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1.
Ann Surg Oncol ; 21(10): 3216-22, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25047475

RESUMO

BACKGROUND: Rapidly evolving advances in the understanding of theorized unique driver mutations within individual patient's cancers, as well as dramatic reduction in the cost of genomic profiling, have stimulated major interest in the role of such testing in routine clinical practice. The aim of this study was to report our initial experience with genomic testing in heavily pretreated breast cancer patients. METHODS: Patients with primary or recurrent breast cancer managed at any of our five hospitals and whose malignancy had failed to respond to therapy or had progressed on all recognized standard-of-care options were offered the opportunity to have their cancer undergo next-generation sequencing genomic profiling. RESULTS: Of a total of 101 patients, 98 (97 %) had at least one specific genomic alteration identified. A total of 465 different somatic genetic abnormalities were revealed in this group of patients. Although 52 % of patients were found to have an abnormality for which an U.S. Food and Drug Administration (FDA)-approved drug was available, 69 % of patients had an FDA-approved agent for an indication other than breast cancer. The most common genomic alterations of potential clinical consequence were PIK3 (25 %), FGFR1 (16 %), AKT (11 %), PTEN (10 %), ERBB2 (8 %), JAK2 (6 %), and RAF1 (5 %). CONCLUSIONS: Almost all advanced breast cancers possess at least one well-characterized genomic alteration that might be actionable at the clinical level. Further, in most cases, a plausible argument can be advanced for the potential biological and clinical relevance of an FDA-approved antineoplastic agent not currently indicated in the treatment of breast cancer.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/genética , Perfilação da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Mutação/genética , Recidiva Local de Neoplasia/genética , Medicina de Precisão , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Terapia Combinada , Feminino , Seguimentos , Predisposição Genética para Doença , Genômica , Humanos , Pessoa de Meia-Idade , Metástase Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Estadiamento de Neoplasias , Seleção de Pacientes , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto Jovem
2.
BMC Urol ; 13: 32, 2013 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-23837903

RESUMO

BACKGROUND: Several studies in the oncology literature have demonstrated the prognostic value of baseline quality of life (QoL). We investigated whether changes in QoL could predict survival in prostate cancer patients. METHODS: We evaluated 250 prostate cancer patients treated at our institution between Jan 2001 and Dec 2009 who were available for a minimum follow-up of 3 months. QoL was evaluated at baseline and after 3 months of treatment initiation using EORTC-QLQ-C30. Cox regression evaluated the prognostic significance of baseline and changes in QoL scores after adjusting for relevant clinical and demographic variables. RESULTS: Median overall survival was 89.1 months (95% CI: 56.5-121.7). Baseline QoL scale predictive of survival upon multivariate analysis was fatigue (p = 0.001). Associations between changes in QoL and survival, upon multivariate analysis, were observed for dyspnea and cognitive functioning. Every 10-point increase (worsening) in dyspnea was associated with a 16% increased risk of death (HR = 1.16; 95% CI = 1.02 to 1.30, p = 0.02), and every 10-point increase (improvement) in cognitive functioning was associated with a 24% decreased risk of death (HR = 0.76; 95% CI = 0.54 to 0.98, p = 0.04). CONCLUSIONS: This study provides preliminary evidence to indicate that prostate cancer patients with better baseline fatigue and patients whose dyspnea and cognitive functioning improves within 3 months of treatment are at a significantly decreased risk of mortality.


Assuntos
Transtornos Cognitivos/mortalidade , Dispneia/mortalidade , Fadiga/mortalidade , Neoplasias da Próstata/mortalidade , Neoplasias da Próstata/psicologia , Qualidade de Vida/psicologia , Adulto , Distribuição por Idade , Idoso , Transtornos Cognitivos/psicologia , Estudos de Coortes , Comorbidade , Intervalo Livre de Doença , Dispneia/psicologia , Fadiga/psicologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Neoplasias da Próstata/diagnóstico , Neoplasias da Próstata/terapia , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Sensibilidade e Especificidade , Análise de Sobrevida , Resultado do Tratamento , Estados Unidos/epidemiologia
3.
Support Care Cancer ; 20(6): 1267-74, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21710307

RESUMO

PURPOSE: While the use of quality of life (QoL) assessment has been increasing in clinical oncology, few studies have examined its prognostic significance in prostate cancer. We investigated the association between QoL at presentation and survival in prostate cancer. METHODS: We retrospectively reviewed 673 patients treated at two single-system cancer centers between January 2001 and December 2008. QoL was evaluated using EORTC-QLQ-C30. Patient survival was defined as the time interval between the date of first patient visit and the date of death/date of last contact. Univariate and multivariate Cox regression was performed to evaluate the prognostic significance of QoL. RESULTS: Mean age at presentation was 63.2 years. Patient stage of disease at diagnosis was I, 4; II, 464; III, 76; IV, 107; and 22 indeterminate. Median overall survival was 89.1 months (95% CI: 46.1-132.0). QoL scales predictive of survival upon univariate analysis were physical, role, emotional, social, fatigue, nausea/vomiting, pain, dyspnea, insomnia, loss of appetite, and constipation (p < 0.01 for all). Multivariate analyses found fatigue (p = 0.02) and constipation (p = 0.01) to be significantly associated with survival. CONCLUSIONS: Baseline QoL provides useful prognostic information in prostate cancer. These findings have important implications for patient stratification in clinical trials and may aid decision making in clinical practice.


Assuntos
Constipação Intestinal/epidemiologia , Fadiga/epidemiologia , Neoplasias da Próstata/patologia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Constipação Intestinal/etiologia , Fadiga/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias da Próstata/psicologia , Estudos Retrospectivos , Análise de Sobrevida , Taxa de Sobrevida
4.
BMC Cancer ; 11: 353, 2011 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-21843358

RESUMO

BACKGROUND: There are conflicting and inconsistent results in the literature on the prognostic role of quality of life (QoL) in cancer. We investigated whether QoL at admission could predict survival in lung cancer patients. METHODS: The study population consisted of 1194 non-small cell lung cancer patients treated at our institution between Jan 2001 and Dec 2008. QoL was evaluated using EORTC-QLQ-C30 prior to initiation of treatment. Patient survival was defined as the time interval between the date of first patient visit and the date of death from any cause/date of last contact. Univariate and multivariate Cox regression evaluated the prognostic significance of QoL. RESULTS: Mean age at presentation was 58.3 years. There were 605 newly diagnosed and 589 previously treated patients; 601 males and 593 females. Stage of disease at diagnosis was I, 100; II, 63; III, 348; IV, 656; and 27 indeterminate. Upon multivariate analyses, global QoL as well as physical function predicted patient survival in the entire study population. Every 10-point increase in physical function was associated with a 10% increase in survival (95% CI = 6% to 14%, p < 0.001). Similarly, every 10-point increase in global QoL was associated with a 9% increase in survival (95% CI = 6% to 11%, p < 0.001). Furthermore, physical function, nausea/vomiting, insomnia, and diarrhea (p < 0.05 for all) in newly diagnosed patients, but only physical function (p < 0.001) in previously treated patients were predictive of survival. CONCLUSIONS: Baseline global QoL and physical function provide useful prognostic information in non-small cell lung cancer patients.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Carcinoma Pulmonar de Células não Pequenas/psicologia , Neoplasias Pulmonares/fisiopatologia , Neoplasias Pulmonares/psicologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Humanos , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Modelos de Riscos Proporcionais , Qualidade de Vida , Inquéritos e Questionários
5.
Health Qual Life Outcomes ; 9: 62, 2011 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-21812962

RESUMO

BACKGROUND: Several studies have demonstrated the predictive significance on survival of baseline quality of life (QoL) in colorectal cancer (CRC) with little information on the impact of changes in QoL scores on prognosis in CRC. We investigated whether changes in QoL during treatment could predict survival in CRC. METHODS: We evaluated 396 stages III-IV CRC patients available for a minimum follow-up of 3 months. QoL was evaluated at baseline and after 3 months of treatment using EORTC QLQ-C30. Cox regression evaluated the prognostic significance of baseline, 3-month and changes in QoL scores after adjusting for age, gender and stage at diagnosis. RESULTS: After adjusting for covariates, every 10-point increase in both baseline appetite loss and global QoL score was associated with a 7% increased risk of death with HR = 1.07 (95% CI, 1.01-1.14; P = 0.02) and (HR = 0.93 (95% CI, 0.87-0.98; P = 0.01) respectively. A lower risk of death was associated with a 10-point improvement in physical function at 3 months (HR, 0.86; 95% CI, 0.78-0.94; P = 0.001). Surprisingly, a higher risk of death was associated with a 10-point improvement in social function at 3 months (HR, 1.08; 95% CI, 1.02-1.13; P = 0.008). CONCLUSIONS: This study provides preliminary evidence to indicate that CRC patients whose physical function improves within 3 months of treatment have a significantly increased probability of survival. These findings should be used in clinical practice to systematically address QoL-related problems of CRC patients throughout their treatment course.


Assuntos
Neoplasias Colorretais/patologia , Qualidade de Vida , Perfil de Impacto da Doença , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estadiamento de Neoplasias , Prognóstico , Análise de Sobrevida , Estados Unidos , Adulto Jovem
6.
Breast J ; 17(6): 571-8, 2011.
Artigo em Inglês | MEDLINE | ID: mdl-21895846

RESUMO

While the use of quality of life (QoL) assessments has been increasing in oncology, few studies have examined the prognostic significance of QoL in breast cancer. We investigated the association between QoL at presentation and survival in breast cancer. We examined 1,511 breast cancer patients treated at two single-system cancer centers between January 2001 and December 2008. QoL was evaluated using the validated survey instrument EORTC-QLQ-C30. Patient survival was defined as the time interval between the date of first patient visit and the date of death from any cause/date of last contact. Univariate and multivariate Cox regression analyses were performed to evaluate the prognostic significance of QoL after controlling for the effects of age, tumor stage, and prior treatment history. Mean age at presentation was 52.5 years. There were 590 analytic and 921 non-analytic patients. Patient stage of disease at diagnosis was I, 335; II, 591; III, 290; IV, 159; and 136 indeterminate. Median overall survival was 32.8 months (95% CI: 27.6-38.0). On univariate analysis, QoL function and symptom scales that were predictive of survival were physical (p < 0.001), role (p < 0.001), cognitive (p = 0.003), social (p < 0.001), fatigue (p < 0.001), nausea/vomiting (p < 0.001), pain (p < 0.001), dyspnea (p < 0.001), loss of appetite (p < 0.001), and constipation (p < 0.001). On multivariate analyses, only role function (degree of impairment of work and/or leisure/hobby related activities) was significantly associated with survival. This study suggests that baseline QoL (in particular, the role function) provides useful prognostic information in breast cancer.


Assuntos
Neoplasias da Mama/psicologia , Qualidade de Vida , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/mortalidade , Feminino , Humanos , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais
7.
Physician Exec ; 36(2): 54-8, 60-2, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20411849

RESUMO

There are many steps to consider when making the move to become an innovative health care organization. Take a look at the people and processes to have in place.


Assuntos
Difusão de Inovações , Eficiência Organizacional , Instalações de Saúde
9.
J Hematol Oncol ; 10(1): 100, 2017 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-28472989

RESUMO

BACKGROUND: Solid tumors residing in tissues and organs leave footprints in circulation through circulating tumor cells (CTCs) and circulating tumor DNAs (ctDNA). Characterization of the ctDNA portraits and comparison with tumor DNA mutational portraits may reveal clinically actionable information on solid tumors that is traditionally achieved through more invasive approaches. METHODS: We isolated ctDNAs from plasma of patients of 103 lung cancer and 74 other solid tumors of different tissue origins. Deep sequencing using the Guardant360 test was performed to identify mutations in 73 clinically actionable genes, and the results were associated with clinical characteristics of the patient. The mutation profiles of 37 lung cancer cases with paired ctDNA and tumor genomic DNA sequencing were used to evaluate clonal representation of tumor in circulation. Five lung cancer cases with longitudinal ctDNA sampling were monitored for cancer progression or response to treatments. RESULTS: Mutations in TP53, EGFR, and KRAS genes are most prevalent in our cohort. Mutation rates of ctDNA are similar in early (I and II) and late stage (III and IV) cancers. Mutation in DNA repair genes BRCA1, BRCA2, and ATM are found in 18.1% (32/177) of cases. Patients with higher mutation rates had significantly higher mortality rates. Lung cancer of never smokers exhibited significantly higher ctDNA mutation rates as well as higher EGFR and ERBB2 mutations than ever smokers. Comparative analysis of ctDNA and tumor DNA mutation data from the same patients showed that key driver mutations could be detected in plasma even when they were present at a minor clonal population in the tumor. Mutations of key genes found in the tumor tissue could remain in circulation even after frontline radiotherapy and chemotherapy suggesting these mutations represented resistance mechanisms. Longitudinal sampling of five lung cancer cases showed distinct changes in ctDNA mutation portraits that are consistent with cancer progression or response to EGFR drug treatment. CONCLUSIONS: This study demonstrates that ctDNA mutation rates in the key tumor-associated genes are clinical parameters relevant to smoking status and mortality. Mutations in ctDNA may serve as an early detection tool for cancer. This study quantitatively confirms the hypothesis that ctDNAs in circulation is the result of dissemination of aggressive tumor clones and survival of resistant clones. This study supports the use of ctDNA profiling as a less-invasive approach to monitor cancer progression and selection of appropriate drugs during cancer evolution.


Assuntos
DNA de Neoplasias/genética , Mutação , Invasividade Neoplásica/genética , Neoplasias/genética , Células Neoplásicas Circulantes , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Quimiorradioterapia , Células Clonais , Progressão da Doença , Receptores ErbB/antagonistas & inibidores , Cloridrato de Erlotinib/uso terapêutico , Feminino , Perfilação da Expressão Gênica , Genes Neoplásicos , Genes erbB-1 , Genes p53 , Genes ras , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Neoplasias/mortalidade , Neoplasias/patologia , Células-Tronco Neoplásicas , Inibidores de Proteínas Quinases/uso terapêutico , Estudos Retrospectivos , Análise de Sequência de DNA , Fumar/genética
10.
Theranostics ; 7(11): 2914-2923, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28824725

RESUMO

Background: Cancers related to tobacco use and African-American ancestry are under-characterized by genomics. This gap in precision oncology research represents a major challenge in the health disparities in the United States. Methods: The Precision Oncology trial at the Wake Forest Baptist Comprehensive Cancer Center enrolled 431 cancer patients from March 2015 to May 2016. The composition of these patients consists of a high representation of tobacco-related cancers (e.g., lung, colorectal, and bladder) and African-American ancestry (13.5%). Tumors were sequenced to identify mutations to gain insight into genetic alterations associated with smoking and/or African-American ancestry. Results: Tobacco-related cancers exhibit a high mutational load. These tumors are characterized by high-frequency mutations in TP53, DNA damage repair genes (BRCA2 and ATM), and chromatin remodeling genes (the lysine methyltransferases KMT2D or MLL2, and KMT2C or MLL3). These tobacco-related cancers also exhibit augmented tumor heterogeneities. Smoking related genetic mutations were validated by The Cancer Genome Atlas dataset that includes 2,821 cases with known smoking status. The Wake Forest and The Cancer Genome Atlas cohorts (431 and 7,991 cases, respectively) revealed a significantly increased mutation rate in the TP53 gene in the African-American subgroup studied. Both cohorts also revealed 5 genes (e.g. CDK8) significantly amplified in the African-American population. Conclusions: These results provide strong evidence that tobacco is a major cause of genomic instability and heterogeneity in cancer. TP53 mutations and key oncogene amplifications emerge as key factors contributing to cancer outcome disparities among different racial/ethnic groups.


Assuntos
Neoplasias Colorretais/patologia , Neoplasias Pulmonares/patologia , Mutação , Fumar Tabaco/efeitos adversos , Neoplasias da Bexiga Urinária/patologia , Negro ou Afro-Americano , Humanos , Patologia Molecular , Análise de Sequência de DNA , Proteína Supressora de Tumor p53/genética , População Branca
11.
Am J Surg ; 192(4): 545-7, 2006 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16978972

RESUMO

INTRODUCTION: Fibroadenomas are a frequently encountered benign tumor that will occur in approximately 10% of women during their lifetime. Although the natural history would suggest fibroadenomas diagnosed with minimally invasive needle core biopsy can be safely observed, the majority are still surgically removed in the operating room. In an effort to limit the more than 500,000 surgical fibroadenoma removals performed each year, percutaneous excision has become a viable alternative. Percutaneous excision of intact fibroadenomas versus removal with a multiple core sampling technique has the dual potential advantage of causing minimal intervention combined with provision of adequate sample for thorough histopathology and margin analysis for confirmation of complete removal. An 18-month retrospective analysis was undertaken to evaluate the utilization of a new radiofrequency-assisted biopsy device in the successful removal and continued absence of histologically confirmed fibroadenomas on 4- to 6-month follow-up imaging. METHODS: Between April 2004 and November 2005, 100 patients underwent ultrasound- or stereotactic-guided, radiofrequency-assisted intact percutaneous excision of 106 diagnosed fibroadenomas of the breast. Patients were comprised of 100 women whose ages ranged from 18-70 years (median age, 45 years). RESULTS: Indications for the procedure included palpable mass, 77; abnormal mammogram, 13; and abnormal ultrasound, 10, as the patient's initial presentation. Ultrasound was used to guide the procedure in 82 patients, and stereotactic was used in 18 patients. One early study procedure was performed under general anesthesia; the remaining studies were performed under local anesthesia (1% lidocaine) using from 10 to 45 mL. On pathologic examination, the tumors ranged in size from 6 to 27 mm (mean diameter, 14 mm) and weighed from 0.6 to 2.0 g (mean weight, 1.0 g). Patients reported minimum discomfort related to the procedure; pain scores ranged from 0 to 10 (mean pain score, <1). Complications were minimal, with only 2 patients having bleeding, which was controlled by conservative measures. At the 4- to 6-month follow-up, 79 of 85 (93%) evaluable patients showed no physical or imaging evidence of residual fibroadenoma, an additional 5 patients have reported no physical findings or further complaints and have required no further need for medical evaluation, 8 have been lost to follow-up, and 2 have yet to be reevaluated. CONCLUSIONS: Percutaneous ultrasound- or stereotactic-guided, radiofrequency-assisted excision of fibroadenomas of the breast may be performed in an ambulatory setting under local anesthesia. The procedure provides intact specimens that in most cases appear to be completely removed after follow-up of 4 to 6 months. The procedure is well tolerated by patients and is associated with minimal complications.


Assuntos
Neoplasias da Mama/cirurgia , Eletrocirurgia/instrumentação , Fibroadenoma/cirurgia , Adolescente , Adulto , Idoso , Procedimentos Cirúrgicos Ambulatórios , Biópsia/instrumentação , Neoplasias da Mama/patologia , Desenho de Equipamento , Feminino , Fibroadenoma/patologia , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
12.
Am J Surg ; 191(4): 489-96, 2006 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16531142

RESUMO

BACKGROUND: Ultrasound has a wide variety of applications in surgery, but until recently few surgeons received any formal training in its use. To facilitate incorporation of ultrasound into surgical practice, the American College of Surgeons (ACoS) developed an ultrasound educational program. The purpose of this study was to evaluate the impact and effectiveness of the ACoS ultrasound education program. METHODS: A survey was mailed to all surgeons who had completed at least one of several ultrasound courses offered by the ACoS from 1998 to 2002. RESULTS: A total of 1,791 surveys were mailed out and 873 completed surveys were returned. Sixty-five percent (576) of respondents reported using ultrasound in their practices after these educational courses. Of those performing ultrasound examinations, 267 did so in one clinical area and 309 in more than one. The most common examination was breast (369 surgeons); vascular, acute/trauma, abdominal, intraoperative/laparoscopic, and head/neck were utilized fairly equally (100-200 surgeons). The number of examinations performed by surgeons before they felt competent was between 11 and 20 and did not vary by the type of ultrasound examination. Of the 267 surgeons performing ultrasound in one clinical area, 176 performed ultrasound-guided procedures. Most surgeons had access to 2 ultrasound machines, but 386 (67%) were restricted from performing ultrasound in certain locations. CONCLUSIONS: The ACoS ultrasound courses are extremely popular and have contributed to the increasing use of ultrasound in surgical practice. Surgeons successfully use ultrasound in their practices including performance of ultrasound-guided procedures but are restricted from using ultrasound in certain patient care areas. Since many surgeons received prior and/or additional training outside of the ACoS, there is a need to facilitate export of ACoS courses to other venues and to focus on incorporating ultrasound training into surgical residency programs.


Assuntos
Educação Médica Continuada , Ultrassonografia de Intervenção , Distribuição de Qui-Quadrado , Currículo , Humanos , Avaliação de Programas e Projetos de Saúde , Inquéritos e Questionários , Estados Unidos
13.
Am J Surg ; 190(4): 570-1, 2005 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-16164922

RESUMO

OBJECTIVE: A randomized, placebo-controlled phase III trial of the breast cancer vaccine Theratope (Biomira Corporation, Edmonton, Alberta, Canada), which expresses the underglycosylated, mucin-associated peptide STn showed that patients treated concomitantly with hormone therapy plus vaccine survived significantly longer than patients treated with hormone therapy plus a control vaccine. The objective of this study was to elucidate a mechanism to explain this effect. METHODS: Tumor cells characterized for expression of estrogen receptor (ER), STn, and Mucin-1 (Muc1) were pretreated (24 hours) with the aromatase inhibitor (AI) formestane, followed by assessment of sensitivity to monocyte-mediated killing in the presence and absence of STn or Muc1 antibodies (Abs) using the (51)Cr-release assay. RESULTS: ER+/STn+/Muc1+ tumor cells cultured in medium were equally sensitive to killing by monocytes in the absence or presence of STn and Muc1 Abs (mean = 54% and 55% cytolysis, respectively, P = not significant). Formestane-pretreated cells showed decreased sensitivity to killing by monocytes in the absence of Abs (mean = 45% cytolysis, P = .07) but significantly increased sensitivity to monocyte-mediated, antibody-dependent cellular cytotoxicity (MM-ADCC) (mean = 65%, P = .003). These effects were not seen with either ER+/STn-/Muc1+ cells or ER-/STn+/Muc1+ cells, indicating the need for both ER and STn positivity of the target tumor cells. CONCLUSIONS: Tumor cells treated with an AI exhibit increased sensitivity to MM-ADCC. The capacity of an AI to "sensitize" tumor cells to this form of antitumor immunity represents a heretofore, undescribed mechanism whereby a hormone-based treatment may collaborate with antigen-specific tumor immunity to produce improved tumor control in vivo in metastatic breast cancer patients.


Assuntos
Androstenodiona/análogos & derivados , Citotoxicidade Celular Dependente de Anticorpos/efeitos dos fármacos , Inibidores da Aromatase/farmacologia , Androstenodiona/farmacologia , Citotoxicidade Celular Dependente de Anticorpos/imunologia , Neoplasias da Mama , Proteínas de Ciclo Celular/imunologia , Linhagem Celular Tumoral , Feminino , Humanos , Monócitos/imunologia , Mucina-1/imunologia , Neoplasias Ovarianas , Fator 1 de Elongação de Peptídeos , Receptores de Estrogênio/imunologia
15.
Onco Targets Ther ; 8: 3323-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26648736

RESUMO

BACKGROUND: ESR1 mutation has recently emerged as one of the important mechanisms involved in endocrine resistance. The incidence and clinical implication of ESR1 mutation has not been well evaluated in heavily pretreated breast cancer patients. METHODS: We conducted a retrospective review of advanced breast cancer patients with tumors who underwent next-generation sequencing genomic profiling using Foundation One test at Cancer Treatment Centers of America(®) regional hospitals between November 2012 and November 2014. RESULTS: We identified a total of 341 patients including 217 (59%) estrogen receptor (ER)+, 177 (48%) progesterone receptor (PR)+, 30 (8%) hormone receptor+/HER2 positive, and 119 (32%) triple negative patients. ESR1 mutation was noted in 27/222 (12.1%) ER+ or PR+ breast cancer patients. All ER+ patients received at least one line of an aromatase inhibitor. All 28 patients were found to harbor ESR1 mutations affecting ligand-binding domain with the most common mutations affecting Y537 (17/28, 60.7%) and D538 (9/28, 32.1%). In this cohort, 19 (67.9%) patients carried three or more, seven (25%) patients had one or two additional genomic alterations and one (3.6%) patient had an ESR1 mutation only. Of 28 patients, three patients were treated with fulvestrant immediately before and two patients were treated after next-generation sequencing testing; only one patient achieved stable disease for 8 months and the other four patients had progression of disease. In all, 3/3 (100%) patients before testing and 2/4 (50%) after testing treated with exemestane and everolimus achieved stable disease for at least 6 months. CONCLUSION: ESR1 mutation was found in 12.1% of a large cohort of advanced breast cancer patients. Exemestane in combination with everolimus might be a reasonable option. Prospective studies are warranted to validate these findings.

16.
Lung Cancer ; 36(1): 17-25, 2002 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-11891029

RESUMO

The cytokines expressed in tumor microenvironments are thought to be important mediators of both the host immune response and tumor survival. The source of these cytokines includes tumor cells, infiltrating leukocytes, fibroblasts, and other stromal elements. We previously reported that tumor-infiltrating lymphocytes (TIL) from human non-small cell lung cancer (NSCLC) express predominantly type 1 cytokines, which are known to enhance cell-mediated immunity. The purpose of this study is to assess the cytokine mRNA expression of human NSCLC primary cell lines and the capacity of the tumor-associated cytokines to modulate the development of TIL cytolytic activity against the autologous tumor. Cytokine mRNA expression was determined by RT-PCR and the capacity of TIL to kill autologous lung tumor cells was measured by the chromium-51 (51Cr) release assay. All NSCLC primary cell lines expressed mRNA for IL-4, IL-6, and transforming growth factor-beta1 (TGFbeta1), whereas IL-10 was expressed in only 1/7 cell lines. When added to TIL cultures stimulated with anti-CD3+IL-2, IL-4 and IL-10 enhanced and TGF-beta1 suppressed the development of TIL cytolytic activity against autologous tumor cells. The effects of IL-6 were inconsistent and for the group, were not statistically significant. These results demonstrate that human NSCLC cells express cytokines with the capacity to regulate the in situ anti-tumor immune response. However, the effects of tumor-derived cytokines varied qualitatively and quantitatively suggesting the balance between specific type 2 cytokines or TGF-beta1 within tumor microenvironments may influence prognosis or response to immunotherapy.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/imunologia , Citotoxicidade Imunológica/imunologia , Neoplasias Pulmonares/imunologia , Linfócitos do Interstício Tumoral/imunologia , Fator de Crescimento Transformador beta/biossíntese , Complexo CD3/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Testes Imunológicos de Citotoxicidade , Primers do DNA/química , Humanos , Interleucinas/metabolismo , Neoplasias Pulmonares/patologia , Estadiamento de Neoplasias , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Fator de Crescimento Transformador beta/imunologia , Células Tumorais Cultivadas
17.
Surgery ; 134(4): 667-73; discussion 673-4, 2003 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-14605628

RESUMO

BACKGROUND: A series of such lesions was studied to determine the validity of applying criteria routinely used to manage palpable breast cysts to the management of mammographically detected, nonpalpable breast lesions characterized as indeterminate on ultrasound (US). METHODS: The clinicopathologic data from a series of 134 patients who underwent US-guided fine needle aspiration biopsy for nonpalpable, mammographically detected breast lesions, categorized as indeterminate on US, were reviewed. RESULTS: Of 139 indeterminate lesions, 78 were consistent with complex cysts, whereas in 61, the cystic-versus-solid nature was indistinguishable. All 71 complex cyst lesions that contained nonbloody fluid and resolved completely were benign. Two of 7 complex cyst lesions that had incomplete resolution, bloody aspirate, or both were malignant. Of 61 cystic-versus-solid lesions, 29 and 32 were primarily solid and cystic, respectively. Three of the 29 solid lesions were malignant. Of the 32 cystic lesions, all 26 that contained nonbloody fluid and resolved completely were benign, whereas 1 of 6 lesions that had incomplete resolution, bloody aspirate, or both was malignant. CONCLUSION: Criteria such as complete resolution and nonbloody aspirate are an effective adjunct to the management of nonpalpable, mammographically detected breast lesions categorized as indeterminate by US.


Assuntos
Biópsia por Agulha , Doenças Mamárias/diagnóstico por imagem , Doenças Mamárias/patologia , Cistos/diagnóstico por imagem , Cistos/patologia , Ultrassonografia Mamária , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Feminino , Humanos , Pessoa de Meia-Idade
18.
Am J Surg ; 188(2): 136-49, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15249239

RESUMO

BACKGROUND: For many years, hormone replacement therapy (HRT) was considered an effective method of restoring the relative protection from coronary artery disease enjoyed by premenopausal women compared with men of similar age. This view has been supported by a substantial number of basic science and observational studies. DATA SOURCES: Results of recent randomized controlled trials have seriously challenged the concept of the protective value of HRT by showing that rather than decreasing the risk of coronary artery disease, HRT actually appears to increase it. In addition, it increases the risk for breast cancer, stroke, venous thromboembolism, and cholecystitis. RESULTS: Despite some benefits such as increased bone mineral density and decreased risk of fracture and colorectal cancer, these data suggest that the risks of HRT outweigh the benefits. CONCLUSIONS: HRT is no longer routinely recommended for prevention of chronic disease. We present the current scientific data, benefits, risks, and consequent clinical recommendations regarding HRT use in postmenopausal women.


Assuntos
Terapia de Reposição de Estrogênios , Neoplasias da Mama/epidemiologia , Proteína C-Reativa/análise , Colecistite/epidemiologia , Doença Crônica/epidemiologia , Doença das Coronárias/epidemiologia , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose/prevenção & controle , Guias de Prática Clínica como Assunto , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia , Trombose Venosa/epidemiologia , Saúde da Mulher
19.
Surg Clin North Am ; 84(4): 973-1000, v, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15261750

RESUMO

Ultrasound (US) of the neck is extremely sensitive in detecting thyroid, parathyroid, and cervical lymph node pathology, and is regarded as the most complete and cost-effective imaging method for evaluating the thyroid and parathyroid glands, as well as for the diagnostic evaluation of the cervical lymph node basin. US is widely used in screening high-risk individuals, evaluation of palpable and nonpalpable thyroid nodules, needle guidance for biopsy of nonpalpable and suspicious nodules, and preoperative evaluation of the extent of thyroid neoplasms, as well as in the detection of residual, recurrent, or metastatic thyroid tumors, and in observing nonsurgical cases. It has thus become an important adjunct to the practice of head and neck surgery.


Assuntos
Adenoma/diagnóstico por imagem , Linfonodos/diagnóstico por imagem , Glândulas Paratireoides/diagnóstico por imagem , Neoplasias das Paratireoides/diagnóstico por imagem , Paratireoidectomia , Glândula Tireoide/diagnóstico por imagem , Nódulo da Glândula Tireoide/diagnóstico por imagem , Tireoidectomia , Algoritmos , Bócio Nodular/diagnóstico por imagem , Bócio Nodular/cirurgia , Humanos , Hiperplasia , Hipertireoidismo/diagnóstico por imagem , Hipertireoidismo/cirurgia , Metástase Linfática , Linfoma/diagnóstico por imagem , Linfoma/cirurgia , Pescoço/cirurgia , Neoplasias das Paratireoides/cirurgia , Paratireoidectomia/métodos , Glândula Tireoide/patologia , Glândula Tireoide/cirurgia , Nódulo da Glândula Tireoide/patologia , Nódulo da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Ultrassonografia
20.
Surg Clin North Am ; 84(4): 1001-34, v-vi, 2004 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-15261751

RESUMO

Ultrasound is becoming an indispensable tool for the surgeon in the diagnosis and treatment of a variety of breast problems. Hands-on ultrasound education for surgeons and the ongoing improvements in imaging technology have made surgeon-performed breast ultrasound an effective method of identifying and diagnosing breast lesions and have increased the surgeon's ability to perform ultrasound-guided interventional procedures. This article reviews the current state of surgeon-performed breast ultrasound.


Assuntos
Doenças Mamárias/diagnóstico por imagem , Doenças Mamárias/cirurgia , Ultrassonografia de Intervenção , Ultrassonografia Mamária , Biópsia por Agulha/métodos , Doenças Mamárias/patologia , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Ablação por Cateter , Criocirurgia , Feminino , Fibroadenoma/diagnóstico por imagem , Fibroadenoma/patologia , Fibroadenoma/cirurgia , Doença da Mama Fibrocística/diagnóstico por imagem , Humanos , Mastectomia Segmentar/métodos , Mamilos/diagnóstico por imagem , Ultrassonografia de Intervenção/métodos , Ultrassonografia Mamária/métodos
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