally advanced or metastatic TNBC previously treated with one to three prior lines of chemotherapy in the advanced setting. Patients were treated with ENMD-2076 250 mg orally once daily with continuous dosing in 4-week cycles until disease progression or unacceptable toxicity occurred. The primary endpoint was 6-month clinical benefit rate (CBR), and secondary endpoints included progression-free survival, pharmacokinetic profile, safety, and biologic correlates in archival and fresh serial tumor biopsies in a subset of patients. RESULTS: Forty-one patients were enrolled. The 6-month CBR was 16.7% (95% CI, 6-32.8%) and included two partial responses. The 4-month CBR was 27.8% (95% CI, 14-45.2%), and the average duration of benefit was 6.5 cycles. Common adverse events included hypertension, fatigue, diarrhea, and nausea. Treatment with ENMD-2076 resulted in a decrease in cellular proliferation and microvessel density and an increase in p53 and p73 expression, consistent with preclinical observations. CONCLUSIONS: Single-agent ENMD-2076 treatment resulted in partial response or clinical benefit lasting more than 6 months in 16.7% of patients with pretreated, advanced, or metastatic TNBC. These results support the development of predictive biomarkers using archival and fresh tumor tissue, as well as consideration of mechanism-based combination strategies. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01639248 . Registered on July 12, 2012.


Asunto(s)
Antineoplásicos/uso terapéutico , Neoplasias de la Mama Masculina/tratamiento farmacológico , Inhibidores de Proteínas Quinasas/uso terapéutico , Pirazoles/uso terapéutico , Pirimidinas/uso terapéutico , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Antineoplásicos/farmacocinética , Aurora Quinasa A/antagonistas & inhibidores , Aurora Quinasa A/metabolismo , Biopsia , Mama/patología , Neoplasias de la Mama Masculina/sangre , Neoplasias de la Mama Masculina/patología , Diarrea/inducido químicamente , Diarrea/epidemiología , Progresión de la Enfermedad , Fatiga/inducido químicamente , Fatiga/epidemiología , Femenino , Humanos , Hipertensión/inducido químicamente , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Náusea/epidemiología , Supervivencia sin Progresión , Inhibidores de Proteínas Quinasas/farmacocinética , Pirazoles/farmacocinética , Pirimidinas/farmacocinética , Neoplasias de la Mama Triple Negativas/sangre , Neoplasias de la Mama Triple Negativas/patología
17.
Breast Cancer Res Treat ; 171(1): 11-20, 2018 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-29725889

RESUMEN

PURPOSE: To provide an overview of clinical data supporting the use of cyclin-dependent kinases 4 and 6 (CDK 4/6) inhibitors in the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), metastatic breast cancer (mBC), from the perspective of the practicing oncologist community. METHODS: A recent roundtable discussion was convened by The Breast Cancer Therapy Expert Group (BCTEG) to review existing data on this topic and its impact on their current practice. RESULTS: Level 1 evidence now supports use of a CDK 4/6 inhibitor in combination with endocrine therapy for patients with HR+, HER2-, mBC. Currently, there are no biomarkers that reliably define patients who will, or will not, benefit from the addition of a CDK 4/6 inhibitor to their endocrine therapy. Additional research is needed to identify the optimal sequencing of CDK 4/6 inhibitors in relation to other therapies as well as the optimal duration of therapy; at present, evidence suggests that use in the upfront setting is better than waiting for a later line of therapy, or adding after endocrine therapy has started. CONCLUSIONS: Thus far, three CDK 4/6 inhibitors-palbociclib, ribociclib, and more recently, abemaciclib-have been approved for use in the setting of HR+, HER2-, mBC.  The degrees to which these agents differ in terms of CDK4/6 affinity, side-effect profiles, dosing, degree of central nervous system (CNS) penetration, optimal use in combination with antiestrogen therapy, and across other subsets of breast cancer, remain an active area of investigation.


Asunto(s)
Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Quinasa 4 Dependiente de la Ciclina/antagonistas & inhibidores , Quinasa 6 Dependiente de la Ciclina/antagonistas & inhibidores , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/metabolismo , Animales , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/mortalidad , Femenino , Humanos , Terapia Molecular Dirigida , Metástasis de la Neoplasia , Estadificación de Neoplasias , Inhibidores de Proteínas Quinasas/farmacología
18.
Breast Cancer Res Treat ; 169(1): 1-7, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29352368

RESUMEN

PURPOSE: Management of breast cancer is a rapidly evolving field, and, although evidence-based guidelines are available for clinicians to provide direction on critical issues in patient care, clinicians often left to address these issues in the context of community practice situations with their patients. These include the patient's comorbid conditions, actual versus perceived benefit of treatments, patient's compliance as well as financial/reimbursement issues, and long-term tolerability of therapy. METHODS: A meeting of global oncology experts was convened in January 2017 with the belief that there is a gap in clinical practice guidance on several fundamental issues in breast cancer care, particularly in the community setting, where oncologists may encounter multiple tumor types. The goal was to discuss some of the most important questions in this area and provide some guidance for practicing oncologists. RESULTS: Topics addressed included risk of contralateral breast cancer recurrence in patients with estrogen receptor-positive early breast cancer who have undergone 5 years of adjuvant endocrine therapy, adverse events associated with endocrine therapy and their management, emergent data on adjuvant bisphosphonate therapy and its apparent benefit in reducing breast cancer recurrence, recent findings of extended adjuvant endocrine therapy trials, and the use of currently available genomic biomarker tests as a means of further informing treatment decisions. CONCLUSIONS: A summary of the discussion on these topics and several 'expert opinion statements' are provided herein in an effort to convey the collective insights of the panel as it relates to current standard practice.


Asunto(s)
Antineoplásicos Hormonales/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Recurrencia Local de Neoplasia/tratamiento farmacológico , Receptores de Estrógenos/genética , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/efectos adversos , Terapia Combinada , Femenino , Humanos , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Tamoxifeno/uso terapéutico
19.
Ann Surg Oncol ; 25(3): 768-775, 2018 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-28887726

RESUMEN

BACKGROUND: Desmoid fibromatosis is a fibroblastic neoplasm driven by aberrations within the WNT pathway, exhibiting mutations in ß-catenin or APC. We review the long-term follow-up of patients in a phase I study treated with an oral gamma secretase inhibitor, PF-03084014. METHODS: PF-03084014 was administered orally at doses ranging from 20 to 330 mg twice daily. Tumor assessments were performed using computed tomography/magnetic resonance imaging (CT/MRI) within 4 weeks of study entry, and every other cycle through cycle 9. After cycle 9, patients were evaluated as clinically indicated. RESULTS: Seven patients with desmoid fibromatosis were treated between December 2009 and December 2016 at the University of Colorado. Five patients (71.4%, 95% confidence interval [CI] 29.0-96.3%) achieved a partial response (PR), with a mean time to achieving response of 11.9 months (95% CI 2.5-21.4 months). All patients who achieved a PR continue to maintain responses between 47.9 and 73+ months. Four patients stopped treatment yet remain free of progression between 11 and 53+ months. One patient had PFS of 42+ months, with a 17% decrease in the target lesion. A biopsy performed at the end of the study showed decreased tumoral cellularity compared with previous biopsies. Effective treatment doses ranged from 80 to 330 mg administered orally twice daily. CONCLUSIONS: PF-03084014 was effective in treating desmoid tumors, with an objective response rate of 71.4% (95% CI 29.0-96.3%) in this small cohort of patients. PF-03084014 exhibits promising activity, even at relatively low doses (80 mg twice daily), with high tolerability leading to prolonged disease control even after therapy discontinuation.


Asunto(s)
Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Fibromatosis Agresiva/tratamiento farmacológico , Tetrahidronaftalenos/administración & dosificación , Valina/análogos & derivados , Administración Oral , Fibromatosis Agresiva/enzimología , Fibromatosis Agresiva/patología , Estudios de Seguimiento , Humanos , Pronóstico , Estudios Retrospectivos , Factores de Tiempo , Valina/administración & dosificación
20.
J Natl Compr Canc Netw ; 16(5S): 605-610, 2018 05.
Artículo en Inglés | MEDLINE | ID: mdl-29784737

RESUMEN

The emergence of CDK4/6 inhibitors has changed the treatment algorithm for advanced/metastatic estrogen receptor-positive breast cancer. In pivotal trials of palbociclib, ribociclib, and abemaciclib, doubling in progression-free survival has been seen. All 3 agents in this class are now included in the NCCN Guidelines for Breast Cancer, and clinicians should be incorporating these agents into their treatment algorithms. The other important issue in this breast cancer setting is extended duration of endocrine therapy. Most of the benefit is modest and toxicity is an issue; therefore, extended-duration endocrine therapy should be highly individualized. For triple-negative disease, platinum agents and PARP inhibitors are helping some patients, but immunotherapies and other novel classes of drugs now in development hold the promise of even better outcomes. In HER2-positive early-stage disease, dual HER2 blockade is of modest benefit, and extended treatment with neratinib may be a good option for some high-risk patients.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias de la Mama/terapia , Sociedades Médicas/normas , Antineoplásicos Hormonales/farmacología , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos Inmunológicos/farmacología , Antineoplásicos Inmunológicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Neoplasias de la Mama/genética , Neoplasias de la Mama/mortalidad , Neoplasias de la Mama/patología , Quimioterapia Adyuvante/métodos , Quimioterapia Adyuvante/normas , Femenino , Humanos , Mastectomía/normas , Oncología Médica/métodos , Oncología Médica/normas , Estadificación de Neoplasias , Inhibidores de Poli(ADP-Ribosa) Polimerasas/farmacología , Inhibidores de Poli(ADP-Ribosa) Polimerasas/uso terapéutico , Supervivencia sin Progresión , Receptor ErbB-2/antagonistas & inhibidores , Receptor ErbB-2/metabolismo , Receptores de Estrógenos/antagonistas & inhibidores , Receptores de Estrógenos/metabolismo , Receptores de Progesterona/antagonistas & inhibidores , Receptores de Progesterona/metabolismo , Factores de Tiempo , Estados Unidos/epidemiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA