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1.
Ann Surg Oncol ; 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38980586

RESUMO

BACKGROUND: Internal mammary lymphadenopathy (IML) plays a role in breast cancer stage and prognosis. We aimed to evaluate method of IML detection, how IML impacts response to neoadjuvant chemotherapy (NAC), and oncologic outcomes. METHODS: We evaluated patients enrolled in the I-SPY-2 clinical trial from 2010 to 2022. We captured the radiographic method of IML detection (magnetic resonance imaging [MRI], positron emission tomography/computed tomography [PET/CT], or both) and compared patients with IML with those without. Rates of locoregional recurrence (LRR), distant recurrence (DR) and event-free survival (EFS) were compared by bivariate analysis. RESULTS: Of 2095 patients, 198 (9.5%) had IML reported on pretreatment imaging. The method of IML detection was 154 (77.8%) MRI only, 11 (5.6%) PET/CT only, and 33 (16.7%) both. Factors associated with IML were younger age (p = 0.001), larger tumors (p < 0.001), and higher tumor grade (p = 0.027). Pathologic complete response (pCR) was slightly higher in the IML group (41.4% vs. 34.0%; p = 0.03). There was no difference in breast or axillary surgery (p = 0.41 and p = 0.16), however IML patients were more likely to undergo radiation (68.2% vs. 54.1%; p < 0.001). With a median follow up of 3.72 years (range 0.4-10.2), there was no difference between IM+ versus IM- in LRR (5.6% vs. 3.8%; p = 0.25), DR (9.1% vs. 7.9%; p = 0.58), or EFS (61.6% vs. 57.2%; p = 0.48). This was true for patients with and without pCR. CONCLUSIONS: In this large cohort of patients treated with NAC, outcomes were not negatively impacted by IML. We demonstrated that IML influences treatment selection but is not a poor prognostic indicator when treated with modern NAC and multidisciplinary disease management.

2.
Ann Surg Oncol ; 31(4): 2212-2223, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38261126

RESUMO

Rates of contralateral mastectomy (CM) among patients with unilateral breast cancer have been increasing in the United States. In this Society of Surgical Oncology position statement, we review the literature addressing the indications, risks, and benefits of CM since the society's 2017 statement. We held a virtual meeting to outline key topics and then conducted a literature search using PubMed to identify relevant articles. We reviewed the articles and made recommendations based on group consensus. Patients consider CM for many reasons, including concerns regarding the risk of contralateral breast cancer (CBC), desire for improved cosmesis and symmetry, and preferences to avoid ongoing screening, whereas surgeons primarily consider CBC risk when making a recommendation for CM. For patients with a high risk of CBC, CM reduces the risk of new breast cancer, however it is not known to convey an overall survival benefit. Studies evaluating patient satisfaction with CM and reconstruction have yielded mixed results. Imaging with mammography within 12 months before CM is recommended, but routine preoperative breast magnetic resonance imaging is not; there is also no evidence to support routine postmastectomy imaging surveillance. Because the likelihood of identifying an occult malignancy during CM is low, routine sentinel lymph node surgery is not recommended. Data on the rates of postoperative complications are conflicting, and such complications may not be directly related to CM. Adjuvant therapy delays due to complications have not been reported. Surgeons can reduce CM rates by encouraging shared decision making and informed discussions incorporating patient preferences.


Assuntos
Neoplasias da Mama , Oncologia Cirúrgica , Neoplasias Unilaterais da Mama , Humanos , Feminino , Mastectomia/métodos , Neoplasias da Mama/patologia , Neoplasias Unilaterais da Mama/cirurgia , Oncologia
3.
Ann Surg Oncol ; 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38995451

RESUMO

BACKGROUND: For patients with clinically node-positive (cN+) breast cancer undergoing neoadjuvant chemotherapy (NAC), retrieving previously clipped, biopsy-proven positive lymph nodes during sentinel lymph node biopsy [i.e., targeted axillary dissection (TAD)] may reduce false negative rates. However, the overall utilization and impact of clipping positive nodes remains uncertain. PATIENTS AND METHODS: We retrospectively analyzed cN+ ISPY-2 patients (2011-2022) undergoing axillary surgery after NAC. We evaluated trends in node clipping and associations with type of axillary surgery [sentinel lymph node (SLN) only, SLN and axillary lymph node dissection (ALND), or ALND only] and event-free survival (EFS) in patients that were cN+ on a NAC trial. RESULTS: Among 801 cN+ patients, 161 (20.1%) had pre-NAC clip placement in the positive node. The proportion of patients that were cN+ undergoing clip placement increased from 2.4 to 36.2% between 2011 and 2021. Multivariable logistic regression showed nodal clipping was independently associated with higher odds of SLN-only surgery [odds ratio (OR) 4.3, 95% confidence interval (CI) 2.8-6.8, p < 0.001]. This was also true among patients with residual pathologically node-positive (pN+) disease. Completion ALND rate did not differ based on clip retrieval success. No significant differences in EFS were observed in those with or without clip placement, both with or without successful clip retrieval [hazard ratio (HR) 0.85, 95% CI 0.4-1.7, p = 0.7; HR 1.8, 95% CI 0.5-6.0, p = 0.3, respectively]. CONCLUSION: Clip placement in the positive lymph node before NAC is increasingly common. The significant association between clip placement and omission of axillary dissection, even among patients with pN+ disease, suggests a paradigm shift toward TAD as a definitive surgical management strategy in patients with pN+ disease after NAC.

4.
J Surg Res ; 295: 327-331, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38061237

RESUMO

INTRODUCTION: Larger tumor size and shorter tumor-to-nipple distance at diagnosis are associated with greater risk of lymph node involvement in breast cancer. However, the relationship between receptor subtype status and lymph node metastasis remains unclear. Our objective was to examine the association between primary tumor size, location, and nodal metastasis across estrogen receptor (ER)+/ progesterone receptor (PR)+/ human epidermal growth factor receptor 2 (HER2)-, ER+/PR-/HER2-, ER+/PR+/HER2+, and ER+/PR-/HER2+ tumors. METHODS: A single-institution retrospective chart review was conducted of breast cancer patients diagnosed between 1998 and 2019 who underwent nodal evaluation during primary surgery. Neoadjuvant chemotherapy, pure ductal carcinoma in situ, inflammatory, recurrent, metastatic, bilateral, multicentric, and multifocal disease were excluded. Descriptive statistics (proportions and frequencies for categorical variables and medians [Q1-Q3] for continuous variables) were used to summarize patient characteristics. Kruskal-Wallis test was applied to test the association of outcome variables and continuous variables. Chi-square test or Fisher exact test was applied to test the association of outcome variables and categorical variables. RESULTS: Six hundred eighteen ER + patients had a median tumor size of 1.7 cm (1.1-2.5 cm). Two hundred ninety six out of 618 (47.9%) were node-positive and 188/618 (30.4%) had axillary dissection. Eighty four point three percent of patients were ER+/PR+/HER2-, 6.31% were ER+/PR-/HER2-, 6.96% were ER+/PR+/HER2+, and 1.13% were ER+/PR-/HER2+. Median tumor size was significantly larger in node-positive cases compared to node-negative cases in ER+/PR+/HER2-, ER+/PR+/HER2+, and ER+/PR-/HER2- subgroups. In ER+/PR+/HER2-patients, median tumor-nipple distance was significantly shorter in node-positive patients compared to node-negative patients. Upper outer quadrant location was significantly associated with nodal positivity in ER+/PR-/HER2- patients. CONCLUSIONS: Across ER + patients, the significance between tumor size, location, and lymph node positivity varied significantly when differentiating by PR and HER2 status.


Assuntos
Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/patologia , Estudos Retrospectivos , Receptores de Estrogênio/metabolismo , Receptor ErbB-2/metabolismo , Metástase Linfática , Linfonodos/patologia , Receptores de Progesterona/metabolismo , Biomarcadores Tumorais/metabolismo
5.
Ann Surg ; 278(3): 320-327, 2023 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-37325931

RESUMO

Neoadjuvant chemotherapy (NAC) increases rates of successful breast-conserving surgery (BCS) in patients with breast cancer. However, some studies suggest that BCS after NAC may confer an increased risk of locoregional recurrence (LRR). We assessed LRR rates and locoregional recurrence-free survival (LRFS) in patients enrolled on I-SPY2 (NCT01042379), a prospective NAC trial for patients with clinical stage II to III, molecularly high-risk breast cancer. Cox proportional hazards models were used to evaluate associations between surgical procedure (BCS vs mastectomy) and LRFS adjusted for age, tumor receptor subtype, clinical T category, clinical nodal status, and residual cancer burden (RCB). In 1462 patients, surgical procedure was not associated with LRR or LRFS on either univariate or multivariate analysis. The unadjusted incidence of LRR was 5.4% after BCS and 7.0% after mastectomy, at a median follow-up time of 3.5 years. The strongest predictor of LRR was RCB class, with each increasing RCB class having a significantly higher hazard ratio for LRR compared with RCB 0 on multivariate analysis. Triple-negative receptor subtype was also associated with an increased risk of LRR (hazard ratio: 2.91, 95% CI: 1.8-4.6, P < 0.0001), regardless of the type of operation. In this large multi-institutional prospective trial of patients completing NAC, we found no increased risk of LRR or differences in LRFS after BCS compared with mastectomy. Tumor receptor subtype and extent of residual disease after NAC were significantly associated with recurrence. These data demonstrate that BCS can be an excellent surgical option after NAC for appropriately selected patients.


Assuntos
Neoplasias da Mama , Mastectomia , Humanos , Feminino , Mastectomia/métodos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Terapia Neoadjuvante/métodos , Estudos Prospectivos , Recidiva Local de Neoplasia/epidemiologia , Recidiva Local de Neoplasia/patologia , Mastectomia Segmentar , Quimioterapia Adjuvante/métodos , Estudos Retrospectivos
6.
New Phytol ; 240(6): 2372-2385, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37837235

RESUMO

Glutamate decarboxylase (GAD) is a Ca2+ -calmodulin-activated, cytosolic enzyme that produces γ-aminobutyrate (GABA) as the committed step of the GABA shunt. This pathway bypasses the 2-oxoglutarate to succinate reactions of the tricarboxylic acid (TCA) cycle. GABA also accumulates during many plant stresses. We tested the hypothesis that AtGAD1 (At5G17330) facilitates Arabidopsis acclimation to Pi deprivation. Quantitative RT-PCR and immunoblotting revealed that AtGAD1 transcript and protein expression is primarily root-specific, but inducible at lower levels in shoots of Pi-deprived (-Pi) plants. Pi deprivation reduced levels of the 2-oxoglutarate dehydrogenase (2-OGDH) cofactor thiamine diphosphate (ThDP) in shoots and roots by > 50%. Growth of -Pi atgad1 T-DNA mutants was significantly attenuated relative to wild-type plants. This was accompanied by: (i) an > 60% increase in shoot and root GABA levels of -Pi wild-type, but not atgad1 plants, and (ii) markedly elevated anthocyanin and reduced free and total Pi levels in leaves of -Pi atgad1 plants. Treatment with 10 mM GABA reversed the deleterious development of -Pi atgad1 plants. Our results indicate that AtGAD1 mediates GABA shunt upregulation during Pi deprivation. This bypass is hypothesized to circumvent ThDP-limited 2-OGDH activity to facilitate TCA cycle flux and respiration by -Pi Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Arabidopsis/metabolismo , Fósforo/metabolismo , Glutamato Descarboxilase/genética , Glutamato Descarboxilase/metabolismo , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Aclimatação , Aminobutiratos/metabolismo , Ácido gama-Aminobutírico/metabolismo , Raízes de Plantas/metabolismo , Fosfatos/metabolismo , Regulação da Expressão Gênica de Plantas
7.
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
8.
Ann Surg Oncol ; 30(11): 6401-6410, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37380911

RESUMO

BACKGROUND: Axillary surgery after neoadjuvant chemotherapy (NAC) is becoming less extensive. We evaluated the evolution of axillary surgery after NAC on the multi-institutional I-SPY2 prospective trial. METHODS: We examined annual rates of sentinel lymph node (SLN) surgery with resection of clipped node, if present), axillary lymph node dissection (ALND), and SLN and ALND in patients enrolled in I-SPY2 from January 1, 2011 to December 31, 2021 by clinical N status at diagnosis and pathologic N status at surgery. Cochran-Armitage trend tests were calculated to evaluate patterns over time. RESULTS: Of 1578 patients, 973 patients (61.7%) had SLN-only, 136 (8.6%) had SLN and ALND, and 469 (29.7%) had ALND-only. In the cN0 group, ALND-only decreased from 20% in 2011 to 6.25% in 2021 (p = 0.0078) and SLN-only increased from 70.0% to 87.5% (p = 0.0020). This was even more striking in patients with clinically node-positive (cN+) disease at diagnosis, where ALND-only decreased from 70.7% to 29.4% (p < 0.0001) and SLN-only significantly increased from 14.6% to 56.5% (p < 0.0001). This change was significant across subtypes (HR-/HER2-, HR+/HER2-, and HER2+). Among pathologically node-positive (pN+) patients after NAC (n = 525) ALND-only decreased from 69.0% to 39.2% (p < 0.0001) and SLN-only increased from 6.9% to 39.2% (p < 0.0001). CONCLUSIONS: Use of ALND after NAC has significantly decreased over the past decade. This is most pronounced in cN+ disease at diagnosis with an increase in the use of SLN surgery after NAC. Additionally, in pN+ disease after NAC, there has been a decrease in use of completion ALND, a practice pattern change that precedes results from clinical trials.


Assuntos
Neoplasias da Mama , Linfonodo Sentinela , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Biópsia de Linfonodo Sentinela/métodos , Terapia Neoadjuvante/métodos , Axila/patologia , Estudos Prospectivos , Metástase Linfática/patologia , Linfonodo Sentinela/cirurgia , Linfonodo Sentinela/patologia , Excisão de Linfonodo
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.
Br J Haematol ; 196(3): 530-547, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34931311

RESUMO

As haematologists, we always seek to follow standardised guidelines for practice and apply the best treatment within our means for our patients with blood diseases. However, treatment can never follow an exact recipe. Opinions differ as to the best approach; sometimes more than one treatment approach results in identical outcomes, or treatments differ only by the manner in which they fail. Furthermore, the haematologist is faced with constraints relating to the local economic environment. Patients too are not the same the world over. Early presentation is commoner in the developed world, as is the patient's understanding of the disease process. This in turn has an impact on the way patients are managed, the rigorousness of patient adhesion to the treatment schedule and the outcome. Here we take a look at the precursor B-cell acute lymphoblastic leukaemia in an adolescent in a range of different settings from low- to high income countries with widely differing challenges for diagnosis, therpy and follow-up. For these reasons, given the same starting conditions, patients will be treated differently according to the institute and the country they are in. Experts from around the world have been tasked to describe their management plan and rationale for a specific disease presentation. Here they explore the management of precursor B-cell acute lymphoblastic leukaemia (pre-B ALL) in five different institutions worldwide with a focus on those with more or less strained economies. We end with a conclusion from an expert in the field comparing and contrasting these different management styles and considering their merits and limitations.


Assuntos
Leucemia-Linfoma Linfoblástico de Células Precursoras B/diagnóstico , Leucemia-Linfoma Linfoblástico de Células Precursoras B/terapia , Tomada de Decisão Clínica , Gerenciamento Clínico , Suscetibilidade a Doenças , Prova Pericial , Saúde Global , Humanos , Estudos Multicêntricos como Assunto , Leucemia-Linfoma Linfoblástico de Células Precursoras B/epidemiologia , Leucemia-Linfoma Linfoblástico de Células Precursoras B/etiologia
11.
Cancer Control ; 29: 10732748221109951, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35976772

RESUMO

Genetic testing for hereditary cancer predisposition is more widely available, resulting in more patients being identified as carriers of pathogenic variants (PV) of cancer susceptibility genes. PV carriers may be at high risk for multiple cancers of different organ systems. Traditional high-risk cancer screening is often organ specific and conducted separately by specialists. However, with many genes associated with 3 or more types of cancer risks, coordination of such cancer screening can be overwhelming for patients and providers. At Moffitt Cancer Center (MCC), GeneHome clinic functions as a "home" to conduct and coordinate prevention, screening, counseling, and education for individuals carrying germline genetic PVs across the entire spectrum of cancer genes. The screening includes, but is not limited to, history review, physical examination, image studies, blood tests, urine tests, and endoscopy. GeneHome is a novel model for genetic high-risk cancer surveillance and has grown in 4 years since establishment. We sought to study various characteristics of the patient population it serves, common themes in referral patterns and evolution of the clinic since its inception. A total of 821 patients were seen over 42 months, encompassing PV carriers of 46 genes. Patients were 84.9% female and 13.3% male. Most PVs were of BRCA1 and BRCA2. Most patients had private insurance, and most were from Florida. Annual increase in patient visits was over 74.7% over the last year. Overall, GeneHome has been well accepted by providers and patients and is a valuable service for patients with a genetic predisposition to cancer.


Assuntos
Neoplasias da Mama , Neoplasias , Detecção Precoce de Câncer , Feminino , Genes BRCA2 , Predisposição Genética para Doença , Testes Genéticos/métodos , Humanos , Masculino , Neoplasias/genética
12.
Eur J Nutr ; 61(3): 1133-1142, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34748060

RESUMO

PURPOSE: The significance of niacin in embryonic development has clinical implications in the counseling of pregnant women and may be used to inform nutrition recommendations. This study, therefore, aims to review the associations between maternal periconceptional niacin intake and congenital anomalies. METHODS: A systematic search of Ovid MEDLINE, ClinicalTrials.gov, AMED, CENTRAL, Emcare, EMBASE, Maternity & Infant Care and Google Scholar was conducted between inception and 30 September 2020. Medical subject heading terms included "nicotinic acids" and related metabolites, "congenital anomalies" and specific types of congenital anomalies. Included studies reported the association between maternal niacin intake and congenital anomalies in their offspring and reported the measure of association. Studies involved solely the women with co-morbidities, animal, in vitro and qualitative studies were excluded. The risk of bias of included studies was assessed using the Newcastle-Ottawa Scale (NOS). A random effects-restricted maximum likelihood model was used to obtain summary estimates, and multivariable meta-regression model was used to adjust study-level covariates. RESULTS: Of 21,908 retrieved citations, 14 case-control studies including 35,743 women met the inclusion criteria. Ten studies were conducted in the U.S, three in Netherlands and one in South Africa. The meta-analysis showed that expectant mothers with an insufficient niacin intake were significantly more likely to have babies with congenital abnormalities (odds ratio 1.13, 95% confidence interval 1.02-1.24) compared to mothers with adequate niacin intake. A similar association between niacin deficiency and congenital anomalies was observed (OR 1.15, 95% CI 1.03-1.26) when sensitivity analysis was conducted by quality of the included studies. Meta-regression showed neither statistically significant impact of study size (p = 0.859) nor time of niacin assessment (p = 0.127). The overall quality of evidence used is high-thirteen studies achieved a rating of six or seven stars out of a possible nine based on the NOS. CONCLUSION: Inadequate maternal niacin intake is associated with an increased risk of congenital anomalies in the offspring. These findings may have implications in dietary counseling and use of niacin supplementation during pregnancy.


Assuntos
Niacina , Estudos de Casos e Controles , Dieta , Feminino , Humanos , Estado Nutricional , Razão de Chances , Gravidez
13.
Ann Surg Oncol ; 28(13): 8777-8788, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34258723

RESUMO

INTRODUCTION: We aim to analyze survival outcomes for sentinel lymph node biopsy (SLNB) versus axillary lymph node dissection (ALND) in human epidermal growth factor receptor (HER2)+ infiltrative ductal carcinoma (IDC) that demonstrate complete clinical response (cCR) to neoadjuvant systemic therapy (NAST) after initial presentation with clinical N1 (cN1) disease. METHODS: NCDB 2004-2017 was utilized for the analysis. Female patients with unilateral HER2+ IDC, stage cT1-T4 cN1, who demonstrated cCR to NAST with reported definitive axillary surgical management were included. Patients were propensity score matched, and overall survival (OS) was compared. Cox regression analysis was used to identify survival predictors. RESULTS: 6453 patients were selected, of whom 2461 (38.1%) had SLNB and 3992 (69.1%) had ALND as definitive axillary surgical management. The trend of SLNB utilization increased from 20% in 2012 to 50% in 2017. A total of 2454 patients were matched from each group with adequate adjustment for all variables. There was no difference in OS between SLNB versus ALND (84.03 ± 0.36 versus 84.62 ± 0.42 months; p = 0.522). Cox regression identified age, cT stage, primary tumor response to NAST, ypN+, and endocrine therapy as significant OS predictors. In subgroup analysis of patients with ypN+ who had SLNB as a definitive procedure, primary tumor response to NAST and continuation of adjuvant chemotherapy were associated with improved OS. CONCLUSION: In cN1 HER2+ IDC patients who demonstrate cCR to NAST, SLNB is a reasonable definitive procedure for axillary management with comparable OS outcomes to ALND. However, higher-level data are required to determine the appropriate management in the case of ypN+.


Assuntos
Neoplasias da Mama , Axila , Neoplasias da Mama/cirurgia , Feminino , Humanos , Excisão de Linfonodo , Terapia Neoadjuvante , Pontuação de Propensão , Biópsia de Linfonodo Sentinela
14.
Proc Natl Acad Sci U S A ; 115(7): 1582-1587, 2018 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-29382747

RESUMO

Janus kinase 2 (JAK2) signal transduction is a critical mediator of the immune response. JAK2 is implicated in the onset of graft-versus-host disease (GVHD), which is a significant cause of transplant-related mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Transfer of JAK2-/- donor T cells to allogeneic recipients leads to attenuated GVHD yet maintains graft-versus-leukemia. Th1 differentiation among JAK2-/- T cells is significantly decreased compared with wild-type controls. Conversely, iTreg and Th2 polarization is significantly increased among JAK2-/- T cells. Pacritinib is a multikinase inhibitor with potent activity against JAK2. Pacritinib significantly reduces GVHD and xenogeneic skin graft rejection in distinct rodent models and maintains donor antitumor immunity. Moreover, pacritinib spares iTregs and polarizes Th2 responses as observed among JAK2-/- T cells. Collectively, these data clearly identify JAK2 as a therapeutic target to control donor alloreactivity and promote iTreg responses after allo-HCT or solid organ transplantation. As such, a phase I/II acute GVHD prevention trial combining pacritinib with standard immune suppression after allo-HCT is actively being investigated (https://clinicaltrials.gov/ct2/show/NCT02891603).


Assuntos
Diferenciação Celular , Doença Enxerto-Hospedeiro/imunologia , Efeito Enxerto vs Leucemia/imunologia , Janus Quinase 2/fisiologia , Mielofibrose Primária/imunologia , Linfócitos T/imunologia , Células Th2/imunologia , Animais , Feminino , Doença Enxerto-Hospedeiro/genética , Doença Enxerto-Hospedeiro/prevenção & controle , Efeito Enxerto vs Leucemia/genética , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Mielofibrose Primária/genética , Mielofibrose Primária/prevenção & controle , Transplante de Pele , Ensaios Antitumorais Modelo de Xenoenxerto
15.
J Surg Oncol ; 121(3): 480-485, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31853990

RESUMO

BACKGROUND: Somatostatin analog functional imaging with gallium-68 (Ga-68) dotatate positron emission tomography/computed tomography (PET/CT) has demonstrated superiority in lesion detection in patients with neuroendocrine tumors (NETs). The clinical impact of this imaging modality on US surgical and medical oncology practices has not been established. METHODS: Consecutive patients with NET at our institution who received an initial Ga-68 dotatate PET/CT between July 2017 and September 2018 were included. Ga-68 dotatate PET/CT was compared with prior imaging. RESULTS: Among 101 eligible patients, 51 of 50 were female/male, site of origin was gastroenteropancreatic (75%), unknown primary (13%), lung (8%), thymus (2%), and other (2%). All NETs were histologically well/moderately differentiated. Ga-68 dotatate imaging findings altered management in 36 (35.6%) patients: documentation of progression led to the initiation of systemic therapy in 14 patients, obviated the need for biopsy in four patients, and altered surgical plans in 7 of 14 (50%) patients referred for surgery. In 11 patients, decisions regarding peptide receptor radionucleotide therapy and somatostatin analogs were altered. CONCLUSIONS: In this series, Ga-68 dotatate PET/CT altered diagnosis and management in one-third of patients and changed operative plans in half of the patients who were referred for surgical evaluation. These results support the routine use of this imaging in the care of patients with early-stage and advanced NETs.


Assuntos
Neoplasias Intestinais/diagnóstico por imagem , Neoplasias Intestinais/terapia , Tumores Neuroendócrinos/diagnóstico por imagem , Tumores Neuroendócrinos/terapia , Compostos Organometálicos , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/terapia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/terapia , Feminino , Radioisótopos de Gálio , Humanos , Neoplasias Intestinais/patologia , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Neoplasias Primárias Desconhecidas/diagnóstico por imagem , Neoplasias Primárias Desconhecidas/patologia , Neoplasias Primárias Desconhecidas/terapia , Tumores Neuroendócrinos/patologia , Neoplasias Pancreáticas/patologia , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Neoplasias Gástricas/patologia , Neoplasias do Timo/diagnóstico por imagem , Neoplasias do Timo/patologia , Neoplasias do Timo/terapia
16.
Adv Exp Med Biol ; 1252: 87-93, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32816266

RESUMO

Breast cancer in pregnancy is a rare entity generally presenting as a persistent breast mass, but is often a delayed finding due to the expected physiologic changes in the breast related to pregnancy and lactation. The preferred diagnostic workup of a persistent breast mass involves a combination of mammographic and ultrasonographic evaluation in addition to tissue diagnosis via core biopsy ; breast MRI is not recommended. Surgical excision should be reserved for definitive treatment in order to minimize fetal exposure to anesthesia. Evaluation for distant metastatic spread can be performed using radiographs and ultrasound to limit fetal radiation exposure . Similar to the non-pregnant patient, prognosis is primarily driven by tumor biology, however, there is limited and conflicting data regarding the impact of pregnancy on breast cancer outcomes with a distinct difference in survival among patients with breast cancer during pregnancy compared to those diagnosed postpartum.


Assuntos
Neoplasias da Mama/diagnóstico , Complicações Neoplásicas na Gravidez/diagnóstico , Feminino , Humanos , Lactação , Gravidez
17.
Health Commun ; 35(7): 832-841, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-30999777

RESUMO

Narrative messages may be superior to didactic messages when providing educational information due to their natural format for information sharing, ability to engage audiences, and engender positive thoughts about the message. Although narrative messages are gaining popularity in health promotion, little guidance exists regarding the development phase. Our team created a psychosocial narrative video intervention grounded in the Health Belief Model to increase breast cancer survivors' attendance at genetic counseling after treatment. Here we report the use of Learner Verification (LV) during an iterative video development process. Using LV, we conducted individual semi-structured interviews with patients and providers, after they viewed the video. Demographic information was analyzed using descriptive statistics, and verbatim interview transcripts were used to conduct a two-phase qualitative content analysis. Patient and provider participants (n = 30) believed the video was attractive, relatable, and informative, and they identified areas for improvement including narrative coherence, changes to text and graphical information, and including more specific information. LV framework elicited audience feedback on the video intervention relevant to theoretical principles of narrative interventions, and highlighted audience preferences. In this study, LV interviews tapped into theoretical constructs of narratives and facilitated the iterative intervention design process.


Assuntos
Neoplasias da Mama , Envio de Mensagens de Texto , Feminino , Promoção da Saúde , Humanos , Narração , Sobreviventes
18.
Breast Cancer Res Treat ; 174(1): 39-45, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30474778

RESUMO

PURPOSE: Awareness of inherited breast cancer has increased bilateral prophylactic mastectomy (BPM) among unaffected genetic mutation carriers, yet many still choose surveillance. We aimed to identify differences among women electing BPM vs high-risk surveillance. METHODS: Participants from an IRB-approved database recruited from 11/2000 to 01/2017 with a deleterious/pathogenic, variant suspected deleterious, or likely pathogenic mutation in ≥ 1 of 11 genes with increased risk for breast cancer (per 2017 NCCN guidelines) were identified. Participants with breast cancer and males were excluded. Sociodemographic and clinical data were collected. The BPM and high-risk surveillance groups were compared using Wilcoxon, Fisher's Exact, and Pearson's Chi-Square analyses. RESULTS: A total of 304 unaffected genetic mutation carriers were identified; 22 men were excluded. 113/282 (40%) underwent BPM. There was no significant difference in age, race, marital status, high school graduates, family history of breast cancer, breast biopsies, chemoprevention use, or understanding implications of genetic mutation carriage. BPM participants were more likely to have a prior pregnancy (p = 0.0005), college education (p = 0.04), income > $50,000/year (p = 0.01), first-degree relative with breast cancer (p = 0.04), higher total number of relatives with breast cancer (p = 0.01), and rate of risk-reducing salpingo-oophorectomy (p = < 0.0001). The high-risk surveillance group was more likely to have a history of ovarian cancer (p = 0.009) and cancer worry (p = < 0.0001). CONCLUSIONS: BPM is a common but not universal choice among unaffected genetic carriers of inherited breast cancer syndromes. Parity, education, income, ovarian cancer history, first-degree relatives with breast cancer, and cancer worry play significant roles in these decisions.


Assuntos
Neoplasias da Mama/terapia , Mastectomia Profilática/tendências , Conduta Expectante/tendências , Adolescente , Adulto , Feminino , Heterozigoto , Humanos , Pessoa de Meia-Idade , Sistema de Registros , Adulto Jovem
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