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1.
Ann Surg Oncol ; 28(10): 5513-5524, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34333705

RESUMO

BACKGROUND: Two-dimensional (2D) specimen radiography (SR) and tomosynthesis (DBT) for breast cancer yield data that lack high-depth resolution. A volumetric specimen imager (VSI) was developed to provide full-3D and thin-slice cross-sectional visualization at a 360° view angle. The purpose of this prospective trial was to compare VSI, 2D SR, and DBT interpretation of lumpectomy margin status with the final pathologic margin status of breast lumpectomy specimens. METHODS: The study enrolled 200 cases from two institutions. After standard imaging and interpretation was performed, the main lumpectomy specimen was imaged with the VSI device. Image interpretation was performed by three radiologists after surgery based on VSI, 2D SR, and DBT. A receiver operating characteristic (ROC) curve was created for each method. The area under the curve (AUC) was computed to characterize the performance of the imaging method interpreted by each user. RESULTS: From 200 lesions, 1200 margins were interpreted. The AUC values of VSI for the three radiologists were respectively 0.91, 0.90, and 0.94, showing relative improvement over the AUCs of 2D SR by 54%, 13%, and 40% and DBT by 32% and 11%, respectively. The VSI has sensitivity ranging from 91 to 94%, specificity ranging from 81 to 85%, a positive predictive value ranging from 25 to 30%, and a negative predicative value of 99%. CONCLUSIONS: The ROC curves of the VSI were higher than those of the other specimen imaging methods. Full-3D specimen imaging can improve the correlation between the main lumpectomy specimen margin status and surgical pathology. The findings from this study suggest that using the VSI device for intraoperative margin assessment could further reduce the re-excision rates for women with malignant disease.


Assuntos
Neoplasias da Mama , Mastectomia Segmentar , Mama , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Estudos Transversais , Feminino , Humanos , Mamografia , Estudos Prospectivos
2.
Ann Surg Oncol ; 28(5): 2512-2521, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33433786

RESUMO

BACKGROUND: Intraoperative radiation therapy (IORT) has been investigated for patients with low-risk, early-stage breast cancer. The The North American experience was evaluated by TARGIT-R (retrospective) to provide outcomes for patients treated in "real-world" clinical practice with breast IORT. This analysis presents a 5-year follow-up assessment. METHODS: TARGIT-R is a multi-institutional retrospective registry of patients who underwent lumpectomy and IORT between the years 2007 and 2013. The primary outcome of the evaluation was ipsilateral breast tumor recurrence (IBTR). RESULTS: The evaluation included 667 patients with a median follow-up period of 5.1 years. Primary IORT (IORT at the time of lumpectomy) was performed for 72%, delayed IORT (after lumpectomy) for 3%, intended boost for 8%, and unintended boost (primary IORT followed by whole-breast radiation) for 17% of the patients. At 5 years, IBTR was 6.6% for all the patients, with 8% for the primary IORT cohort and 1.7% for the unintended-boost cohort. No recurrences were identified in the delayed IORT or intended-boost cohorts. Noncompliance with endocrine therapy (ET) was associated with higher IBTR risk (hazard ratio [HR], 3.67). Patients treated with primary IORT who were complaint with ET had a 5-year IBTR rate of 3.9%. CONCLUSION: The local recurrence rates in this series differ slightly from recent results of randomized IORT trials and are notably higher than in previous published studies using whole-breast radiotherapy for similar patients with early-stage breast cancer. Understanding differences in this retrospective series and the prospective trials will be critical to optimizing patient selection and outcomes going forward.


Assuntos
Neoplasias da Mama , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Seguimentos , Humanos , Cuidados Intraoperatórios , Mastectomia Segmentar , Recidiva Local de Neoplasia/radioterapia , América do Norte , Estudos Prospectivos , Estudos Retrospectivos
3.
J Surg Oncol ; 119(1): 101-108, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30481371

RESUMO

BACKGROUND/OBJECTIVES: Proficiency of performing sentinel lymph node biopsy (SLNB) for breast cancer varies among hospitals and may be reflected in the hospital's SLNB positivity rate. Our objectives were to examine whether hospital characteristics are associated with variation in SLNB positivity rates and whether hospitals with lower-than-expected SLNB positivity rates have worse patient survival. METHODS: Using the National Cancer Data Base, stage I to III breast cancer patients were identified (2004-2012). Hospital-level SLNB positivity rates were adjusted for tumor and patient factors. Hospitals were divided into terciles of SLNB positivity rates (lower-, higher-, as-expected). Hospital characteristics and survival were examined across terciles. RESULTS: Of 438 610 SLNB patients (from 1357 hospitals), 78 104 had one or more positive SLN (21.3%). Hospitals in the low and high terciles were more likely to be low volume (low: RRR, 4.40; 95% CI, 2.89-6.57; P < 0.001; and high: RRR, 1.79; 95% CI, 1.21-2.64; P < 0.001) compared to hospitals with as-expected (middle tercile) SLNB positivity rates. Stage I patients at low- and high-tercile hospitals had statistically worse survival. CONCLUSIONS: There is a wide variation in hospital SLNB positivity rates. Hospitals with lower- or higher-than-expected SLNB positivity rates were associated with survival differences. Hospital SLNB positivity rates may be a novel 'process measure' to report to hospitals for internal quality assessment.


Assuntos
Neoplasias da Mama/patologia , Hospitais/estatística & dados numéricos , Hospitais/normas , Linfonodo Sentinela/patologia , Idoso , Idoso de 80 Anos ou mais , Axila , Neoplasias da Mama/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Linfonodo Sentinela/cirurgia , Biópsia de Linfonodo Sentinela
4.
Breast J ; 24(4): 620-623, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29286191

RESUMO

We aimed to better quantify the impact of a postexcision preirradiation mammogram (PPM), first by identifying factors associated with abnormal results and then incorporating these findings into a nomogram. Beginning February 2011, our institution made a practice change to obtain a PPM on all patients with any calcifications identified. A total of 530 patients underwent a PPM. Suspicious abnormalities were reported in 61 patients (11.5%), with the PPM leading to a change in management in 47 instances (8.9%). A nomogram was created based on patient and tumor characteristics to identify patients most likely to have an abnormal PPM.


Assuntos
Neoplasias da Mama/radioterapia , Carcinoma Intraductal não Infiltrante/radioterapia , Neoplasia Residual/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Humanos , Mamografia , Mastectomia Segmentar , Pessoa de Meia-Idade , Nomogramas , Estudos Prospectivos , Radioterapia Adjuvante/métodos , Fatores de Risco
5.
Ann Surg Oncol ; 24(5): 1258-1261, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27853900

RESUMO

OBJECTIVE: The aim of this study was to evaluate outcomes after breast-conserving surgery (BCS) and intraoperative radiotherapy (IORT), and to identify risk factors associated with complications. MATERIALS/METHODS: We evaluated patients with early-stage breast cancer treated from January 1, 2011 to January 31, 2014 with BCS and IORT at a single institution. The presence of breast cancer recurrences, complications, or fat necrosis were assessed at subsequent follow-up visits using physical examination and breast imaging. RESULTS: Overall, 113 patients, of whom three were undergoing bilateral treatments, were identified. The median length of time for IORT was 29 min and 36 s (range 15:50-59:00). Fifteen patients received additional external beam radiotherapy (EBRT), and the median follow-up was 40.3 months (range 1.6-58.3) for all patients. To date, one biopsy-proven ipsilateral recurrence has been noted (0.9%), for which the patient elected to undergo a mastectomy. Nine patients were found to have wound complications (7.7%) and two had fat necrosis (1.7%) on follow-up. Of all the evaluated risk factors, only applicator size (p < 0.01) had a statistically significant association with an increase in complications. CONCLUSIONS: With a short follow-up, IORT appears to be a safe treatment modality for a select group of patients, leading to a reasonable increase in operating room time and complication rates following BCS. The utilization of larger applicators at the time of IORT was associated with an increase in wound complications and fat necrosis.


Assuntos
Tecido Adiposo/patologia , Neoplasias da Mama/terapia , Mastectomia Segmentar/efeitos adversos , Recidiva Local de Neoplasia , Complicações Pós-Operatórias/etiologia , Radioterapia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Feminino , Humanos , Cuidados Intraoperatórios/efeitos adversos , Pessoa de Meia-Idade , Necrose/etiologia , Estadiamento de Neoplasias , Radioterapia/instrumentação , Fatores de Risco
6.
Ann Surg Oncol ; 23(8): 2446-55, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27169774

RESUMO

BACKGROUND: Current guidelines recommend postmastectomy radiotherapy (PMRT) for patients with ≥4 positive lymph nodes and suggest strong consideration of PMRT in those with 1-3 positive nodes. These recommendations were incorporated into a Commission on Cancer quality measure in 2014. However, national adherence with these recommendations is unknown. Our objectives were to describe PMRT use in the United States in patients with stage I to III invasive breast cancer and to examine possible factors associated with the omission of PMRT. METHODS: From the National Cancer Data Base, 753,536 mastectomies at 1123 hospitals were identified from 1998 to 2011. PMRT use over time was examined using random effects logistic regression analyses, adjusting for patient, tumor, and hospital characteristics. Analyses were stratified by nodal status (≥4 nodes positive, 1-3 nodes positive, node negative). RESULTS: The proportion of patients receiving PMRT increased from 1998 to 2011 (>4 positive nodes: 56.2 to 66.6 %; 1-3 positive nodes: 28.0 to 39.1 %; node-negative: 8.3 to 10.0 %, p < 0.001 for all). In adjusted analyses, patients with ≥4 positive nodes were more likely to have PMRT omitted if they had smaller tumors. Patients with 1-3 positive nodes were more likely to have PMRT omitted if they had lower grade or smaller tumors. Irrespective of patients' nodal status, PMRT utilization rates decreased as age increased. CONCLUSIONS: Though PMRT rates increased over time in patients with ≥4 and 1-3 positive nodes, PMRT in patients with ≥4 positive nodes remains underutilized. Feedback to hospitals using the new Commission on Cancer PMRT measure may help to improve adherence rates.


Assuntos
Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Mastectomia , Garantia da Qualidade dos Cuidados de Saúde , Radioterapia Adjuvante , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Seleção de Pacientes , Resultado do Tratamento , Estados Unidos
7.
Ann Surg Oncol ; 23(9): 2809-15, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27160524

RESUMO

BACKGROUND: Single-dose intraoperative radiotherapy (IORT) is an emerging treatment for women with early stage breast cancer. The objective of this study was to define the frequency of IORT use, patient selection, and outcomes of patients treated in North America. METHODS: A multi-institutional retrospective registry was created, and 19 institutions using low-kilovoltage IORT for the treatment of breast cancer entered data on patients treated at their institution before July 31, 2013. Patient selection, IORT treatment details, complications, and recurrences were analyzed. RESULTS: From 2007 to July 31, 2013, a total of 935 women were identified and treated with lumpectomy and IORT. A total of 822 patients had at least 6 months' follow-up documented and were included in the analysis. The number of IORT cases performed increased significantly over time (p < 0.001). The median patient age was 66.8 years. Most patients had disease that was <2 cm in size (90 %) and was estrogen positive (91 %); most patients had invasive ductal cancer (68 %). Of those who had a sentinel lymph node procedure performed, 89 % had negative sentinel lymph nodes. The types of IORT performed were primary IORT in 79 %, secondary IORT in 7 %, or planned boost in 14 %. Complications were low. At a median follow-up of 23.3 months, crude in-breast recurrence was 2.3 % for all patients treated. CONCLUSIONS: IORT use for the treatment of breast cancer is significantly increasing in North America, and physicians are selecting low-risk patients for this treatment option. Low complication and local recurrence rates support IORT as a treatment option for selected women with early stage breast cancer.


Assuntos
Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Recidiva Local de Neoplasia , Seleção de Pacientes , Radioterapia/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/patologia , Canadá , Carcinoma Ductal de Mama/secundário , Intervalo Livre de Doença , Feminino , Humanos , Cuidados Intraoperatórios , Metástase Linfática , Mastectomia Segmentar/efeitos adversos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasia Residual , Radioterapia/métodos , Dosagem Radioterapêutica , Sistema de Registros , Estudos Retrospectivos , Linfonodo Sentinela/patologia , Carga Tumoral , Estados Unidos
8.
Phys Chem Chem Phys ; 18(16): 10700-7, 2016 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-26967595

RESUMO

We present a facile alternative to other well known strategies for synthesizing flexible thermoelectric materials. Instead of printing thin active layers on flexible substrates or doping conductive polymers, we produce thermoelectric pastes, using a mixture of graphite, copper(I) oxide and polychlorotrifluoroethene. The Seebeck coefficient of the investigated pastes varies between 10 and 600 µV K(-1), while the electrical conductivity spans over an even wider range of 10(-4) to 10(2) S m(-1). Here, the influence of phenomena such as percolation on the electrical transport is revealed. The resulting power factor reaches 5.69 × 10(-4) ± 0.70 × 10(-4) µW m(-1) K(-2) for the graphite-polymer paste, with an unexpected minimum at a graphite molar fraction of approximately 0.4. The values are comparable to those of the powder mixtures, which are slightly higher, but less precisely tunable. Such compounds are further evaluated for practical applications. The graphite-polymer paste is used to exemplify, how a flexible thermoelectric sensor can be easily manufactured, step by step. Our results represent a proof of principle, that thermoelectric pastes are viable alternatives to current solutions. A further expansion of the scope for the composites can be achieved by using high performance thermoelectric materials and conductive polymers.

9.
Breast Cancer Res Treat ; 151(3): 629-38, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26006067

RESUMO

The purpose of this study is to evaluate the efficacy and safety of neoadjuvant treatment with carboplatin and eribulin in patients with early-stage triple negative breast cancer (TNBC), and to explore biomarkers based on DNA and protein expression profiles as predictors of response. Patients with histologically confirmed early-stage TNBC received carboplatin AUC 6 iv every 21 days, and eribulin 1.4 mg/m(2) day 1 and day 8 every 21 days for four cycles. The primary endpoint of the study was pathologic complete response (pCR), with secondary endpoints including clinical response and safety of the combination. Exploratory studies assessed DNA-based biomarkers [homologous recombination deficiency (HRD) score, and HR deficiency status (HRD score + BRCA1/BRCA2 mutation status)], protein-based biomarkers (Ki67, TP53, androgen receptor, Cyclin E, CDK2, Cyclin D, CDK4, Pin1 and Smad3), and clinical pretreatment factors as predictors of pCR. 13/30 (43.3 %) patients enrolled in the study achieved pCR. 24 (80.0 %) had a clinical complete or partial response. The combination was safe with mostly grade 1 and 2 toxicities. HRD score (P = 0.0024) and HR deficiency status (P = 0.0012) significantly predicted pCR. Pretreatment cytoplasmic CDK2 was also associated with pCR (P = 0.021). Significant differences in pre- versus post-treatment expression levels of nuclear Cyclin D (P = 0.020), nuclear CDK4 (P = 0.0030), and nuclear Smad3 (P = 0.015) were detected. The combination of carboplatin and eribulin is safe and efficacious in the treatment of early-stage TNBC. HRD score, HR deficiency status, and cytoplasmic CDK2 predicted pCR in this patient population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores , Carboplatina/administração & dosagem , Feminino , Furanos/administração & dosagem , Genes BRCA1 , Genes BRCA2 , Humanos , Estimativa de Kaplan-Meier , Cetonas/administração & dosagem , Pessoa de Meia-Idade , Mutação , Terapia Neoadjuvante , Gradação de Tumores , Estadiamento de Neoplasias , Razão de Chances , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias de Mama Triplo Negativas/mortalidade
10.
Ann Surg Oncol ; 21(2): 384-8, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24121881

RESUMO

BACKGROUND: Despite the growing interest in the advantages of tumescent mastectomy technique, there remain concerns that tumescent solution may increase postoperative complication rates. This study evaluates patient outcomes following tumescent mastectomy in the setting of immediate prosthetic reconstruction. METHODS: Retrospective review of 1,491 breasts (1,030 patients) treated by 4 oncologic and 2 reconstructive surgeons between 2004 and 2012 at a single institution. The primary outcomes of interest included seroma, hematoma, infection, and mastectomy flap necrosis, as well as conversion to autologous reconstruction. Multiple logistic regression was used to determine the adjusted influence of tumescence on outcomes. RESULTS: The tumescent cohort (n = 890 breasts) was younger and experienced lower rates of preoperative radiation than the nontumescent cohort (n = 601 breasts). Mean follow-up was 21.2 months. While tumescent procedures were on average 20 min faster, postoperative complication rates did not significantly differ between cohorts. Regression analysis controlling for potential confounders, including differences in surgeon technique, failed to identify tumescent mastectomy as an independent risk factor for complication [odds ratio (OR) = 1.2, 95% confidence interval (CI) = 0.8-1.8, p = 0.385]. Individually, neither seroma, hematoma, infection, nor flap necrosis was affected significantly by the use of tumescence (OR = 1.66, 95% CI = 0.73-3.78, p = 0.229; OR = 1.11, 95% CI = 0.42-2.95, p = 0.837; OR = 0.84, 95% CI = 0.4-1.75, p = 0.689; OR = 1.19, 95% CI = 0.7-2.03, p = 0.67, respectively). DISCUSSION: This longitudinal study is well equipped to assess the influence of tumescent mastectomy technique in the hands of experienced and high-volume oncologic surgeons on postoperative outcomes. Our analysis suggests that in the setting of an immediate prosthetic reconstruction, tumescent mastectomy does not independently affect postoperative complication rates.


Assuntos
Anestésicos Locais/administração & dosagem , Neoplasias da Mama/cirurgia , Mamoplastia , Mastectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Neoplasias da Mama/patologia , Chicago/epidemiologia , Feminino , Seguimentos , Sobrevivência de Enxerto , Humanos , Estudos Longitudinais , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Retalhos Cirúrgicos , Resultado do Tratamento
11.
Breast J ; 20(3): 288-94, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24689860

RESUMO

Thirty-day hospital readmission has emerged as an important variable in health care quality improvement. Our purpose was to investigate the unplanned readmission rate following excisional breast surgery and to identify risk factors associated with readmission. The 2011 National Surgical Quality Improvement Program registry was retrospectively reviewed for patients undergoing excisional breast surgery. Logistic regression was used to investigate the relationship between pre- and perioperative variables and 30-day readmission. Of 13,610 women identified, 292 (2.15%) were readmitted within the 30-day tracking period. The readmitted cohort demonstrated significantly more comorbidities and postoperative complications, as well as longer operative times and hospital stays. Postoperative complications were the best predictors for readmission; however, age, a history of bleeding disorders, immunosuppression, cardiovascular disease, and inpatient hospitalization were also significant independent predictors for readmission. Risk factors for readmission include both pre- and perioperative variables. Perioperative complications, most often infectious in nature, are the strongest predictors; however, comorbidities including immunosuppression, bleeding disorders, and cardiovascular disease also significantly increase the risk for readmission. Although readmission is relatively rare, identifying and managing high-risk patients in addition to more effective methods to prevent and manage postoperative complications will be critical to reducing readmissions and improving patient care.


Assuntos
Mastectomia Segmentar/efeitos adversos , Mastectomia Segmentar/estatística & dados numéricos , Readmissão do Paciente/estatística & dados numéricos , Adulto , Idoso , Comorbidade , Feminino , Humanos , Modelos Logísticos , Pessoa de Meia-Idade , Morbidade , Complicações Pós-Operatórias/epidemiologia , Fatores de Risco , Estados Unidos
12.
Ann Surg Oncol ; 20(5): 1522-9, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23224903

RESUMO

INTRODUCTION: The accuracy of breast magnetic resonance imaging (MRI) for detection of ductal carcinoma in situ (DCIS) has prompted recommendations for its routine preoperative use, but its clinical benefit is debated. We reviewed our experience with MRI in DCIS patients to assess the utility of MRI for surgical planning. METHODS: DCIS patients (2008-2010) were identified through a prospectively maintained database and grouped into MRI and no-MRI groups. The rates of additional biopsies, altered surgical management, and reoperation were compared. Additionally, DCIS size ascertained by mammography, MRI, and final pathology was compared. RESULTS: Of 352 DCIS patients, 217 received MRI and 135 did not. The type of initial operation and number of reoperations were similar between the two groups, but successful breast conservation was more frequent in the no-MRI group (p = 0.06). The additional biopsy rate was 38 % in the MRI group versus 7 % in the no-MRI group; ≥2 additional biopsies were performed in 18 % of the MRI group and 2 % of the no-MRI group (p < 0.0001). These yielded a cancer diagnosis in 26 % of MRI and 33 % of no-MRI patients (p = 0.73). MRI was not superior to mammogram in detecting size of DCIS lesions preoperatively; 52 % of mammograms were accurate (within 1 cm) compared with 41 % of MRIs. CONCLUSIONS: DCIS patients who undergo preoperative breast MRI are far more likely to undergo additional biopsies. Unless these can be demonstrated to lead to improved long-term outcomes, the utility of routine preoperative MRI in DCIS patients remains questionable.


Assuntos
Neoplasias da Mama/diagnóstico , Carcinoma in Situ/diagnóstico , Carcinoma Ductal de Mama/diagnóstico , Imageamento por Ressonância Magnética , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Neoplasias da Mama/cirurgia , Carcinoma in Situ/cirurgia , Carcinoma Ductal de Mama/cirurgia , Feminino , Humanos , Mamografia , Mastectomia Segmentar , Pessoa de Meia-Idade , Reoperação , Estudos Retrospectivos
13.
Breast Cancer Res Treat ; 132(3): 833-42, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21359953

RESUMO

Lapatinib, a dual kinase inhibitor against epidermal growth factor receptor (EGFR) and human epidermal receptor two (HER2) has shown efficacy in treating HER2 positive breast cancer. Nanoparticle albumin bound (nab) paclitaxel was developed to reduce toxicities from paclitaxel and improve its efficacy. Thirty patients with stage I-III HER2 positive breast cancer were treated in the neoadjuvant setting with lapatinib 1,000 mg/day and nab-paclitaxel 260 mg/m(2) every 3 weeks for four cycles. The primary end point of the trial was clinical response rate (cRR) with secondary end points including pathologic complete response rate (pCR), tolerability of the combination, and marker response. The cRR was 82.8% (24 patients) with six (20.7%) patients having complete clinical response, 18 (62.1%) having partial clinical response, and five (17.2%) stable disease. A pCR was observed in five of the 28 patients (17.9%). The most frequent grade 2 toxicities were neuropathy in nine patients (30%), fatigue in seven patients (23.3%), rash in 11 patients (36.7%), and bone pain in 10 patients (33.3%). There was no significant drop in the left ventricular ejection fraction (LVEF). Of the tissue markers examined, we were not able to find a predictor of response. The combination of lapatinib and nab-paclitaxel was well tolerated and provided good efficacy in women with HER2 positive breast cancer. This combination offers an alternative non-anthracycline-containing regimen for women with HER2 positive breast cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/tratamento farmacológico , Carcinoma Ductal de Mama/tratamento farmacológico , Terapia Neoadjuvante , Receptor ErbB-2/metabolismo , Adulto , Idoso , Albuminas/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/metabolismo , Neoplasias da Mama/mortalidade , Carcinoma Ductal de Mama/metabolismo , Carcinoma Ductal de Mama/mortalidade , Diarreia/induzido quimicamente , Feminino , Testes de Função Cardíaca , Humanos , Estimativa de Kaplan-Meier , Lapatinib , Pessoa de Meia-Idade , Paclitaxel/administração & dosagem , Projetos Piloto , Quinazolinas/administração & dosagem , Resultado do Tratamento
14.
Ann Surg Oncol ; 19(4): 1167-73, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-21997350

RESUMO

BACKGROUND: Breast cancers (BCs) diagnosed after a recent pregnancy display features associated with poor prognosis, including hormone receptor negativity, but other tumor markers have not been examined. We sought to define the tumor marker profile of these cancers, including HER-2 and p53 expression, and examine the time interval over which this adverse profile is observed, relative to last pregnancy. METHODS: A prospectively maintained database was reviewed to identify women with a BC diagnosis between 1998 to 2011. Parous women were categorized on the basis of the interval between pregnancy and BC diagnosis; 0-2 years, >2-5 years, >5-10 years, and >10-15 years. Tumor characteristics of parous cases were compared to those of nulliparous BC patients, who were frequency matched by age. RESULTS: A total of 175 parous and 114 nulliparous women were identified. Women who were 0-2 years from last parity at the time of BC diagnosis were the only group who were more likely than control women to have grade 3 tumors (P<0.01), positive lymph nodes (P=0.02), and triple negative tumors (P=0.01, odds ratio 3.2, 95% confidence interval 1.2-8.5). There was no difference noted in HER-2 or p53 status relative to interval from pregnancy. CONCLUSIONS: BC diagnosed within 2 years of pregnancy is more likely to have poor prognostic features and to be triple negative. More work is needed to delineate the time frame of pregnancy-associated BC and to define them on a molecular level, so as to devise better prevention and therapy for this devastating problem.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/metabolismo , Paridade , Receptor ErbB-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adulto , Neoplasias da Mama/patologia , Feminino , Humanos , Metástase Linfática , Pessoa de Meia-Idade , Gradação de Tumores , Gravidez , Prognóstico , Transtornos Puerperais/epidemiologia , Transtornos Puerperais/metabolismo , Fatores de Risco
15.
Clin Pharmacol Ther ; 109(3): 728-738, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32996592

RESUMO

Oral breast cancer prevention medications entail systemic exposure, limiting acceptance by high-risk women. Delivery through the breast skin, although an attractive alternative, requires demonstration of drug distribution throughout the breast. We conducted a randomized double-blind, placebo-controlled phase II clinical trial comparing telapristone acetate, a progesterone receptor antagonist, administered orally (12 mg/day) or transdermally (12 mg/breast) for 4 ± 1 weeks to women planning mastectomy. Plasma and tissue concentrations, measured at five locations in the mastectomy specimen using liquid chromatography tandem mass spectrometry were compared. In 60 evaluable subjects, median drug concentration (ng/g tissue) was 103 (interquartile range (IQR): 46.3-336) in the oral vs. 2.82 (IQR: 1.4-5.5) in the transdermal group. Despite poor dermal permeation, within-breast drug distribution pattern was identical in both groups (R2  = 0.88, P = 0.006), demonstrating that transdermally and orally delivered drug is distributed similarly through the breast, and is strongly influenced by tissue adiposity (P < 0.0001). Other skin-penetrant drugs should be tested for breast cancer prevention.


Assuntos
Antineoplásicos/administração & dosagem , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante , Norpregnadienos/administração & dosagem , Absorção Cutânea , Adiposidade , Administração Cutânea , Administração Oral , Adulto , Antineoplásicos/efeitos adversos , Antineoplásicos/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/cirurgia , Quimioterapia Adjuvante , Cromatografia Líquida , Método Duplo-Cego , Monitoramento de Medicamentos , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Norpregnadienos/efeitos adversos , Norpregnadienos/sangue , Espectrometria de Massas em Tandem , Fatores de Tempo , Distribuição Tecidual , Resultado do Tratamento , Estados Unidos
16.
Aesthet Surg J ; 30(2): 194-200, 2010 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-20442096

RESUMO

BACKGROUND: Crescentric tissue expanders have the potential to improve postoperative aesthetic results via selective lower pole expansion; however, limited data are available on their efficacy. OBJECTIVES: The authors assess postoperative functional and cosmetic outcomes of acellular dermis-assisted breast reconstruction with crescentric tissue expansion. METHODS: This study is a single-institution, retrospective review of 40 consecutive patients who underwent acellular dermis-assisted breast reconstruction with crescentric tissue expansion. Demographic data, operative details, and procedural outcomes were recorded and assessed. Cosmetic outcomes were assessed using the Breast Evaluation Questionnaire. RESULTS: Fifty-eight breasts representing 36 bilateral and 22 unilateral reconstructions were analyzed. Of these, 45 (78%) underwent tissue expander (TE) to implant exchange. The mean interval between stage 1 and stage 2 was 92 +/- 20 days, with a total follow-up time of 141 +/- 16 days. The average intraoperative expander fill volume was 213.5 mL, with an average final fill of 285 mL (range, 180-740 mL). The average number of expansions was 1.6. Overall, there were five complications (8.6%). Eighty-three percent of patients participated in the breast evaluation questionnaire. Answers to each question were reported using a qualitative five-point scale that ranged from 1 (very dissatisfied) to 5 (very satisfied). For the bilateral reconstructions, the average score in all contexts was 4.5 +/- 0.3, 4.33 +/- 0.5, and 4.36 +/- 0.33 for size, shape, and firmness, respectively. For unilateral reconstructions, the average scores were 4.0 +/- 0.58, 3.93 +/- 0.38, and 4.13 +/- 0.21, respectively. CONCLUSIONS: Crescentric expander-based reconstruction with acellular dermis assistance is well tolerated, especially in smaller breasted women. Functional and cosmetic outcomes were acceptable and comparable to previous reports of traditional expander-based reconstructions.


Assuntos
Implantes de Mama , Mamoplastia/métodos , Expansão de Tecido/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Estética , Feminino , Humanos , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Estudos Retrospectivos , Inquéritos e Questionários , Resultado do Tratamento
17.
Rev Sci Instrum ; 91(1): 016102, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32012533

RESUMO

Efficient soft X-ray spectroscopy in the laboratory is still a challenging task. Here, we report on new toroidal multilayer optics designed and applied with the laser-produced plasma (LPP) source of the Berlin Laboratory for innovative X-ray technologies. The optics are described and characterized, and the application of the updated source to scanning-free grazing emission X-ray fluorescence is demonstrated on thermoelectric gold-doped copper oxide nanofilms. The comparison with synchrotron measurements allows estimating a flux on the sample of approximately 7.5 × 109 photons/s in the 1 keV range on a 100 µm × 100 µm spot, emphasizing the suitability of the updated LPP source for the application in photon hungry experiments.

18.
RSC Adv ; 10(49): 29394-29401, 2020 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-35521098

RESUMO

The development of thin-film thermoelectric applications in sensing and energy harvesting can benefit largely from suitable deposition methods for earth-abundant materials. In this study, p-type copper oxide thin films have been prepared on soda lime silicate glass by direct current (DC) magnetron sputtering at room temperature from a pure copper metallic target in an argon atmosphere, followed by subsequent annealing steps at 300 °C under various atmospheres, namely air (CuO:air), nitrogen (CuO:N) and oxygen (CuO:O). The resultant films have been studied to understand the influence of various annealing atmospheres on the structural, spectroscopic and thermoelectric properties. X-ray diffraction (XRD) patterns of the films showed reflexes that could be assigned to those of crystalline CuO with a thin mixed Cu(I)Cu(II) oxide, which was also observed by near edge X-ray absorption fine structure spectroscopy (NEXAFS). The positive Seebeck coefficient (S) reached values of up to 204 µV K-1, confirming the p-type behavior of the films. Annealing under oxygen provided a significant improvement in the electrical conductivity up to 50 S m-1, resulting in a power factor of 2 µW m-1 K-2. The results reveal the interplay between the intrinsic composition and the thermoelectric performance of mixed copper oxide thin films, which can be finely adjusted by simply varying the annealing atmosphere.

19.
Clin Cancer Res ; 26(1): 25-34, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31570566

RESUMO

PURPOSE: Selective progesterone receptor modulators (SPRMs) show preclinical activity against hormone-sensitive breast cancer, but have not been tested in patients with early, treatment-naïve tumors. PATIENTS AND METHODS: In a double-blind presurgical window trial of oral telapristone acetate (TPA) 12 mg daily versus placebo, 70 patients with early-stage breast cancer were randomized 1:1 (stratified by menopause) and treated for 2 to 10 weeks. The primary endpoint was change in Ki67 between diagnostic biopsy and surgical specimens. Gene expression pre- and posttherapy was assessed using RNA-sequencing and gene set enrichment analysis was performed to determine pathways enriched in response to TPA and placebo treatments. RESULTS: Among 61 evaluable women (29 placebo and 32 telapristone acetate), 91% of tumors were ER/PR positive. The mean Ki67 declined by 5.5% in all women treated with telapristone acetate (P = 0.003), and by 4.2% in all women treated with placebo (P = 0.04). After menopausal stratification, the Ki67 decline remained significant in 22 telapristone acetate-treated premenopausal women (P = 0.03). Differential gene expression analysis showed no significant modulation overall. However, in a subset of tumors that demonstrated ≥30% relative reduction in Ki67 in the telapristone acetate group, genes related to cell-cycle progression, and those in the HER2 amplicon were significantly downregulated. In contrast, no significantly enriched pathways were identified in the placebo group. CONCLUSIONS: Patients treated with telapristone acetate whose Ki67 decreased by ≥30% demonstrated a selective antiproliferative signal, with a potentially important effect on HER2 amplicon genes. Evaluation of SPRMs in a neoadjuvant trial is merited, with attention to predictors of response to SPRM therapy, and inclusion of pre- and postmenopausal women.


Assuntos
Neoplasias da Mama/tratamento farmacológico , Antagonistas de Hormônios/uso terapêutico , Norpregnadienos/uso terapêutico , Receptores de Progesterona/antagonistas & inibidores , Antineoplásicos/uso terapêutico , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Método Duplo-Cego , Feminino , Perfilação da Expressão Gênica/métodos , Humanos , Antígeno Ki-67/metabolismo , Menopausa , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Receptor ErbB-2/genética , Análise de Sequência de RNA/métodos , Resultado do Tratamento
20.
Surg Oncol ; 27(1): 95-99, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29549911

RESUMO

PURPOSE: The current standard of care for women diagnosed with early stage breast cancer is breast-conserving surgery (BCS) followed by external beam radiation therapy, commonly delivered over 3-6 weeks. As an alternative, select patients can undergo intra-operative radiation therapy (IORT) at the time of BCT. This technique delivers a single fraction of radiation at the time of surgery, enabling patients to undergo both surgery and radiation in a single session. Our current study analyzed the value of incorporating breast MRI into the routine work-up of patients deemed eligible for IORT, to quantify the impact on patient eligibility and requirement for additional work-up. MATERIALS AND METHODS: We retrospectively identified patients treated by a single surgeon who were eligible for IORT based on institutional eligibility criteria which included: women age ≥55, grades 1-2, size <3 cm, estrogen receptor (ER) positive, Her-2 neu non-amplified and low/intermediate Ki-67, unifocal invasive ductal/mixed histology carcinomas. All patients must have undergone a physical exam and bilateral diagnostic mammography with ultrasound. From this population, we identified all patients who had undergone bilateral breast MRI as part of pre-operative evaluation. RESULTS: A total of 215 women were identified who met all eligibility criteria. MRI detected additional abnormalities in the breast in 89 patients (41%). Sixty-eight women underwent additional biopsies, with a total of 117 separate lesions biopsied. Of these, pathology was benign in 61 (52.1%), atypical ductal hyperplasia (ADH) in 21 (18%), ductal carcinoma in-situ (DCIS) in 17 (14.5%) and invasive disease in 18 (15.4%). Six patients had MRI-detected abnormalities in the contralateral breast only, with biopsies identifying invasive disease (3), DCIS (1) and benign (2) findings. MRI showed abnormalities in both breasts in 6 patients and 18 additional lesions were biopsied which reveled invasive carcinoma (6), DCIS (7), ADH (3) and benign findings (2). Fifteen patients had either multifocal/multicentric disease or index lesion >3 cm on MRI and were deemed ineligible for IORT. Based on either MRI size or biopsy results, management was ultimately changed for 27 patients (12.5%). Extramammary findings were observed in 17 patients and 11 of these patients underwent further imaging studies all of which returned negative results. CONCLUSION: Preoperative bilateral breast MRI is a valuable tool in the proper selection of patients best suited for IORT. Even in highly selected, favorable risk patients, MRI detected additional lesions that changed surgical and radiation therapy recommendations in 12.5% of patients. However, the cost/benefit ratio needs to be taken into consideration given the high frequency of benign biopsies and additional radiological work-up.


Assuntos
Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Intraductal não Infiltrante/patologia , Imageamento por Ressonância Magnética/métodos , Mastectomia Segmentar , Seleção de Pacientes , Cuidados Pré-Operatórios , Idoso , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/radioterapia , Neoplasias da Mama/cirurgia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/radioterapia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Intraductal não Infiltrante/diagnóstico por imagem , Carcinoma Intraductal não Infiltrante/radioterapia , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Seguimentos , Humanos , Mamografia , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Taxa de Sobrevida
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