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1.
Ann Surg Oncol ; 2022 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-35039947

RESUMO

BACKGROUND: The optimal treatment strategy for small node-negative human epidermal growth factor receptor 2-positive (HER2+) breast cancer remains controversial. Neoadjuvant chemotherapy may risk overtreatment, whereas surgery first fails to identify patients with residual disease in need of escalated adjuvant systemic therapy. We investigated patient characteristics associated with receipt of neoadjuvant chemotherapy. METHODS: Adult women with cT1-T2/N0, HER2+ breast cancer between 2013 and 2017 in the National Cancer Database who underwent surgery within 8 months of diagnosis were included. Patients were classified as receiving neoadjuvant chemotherapy versus a surgery-first approach. We assessed the sociodemographic and clinical predictors of neoadjuvant chemotherapy versus surgery first and associations between neoadjuvant chemotherapy and breast cancer treatments using multivariable regression models. RESULTS: We identified 56,784 women, of whom 12,758 (22%) received neoadjuvant chemotherapy, 29,139 (53%) received adjuvant chemotherapy, 12,907 (24%) received no chemotherapy, and 1980 were missing chemotherapy information. After adjustment, cT2 stage was the strongest predictor of neoadjuvant chemotherapy compared with surgery first. Younger age and later diagnosis year were positively associated with receipt of neoadjuvant chemotherapy. In contrast, hormone receptor positivity, Black race, rural county, and government-funded or no health insurance were inversely associated with neoadjuvant chemotherapy. In multivariable analyses, patients who received neoadjuvant chemotherapy were more likely to have a mastectomy (vs. lumpectomy) and sentinel lymph node biopsy or no nodal surgery (vs. axillary lymph node dissection). Patients who received neoadjuvant chemotherapy were more likely to receive multi-agent (vs. single-agent) chemotherapy than those who received adjuvant chemotherapy. CONCLUSIONS: Substantial differences in the utilization of neoadjuvant chemotherapy exist in women with HER2+ breast cancer, which reflect both clinical parameters and disparities. Optimal treatment strategies should be implemented equitably across sociodemographic groups.

3.
Pract Radiat Oncol ; 2021 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-34920164

RESUMO

PURPOSE/OBJECTIVE(S): Approximately 30% of women who receive post-mastectomy radiation therapy (PMRT) in the setting of breast reconstruction suffer from reconstruction complications. This study aims to assess clinical and dosimetric factors associated with the risk of reconstruction complications after PMRT, with the ultimate goal of identifying a dosimetric constraint that can be utilized clinically to limit this risk. MATERIALS/METHODS: We retrospectively identified 41 patients who underwent modified radical (MRM) or total mastectomy followed by immediate or delayed reconstruction (autologous or implant-based) and radiation at a single institution from 2014-2020. Reconstruction complications were defined as flap or implant failure, necrosis, capsular contracture, cellulitis/infection, implant rupture, implant malposition, leakage/rupture, unplanned operation, and hematoma/seroma. Clinical and dosimetric variables associated with complications were assessed with univariate analyses. RESULTS: 12 patients (29%) suffered reconstruction complications which led to flap or implant failure in 5 patients. Median time to complication following reconstruction was 8 months. 32% of patients with immediate and 20% with delayed reconstruction suffered a complication, respectively. There were no local failures. Smoking (p=0.02), use of bolus (p=0.03), and V107 > 11% (p=0.03) were associated with increased complication rates. The complication rates were 42% when V107 > 11% versus 12% when V107 < 11%; 58% in smokers versus 17% in nonsmokers; and 42% with bolus versus 7% without. CONCLUSION: Plan heterogeneity appears to be associated with the risk of reconstruction complications. Pending further validation, V107 < 11% may serve as a reasonable guide to limit this risk. Further consideration should be given to the selective use of bolus in this setting and optimization of clinical factors such as smoking cessation.

4.
J Clin Oncol ; : JCO2101329, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34731032

RESUMO

PURPOSE: Medullary thyroid carcinoma (MTC) is an aggressive neuroendocrine tumor (NET) arising from the calcitonin-producing C cells. Unlike other NETs, there is no widely accepted pathologic grading scheme. In 2020, two groups separately developed slightly different schemes (the Memorial Sloan Kettering Cancer Center and Sydney grade) on the basis of proliferative activity (mitotic index and/or Ki67 proliferative index) and tumor necrosis. Building on this work, we sought to unify and validate an internationally accepted grading scheme for MTC. PATIENTS AND METHODS: Tumor tissue from 327 patients with MTC from five centers across the United States, Europe, and Australia were reviewed for mitotic activity, Ki67 proliferative index, and necrosis using uniform criteria and blinded to other clinicopathologic features. After reviewing different cutoffs, a two-tiered consensus grading system was developed. High-grade MTCs were defined as tumors with at least one of the following features: mitotic index ≥ 5 per 2 mm2, Ki67 proliferative index ≥ 5%, or tumor necrosis. RESULTS: Eighty-one (24.8%) MTCs were high-grade using this scheme. In multivariate analysis, these patients demonstrated decreased overall (hazard ratio [HR] = 11.490; 95% CI, 3.118 to 32.333; P < .001), disease-specific (HR = 8.491; 95% CI, 1.461 to 49.327; P = .017), distant metastasis-free (HR = 2.489; 95% CI, 1.178 to 5.261; P = .017), and locoregional recurrence-free (HR = 2.114; 95% CI, 1.065 to 4.193; P = .032) survivals. This prognostic power was maintained in subgroup analyses of cohorts from each of the five centers. CONCLUSION: This simple two-tiered international grading system is a powerful predictor of adverse outcomes in MTC. As it is based solely on morphologic assessment in conjunction with Ki67 immunohistochemistry, it brings the grading of MTCs in line with other NETs and can be readily applied in routine practice. We therefore recommend grading of MTCs on the basis of mitotic count, Ki67 proliferative index, and tumor necrosis.

5.
Am Surg ; : 31348211047205, 2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587799

RESUMO

BACKGROUND: The COVID-19 pandemic has required new treatment paradigms to limit exposures and optimize hospital resources, including the use of neoadjuvant endocrine therapy (NAET) as bridging therapy for HR+/HER2-invasive tumors and DCIS. While this approach has been used in locally advanced disease, it is unclear how it may affect outcomes in resectable HR+/HER2- tumors. METHODS: Women ≥18 years diagnosed with in situ (Tis) or non-metastatic HR+/HER2- breast cancer from March-May 2019 and 2020 were included. Fisher's exact test and two-sample t test were used to compare baseline characteristics and surgical outcomes between strata. Sub-analysis was performed between patients who received primary surgery vs a bridging NAET approach. RESULTS: Despite similar clinical characteristics, patients in 2019 were more likely to have a surgery-first approach (75% vs 42%, P-value = .0007), receive surgery sooner (22 vs 29 days, P-value < .001), and within 60 days from diagnosis date (100% vs 85%, P-value = .0301). Neoadjuvant endocrine therapy was a more prevalent approach in 2020 (48% vs 7%, P-value < .0001). Rates of clinical to pathologic up-staging remained consistent across primary surgery vs bridging NAET subgroups (P-value = .9253). DISCUSSION: Pandemic-driven treatment protocols provide a unique opportunity to assess the utility of bridging endocrine therapy for resectable HR+/HER2- tumors. Differences in clinical and pathologic staging were similar across groups and did not appear to be affected by receipt of NAET. Our limited cohort demonstrates this strategic therapeutic avenue can optimize health care utilization and may be a reasonable approach when delaying surgery is preferred.

6.
Am J Clin Oncol ; 44(9): 456-462, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34190716

RESUMO

INTRODUCTION: Preclinical data supports antitumor activity of tyrosine kinase inhibitor vandetanib with Ret as the therapeutic target in breast cancer. We investigated the effect of preoperative vandetanib on markers of proliferation and apoptosis in breast cancer. METHODS: Patients with invasive breast cancer were randomly assigned vandetanib 300 mg or placebo PO daily for 2 weeks before operative resection from January 2014 to June 2017. Pretreatment and posttreatment specimens were analyzed by immunohistochemistry for Ki-67, TUNEL, and p-ERK with stratification by Ret expression by immunohistochemistry. RESULTS: Ten patients were enrolled. There was no statistically significant difference in ERK activation compared with placebo (P=0.45); however, ERK activation was reduced 74% compared with pretreatment biopsy with vandetinib treatment (P=0.005) without a significant reduction in the placebo group (-29%, P=0.55). Mean change in Ki-67 after vandetanib treatment was +0.3% compared with +2.0% in placebo treated patients, P=0.72. Mean change in TUNEL was +0.48 apoptotic nuclei per HPF in the vandetanib arm compared with +1.02 in the placebo arm, P=0.32. In vandetanib treated patients, Ki-67 was reduced 0.3% in RET-positive tumors compared with increased 1.0% in RET-negative tumors, P=0.43 and TUNEL was increased 0.77 in RET-positive tumors and 0.2 in RET-negative tumors, P=0.21. CONCLUSIONS: In this pilot study, no statistically significant differences on prespecified markers were seen with vandetanib compared with placebo. In accordance with the investigational hypothesis, there was a nonsignificant trend with vandetanib treatment of reduction in p-ERK and increased effects in Ret expressing tumors.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Piperidinas/uso terapêutico , Quinazolinas/uso terapêutico , Idoso , Apoptose/efeitos dos fármacos , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Feminino , Humanos , Antígeno Ki-67/metabolismo , Pessoa de Meia-Idade , Projetos Piloto , Cuidados Pré-Operatórios , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-ret/metabolismo , Resultado do Tratamento
7.
J Surg Oncol ; 123(8): 1792-1800, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33751586

RESUMO

BACKGROUND AND OBJECTIVES: Synovial, clear cell, angiosarcoma, rhabdomyosarcoma, and epithelioid (SCARE) soft tissue sarcoma are at risk for nodal involvement, although the nodal positivity rates and impact on prognostication in clinically node negative patients are not well described. METHODS: Patients with extremity SCARE sarcoma without clinical nodal involvement undergoing surgical resection in the National Cancer Database (2004-2017) were included. Logistic regression was used to evaluate the likelihood of nodal surgery and nodal positivity. Kaplan-Meier method and Cox regression were used to assess associations of nodal status to overall survival. RESULTS: We included 4158 patients, and 669 patients (16%) underwent regional lymph node surgery (RLNS). On multivariable logistic analysis, patients with epithelioid (odds ratio [OR]: 3.77; p < .001) and clear cell (OR: 6.38; p < .001) were most likely to undergo RLNS. Forty-five patients (7%) had positive nodes. Clear cell sarcoma (14%) and angiosarcoma (13%) had the highest rates of nodal positivity. Patients with positive nodes had reduced 5-year overall survival, and the stratification was largest in clear cell and angiosarcoma. CONCLUSION: Discordance exists between selection for pathologic nodal evaluation and factors associated with nodal positivity. Clinically node negative patients with clear cell and angiosarcoma should be considered for pathologic nodal evaluation.


Assuntos
Extremidades , Sarcoma/patologia , Neoplasias de Tecidos Moles/patologia , Adolescente , Adulto , Idoso , Bases de Dados Factuais , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Sarcoma/mortalidade , Sarcoma/terapia , Neoplasias de Tecidos Moles/mortalidade , Neoplasias de Tecidos Moles/terapia , Taxa de Sobrevida , Adulto Jovem
8.
Ann Surg Oncol ; 28(11): 6572-6579, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33748897

RESUMO

BACKGROUND: Patients with medullary thyroid carcinoma (MTC) often receive lateral lymph node dissection with total thyroidectomy when calcitonin levels are elevated, even in the absence of structural disease, but the effect of this intervention on disease-specific outcomes is not known. PATIENTS AND METHODS: We retrospectively reviewed patients from 1986 to 2017 who underwent thyroidectomy with curative intent for MTC at our institution. The association of disease-specific survival and clinicopathologic features was examined using univariate and multivariate Cox regression. RESULTS: We identified 316 patients who underwent curative resection for MTC. Overall and disease-specific survival were 76% and 86%, respectively, at 10 years. To investigate the effect of prophylactic ipsilateral lateral lymph node dissection, we analyzed 89 patients without known structural disease in the neck lymph nodes at the time of resection and preoperative calcitonin > 200 pg/ml, of whom 45 had an ipsilateral lateral lymph node dissection (LND) and 44 did not. There were no differences in tumor size or preoperative calcitonin levels. There was no difference at 10 years in cumulative incidence of recurrence in the neck (20.9% LND vs. 30.4% no LND, p = 0.46), cumulative incidence of distant recurrence (18.3% vs. 18.4%, p = 0.97), disease-specific survival (86% vs. 93%, p = 0.53), or overall survival (82% vs. 90%, p = 0.6). CONCLUSION: Lateral neck dissection in the absence of clinical or radiologic abnormal lymph nodes is not associated with improved survival in patients with MTC.


Assuntos
Esvaziamento Cervical , Neoplasias da Glândula Tireoide , Humanos , Metástase Linfática , Recidiva Local de Neoplasia/cirurgia , Estudos Retrospectivos , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia
9.
Ann Surg Oncol ; 28(4): 2182-2190, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32974693

RESUMO

BACKGROUND: Inflammatory breast cancer (IBC) has historically been characterized by high rates of recurrence and poor survival; however, there have been significant improvements in systemic therapy. We sought to investigate modern treatment of IBC and define the yield and prognostic significance of axillary lymph nodes after neoadjuvant chemotherapy (NAC). METHODS: Women with clinical stage T4d, N0-N3, M0 IBC from 2012 to 2016 in the National Cancer Database were included. Kaplan-Meier survival curves and Cox regression were used to assess mortality by receptor subtype and nodal status. RESULTS: We identified 5265 patients; 37% hormone receptor (HR) +/HER2 - , 19% HR +/HER2 + , 18% HR -/HER2 + , and 26% triple-negative, and 5-year overall survival was 51.6%. Only 34% were treated according to guidelines with NAC, modified radical mastectomy, and adjuvant radiation. Pathologically positive lymph nodes (ypN +) after NAC varied by subtype and clinical nodal status (cN) ranging from 82% in cN + HR +/HER2 - patients to 19% in cN0 HR -/HER2 + patients. ypN + strongly correlated with survival in all subtypes with the most pronounced impact in HR +/HER2 + patients, with 90% 5-year overall survival in ypN0 versus 66% for ypN + (HR 4.29, 95% CI 1.58-11.70, p = 0.03). CONCLUSIONS: Five-year survival in M0 IBC is 51.6%. Positive nodes after NAC varied by subtype and clinical N status but is sufficiently high and provided meaningful prognostication in all subtypes to support continued routine pathologic assessment. Future study is warranted to identify reliable, less morbid, methods of staging the axilla in IBC patients appropriate for deescalation of axillary surgery.


Assuntos
Neoplasias da Mama , Neoplasias Inflamatórias Mamárias , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Axila/patologia , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Feminino , Humanos , Neoplasias Inflamatórias Mamárias/patologia , Mastectomia , Terapia Neoadjuvante , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Prognóstico , Receptor ErbB-2
11.
Mod Pathol ; 33(9): 1690-1701, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32313184

RESUMO

Medullary thyroid carcinoma (MTC) is a rare nonfollicular cell-derived tumor. A robust grading system may help better stratify patients at risk for recurrence and death from disease. In total, 144 MTC between 1988 and 2018 were subjected to a detailed histopathologic evaluation. Clinical and pathologic data were correlated with disease specific survival (DSS), local recurrence free survival (LRFS)  and distant metastasis free survival (DMFS). Median age was 53 years (range: 3-88). Median tumor size was 1.8 cm (range: 0.2-11). Lymph node metastases were present in 84 (58%) cases while distant metastases at presentation were found in 9 (6%) patients. Seven (5%) had ≥5 mitoses/10 HPFs. Tumor necrosis was present in 30 cases (20%) while lymphovascular invasion occurred in 41 (28%) of tumors. Extra-thyroidal extension was found in 44 (31%) and positive margins were seen in 19 (14%). There was a strong correlation between increasing tumor size and tumor necrosis (p < 0.001). Median follow up was 39 months. In univariate analysis, male gender, higher American Joint Committee on Cancer (AJCC) stage group, larger tumor size, tumor necrosis, high mitotic index (≥5/10 HPF), nodal status, size of largest nodal metastasis, and elevated postoperative serum calcitonin predicted worse DSS, LRFS, and DMFS (p < 0.05). Extra-thyroidal extension correlated with DSS and DMFS while positive margins and distant metastasis at presentation imparted worse DSS (p < 0.05). In multivariate analysis, tumor necrosis and mitotic activity (5 mitosis/10 HPFs as the cutoff) were the only independent predictors for DSS (p = 0.008 and 0.026, respectively). Tumor necrosis was the sole independent prognostic factor for LRFS and DMFS (p = 0.001 and 0.003, respectively). The presence of tumor necrosis and high mitotic rate are powerful independent prognostic factors in MTC and outperform serum calcitonin and stage. We propose a grading system based on tumor necrosis and mitotic activity to better stratify MTC patients for counseling, post-resection surveillance, and therapy.


Assuntos
Carcinoma Medular/patologia , Metástase Linfática/patologia , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Medular/cirurgia , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Índice Mitótico , Necrose/patologia , Necrose/cirurgia , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia , Adulto Jovem
12.
Ann Surg Oncol ; 26(13): 4423-4429, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31549322

RESUMO

INTRODUCTION: Long-term outcomes after curative resection in patients with germline RET mutations and medullary thyroid cancer (MTC) are highly variable and mutation-specific oncologic outcomes are not well-described. METHODS: Sixty-six patients identified from 1986 to 2017 from a single-institution cancer database were assessed for recurrence and survival using Kaplan-Meier estimates, and correlated with clinicopathologic features using log-rank or Cox proportional hazards. RESULTS: Median follow-up was 9.3 years (range 0.3-31.5), median tumor diameter was 1.5 cm (range 0.1-7.5), and preoperative calcitonin was known in 41 patients [median 636 (range 0-9600)]. Overall survival (OS) of the cohort was 94% at 10 years, the cumulative incidence of locoregional recurrence was 38% at 10 years, and 19/24 (79%) patients underwent repeat neck operation. The cumulative incidence of distant recurrence was 27% at 10 years. Predictors of distant recurrence were tumor size, positive lymph nodes, and pre- and postoperative carcinoembryonic antigen, but not calcitonin. M918T mutation-bearing patients had 10-year distant recurrence-free survival of 0%, compared with 83% in all other patients (p < 0.001), and equivalent 10-year OS (100% vs. 92%; p = 0.49). CONCLUSIONS: Structural and metastatic recurrence is common in patients with germline RET mutations, and MTC and can occur 20 years after initial treatment, however survival remains high. Management should focus on optimal surveillance strategies and long-term control of structural disease.


Assuntos
Carcinoma Medular/congênito , Neoplasia Endócrina Múltipla Tipo 2a/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adolescente , Adulto , Idoso , Carcinoma Medular/cirurgia , Criança , Pré-Escolar , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Esvaziamento Cervical , Recidiva Local de Neoplasia/epidemiologia
14.
Ann Surg Oncol ; 26(7): 2136-2143, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30783853

RESUMO

BACKGROUND: Malignant/borderline phyllodes tumors (PTs) are rare, and little is known about their long-term prognosis. This study sought to evaluate recurrence rates and identify factors associated with local and distant failure. METHODS: From 1957 to 2017, we identified 124 patients with 125 PTs (86 malignant and 39 borderline). Recurrence rates and survival were assessed using the Kaplan-Meier method, and correlated with clinicopathologic factors using the log-rank test. RESULTS: The median age of the patients was 44 years, and the median tumor size was 5 cm. Breast-conserving surgery was performed for 57% of the patients. At a median follow-up of 7.1 years, 14 patients experienced a locoregional recurrence (LRR), with a 10-year cumulative LRR incidence of 12%. On univariable analysis, age younger than 40 years (p = 0.02) and close/positive margins (p = 0.001) were associated with increased risk of LRR. Seven patients developed distant disease, all occurring in malignant PTs. The 10-year distant recurrence-free survival was 94%. Uniformly poor pathologic features consisting of marked stromal cellularity, stromal overgrowth, infiltrative borders, and 10 or more mitoses per 10 high-power fields (hpf) were identified in 25 PTs (20%), and all distant recurrences occurred in this group. For the patients who did not have uniformly poor features, the 10-year disease-specific survival was 100%, and the overall survival was 94% compared with 66% and 57%, respectively, among those with poor features. CONCLUSION: Malignant/borderline PTs without uniformly poor histologic features have an excellent prognosis after surgical resection, with a 10-year disease-specific survival of 100%. The presence of uniformly poor pathologic features predicts a poor prognosis. Efforts should be directed toward new treatment approaches for these tumors.


Assuntos
Neoplasias da Mama/cirurgia , Margens de Excisão , Mastectomia Segmentar/mortalidade , Mastectomia/mortalidade , Recidiva Local de Neoplasia/cirurgia , Tumor Filoide/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Tumor Filoide/patologia , Prognóstico , Taxa de Sobrevida , Adulto Jovem
15.
Int J Med Robot ; 13(4)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28568650

RESUMO

BACKGROUND: Despite increasing use of robotic surgery for rectal cancer, few series have been published from the practice of generalizable US surgeons. METHODS: A retrospective chart review was performed for 71 consecutive patients who underwent robotic low anterior resection (LAR) or abdominoperineal resection (APR) for rectal adenocarcinoma between 2010 and 2014. RESULTS: 46 LARs (65%) and 25 APRs (35%) were identified. Median procedure time was 219 minutes (IQR 184-275) and mean blood loss 164.9 cc (SD 155.9 cc). Radial margin was negative in 70/71 (99%) patients. Total mesorectal excision integrity was complete/near complete in 38/39 (97%) of graded specimens. A mean of 16.8 (SD+/- 8.9) lymph nodes were retrieved. At median follow-up of 21.9 months, there were no local recurrences. CONCLUSIONS: Robotic proctectomy for rectal cancer was introduced into typical colorectal surgery practice by a single surgeon, with a low conversion rate, low complication rate, and satisfactory oncologic outcomes.


Assuntos
Neoplasias Colorretais/cirurgia , Proctocolectomia Restauradora/métodos , Neoplasias Retais/cirurgia , Procedimentos Cirúrgicos Robóticos/métodos , Robótica/métodos , Idoso , Índice de Massa Corporal , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Proctocolectomia Restauradora/instrumentação , Estudos Retrospectivos , Procedimentos Cirúrgicos Robóticos/instrumentação , Robótica/instrumentação , Resultado do Tratamento , Estados Unidos
16.
Am J Surg ; 214(2): 323-328, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27692792

RESUMO

BACKGROUND: Recent incidence, treatment patterns, and outcomes for node negative microscopically invasive breast cancer (MIBC) have not been reported. METHODS: State Health Registry of Iowa data identified women with ductal carcinoma in situ (DCIS), MIBC, and stage I breast cancer excluding MIBC (stage 1BC). RESULTS: From 2000 to 2013, 1,706, 193, and 4,514 women were diagnosed with DCIS, MIBC, and stage 1BC, respectively. MIBC increased at an annual percentage change of 2.1 (P = .041). MIBC was more frequently human epidermal growth factor receptor 2 positive than stage 1BC (39.7% vs 9.6%, P < .001). Mastectomy was performed more frequently in MIBC than DCIS (40.9% vs 30.6%, P = .014) or stage 1BC (40.9% vs 33.8%, P = .119). Chemotherapy was given to 4.1% of women with MIBC. Survival for women with MIBC was intermediate between DCIS and stage 1BC. CONCLUSIONS: Management of MIBC is an increasingly frequent clinical scenario. Women with MIBC receive more aggressive local and systemic therapy than women with DCIS.


Assuntos
Neoplasias da Mama , Carcinoma Intraductal não Infiltrante , Neoplasias da Mama/química , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Carcinoma Intraductal não Infiltrante/química , Carcinoma Intraductal não Infiltrante/epidemiologia , Carcinoma Intraductal não Infiltrante/patologia , Carcinoma Intraductal não Infiltrante/terapia , Feminino , Humanos , Incidência , Iowa , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , Receptor ErbB-2/análise , Programa de SEER
17.
Mol Cancer Ther ; 15(3): 503-11, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26832794

RESUMO

Expression of TFAP2C in luminal breast cancer is associated with reduced survival and hormone resistance, partially explained through regulation of RET. TFAP2C also regulates EGFR in HER2 breast cancer. We sought to elucidate the regulation and functional role of EGFR in luminal breast cancer. We used gene knockdown (KD) and treatment with a tyrosine kinase inhibitor (TKI) in cell lines and primary cancer isolates to determine the role of RET and EGFR in regulation of p-ERK and tumorigenesis. KD of TFAP2C decreased expression of EGFR in a panel of luminal breast cancers, and chromatin immunoprecipitation sequencing (ChIP-seq) confirmed that TFAP2C targets the EGFR gene. Stable KD of TFAP2C significantly decreased cell proliferation and tumor growth, mediated in part through EGFR. While KD of RET or EGFR reduced proliferation (31% and 34%, P < 0.01), combined KD reduced proliferation greater than either alone (52% reduction, P < 0.01). The effect of the TKI vandetanib on proliferation and tumor growth response of MCF-7 cells was dependent upon expression of TFAP2C, and dual KD of RET and EGFR eliminated the effects of vandetanib. The response of primary luminal breast cancers to TKIs assessed by ERK activation established a correlation with expression of RET and EGFR. We conclude that TFAP2C regulates EGFR in luminal breast cancer. Response to vandetanib was mediated through the TFAP2C target genes EGFR and RET. Vandetanib may provide a therapeutic effect in luminal breast cancer, and RET and EGFR can serve as molecular markers for response.


Assuntos
Antineoplásicos/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Receptores ErbB/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Piperidinas/farmacologia , Quinazolinas/farmacologia , Fator de Transcrição AP-2/metabolismo , Animais , Biomarcadores Tumorais , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Carcinogênese/genética , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Feminino , Humanos , Células MCF-7 , Proteínas Proto-Oncogênicas c-ret/genética , Proteínas Proto-Oncogênicas c-ret/metabolismo , Fator de Transcrição AP-2/genética , Carga Tumoral/efeitos dos fármacos , Carga Tumoral/genética , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Ann Surg Oncol ; 22(13): 4287-94, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25971960

RESUMO

BACKGROUND: Preliminary data indicate that tyrosine kinase inhibitors (TKIs) function through rearranged during transfection (RET) in breast cancer. However, TKIs are not specific and can block several receptor tyrosine kinases (RTKs). This study used cell lines and primary breast cancer specimens to determine factors associated with TKI response. METHODS: Proliferation was assessed after short interfering RNA knockdown with or without sunitinib in breast cancer cell lines by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide). Breast cancer tissue and matched normal breast was obtained from 30 women with invasive breast carcinoma. Gene expression was assessed by reverse transcriptase-polymerase chain reaction. Fresh tissue was treated in vitro with sunitinib or control media for 30 min, and response was assessed by phosphorylation-specific western blot. RESULTS: The RTKs including epidermal growth factor receptor (EGFR), vascular endothelial growth factor receptor (VEGFR1-3), platelet-derived growth factor receptor (PDGFRa/b), and Kit were overexpressed in triple-negative breast tumors relative to HER2- and estrogen receptor-alpha (ERα)-positive tumors and normal breast tissue. Knockdown of EGFR reduced in vitro proliferation in MCF-7 and MDA-MB-231 but not in SKBR-3 or ZR-75-1 breast cancer cells. With the exception of RET, response to sunitinib was independent of RTK expression in all four cell lines. Both ERα-positive and low-EGFR-expressing tumors had an increased in vitro sunitinib response, as determined by alteration of Erk activation. Expression of other RTKs and additional clinical factors were not associated with response. CONCLUSION: Triple-negative breast cancers overexpress RTKs but have decreased in vitro response to the TKI sunitinib. In addition to RET, TKIs that block EGFR may increase the therapeutic efficacy of TKIs in breast cancer.


Assuntos
Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , Indóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirróis/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fosforilação/efeitos dos fármacos , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Sunitinibe , Células Tumorais Cultivadas
19.
Ann Surg Oncol ; 22(3): 866-73, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25326397

RESUMO

BACKGROUND: Locally advanced breast cancer (LABC) poses complex management issues due to failure of response to chemotherapy and progression to local complications such as skin erosion, superinfection, and lymphedema. Most cell line and animal models are not adequate to study LABC. METHODS: A patient-derived xenograft (IOWA-1T) from a patient with LABC was characterized for expression profile, short tandem repeat profile, oncogenic mutations, xenograft growth, and response to therapy. RESULTS: Short tandem repeat profile authenticated the cell line as derived from a human woman. The primary tumor and derived xenografts were weakly estrogen receptor alpha positive (<5%), progesterone receptor negative, and HER2 nonamplified. Expression array profile compared to MCF-7 and BT-549 cell lines indicate that IOWA-1T was more closely related to basal breast cancer. IOWA-1T harbors a homozygous R248Q mutation of the TP53 gene; in vitro invasion assay was comparable to BT-549 and greater than MCF-7. IOWA-1T xenografts developed palpable tumors in 9.6 ± 1.6 days, compared to 49 ± 13 days for parallel experiments with BT-20 cells (p < 0.002). Tumor xenografts became locally advanced, growing to >2 cm in 21.6 ± 2 days, characterized by skin erosion necessitating euthanasia. The SUMO inhibitor anacardic acid inhibited the outgrowth of IOWA-1T xenografts, while doxorubicin had no effect on tumorigenesis. CONCLUSIONS: IOWA-1T is a novel cell line with an expression pattern consistent with basal breast cancer. Xenografts recapitulated LABC and provide a novel model for testing therapeutic drugs that may be effective in cases resistant to conventional chemotherapy.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Animais , Biomarcadores Tumorais/metabolismo , Western Blotting , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Carcinoma Ductal de Mama/genética , Carcinoma Ductal de Mama/metabolismo , Proliferação de Células , Feminino , Citometria de Fluxo , Imunofluorescência , Humanos , Camundongos , Camundongos Nus , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
20.
JAMA Surg ; 149(10): 1022-9, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25143027

RESUMO

IMPORTANCE: Splenectomy is a commonly performed operation; however, data from large series regarding operative outcomes to help guide decision making and informed consent are lacking. OBJECTIVE: To evaluate clinical and pathologic variables associated with morbidity and mortality following elective splenectomy for benign and malignant hematologic conditions in the United States. DESIGN, SETTING, AND PARTICIPANTS: A review of the American College of Surgeons National Surgical Quality Improvement Program data for elective splenectomy between January 1, 2005, and December 31, 2011, was performed, and 1715 eligible individuals were identified. INTERVENTION: Elective splenectomy for hematologic conditions. MAIN OUTCOMES AND MEASURES: Complications and operative mortality were evaluated for the entire cohort and compared between patients with benign vs malignant diseases. Multivariable logistic regression was used to evaluate factors predictive of operative complications and death. RESULTS: Splenectomy was performed in 1344 patients (78.4%) for benign disease and in 371 patients (21.6%) for malignant disease. Two hundred ninety-one patients (17.0%) had a complication, and operative mortality occurred in 27 patients (mortality rate, 1.6%). Patients treated for malignant disease had a higher rate of overall complications (27.2%) compared with patients treated for benign disease (14.1%) (P < .001). Several variables were independent predictors of complications, including malignant disease (vs benign) (Odds Ratio [OR], 1.86; 95% CI, 1.23-2.80; P = .003), independent performance status (vs dependent) (OR, 0.33; 95% CI, 0.07-1.52; P = .02), and increasing albumin level (OR, 0.75; 95% CI, 0.66-0.86; P < .001). Increasing age (OR, 1.03; 95% CI, 1.00-1.06; P = .05) was an independent predictor of mortality while increasing albumin level (OR, 0.63; 95% CI, 0.46-0.86; P = .003) predicted lower risk of operative death. From these data, a patient older than 60 years with a low preoperative albumin level has a predicted probability for operative death as high as 10.0%. CONCLUSIONS AND RELEVANCE: Preoperative performance and nutritional status are significant risk factors for complications and mortality following elective splenectomy. Although operative mortality continues to decrease over time, specific preoperative variables may help with patient selection before elective splenectomy for certain patients.


Assuntos
Doenças Hematológicas/mortalidade , Doenças Hematológicas/cirurgia , Morbidade , Complicações Pós-Operatórias/mortalidade , Melhoria de Qualidade , Esplenectomia/mortalidade , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Procedimentos Cirúrgicos Eletivos/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Estados Unidos/epidemiologia
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