RESUMO
A mild photocatalytic phenol oxygenation enabled by a continuous-flow photoreactor using visible light and pressurized air is described herein. Products for wide-ranging applications, including the synthesis of vitamins, were obtained in high yields by precisely controlling principal process parameters. The reactor design permits low organophotocatalyst loadings to generate singlet oxygen. It is anticipated that the efficient aerobic phenol oxygenation to benzoquinones and p-quinols contributes to sustainable synthesis.
Assuntos
Luz , Fenóis , Benzoquinonas , Fenol , Oxigênio SingleteRESUMO
Accelerated partial breast irradiation (APBI), a radiation technique in which only the tumor bed is treated, has now become an acceptable radiation modality for selected early-stage breast cancer patients. Compared to conventional whole breast irradiation (WBI), APBI has some benefits with regard to the reduced total irradiated breast volume and the shorter treatment time. The role of APBI, which can be delivered using diverse techniques, has been evaluated in several prospective randomized phase III trials. These clinical trials demonstrate diverging outcomes relating to local recurrence, while establishing comparable effect in terms of survival between APBI with WBI. The aim of this study was to review the current status of APBI with a focus on clinical practice.
Assuntos
Neoplasias da Mama/radioterapia , Radioterapia/métodos , Feminino , Humanos , Metanálise como Assunto , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Padrões de Prática Médica , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Inflammatory breast cancer (IBC) is a rare and aggressive form of invasive breast cancer accounting for 2.5% of all breast cancer cases. It is characterized by rapid progression, local and distant metastases, younger age of onset, and lower overall survival compared with other breast cancers. Historically, IBC is a lethal disease with less than a 5% survival rate beyond 5 years when treated with surgery or radiation therapy. Because of its rarity, IBC is often misdiagnosed as mastitis or generalized dermatitis. This review examines IBC's unique clinical presentation, pathology, epidemiology, imaging, and biology and details current multidisciplinary management of the disease, which comprises systemic therapy, surgery, and radiation therapy.
Assuntos
Neoplasias Inflamatórias Mamárias/diagnóstico , Neoplasias Inflamatórias Mamárias/terapia , Biomarcadores Tumorais/genética , Índice de Massa Corporal , Quimioterapia Adjuvante , Terapia Combinada/métodos , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Incidência , Neoplasias Inflamatórias Mamárias/epidemiologia , Neoplasias Inflamatórias Mamárias/genética , Imageamento por Ressonância Magnética , Mamografia , Estadiamento de Neoplasias , Obesidade/complicações , Tomografia por Emissão de Pósitrons , Prognóstico , Radioterapia Adjuvante , Doenças Raras , Medição de Risco , Fatores de Risco , Taxa de Sobrevida , Tomografia Computadorizada por Raios X , Ultrassonografia Mamária , Estados Unidos/epidemiologiaRESUMO
Skin sparing mastectomy, a surgical procedure sparing a large portion of the overlying skin of the breast, and nipple-sparing mastectomy, sparing the whole nipple-areolar complex, are increasingly used, although their oncologic efficacy remains unclear. The aim of this study was to assess the radiation oncologists' opinions regarding the indications of radiation therapy (RT) after skin-sparing mastectomy and nipple-sparing mastectomy. Radiation oncology members of four national and international societies were invited to complete a questionnaire comprising of 22 questions to assess their opinions regarding RT indications in the context of skin-sparing and nipple-sparing mastectomy. A total of 298 radiation oncologists answered the questionnaire. 90.9% of respondents affirmed that breast cancer is one of their specializations. The majority declared that post-mastectomy RT is indicated for early-stage (stages I and II) breast cancer patients who present with risk factors for recurrence after skin-sparing or nipple-sparing mastectomy (87.2% and 80.2%, respectively). All suggested risk factors (tumor size, lymph node involvement, extracapsular extension, lymphovascular space invasion, positive surgical margins, triple negative tumor, multicentric tumor, and age) were considered as major elements (important or very important). There is no consensus regarding the necessity of evaluating residual breast tissue or the definition of residual breast tissue after mastectomy. All classic factors were considered as major elements, potentially influencing the decision to advice or not postoperative RT. Many uncertainties remain about the indications for RT after skin-sparing mastectomy or nipple-sparing mastectomy.
Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia Subcutânea/métodos , Padrões de Prática Médica , Radio-Oncologistas , Neoplasias da Mama/patologia , Europa (Continente) , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Margens de Excisão , Recidiva Local de Neoplasia/patologia , Mamilos/cirurgia , América do Norte , América do Sul , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Galectin-3 (Gal3) plays diverse roles in cancer initiation, progression, and drug resistance depending on tumor type characteristics that are also associated with cancer stem cells (CSCs). Recurrence of breast carcinomas may be attributed to the presence of breast CSCs (BCSCs). BCSCs exist in mesenchymal-like or epithelial-like states and the transition between these states endows BCSCs with the capacity for tumor progression. The discovery of a feedback loop with galectins during epithelial-to-mesenchymal transition (EMT) prompted us to investigate its role in breast cancer stemness. METHOD: To elucidate the role of Gal3 in BCSCs, we performed various in vitro and in vivo studies such as sphere-formation assays, Western blotting, flow cytometric apoptosis assays, and limited dilution xenotransplant models. Histological staining for Gal3 in tissue microarrays of breast cancer patients was performed to analyze the relationship of clinical outcome and Gal3 expression. RESULTS: Here, we show in a cohort of 87 node-positive breast cancer patients treated with doxorubicin-based chemotherapy that low Gal3 was associated with increased lymphovascular invasion and reduced overall survival. Analysis of in vitro BCSC models demonstrated that Gal3 knockdown by small hairpin RNA (shRNA) interference in epithelial-like mammary spheres leads to EMT, increased sphere-formation ability, drug-resistance, and heightened aldefluor activity. Furthermore, Gal3negative BCSCs were associated with enhanced tumorigenicity in orthotopic mouse models. CONCLUSIONS: Thus, in at least some breast cancers, loss of Gal3 might be associated with EMT and cancer stemness-associated traits, predicts poor response to chemotherapy, and poor prognosis.
Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Galectina 3/genética , Expressão Gênica , Células-Tronco Neoplásicas/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Biomarcadores Tumorais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Feminino , Galectina 3/metabolismo , Técnicas de Silenciamento de Genes , Xenoenxertos , Humanos , Metástase Linfática , Camundongos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Esferoides Celulares , Células Tumorais Cultivadas , Via de Sinalização Wnt , Adulto JovemRESUMO
BACKGROUND: It is currently unclear whether the superior normal organ-sparing effect of intensity-modulated radiotherapy (IMRT) compared with 3-dimensional radiotherapy (3D) has a clinical impact on survival and cardiopulmonary mortality in patients with esophageal cancer (EC). METHODS: The authors identified 2553 patients aged > 65 years from the Surveillance, Epidemiology, and End Results (SEER)-Medicare and Texas Cancer Registry-Medicare databases who had nonmetastatic EC diagnosed between 2002 and 2009 and were treated with either 3D (2240 patients) or IMRT (313 patients) within 6 months of diagnosis. The outcomes of the 2 cohorts were compared using inverse probability of treatment weighting adjustment. RESULTS: Except for marital status, year of diagnosis, and SEER region, both radiation cohorts were well balanced with regard to various patient, tumor, and treatment characteristics, including the use of IMRT versus 3D in urban/metropolitan or rural areas. IMRT use increased from 2.6% in 2002 to 30% in 2009, whereas the use of 3D decreased from 97.4% in 2002 to 70% in 2009. On propensity score inverse probability of treatment weighting-adjusted multivariate analysis, IMRT was not found to be associated with EC-specific mortality (hazard ratio [HR], 0.93; 95% confidence interval [95% CI], 0.80-1.10) or pulmonary mortality (HR, 1.11; 95% CI, 0.37-3.36), but was significantly associated with lower all-cause mortality (HR, 0.83; 95% CI, 0.72-0.95), cardiac mortality (HR, 0.18; 95% CI, 0.06-0.54), and other-cause mortality (HR, 0.54; 95% CI, 0.35-0.84). Similar associations were noted after adjusting for the type of chemotherapy, physician experience, and sensitivity analysis removing hybrid radiation claims. CONCLUSIONS: In this population-based analysis, the use of IMRT was found to be significantly associated with lower all-cause mortality, cardiac mortality, and other-cause mortality in patients with EC.
Assuntos
Doenças Cardiovasculares/mortalidade , Neoplasias Esofágicas/radioterapia , Pneumopatias/mortalidade , Tratamentos com Preservação do Órgão/métodos , Radioterapia Conformacional/efeitos adversos , Radioterapia de Intensidade Modulada/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/etiologia , Feminino , Humanos , Imageamento Tridimensional , Pneumopatias/etiologia , Masculino , Medicare , Razão de Chances , Pontuação de Propensão , Sistema de Registros , Medição de Risco , Programa de SEER , Texas/epidemiologia , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: The authors compared longitudinal patient-reported outcomes and physician-rated cosmesis with conventionally fractionated whole-breast irradiation (CF-WBI) versus hypofractionated whole-breast irradiation (HF-WBI) within the context of a randomized trial. METHODS: From 2011 to 2014, a total of 287 women with American Joint Committee on Cancer stage 0 to stage II breast cancer were randomized to receive CF-WBI (at a dose of 50 grays in 25 fractions plus a tumor bed boost) or HF-WBI (at a dose of 42.56 grays in 16 fractions plus a tumor bed boost) after breast-conserving surgery. Patient-reported outcomes were assessed using the Breast Cancer Treatment Outcome Scale (BCTOS), the Functional Assessment of Cancer Therapy-Breast, and the Body Image Scale and were recorded at baseline and 0.5, 1, 2, and 3 years after radiotherapy. Physician-rated cosmesis was assessed at the same time points. Outcomes by treatment arm were compared at each time point using a 2-sided Student t test. Multivariable mixed effects growth curve models assessed the effects of treatment arm and time on longitudinal outcomes. RESULTS: Of the 287 patients enrolled, 149 were randomized to CF-WBI and 138 were randomized to HF-WBI. At 2 years, the Functional Assessment of Cancer Therapy-Breast Trial Outcome Index score was found to be modestly better in the HF-WBI arm (mean 79.6 vs 75.9 for CF-WBI; P = .02). In multivariable mixed effects models, treatment arm was not found to be associated with longitudinal outcomes after adjusting for time and baseline outcome measures (P≥.14). The linear effect of time was significant for BCTOS measures of functional status (P = .001, improved with time) and breast pain (P = .002, improved with time). CONCLUSIONS: In this randomized trial, longitudinal outcomes did not appear to differ by treatment arm. Patient-reported functional and pain outcomes improved over time. These findings are relevant when counseling patients regarding decisions concerning radiotherapy. Cancer 2016. © 2016 American Cancer Society. Cancer 2016;122:2886-2894. © 2016 American Cancer Society.
Assuntos
Neoplasias da Mama/radioterapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Fracionamento da Dose de Radiação , Feminino , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Radioterapia AdjuvanteRESUMO
OBJECTIVE: To evaluate complications after postmastectomy breast reconstruction, particularly in the setting of adjuvant radiotherapy. BACKGROUND: Most studies of complications after breast reconstruction have been conducted at centers of excellence; relatively little is known about complication rates in irradiated patients treated in the broader community. This information is relevant for decision making in patients with breast cancer. METHODS: Using the claims-based MarketScan database, we described complications in 14,894 women undergoing mastectomy for breast cancer from 1998 to 2007 and who underwent immediate autologous reconstruction (n = 2637), immediate implant-based reconstruction (n = 3007), or no reconstruction within the first 2 postoperative years (n = 9250). We used a generalized estimating equation to evaluate associations between complications and radiotherapy over time. RESULTS: Wound complications were diagnosed within the first 2 postoperative years in 2.3% of patients without reconstruction, 4.4% patients with implants, and 9.5% patients with autologous reconstruction (P < 0.001). Infection was diagnosed within the first 2 postoperative years in 12.7% of patients without reconstruction, 20.5% with implants, and 20.7% with autologous reconstruction (P < 0.001). A total of 5219 (35%) women received radiation. Radiation was not associated with infection in any surgical group within the first 6 months but was associated with an increased risk of infection in months 7 to 24 in all 3 groups (each P < 0.001). In months 7 to 24, radiation was associated with higher odds of implant removal in patients with implant reconstruction (odds ratio = 1.48; P < 0.001) and fat necrosis in those with autologous reconstruction (odds ratio = 1.55; P = 0.01). CONCLUSIONS: Complication risks after immediate breast reconstruction differ by approach. Radiation therapy seems to modestly increase certain risks, including infection and implant removal.
Assuntos
Neoplasias da Mama/cirurgia , Mamoplastia , Mastectomia , Complicações Pós-Operatórias/etiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/radioterapia , Bases de Dados Factuais , Feminino , Seguimentos , Humanos , Modelos Logísticos , Mamoplastia/métodos , Pessoa de Meia-Idade , Complicações Pós-Operatórias/epidemiologia , Radioterapia Adjuvante/efeitos adversos , Fatores de Risco , Resultado do TratamentoRESUMO
PURPOSE: Value in healthcare-i.e., patient-centered outcomes achieved per healthcare dollar spent-can define quality and unify performance improvement goals with health outcomes of importance to patients across the entire cycle of care. We describe the process through which value-based measures for breast cancer patients and dynamic capture of these metrics via our new electronic health record (EHR) were developed at our institution. METHODS: Contemporary breast cancer literature on treatment options, expected outcomes, and potential complications was extensively reviewed. Patient perspective was obtained via focus groups. Multidisciplinary physician teams met to inform a 3-phase process of (1) concept development, (2) measure specification, and (3) implementation via EHR integration. RESULTS: Outcomes were divided into 3 tiers that reflect the entire cycle of care: (1) health status achieved, (2) process of recovery, and (3) sustainability of health. Within these tiers, 22 patient-centered outcomes were defined with inclusion/exclusion criteria and specifications for reporting. Patient data sources will include the Epic Systems EHR and validated patient-reported outcome questionnaires administered via our institution's patient portal. CONCLUSIONS: As healthcare costs continue to rise in the United States and around the world, a value-based approach with explicit, transparently reported patient outcomes will not only create opportunities for performance improvement but will also enable benchmarking across providers, healthcare systems, and even countries. Similar value-based breast cancer care frameworks are also being pursued internationally.
Assuntos
Neoplasias da Mama/terapia , Gerenciamento Clínico , Registros Eletrônicos de Saúde , Avaliação de Resultados em Cuidados de Saúde , Aquisição Baseada em Valor , Feminino , Grupos Focais , Humanos , Pessoa de Meia-Idade , Qualidade da Assistência à Saúde , Texas , Estados UnidosRESUMO
INTRODUCTION: Inflammatory breast cancer (IBC) is an aggressive type of breast cancer, characterized by very rapid progression, enlargement of the breast, skin edema causing an orange peel appearance (peau d'orange), erythema, thickening, and dermal lymphatic invasion. It is characterized by E-cadherin overexpression in the primary and metastatic disease, but to date no robust molecular features that specifically identify IBC have been reported. Further, models that recapitulate all of these clinical findings are limited and as a result no studies have demonstrated modulation of these clinical features as opposed to simply tumor cell growth. METHODS: Hypothesizing the clinical presentation of IBC may be mediated in part by the microenvironment, we examined the effect of co-injection of IBC xenografts with mesenchymal stem/stromal cells (MSCs). RESULTS: MSCs co-injection significantly increased the clinical features of skin invasion and metastasis in the SUM149 xenograft model. Primary tumors co-injected with MSCs expressed higher phospho-epidermal growth factor receptor (p-EGFR) and promoted metastasis development after tumor resection, effects that were abrogated by treatment with the epidermal growth factor receptor (EGFR) inhibitor, erlotinib. E-cadherin expression was maintained in primary tumor xenografts with MSCs co-injection compared to control and erlotinib treatment dramatically decreased this expression in control and MSCs co-injected tumors. Tumor samples from patients demonstrate correlation between stromal and tumor p-EGFR staining only in IBC tumors. CONCLUSIONS: Our findings demonstrate that the IBC clinical phenotype is promoted by signaling from the microenvironment perhaps in addition to tumor cell drivers.
Assuntos
Neoplasias Inflamatórias Mamárias/metabolismo , Neoplasias Inflamatórias Mamárias/patologia , Células-Tronco Mesenquimais/metabolismo , Fenótipo , Animais , Antineoplásicos/farmacologia , Caderinas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Meios de Cultivo Condicionados/metabolismo , Meios de Cultivo Condicionados/farmacologia , Modelos Animais de Doenças , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/farmacologia , Feminino , Xenoenxertos , Humanos , Neoplasias Inflamatórias Mamárias/genética , Neoplasias Inflamatórias Mamárias/mortalidade , Camundongos , Invasividade Neoplásica , Metástase Neoplásica , Transdução de Sinais/efeitos dos fármacos , Células Estromais/metabolismo , Carga Tumoral/efeitos dos fármacosRESUMO
BACKGROUND: This study sought to determine outcomes for patients with metastatic breast cancer (MBC) with no evidence of disease (NED) after treatment and to identify factors predictive of outcomes once the status of NED was attained. METHODS: This study reviewed 570 patients with MBC who were consecutively treated between January 2003 and December 2005. Ninety patients (16%) attained NED, which was defined as a complete metabolic response on positron emission tomography or sclerotic healing of bone metastases on computed tomography or magnetic resonance imaging. The median follow-up for patients attaining NED was 100 months (range, 14-134 months). RESULTS: The 3- and 5-year overall survival (OS) rates were 44% and 24%, respectively, for the entire group and 96% and 78%, respectively, for those attaining NED. According to a landmark analysis, NED status was significantly associated with survival at 2 (P < .001; hazard ratio [HR], 0.23; 95% confidence interval [CI], 0.16-0.34) and 3 years (P < .001; HR, 0.20; 95% CI, 0.14-0.30). From the time of NED, the median survival was 102 months (range, 14-134 months) with 5-year OS and progression-free survival (PFS) rates of 77% and 40%, respectively. According to a multivariate analysis, human epidermal growth factor receptor 2 positivity was significantly associated with OS in comparison with estrogen receptor positivity (P = .02; HR, 0.44; 95% CI, 0.21-0.90), and trastuzumab use was significantly associated with PFS (P = .007; HR, 0.48; 95% CI, 0.28-0.82). Thirty-one patients (34%) with NED remained in remission at the last follow-up. CONCLUSIONS: MBC patients who attain the status of NED have significantly prolonged survival with a durable response to therapy. Ultimately, this study provides essential outcome data for clinicians and patients living with MBC.
Assuntos
Antineoplásicos Hormonais/uso terapêutico , Neoplasias Ósseas/terapia , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/terapia , Neoplasias Hepáticas/terapia , Neoplasias Pulmonares/terapia , Trastuzumab/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/secundário , Carcinoma Lobular/diagnóstico , Carcinoma Lobular/secundário , Estudos de Coortes , Intervalo Livre de Doença , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/secundário , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Prognóstico , Radioterapia/métodos , Indução de Remissão , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Adulto JovemRESUMO
Inflammatory breast cancer (IBC) is a rare and aggressive disease. Previous studies have shown that among patients with stage III breast cancer, IBC is associated with a worse prognosis than noninflammatory breast cancer (non-IBC). Whether this difference holds true among patients with stage IV breast cancer has not been studied. We tested the hypothesis that overall survival (OS) is worse in patients with IBC than in those with non-IBC among patients with distant metastasis at diagnosis (stage IV disease). We reviewed the records of 1504 consecutive patients with stage IV breast cancer (IBC: 206; non-IBC: 1298) treated at our institution from 1987 through 2012. Survival curves for IBC and non-IBC subcohorts were compared. The Cox proportional hazards model was used to determine predictors of OS. The median follow-up period was 4.7 years. IBC was associated with shorter median OS time than non-IBC (2.27 vs. 3.40 years; P = 0.0128, log-rank test). In a multicovariate Cox model that included 1389 patients, the diagnosis of IBC was a significant independent predictor of worse OS (hazard ratio = 1.431, P = 0.0011). Other significant predictors of worse OS included Black (vs. White) ethnicity, younger age at diagnosis, negative HER2 status, and visceral (vs. nonvisceral) site of metastasis. IBC is associated with shorter OS than non-IBC in patients with distant metastasis at diagnosis. The prognostic impact of IBC should be taken into consideration among patients with stage IV breast cancer.
Assuntos
Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Neoplasias Inflamatórias Mamárias/mortalidade , Neoplasias Inflamatórias Mamárias/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/terapia , Feminino , Seguimentos , Humanos , Neoplasias Inflamatórias Mamárias/epidemiologia , Neoplasias Inflamatórias Mamárias/terapia , Pessoa de Meia-Idade , Metástase Neoplásica , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Adulto JovemRESUMO
Thymidylate synthase (TYMS) is involved in the folate metabolism and provision of nucleotides needed for DNA synthesis and repair. Thus, functional genetic variants in TYMS may alter cancer risk. In the study, we evaluated associations of three germline variants (rs2790 A > G, rs16430 6 bp > 0 bp, and rs1059394 C > T) in the predicted miRNA-binding sites of TYMS with risk of sporadic breast cancer in non-Hispanic white women aged ≤ 55. We found that carriers of the rs16430 0 bp variant allele had an increased risk of breast cancer [adjusted odd ratio (OR) = 1.37, 95% confidence interval (CI): 1.08-1.73; P = 0.010], compared with carriers of the 6 bp/6 bp genotype. This increased risk was more evident in older subjects (OR = 1.47, 95% CI = 1.06-2.03, P = 0.022), never smokers (OR = 1.67, 95% CI = 1.23-2.25, P < 0.001), never drinkers (OR = 1.44, 95% CI = 1.01-2.05, P = 0.043), and estrogen receptor-positive patients (OR = 1.46, 95% CI = 1.11-1.92, P = 0.006), regardless of tumor stages. The results are consistent with the functional analyses of rs16430 as previously reported, which showed that the 0 bp allele had a decrease in both luciferase activity by â¼ 70% and mRNA levels by â¼ 50% compared with the 6bp allele. Additionally, the rs16430 variant was predicted to influence the binding activity of miR-561. Taken together, these findings indicate that the TYMS rs16430 may contribute to the etiology of sporadic breast cancer in non-Hispanic white women aged ≤ 55 yr. Further validation in large population-based or cohort studies is needed.
Assuntos
Neoplasias da Mama/genética , MicroRNAs/metabolismo , Polimorfismo de Nucleotídeo Único , Timidilato Sintase/genética , População Branca/genética , Regiões 3' não Traduzidas , Sequência de Bases , Sítios de Ligação , Mama/metabolismo , Neoplasias da Mama/epidemiologia , Feminino , Predisposição Genética para Doença , Variação Genética , Humanos , Desequilíbrio de Ligação , MicroRNAs/química , MicroRNAs/genética , Pessoa de Meia-Idade , Fatores de Risco , Alinhamento de Sequência , Timidilato Sintase/metabolismoRESUMO
Neoadjuvant chemotherapy is a standard treatment option for patients with locally advanced operable breast cancer and is increasingly used in early breast cancer. Initial randomized trials of neoadjuvant chemotherapy established equivalency to adjuvant chemotherapy in terms of survival, but they also demonstrated improved rates of breast conservation and the ability to modify the risk of locoregional recurrence after a favorable response to chemotherapy. High-quality nonrandomized data have helped to tailor radiotherapy treatment recommendations after neoadjuvant chemotherapy and breast-conserving surgery or mastectomy. Results from an ongoing phase 3 randomized trial (NSABP B-51/RTOG 1304) will help to clarify the value of locoregional radiotherapy for patients with clinical N1 disease that becomes node negative after neoadjuvant chemotherapy.
Assuntos
Neoplasias da Mama/terapia , Terapia Neoadjuvante , Radioterapia Adjuvante , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Ensaios Clínicos como Assunto , Terapia Combinada , Feminino , Humanos , Mastectomia , Prognóstico , Taxa de SobrevidaRESUMO
OBJECTIVE: The purpose of this study was to identify the prevalence of occult nodal metastases on routine ultrasound examination of internal mammary (IM) nodal basins in patients with breast cancer. MATERIALS AND METHODS: Patients with primary breast cancer (n = 595) underwent breast ultrasound evaluation between September 1, 2011, and April 1, 2012. For all patients, ultrasound examination included a survey of the axillary, infraclavicular, IM, and supraclavicular nodal basins. Patient demographics, breast cancer histopathologic type, and grade, size, location, and presence of metastatic nodes in regional nodal basins were recorded. Fisher exact test and Wilcoxon rank test were used for statistical analysis. RESULTS: Fifty-eight of 595 (10%) patients had positive IM ultrasound finding, with eight (1.3%) patients having isolated IM involvement. Patients with positive IM ultrasound findings were statistically significantly younger than those without such findings (median age, 42 vs 57 years; p < 0.0001). Of the 58 patients with positive IM ultrasound, 29 (50%) underwent ultrasound-guided needle biopsy, which confirmed malignancy in 26 of 29 (90%) patients. Nonlateral (p < 0.001) grade 3 (p < 0.001) tumors larger than 5 cm (p < 0.0006) with the estrogen receptor-negative HER2/neu-negative subtype (p < 0.001) associated with axillary, infraclavicular, or supraclavicular metastases (p < 0.001) were more likely to be associated with positive IM ultrasound findings. IM ultrasound resulted in an N status change for 46 of 595 (8%) patients and of the overall clinical stage for 38 (6.4%) patients. CONCLUSION: IM ultrasound and ultrasound-guided fine-needle aspiration biopsy are feasible, sensitive, and specific. Application of IM ultrasound and ultrasound-guided needle biopsy in a selected subpopulation of young patients with medial or central estrogen receptor-negative HER2/neu-negative breast cancer may result in a change in clinical stage and modify the treatment plan.
Assuntos
Neoplasias da Mama/diagnóstico por imagem , Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Linfonodos/diagnóstico por imagem , Metástase Linfática/diagnóstico por imagem , Ultrassonografia Mamária , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Ultrassonografia DopplerRESUMO
BACKGROUND: Intensity-modulated radiation therapy (IMRT) is a technologically advanced, and more expensive, method of delivering radiation therapy with a goal of minimizing toxicity. It has been widely adopted for head and neck cancers; however, its comparative impact on cancer control and survival remains unknown. The goal of this analysis was to compare the cause-specific survival (CSS) for patients with head and neck cancers treated with IMRT versus non-IMRT from 1999 to 2007. METHODS: CSS was determined using the Surveillance, Epidemiology, and End Results (SEER)-Medicare database and analyzed regarding treatment details, including the use of IMRT versus non-IMRT, using claims data. Hazard ratios (HRs) were estimated by the frailty model with a propensity score matching cohort and instrumental variable analysis. RESULTS: A total of 3172 patients were identified. With a median follow-up of 40 months, patients treated with IMRT had a statistically significant improvement in CSS compared with those treated with non-IMRT (84.1% versus 66.0%; P < .001). When each anatomic subsite was analyzed separately, all respective subgroups of patients treated with IMRT had better CSS than those treated with non-IMRT. In multivariable survival analyses, patients treated with IMRT were associated with better CSS (HR = 0.72, 95% confidence interval = 0.59 to 0.90 for propensity score matching; HR = 0.60, 95% confidence interval = 0.41 to 0.88 for instrumental variable analysis). CONCLUSIONS: Patients with head and neck cancers who were treated with IMRT experienced significant improvements in CSS compared with patients treated with non-IMRT techniques. This suggests there may be benefits to IMRT in cancer outcomes, in addition to toxicity reduction, for this patient population.
Assuntos
Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/radioterapia , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/radioterapia , Radioterapia de Intensidade Modulada , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Medicare , Pontuação de Propensão , Programa de SEER , Resultado do Tratamento , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: We sought to compare hospice utilization for American Indian and White Medicare beneficiaries dying of cancer. METHODS: We used the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked databases to analyze claims for 181,316 White and 690 American Indian patients dying of breast, cervix, colorectal, kidney, lung, pancreas, prostate cancer, or stomach cancer from 2003 to 2009. RESULTS: A lower proportion of American Indians enrolled in hospice compared to White patients (54% vs 65%, respectively; P < .0001). While the proportion of White patients who used hospice services in the last 6 months of life increased from 61% in 2003 to 68% in 2009 (P < .0001), the proportion of American Indian patients using hospice care remained unchanged (P = .57) and remained below that of their White counterparts throughout the years of study. CONCLUSION: Continued efforts should be made to improve access to culturally relevant hospice care for American Indian patients with terminal cancer.
Assuntos
Disparidades em Assistência à Saúde/etnologia , Cuidados Paliativos na Terminalidade da Vida/estatística & dados numéricos , Indígenas Norte-Americanos/estatística & dados numéricos , Medicare/estatística & dados numéricos , Neoplasias/etnologia , Doente Terminal/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais para Doentes Terminais/estatística & dados numéricos , Humanos , Masculino , Neoplasias/mortalidade , Neoplasias/terapia , Programa de SEER , Estados Unidos , População Branca/estatística & dados numéricosRESUMO
BACKGROUND: Our goal was to investigate utilization trends for advanced radiation therapy (RT) technologies, such as intensity-modulated radiation therapy (IMRT) and stereotactic radiosurgery (SRS), in the last year of life among patients diagnosed with metastatic cancer. METHODS: We used the Surveillance, Epidemiology and End Results (SEER)-Medicare linked databases to analyze claims data in the last 12 months of life for 64,525 patients diagnosed with metastatic breast, colorectal, lung, pancreas, and prostate cancers from 2000 to 2007. Logistic regression modeling was conducted to analyze potential demographic, health services, and treatment-related variables' influences on receipt of advanced RT. RESULTS: Among the 19,161 (29.7%) patients who received radiation therapy, there was a significant decrease in the proportion of patients who received the simplest radiation technique (ie, 2D-radiation therapy) (P < .0001), and significant increases in the proportions of patients receiving more advanced radiation techniques (ie, IMRT, and SRS; P < .0001 for all curves); although the rates for use of IMRT and SRS in 2007 remained under 5%. On multivariate analyses, receipt of RT varied significantly by non-clinical characteristics such as race, marital status, neighborhood income, and SEER region. Patients who received hospice care in the last year of life were more likely to receive radiation therapy (OR = 1.35, 95% CI = 1.30-1.40) but less likely to be treated with IMRT (OR = 0.76, 95% CI = 0.62-0.92). CONCLUSIONS: Although the proportion of patients receiving RT in the last year of life for metastatic cancer did not change for most of the past decade, we observed significant trends toward more advanced radiation techniques.