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1.
Curr Oncol ; 30(12): 10351-10362, 2023 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-38132388

RESUMO

BACKGROUND: Axillary node status is an important prognostic factor in breast cancer. The primary aim was to evaluate tumor size and other characteristics relative to axillary disease. MATERIALS AND METHODS: Single institution retrospective chart review of stage I-III breast cancer patients collected demographic and clinical/pathologic data from 1998-2019. Student's t-test, Chi-squared test (or Fisher exact test if applicable), and logistic regression models were used for testing the association of pN+ to predictive variables. RESULTS: Of 728 patients (mean age 59 yrs) with mean follow up of 50 months, 86% were estrogen receptor +, 10% Her2+, 78% ER+HER2-negative, and 10% triple-negative. In total, 351/728 (48.2%) were pN+ and mean tumor size was larger in pN+ cases compared to pN- cases (mean = 27.7 mm versus 15.5 mm) (p < 0.001). By univariate analysis, pN+ was associated with lymphovascular invasion (LVI), higher grade, Her2, and histology (p < 0.005). Tumor-to-nipple distance was shorter in pN+ compared to pN- (45 mm v. 62 mm; p< 0.001). Age < 60, LVI, recurrence, mastectomy, larger tumor size, and shorter tumor-nipple distance were associated with 3+ positive nodes (p < 0.05). CONCLUSIONS: Larger tumor size and shorter tumor-nipple distance were associated with higher lymph node positivity. Age less than 60, LVI, recurrence, mastectomy, larger tumor size, and shorter tumor-nipple distance were all associated with 3+ positive lymph nodes.


Assuntos
Neoplasias da Mama , Humanos , Pessoa de Meia-Idade , Feminino , Neoplasias da Mama/patologia , Mastectomia , Estudos Retrospectivos , Linfonodos/patologia , Modelos Logísticos
3.
Ann Surg Oncol ; 30(12): 7081-7090, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37552349

RESUMO

BACKGROUND: SmartClipTM is a food and drug administration-approved, electromagnetic chip (EMC) localization system that provides three-dimensional navigation for the excision of soft tissue lesions. The purpose of this study was to analyze the accuracy and feasibility of EMC radiologic and surgical localization for benign and malignant breast lesions. PATIENTS AND METHODS: An institutional review board-approved, single institution, prospective study from October 2020 to September 2022 of 38 women undergoing breast conserving surgery with EMC localization of a single lesion > 5 mm on mammogram (MMG) or ultrasound (US) imaging. Surveys from performing breast radiologists and breast surgeons were collected after image-guided localization and surgical excision. RESULTS: Seventy-six survey responses from nine radiologists and four surgeons were received. The deployment needle and EMC were highly visible in 86.8% and 76.3% of procedures, respectively. There was no difficulty in deployment for 92.1% of procedures. The EMC was in the correct location on postdeployment MMG in 97.4% of cases. Three instances of EMC migration occurred, one 1 cm from target lesion. The targeted mass and EMC were within the surgical specimen in 97.4% of cases. On specimen radiograph, 39.5% of the EMCs were 0-1 mm from the center of the target lesion, 18.4% were within 2-4 mm, and 23.7% were within 5-10 mm. Mean operating room time for all cases was 65 min. One case required US to localize the target due to console malfunction. CONCLUSION: There was successful EMC deployment by radiologists with accurate visualization and successful surgical excision in most cases. The EnVisioTM SmartClipTM system is a reproducible and accurate localization method for benign and malignant breast lesions.


Assuntos
Neoplasias da Mama , Cirurgiões , Feminino , Humanos , Estudos Prospectivos , Mamografia , Fenômenos Eletromagnéticos , Radiologistas , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia
5.
Nat Med ; 29(2): 450-457, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36759673

RESUMO

Talimogene laherparepvec (T-VEC) is an oncolytic virus hypothesized to enhance triple-negative breast cancer (TNBC) responses to neoadjuvant chemotherapy (NAC). This article describes the phase 2 trial of T-VEC plus NAC (ClinicalTrials.gov ID: NCT02779855 ). Patients with stage 2-3 TNBC received five intratumoral T-VEC injections with paclitaxel followed by doxorubicin and cyclophosphamide and surgery to assess residual cancer burden index (RCB). The primary end point was RCB0 rate. Secondary end points were RCB0-1 rate, recurrence rate, toxicity and immune correlates. Thirty-seven patients were evaluated. Common T-VEC toxicities were fevers, chills, headache, fatigue and injection site pain. NAC toxicities were as expected. Four thromboembolic events occurred. The primary end point was met with an estimated RCB0 rate = 45.9% and RCB0-1 descriptive rate = 65%. The 2-year disease-free rate is equal to 89% with no recurrences in RCB0-1 patients. Immune activation during treatment correlated with response. T-VEC plus NAC in TNBC may increase RCB0-1 rates. These results support continued investigation of T-VEC plus NAC for TNBC.


Assuntos
Melanoma , Terapia Viral Oncolítica , Neoplasias de Mama Triplo Negativas , Humanos , Terapia Viral Oncolítica/métodos , Melanoma/patologia , Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas/patologia
6.
Clin Breast Cancer ; 22(8): e922-e927, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36055918

RESUMO

BACKGROUND: Microporous polysaccharide particles (MPP, proprietary name "Arista AH"), derived from purified plant starch, are used to augment hemostasis at surgery. The effect of MPP regarding short-term complications after mastectomy remains an area of ongoing investigation. PATIENTS AND METHODS: A single-institution, retrospective chart review of patients undergoing unilateral mastectomy without reconstruction from January 2019 to 2021 was performed. Primary endpoints included antibiotic prescription, seroma or abscess drainage, readmission, wound dehiscence, and time to drain removal within 30 days of initial surgery. Wilcoxon rank sum test or Student t test was used for group comparisons for continuous variables; Chi-square test or Fisher exact test was used to evaluate the associations among categorical variables. RESULTS: One hundred ninety patients were included; 119 received MPP and 71 did not. There was no difference in antibiotic prescription, infection drainage, hematoma, readmission, dehiscence, or time to drain removal with regards to MPP use. MPP treated patients were older (65.8 years vs. 59.1, P < .001) and had lower albumin levels (4.1 g/dL vs. 4.3, P = .025). Patients who underwent abscess drainage had higher body mass index ( mean 36.1 vs. 30.1 P = .036). Patients requiring seroma drainage were more likely to be diabetic (12.8% vs. 4%, P = .035) and to have been treated with lymphovenous anastomosis (LVA, 15.6% vs. 3.8%, P = .009). Patients who had LVA were significantly less likely to receive MPP when compared to other groups (3.1% vs. 74.7% P < .001). CONCLUSION: Consider utilizing MPP in patients at higher risk of seroma, such as those undergoing axillary surgery including LVA.


Assuntos
Neoplasias da Mama , Mastectomia , Humanos , Feminino , Mastectomia/efeitos adversos , Seroma/epidemiologia , Seroma/etiologia , Estudos Retrospectivos , Abscesso/complicações , Neoplasias da Mama/complicações , Drenagem , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Polissacarídeos , Antibacterianos
7.
Biol Res Nurs ; 24(4): 433-447, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35499926

RESUMO

Introduction: Emerging evidence suggests that Chemotherapy (CT) treated breast cancer survivors (BCS) who have "risk variants" in genes may be more susceptible to cognitive impairment (CI) and/or poor cardiac phenotypes. The objective of this preliminary study was to examine whether there is a relationship between genetic variants and objective/subjective cognitive or cardiac phenotypes. Methods and Analysis: BCS were recruited from Moffitt Cancer Center, Morsani College of Medicine, AdventHealth Tampa and Sarasota Memorial Hospital. Genomic DNA were collected at baseline for genotyping analysis. A total of 16 single nucleotide polymorphisms (SNPs) from 14 genes involved in cognitive or cardiac function were evaluated. Three genetic models (additive, dominant, and recessive) were used to test correlation coefficients between genetic variants and objective/subjective measures of cognitive functioning and cardiac outcomes (heart rate, diastolic blood pressure, systolic blood pressure, respiration rate, and oxygen saturation). Results: BCS (207 participants) with a mean age of 56 enrolled in this study. The majority were non-Hispanic white (73.7%), married (63.1%), and received both CT and radiation treatment (77.3%). Three SNPs in genes related to cognitive functioning (rs429358 in APOE, rs1800497 in ANKK1, rs10119 in TOMM40) emerged with the most consistent significant relationship with cognitive outcomes. Among five candidate SNPs related to cardiac functioning, rs8055236 in CDH13 and rs1801133 in MTHER emerged with potential significant relationships with cardiac phenotype. Conclusions: These preliminary results provide initial targets to further examine whether BCS with specific genetic profiles may preferentially benefit from interventions designed to improve cognitive and cardiac functioning following CT.


Assuntos
Neoplasias da Mama , Sobreviventes de Câncer , Disfunção Cognitiva , Cardiopatias , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Cognição/fisiologia , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/genética , Disfunção Cognitiva/psicologia , Feminino , Perfil Genético , Genômica , Cardiopatias/induzido quimicamente , Humanos , Proteínas Serina-Treonina Quinases , Sobreviventes/psicologia
8.
Int J Surg Pathol ; 30(5): 569-573, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35138180

RESUMO

Adenomyoepithelioma comprises a spectrum of lesions with variable morphology and clinical behavior, presenting at a wide age range. The most common presenting symptom is palpable abnormality. Mammographic abnormalities include focal asymmetries, masses and microcalcifications. Adenomyoepithelioma is a biphasic neoplasm characterized by proliferation of epithelial and myoepithelial cells. Adenomyoepitheliomas can be benign, atypical and malignant (adenomyoepithelioma with carcinoma). Malignant transformation occurs in either one or both cellular components leading to the development of invasive carcinoma. Invasive carcinoma types include invasive breast carcinoma of no special type, invasive lobular carcinoma, invasive carcinoma of special types, myoepithelial carcinoma, metaplastic carcinoma and biphasic carcinoma such as epithelial-myoepithelial carcinoma. While the majority of classic adenomyoepitheliomas have a benign clinical course and can be treated by local excision, local recurrence and distant metastasis have been reported. In malignant cases, treatment is determined by the associated carcinoma to include radiotherapy after breast conserving surgery and sentinel lymph node biopsy or axillary lymph node dissection, as indicated. Herein we report a case of a 62 year old woman who was found to have focal asymmetry on screening mammogram. She underwent a core biopsy of the lesion which showed atypical epithelial-myoepithelial neoplasm and excision was recommended. Upon excision, a diagnosis of malignant adenomyoepithelioma with associated epithelial-myoepithelial carcinoma was rendered with negative margins. The patient declined additional surgery for sentinel lymph node biopsy and declined adjuvant therapy. Six months after surgery, the patient is doing well with no complains. A follow-up mammogram and ultrasound of the axilla showed no abnormalities.


Assuntos
Adenomioepitelioma , Neoplasias da Mama , Carcinoma , Mioepitelioma , Adenomioepitelioma/patologia , Adenomioepitelioma/cirurgia , Mama/patologia , Neoplasias da Mama/patologia , Carcinoma/patologia , Feminino , Humanos , Mamografia , Mastectomia Segmentar , Pessoa de Meia-Idade , Mioepitelioma/patologia , Mioepitelioma/cirurgia
9.
Am J Transplant ; 22(3): 717-730, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34668635

RESUMO

Prevention of allograft rejection often requires lifelong immune suppression, risking broad impairment of host immunity. Nonselective inhibition of host T cell function increases recipient risk of opportunistic infections and secondary malignancies. Here we demonstrate that AJI-100, a dual inhibitor of JAK2 and Aurora kinase A, ameliorates skin graft rejection by human T cells and provides durable allo-inactivation. AJI-100 significantly reduces the frequency of skin-homing CLA+ donor T cells, limiting allograft invasion and tissue destruction by T effectors. AJI-100 also suppresses pathogenic Th1 and Th17 cells in the spleen yet spares beneficial regulatory T cells. We show dual JAK2/Aurora kinase A blockade enhances human type 2 innate lymphoid cell (ILC2) responses, which are capable of tissue repair. ILC2 differentiation mediated by GATA3 requires STAT5 phosphorylation (pSTAT5) but is opposed by STAT3. Further, we demonstrate that Aurora kinase A activation correlates with low pSTAT5 in ILC2s. Importantly, AJI-100 maintains pSTAT5 levels in ILC2s by blocking Aurora kinase A and reduces interference by STAT3. Therefore, combined JAK2/Aurora kinase A inhibition is an innovative strategy to merge immune suppression with tissue repair after transplantation.


Assuntos
Aurora Quinase A , Imunidade Inata , Animais , Aurora Quinase A/metabolismo , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Humanos , Janus Quinase 2 , Camundongos , Camundongos Endogâmicos C57BL , Células Th17 , Transplante Homólogo
10.
Cancer Med ; 10(21): 7665-7672, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34590788

RESUMO

BACKGROUND: Combination CDK4/6 inhibitor and endocrine therapy has been shown to significantly improve progression-free survival (PFS) in patients with hormone receptor (HR)-positive, HER2-negative metastatic breast cancer (mBC). The aim of this retrospective study was to evaluate the real-world benefit of first-line combination therapy in this cohort and to correlate treatment efficacy with neutropenia, a common toxicity of CDK4/6 inhibitors. METHODS: This study included HR-positive, HER2-negative advanced or mBC patients who were treated with palbociclib plus endocrine therapy, mainly letrozole, between 1 January 2015 and 1 March 2018. Progression-free survival (PFS) was determined using Kaplan-Meier analysis. The predictive value of absolute neutrophil count (ANC) and neutrophil-to-lymphocyte ratio (NLR) for PFS were explored using Cox regression models. Both ANC and NLR were used as a time-dependent variable. RESULTS: In total, 165 patients were included with median PFS of 24.19 months (95% CI 18.93-NR). Median PFS for patients with bone-only metastases (n = 54) was not reached (95% CI 18.21-NR). Among patients with all other metastases (n = 111), median PFS was 24.19 months (95% CI 16.33-33.82). Lower ANC was correlated with decreased risk of progression (HR 0.84, 95% CI 0.71-0.97, p = 0.008). There was no significant association between NLR and the risk of disease progression (HR 1.07, 95% CI 0.97-1.18, p = 0.203). CONCLUSION: The effectiveness of palbociclib and endocrine therapy in the treatment of HR-positive, HER2-negative mBC in the real-world setting is similar to the efficacy reported in the PALOMA-2 trial. Patients with lower neutrophil count may have a lower risk of early disease progression.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Letrozol/uso terapêutico , Neutropenia/induzido quimicamente , Piperazinas/uso terapêutico , Piridinas/uso terapêutico , Idoso , Neoplasias da Mama/genética , Neoplasias da Mama/imunologia , Neoplasias da Mama/patologia , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Letrozol/efeitos adversos , Contagem de Leucócitos , Pessoa de Meia-Idade , Metástase Neoplásica , Neutrófilos , Piperazinas/efeitos adversos , Intervalo Livre de Progressão , Piridinas/efeitos adversos , Receptor ErbB-2/análise , Fatores de Transcrição/análise
11.
Clin Imaging ; 75: 157-164, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33607537

RESUMO

Adenomyoepithelioma of the breast is a rare tumor consisting of both epithelial and myoepithelial cells. Malignant transformation of either cell line can occur. We describe the imaging features, clinical presentation, and management of seven cases of biopsy-proven adenomyoepithelioma at our institution.


Assuntos
Adenomioepitelioma , Neoplasias da Mama , Adenomioepitelioma/diagnóstico por imagem , Adenomioepitelioma/cirurgia , Biópsia , Neoplasias da Mama/diagnóstico por imagem , Transformação Celular Neoplásica , Humanos
12.
J Natl Compr Canc Netw ; 19(1): 40-47, 2021 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-33406495

RESUMO

BACKGROUND: Results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial supports omission of completion axillary lymph node dissection (CLND) after breast-conservation surgery with a positive sentinel lymph node biopsy (SLNB). We hypothesized that CLND also does not impact outcomes in women with clinically node-negative (cN0), pathologically node-positive breast cancer undergoing mastectomy. MATERIALS AND METHODS: A single-institution retrospective review was performed of patients with SLN-positive breast cancer treated from July 1999 through May 2018. Clinicopathologic and outcome data were collected. Patients with SLNBs were compared with those receiving SLNB and CLND. The Kruskal-Wallis, chi-square, and Fisher exact tests were used to assess for differences between continuous and categorical variables. The log-rank test was used for time-to-event analyses, and Cox proportional hazards models were fit for locoregional and distant recurrence and overall survival (OS). RESULTS: Of 329 patients with SLN-positive breast cancer undergoing mastectomy, 60% had CLND (n=201). Median age at diagnosis was 53 years (interquartile range [IQR], 46-62 years). The median number of SLNs sampled was 3 (IQR, 2-4), and the median number of positive SLNs was 1 (IQR, 1-2). Patients receiving CLND had higher tumor grades (P=.02) and a higher proportion of hormone receptor negativity (estrogen receptor, 19%; progesterone receptor, 27%; both P=.007). A total of 44 patients (22%) had increased N stage after CLND. Median follow-up was 51 months (IQR, 29-83 months). No association was found between CLND and change in OS and locoregional or distant recurrence. Completion of postmastectomy radiotherapy was associated with improved OS (P=.04). CONCLUSIONS: CLND is not significantly correlated with reduced recurrence or improved OS among patients who have cN0, SLN-positive breast cancer treated with mastectomy. CLND was significantly correlated with receipt of adjuvant systemic therapy. Completion of postmastectomy radiotherapy was associated with improved OS.


Assuntos
Neoplasias da Mama , Excisão de Linfonodo , Biópsia de Linfonodo Sentinela , Axila , Neoplasias da Mama/cirurgia , Dissecação , Feminino , Humanos , Metástase Linfática , Mastectomia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Estudos Retrospectivos
13.
Clin Breast Cancer ; 21(3): e189-e193, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-32893094

RESUMO

INTRODUCTION: Neoadjuvant chemotherapy (NAC) is commonly used for patients with clinically detected nodal metastases. Sentinel lymph node biopsy (SLNB) after NAC is feasible. Excision of biopsy-proven positive lymph nodes in addition to SLNB, termed targeted axillary dissection (TAD), decreases the false-negative rate of SLNB alone. Positive nodes can be marked with radar reflector-localization (RRL) clips. We report our institutional experience with RRL-guided TAD and demonstrate its safety and feasibility. PATIENTS AND METHODS: We performed an institutional review board-approved retrospective review of consecutive clinically node-positive female patients with breast cancer treated with NAC and RRL-guided TAD between January 2017 and September 2019. Clinicopathologic and treatment data were collected; descriptive statistics are reported. RESULTS: Forty-five patients were analyzed; the median age was 55 years (range, 20-72 years), and the median body mass index was 27.2 kg/m2 (range, 16.5-40.4 kg/m2). All patients received NAC, primary breast surgery, and TAD. All clinically detected nodal metastases were confirmed with percutaneous biopsy and marked with a biopsy clip. RRL clips were implanted a median of 8 days (range, 1-167 days) prior to surgery; all were retrieved without complications. The RRL node was identified as the sentinel lymph node in 36 (80%) patients. Twenty-five patients had positive nodes, of which 24 were identified by RRL node excision, and 1 (4%) patient had a positive node identified by SLNB but not RRL. Over a median follow-up time of 29.6 months, 5 patients recurred (1 local, 4 distant). CONCLUSIONS: RRL-guided TAD after NAC is safe and feasible. This technique allows for adequate assessment of the nodal basin and helps confirm excision of the previously biopsied positive axillary node.


Assuntos
Neoplasias da Mama/patologia , Excisão de Linfonodo/métodos , Linfonodo Sentinela/patologia , Linfonodo Sentinela/cirurgia , Adulto , Neoplasias da Mama/diagnóstico por imagem , Estudos de Viabilidade , Feminino , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante , Estadiamento de Neoplasias , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela/métodos , Resultado do Tratamento , Adulto Jovem
14.
Clin Breast Cancer ; 21(1): 74-79, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32917535

RESUMO

BACKGROUND: The standard of care for clinically node-negative (cN0) patients following positive sentinel lymph node biopsy (SLNB) was completion axillary lymph node dissection (CALND). Publication of ACOSOG Z0011 in 2010 changed this standard for patients undergoing lumpectomy. Clinicians have since expanded this practice to mastectomy patients, and ongoing prospective studies are seeking to validate this practice. Here, we evaluate patient and tumor characteristics that led surgeons to forego a second surgery for CALND in cN0 mastectomy patients with positive SLNB. PATIENTS AND METHODS: A single institution, retrospective review of cN0 patients with invasive primary breast cancer and positive SLNB from 2010 to 2016 was performed. Patients with T4 disease, positive preoperative axillary biopsy, prior neoadjuvant therapy or axillary surgery were excluded. Patients with positive SLNB undergoing CALND were compared with patients for whom CALND was omitted. Statistical analysis was performed using Kruskal-Wallis tests for continuous variables and χ2 tests or Fischer exact tests for categorical variables. RESULTS: Of 259 patients with positive SLNB, 180 (69.4%) patients underwent mastectomy. CALND was performed at the time of mastectomy in 54 (30%) patients, at time of second operation in 22 (12.2%) patients, and not performed in 104 (57%) patients. Delayed CALND was significantly associated with younger age, larger tumors, increased number of positive sentinel nodes, invasive lobular carcinoma, extranodal extension, and lymphovascular invasion. CONCLUSIONS: The management of cN0 patients with positive SLNB that do not meet ACOSOG Z0011 criteria is evolving and is influenced by tumor and patient characteristics in an attempt to balance the morbidity of CALND with the low rate of local regional recurrence.


Assuntos
Neoplasias da Mama/cirurgia , Metástase Linfática/terapia , Biópsia de Linfonodo Sentinela/estatística & dados numéricos , Linfonodo Sentinela/cirurgia , Adulto , Idoso , Neoplasias da Mama/patologia , Feminino , Humanos , Metástase Linfática/patologia , Pessoa de Meia-Idade , Seleção de Pacientes , Estudos Retrospectivos , Linfonodo Sentinela/patologia
15.
Clin Cancer Res ; 27(4): 1012-1018, 2021 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-33219014

RESUMO

PURPOSE: Talimogene laherparepvec (TVEC) is an oncolytic herpes simplex 1 virus approved for treatment of melanoma. We hypothesized intratumoral TVEC may enhance response to neoadjuvant chemotherapy (NAC). This article reports the results of a trial combining NAC with TVEC for triple-negative breast cancer (TNBC). PATIENTS AND METHODS: Patients with stage II-III TNBC enrolled in a 3+3 phase I trial (NCT02779855) of two TVEC dose levels [DL; DL 1 = 106 plaque-forming units (PFU) × 5 doses; DL 2 = 106 PFUs first dose, then 108 PFUs × 4 doses] on weeks 1, 4, 6, 8, and 10 plus weekly paclitaxel (80 mg/m2) for 12 weeks, followed by doxorubicin/cyclophosphamide (60/600 mg/m2) every 2 weeks for 8 weeks. Postoperative response assessment using residual cancer burden (RCB) was performed. Primary endpoints were safety and MTD. Secondary endpoints were RCB0 rate and immune correlates. Dose-limiting toxicity (DLT) rule was grade 3-5 adverse events due to TVEC during first 5 weeks. RESULTS: Nine patients [DL 1 (n = 3); DL 2 (n = 6)] were enrolled. Six had stage II disease, and 3 had stage III (6 clinically N+). No DLTs occurred, and MTD was DL 2. Most common toxicities with TVEC were fever (n = 8), chills (n = 3), hematomas (n = 3), and injection site pain (n = 3). Thromboembolic events (n = 2) and bradycardia (n = 1) occurred during or after NAC. Five patients (55%) achieved RCB0, 2 had RCB1 (22%), and 2 had RCB2 (22%). CONCLUSIONS: The addition of TVEC to NAC was feasible at the approved dose, with manageable toxicity. The complete response rate was 55%.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Produtos Biológicos/administração & dosagem , Terapia Neoadjuvante/métodos , Terapia Viral Oncolítica/métodos , Neoplasias de Mama Triplo Negativas/terapia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Produtos Biológicos/efeitos adversos , Quimioterapia Adjuvante/efeitos adversos , Quimioterapia Adjuvante/métodos , Estudos de Viabilidade , Feminino , Herpesvirus Humano 1 , Humanos , Pessoa de Meia-Idade , Terapia Neoadjuvante/efeitos adversos , Estadiamento de Neoplasias , Terapia Viral Oncolítica/efeitos adversos , Resultado do Tratamento , Neoplasias de Mama Triplo Negativas/diagnóstico , Neoplasias de Mama Triplo Negativas/imunologia
16.
J Surg Res ; 254: 378-383, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32535256

RESUMO

BACKGROUND: The present literature is conflicting regarding the management of microinvasive ductal carcinoma in situ (miDCIS) as to following recommendations for DCIS (margin status, surgical axillary staging, and possible observation) versus invasive breast cancer. We hypothesize that miDCIS represents more aggressive disease than pure DCIS. METHODS: We performed a retrospective review of female miDCIS patients compared with age-matched cohorts of DCIS and T1b/c patients with invasive breast cancer. We collected demographic, clinicopathologic, treatment, and outcome information. Analysis of variance or Kruskal-Wallis tests were used to analyze continuous variables and chi-square or Fisher's exact tests for categorical variables. Survival outcomes were analyzed using Kaplan-Meier curves. RESULTS: We included 375 patients (125 in each group) with median age 59 y (range 33-91 y). miDCIS tumors were more likely to be hormone receptor negative and human epidermal growth factor receptor 2 positive compared with DCIS or invasive ductal carcinoma (IDC; all P < 0.001). Subgroup analysis by miDCIS focality demonstrated no significant differences. The number of involved lymph nodes was not significantly different from DCIS patients but was significantly fewer than invasive cancer patients. Of 115 miDCIS patients (88%) staged with sentinel lymph node biopsy, eight (7%) had nodal metastases. Six miDCIS patients (5%) were treated with adjuvant chemotherapy. Over a median follow-up of 23.3 mo, there were no significant differences in local or distant recurrence. CONCLUSIONS: Based on our results, miDCIS has more aggressive pathologic features compared with DCIS and warrants surgical treatment and nodal staging similar to the management of IDC. In addition, similar to IDC, nodal and receptor status may influence medical management.


Assuntos
Neoplasias da Mama/patologia , Mama/patologia , Carcinoma Ductal de Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Feminino , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
JCI Insight ; 5(9)2020 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-32255769

RESUMO

Immunosuppressive donor Tregs can prevent graft-versus-host disease (GVHD) or solid-organ allograft rejection. We previously demonstrated that inhibiting STAT3 phosphorylation (pSTAT3) augments FOXP3 expression, stabilizing induced Tregs (iTregs). Here we report that human pSTAT3-inhibited iTregs prevent human skin graft rejection and xenogeneic GVHD yet spare donor antileukemia immunity. pSTAT3-inhibited iTregs express increased levels of skin-homing cutaneous lymphocyte-associated antigen, immunosuppressive GARP and PD-1, and IL-9 that supports tolerizing mast cells. Further, pSTAT3-inhibited iTregs significantly reduced alloreactive conventional T cells, Th1, and Th17 cells implicated in GVHD and tissue rejection and impaired infiltration by pathogenic Th2 cells. Mechanistically, pSTAT3 inhibition of iTregs provoked a shift in metabolism from oxidative phosphorylation (OxPhos) to glycolysis and reduced electron transport chain activity. Strikingly, cotreatment with coenzyme Q10 restored OxPhos in pSTAT3-inhibited iTregs and augmented their suppressive potency. These findings support the rationale for clinically testing the safety and efficacy of metabolically tuned, human pSTAT3-inhibited iTregs to control alloreactive T cells.


Assuntos
Rejeição de Enxerto , Doença Enxerto-Hospedeiro , Fator de Transcrição STAT3/fisiologia , Linfócitos T Reguladores , Animais , Rejeição de Enxerto/imunologia , Rejeição de Enxerto/metabolismo , Doença Enxerto-Hospedeiro/imunologia , Doença Enxerto-Hospedeiro/metabolismo , Humanos , Camundongos , Oxirredução , Linfócitos T Reguladores/citologia , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/metabolismo
18.
Breast J ; 26(3): 514-516, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31495018

RESUMO

Postoperative chyle leak is an exceedingly rare complication following breast and axillary surgery. We present the first described case of chyle leak following breast-conserving surgery and sentinel lymph node biopsy. Management should begin with appropriated conservative measures aimed at reduction of lymph production and flow. Intervention is warranted when conservative strategies fail and include sclerotherapy, lymphangiography, embolization, and surgery. Breast surgeons should be mindful of this potential complication when operating in the axilla and be familiar with its stepwise management.


Assuntos
Neoplasias da Mama , Quilo , Axila , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Linfonodos , Metástase Linfática , Mastectomia Segmentar , Biópsia de Linfonodo Sentinela/efeitos adversos
19.
Clin Breast Cancer ; 20(1): e14-e19, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31780380

RESUMO

INTRODUCTION: Implant-sparing mastectomy (ISM) is a skin-sparing mastectomy that preserves a retropectoral implant and potentially eliminates the need for tissue expansion or complex reconstruction. This study aimed to determine oncologic and surgical outcomes and reconstructive patterns in patients undergoing ISM. PATIENTS AND METHODS: A single-institution, retrospective review of patients undergoing ISM from 2006 to 2018 was performed. Patient/tumor characteristics, stage, adjuvant therapy use, 90-day complication rates, reconstruction type, and disease recurrence were collected. RESULTS: A total of 121 ISMs in 73 women were performed. Seventy (57.9%) ISMs were for breast cancer (BC) treatment and 51 (42.1%) for prophylaxis. Among BC cases, 72.3% were cT1/cT2 and 73.8% were cN0; 72.3% received systemic therapy and 33.8% received radiation therapy. There were 3 deaths owing to BC at the median follow-up of 35 months. Among 5 recurrences, only 1 was local. There was no BC identified after prophylactic ISM. Total 90-day complication rate per ISM was 15.7%. Rates were 0.8% for both seroma and wound infection, 2.5% for wound dehiscence, 3.3% for hematoma, and 8.2% for skin necrosis. The majority (72.6%) of patients required only implant exchange for reconstruction. Overall use of autologous reconstruction was low (12.3%); 77.8% of flaps were performed in patients receiving radiation therapy. CONCLUSION: ISM is a unique approach for patients pursuing mastectomy for BC treatment or prevention with equivalent oncologic outcomes and complication rates to mastectomy with reconstruction. Reconstruction for the majority was markedly simplified by elimination of tissue expansion while maintaining a low rate of flap reconstruction.


Assuntos
Implantes de Mama , Neoplasias da Mama/terapia , Mamoplastia/métodos , Mastectomia Subcutânea/efeitos adversos , Recidiva Local de Neoplasia/epidemiologia , Complicações Pós-Operatórias/epidemiologia , Adulto , Idoso , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Quimioterapia Adjuvante , Feminino , Seguimentos , Humanos , Mamoplastia/instrumentação , Mastectomia Subcutânea/métodos , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Recidiva Local de Neoplasia/prevenção & controle , Complicações Pós-Operatórias/etiologia , Radioterapia Adjuvante , Estudos Retrospectivos , Retalhos Cirúrgicos/transplante , Resultado do Tratamento , Adulto Jovem
20.
Cancer Control ; 26(1): 1073274819827284, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30808195

RESUMO

The purpose of this article is to review closure options for complex chest wounds in patients with locally advanced breast cancer. Experiences of the plastic and oncologic surgery teams at Moffitt Cancer Center were reviewed, and the literature researched for various surgical options of complex chest wound closure. Multiple treatment modalities exist for reconstruction of complex chest wall wounds with the external oblique and V-Y latissimus dorsi musculocutaneous advancement flaps serving as workhorses in reconstruction. Treatment of cancer has moved from simply a surgical solution to include other modalities such as hormonal therapy, chemotherapy, and radiation-the latter 2 having serious consequences for wound healing. A team approach and knowledge of available flap options are vital for closure of complex wounds in a timely manner. Appropriate planning can optimize the primary goal of the oncologic surgeon to remove the cancer and the plastic surgeon's objective to reconstruct the defect and achieve a closed, durable wound prior to chemotherapy and radiation. We present the experience at the Moffitt Cancer Center in reconstructing challenging chest defects and review the reconstructive ladder.


Assuntos
Neoplasias da Mama/terapia , Mastectomia/efeitos adversos , Procedimentos de Cirurgia Plástica/métodos , Parede Torácica/cirurgia , Mama/patologia , Mama/cirurgia , Neoplasias da Mama/patologia , Quimiorradioterapia Adjuvante/efeitos adversos , Feminino , Humanos , Recidiva Local de Neoplasia , Músculos Superficiais do Dorso/transplante , Retalhos Cirúrgicos/transplante , Parede Torácica/efeitos dos fármacos , Parede Torácica/efeitos da radiação , Resultado do Tratamento , Cicatrização/efeitos dos fármacos , Cicatrização/efeitos da radiação
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