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1.
Ann Surg Oncol ; 29(10): 6428-6437, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35913669

RESUMO

BACKGROUND: Lymphedema is a potential lifelong sequela of breast cancer treatment. We sought to: (1) evaluate the worry and knowledge of patients about lymphedema, (2) quantify patients reporting lymphedema education and screening, and (3) determine willingness to participate in lymphedema screening and prevention programs. PATIENTS AND METHODS: A survey evaluating lymphedema-related knowledge and worry was sent to patients treated for stage 0-III breast cancer. Exclusion criteria included > 10 years since diagnosis, missing clinical staging, and those without axillary surgery. Responses were linked with clinicopathologic information. RESULTS: Of 141 patients meeting inclusion criteria, 89% of those without lymphedema were not at all or slightly worried about lymphedema. Higher levels of worry were associated with clinical stage II-III disease [odds ratio (OR) 2.63, p = 0.03], a history of axillary lymph node dissection (ALND) (OR 4.58, p < 0.01), and employment (OR 2.21, p = 0.05). A total of 102 (72%) patients recalled receiving lymphedema education. Lymphedema knowledge was limited, with < 25% of respondents answering > 50% of the risk factor questions correctly. Worry and knowledge were not significantly associated. Of patients without lymphedema, 36% were interested in learning more about lymphedema and 64% were willing to participate in or learn more about a screening program. Most (66%) felt that lymphedema information should be provided before and after cancer treatment. DISCUSSION: A majority of our breast cancer survivors had limited knowledge about lymphedema risk factors. While most patients were not worried about developing lymphedema, higher worry was seen in patients with a higher clinical stage at diagnosis, ALND, and employment. Our findings suggest potential targets and timing for patient-centered educational interventions.


Assuntos
Neoplasias da Mama , Linfedema , Axila/patologia , Neoplasias da Mama/complicações , Neoplasias da Mama/patologia , Feminino , Humanos , Excisão de Linfonodo/efeitos adversos , Linfedema/cirurgia , Biópsia de Linfonodo Sentinela/efeitos adversos
2.
Breast Cancer Res Treat ; 188(1): 191-202, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33582888

RESUMO

PURPOSE: Iowa is among several rural Midwestern states with the highest proportions of contralateral prophylactic mastectomy (CPM) in women < 45 years of age. We evaluated the role of rurality and travel distance in these surgical patterns. METHODS: Women with unilateral breast cancer (2007-2017) were identified using Iowa Cancer Registry records. Patients and treating hospitals were classified as metro, nonmetro, and rural based on Rural-Urban Continuum Codes. Differences in patient, tumor, and treatment characteristics and median travel distance (MTD) were compared. Characteristics associated with CPM were evaluated with multivariate logistic regression. RESULTS: 22,158 women were identified: 57% metro, 26% nonmetro and 18% rural. Young rural women had the highest proportion of CPM (52%, 39% and 40% for rural, metro, nonmetro women < 40 years). Half of all rural women had surgery at metro hospitals; these women had the longest MTD (62 miles). Among all women treated at metro hospitals, rural women had the highest proportion of CPM (17% rural vs 14% metro/nonmetro, p = 0.007). On multivariate analysis, traveling ≥ 50 miles (ORs 1.43-2.34) and rural residence (OR = 1.29) were independently predictive of CPM. Other risk factors were young age (< 40 years: OR = 7.28, 95% CI 5.97-8.88) and surgery at a metro hospital that offers reconstruction (OR = 2.30, 95% CI 1.65-3.21) and is not NCI-designated (OR = 2.34, 95% CI 1.92-2.86). CONCLUSION: There is an unexpectedly high proportion of CPM in young rural women in Iowa, and travel distance and availability of reconstructive services likely influence decision-making. Improving access to multidisciplinary care in rural states may help optimize decision-making.


Assuntos
Neoplasias da Mama , Mastectomia Profilática , Adulto , Neoplasias da Mama/cirurgia , Feminino , Humanos , Mastectomia , Sistema de Registros , População Rural
3.
Ann Surg Oncol ; 28(13): 8752-8765, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34251554

RESUMO

BACKGROUND: Differences in patient characteristics and decision-making preferences have been described between those who elect breast-conserving surgery (BCS), unilateral mastectomy (UM), or contralateral prophylactic mastectomy (CPM) for breast cancer. However, it is not known whether preferred and actual decision-making roles differ across these surgery types, or whether surgery choice reflects a woman's goals or achieves desired outcomes. METHODS: Women diagnosed with stage 0-III unilateral breast cancer across eight large medical centers responded to a mailed questionnaire regarding treatment decision-making goals, roles, and outcomes. These data were linked to electronic medical records. Differences were assessed using descriptive analyses and logistic regression. RESULTS: There were 750 study participants: 60.1% BCS, 17.9% UM, and 22.0% CPM. On multivariate analysis, reducing worry about recurrence was a more important goal for surgery in the CPM group than the others. Although women's preferred role in the treatment decision did not differ by surgery, the CPM group was more likely to report taking a more-active-than-preferred role than the BCS group. On multivariate analysis that included receipt of additional surgery, posttreatment worry about both ipsilateral and contralateral recurrence was higher in the BCS group than the CPM group (both p < 0.001). The UM group was more worried than the CPM group about contralateral recurrence only (p < 0.001). CONCLUSIONS: Women with CPM were more likely to report being able to reduce worry about recurrence as a very important goal for surgery. They were also the least worried about ipsilateral breast recurrence and contralateral breast cancer almost two years postdiagnosis.


Assuntos
Neoplasias da Mama , Mastectomia Profilática , Neoplasias da Mama/cirurgia , Tomada de Decisões , Feminino , Objetivos , Humanos , Mastectomia , Recidiva Local de Neoplasia/prevenção & controle , Inquéritos e Questionários
4.
Breast Cancer Res Treat ; 175(3): 675-689, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30852760

RESUMO

PURPOSE: Chronic upper extremity disability (UED) is common after breast cancer treatment but under-identified and under-treated. Although UED has been linked to quality of life (QoL), the role of UED as mediator between contemporary treatment practices and QoL has not been quantified. This investigation describes UED in a contemporary sample of breast cancer patients and examines its relationship with personal and treatment factors and QoL. METHODS: Eight hundred and thirty-three women diagnosed at eight medical institutions during 2013-2014 with microscopically confirmed ductal carcinoma in situ or invasive stage I-III breast cancer were surveyed an average of 22 months after diagnosis. UED was measured with a modified QuickDASH and QoL with the FACT-B. The questionnaire also collected treatments, sociodemographic information, comorbidity, body mass index, and a 3-item health literacy screener. RESULTS: Women who received post-mastectomy radiation and chemotherapy experienced significantly worse UED and QoL. Women who had lower income, lower health literacy and prior diabetes, arthritis or shoulder diagnoses had worse UED. Patients with worse UED reported significantly worse QoL. Income and health literacy were independently associated with QoL after adjustment for UED but treatment and prior conditions were not, indicating mediation by UED. UED mediated 52-79% of the effect of mastectomy-based treatments on QoL as compared with unilateral mastectomy without radiation. UED and QoL did not differ by type of axillary surgery or post-mastectomy reconstruction. CONCLUSIONS: A large portion of treatment effect on QoL is mediated by UED. Rehabilitation practices that prevent and alleviate UED are likely to improve QoL for breast cancer survivors.


Assuntos
Traumatismos do Braço/psicologia , Neoplasias da Mama/terapia , Terapia Combinada/métodos , Qualidade de Vida/psicologia , Lesões do Ombro/psicologia , Adulto , Idoso , Traumatismos do Braço/etiologia , Neoplasias da Mama/psicologia , Tratamento Farmacológico , Feminino , Humanos , Mastectomia , Pessoa de Meia-Idade , Invasividade Neoplásica , Radioterapia , Lesões do Ombro/etiologia , Inquéritos e Questionários , Extremidade Superior
5.
Psychooncology ; 28(11): 2210-2217, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31430830

RESUMO

OBJECTIVE: Oncologic breast surgeries carry a risk for persistent postsurgical pain. This study was a randomized pilot and feasibility study of a single-session Acceptance and Commitment Therapy (ACT) intervention compared with treatment as usual among women undergoing surgery for breast cancer or ductal carcinoma in situ. METHODS: Participants were recruited via letter of invitation and follow-up phone call from a single site in the United States from 2015 to 2017. Participants were at risk for persistent postsurgical pain, based on young age (<50), a preexisting chronic pain condition, or elevated anxiety, depression, or pain catastrophizing. RESULTS: The 54 participants were female with a mean age of 52.91 years (SD=11.80). At 3-month postsurgery, 11% of the sample reported moderate-severe pain (>3 on a 0-10 numeric rating scale) in the operative breast or with arm movement. Written qualitative responses indicated that the majority of participants who received the intervention understood the concepts presented and reported continued practice of exercises learned in the session. The between group effect sizes for moderate-severe pain and elevated anxiety at 3-month post-surgery were small (Phi=0.08 and 0.16, respectively). The between group effect sizes for depression, pain acceptance, and pain catastrophizing at 3-month postsurgery were minimal. CONCLUSIONS: This study found small positive effects on postsurgical pain and anxiety for a single-session ACT intervention among women with breast cancer. This study supports the use of ACT with this population.


Assuntos
Terapia de Aceitação e Compromisso/métodos , Neoplasias da Mama/psicologia , Catastrofização/psicologia , Dor Pós-Operatória/psicologia , Adaptação Psicológica , Adulto , Ansiedade/psicologia , Neoplasias da Mama/cirurgia , Catastrofização/prevenção & controle , Depressão/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Dor Pós-Operatória/prevenção & controle , Projetos Piloto , Procedimentos de Cirurgia Plástica
6.
Ann Surg Oncol ; 25(7): 1928-1935, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29671138

RESUMO

BACKGROUND: High-volume single-institution studies support the oncologic safety of nipple sparing mastectomy (NSM). Concerns remain regarding the increased potential for complications, recurrence, and delays to subsequent adjuvant therapy. A national database was used to examine treatment and outcomes for NSM patients. METHODS: Women undergoing unilateral NSM or skin sparing mastectomy (SSM) for stage 0-4 breast cancer from 2004 to 2013 were identified from the National Cancer Database. Demographic and oncologic characteristics, short-term outcomes and time to local and systemic treatment were compared. RESULTS: NSM was performed on 8173 patients: 8.7% were node positive, and for stage 1-4 disease, 10.6% were triple negative (TN) and 15.3% were HER2-positive. NSM patients were less likely than SSM patients to receive chemotherapy [CT] (37.4 vs. 43.4%) or radiation [PMRT] (15.6 vs. 16.9%), and were also more likely to present with clinically early-stage disease. NSM patients with high-risk features were more likely to receive CT in the neoadjuvant [NCT] than adjuvant setting [AC] (OR 3.76, 1.81, and 1.99 for clinical N2/3, TN, and HER2-positive disease, all p < 0.001). On multivariate analysis, NSM patients had a higher rate of pathologic complete response [pCR] (OR 1.41, p < 0.001). Readmission rate, positive margin rate and time to CT, PMRT or hormonal therapy were not increased for NSM compared to SSM patients. CONCLUSIONS: Over one third of NSM patients received chemotherapy and/or radiation. NSM patients with high-risk features were more likely to receive NAC and obtain a pCR. NSM patients did not experience worse outcomes or delayed adjuvant therapy compared to SSM.


Assuntos
Neoplasias da Mama/cirurgia , Quimiorradioterapia Adjuvante , Terapia Neoadjuvante , Recidiva Local de Neoplasia/cirurgia , Mamilos/cirurgia , Tratamentos com Preservação do Órgão , Tempo para o Tratamento , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/terapia , Feminino , Seguimentos , Humanos , Mamoplastia , Mastectomia , Pessoa de Meia-Idade , Invasividade Neoplásica , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/terapia , Prognóstico , Taxa de Sobrevida
7.
Ann Surg Oncol ; 25(10): 3004-3010, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30030731

RESUMO

BACKGROUND: Access to health care poses particular challenges for patients living in rural communities. Intraoperative radiotherapy (IORT) offers a treatment alternative to traditional whole-breast radiation therapy (WBRT) for select patients. This study aimed to analyze the use of IORT for patients undergoing breast-conserving surgery at an academic institution located in a rural state. METHODS: A retrospective review analyzed all patients at a single institution with a diagnosis of ductal carcinoma in situ (DCIS) or invasive breast cancer from April 2012 to January 2017 who were undergoing breast-conserving surgery with either IORT or WBRT. Student's t test or Fisher's exact test was used to make statistical comparisons. RESULTS: Patients undergoing IORT (n = 117) were significantly older than patients treated with WBRT (n = 191) (65.6 vs 58.6 years; p < 0.001) and had smaller tumors on both preoperative imaging (1.04 vs 1.66 cm; p < 0.05) and final pathology (0.99 vs 1.48 cm; p < 0.05). Patients receiving IORT lived farther from the treating facility than patients treated with WBRT (67.2 vs 30.8 miles; p < 0.05). To account for biases created in the IORT selection criteria, subgroup analysis was performed for women receiving WBRT who fulfilled IORT selection criteria, and distance traveled remained significant (67.2 vs 31.4 miles; p < 0.05). Neither recurrence nor survival differed between the IORT and WBRT groups. Medicare reimbursement for IORT was approximately 50% more than for WBRT. CONCLUSIONS: For women from rural communities, IORT appears to be an attractive option because these women tend to be older and to live farther from the treatment facility.


Assuntos
Neoplasias da Mama/terapia , Carcinoma Ductal de Mama/terapia , Carcinoma Lobular/terapia , Cuidados Intraoperatórios , Mastectomia Segmentar/métodos , Recidiva Local de Neoplasia/diagnóstico , Radioterapia , Idoso , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/patologia , Carcinoma Lobular/patologia , Terapia Combinada , Feminino , Seguimentos , Humanos , Iowa/epidemiologia , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/epidemiologia , Prognóstico , Estudos Retrospectivos , População Rural
9.
J Cell Sci ; 126(Pt 6): 1440-53, 2013 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-23418360

RESUMO

MicroRNAs are known to play regulatory roles in gene expression associated with cancer development. We analyzed levels of the microRNA miR-24 in patients with breast carcinoma and found that miR-24 was higher in breast carcinoma samples than in benign breast tissues. We generated constructs expressing miR-24 and studied its functions using both in vitro and in vivo techniques. We found that the ectopic expression of miR-24 promoted breast cancer cell invasion and migration. In vivo experiments in mice indicated that the expression of miR-24 enhanced tumor growth, invasion into local tissues, metastasis to lung tissues and decreased overall mouse survival. In the miR-24-expressing cells and tumors, EGFR was highly phosphorylated, whereas expression of the phosphatases tyrosine-protein phosphatase non-receptor type 9 (PTPN9) and receptor-type tyrosine-protein phosphatase F (PTPRF) were repressed. We confirmed that miR-24 could directly target both PTPN9 and PTPRF. Consistent with this, we found that the levels of phosphorylated epidermal growth factor receptor (pEGFR) were higher whereas the levels of PTPN9 and PTPRF were lower in the patients with metastatic breast carcinoma. Ectopic expression of PTPN9 and PTPRF decreased pEGFR levels, cell invasion, migration and tumor metastasis. Furthermore, we found that MMP2, MMP11, pErk, and ADAM15 were upregulated, whereas TIMP2 was downregulated; all of which supported the roles of miR-24 in tumor invasion and metastasis. Our results suggest that miR-24 plays a key role in breast cancer invasion and metastasis. miR-24 could potentially be a target for cancer intervention.


Assuntos
Neoplasias da Mama/patologia , MicroRNAs/metabolismo , Proteínas Tirosina Fosfatases não Receptoras/metabolismo , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/metabolismo , Animais , Neoplasias da Mama/genética , Processos de Crescimento Celular/genética , Fator de Crescimento Epidérmico/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HEK293 , Humanos , Camundongos , Camundongos Endogâmicos BALB C , MicroRNAs/genética , Invasividade Neoplásica/genética , Metástase Neoplásica , Transplante de Neoplasias , Proteínas Tirosina Fosfatases não Receptoras/genética , Proteínas Tirosina Fosfatases Classe 2 Semelhantes a Receptores/genética , Transdução de Sinais/genética , Transgenes/genética
10.
Ann Surg Oncol ; 22(13): 4287-94, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25971960

RESUMO

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


Assuntos
Neoplasias da Mama/metabolismo , Resistencia a Medicamentos Antineoplásicos , Receptores ErbB/metabolismo , Indóis/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Pirróis/farmacologia , Apoptose/efeitos dos fármacos , Western Blotting , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Feminino , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fosforilação/efeitos dos fármacos , Prognóstico , RNA Mensageiro/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Sunitinibe , Células Tumorais Cultivadas
11.
Ann Surg Oncol ; 21(13): 4133-8, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24934585

RESUMO

BACKGROUND: Women with breast cancer increasingly undergo contralateral prophylactic mastectomy (CPM). We evaluated the relationship between preoperative magnetic resonance imaging (MRI) findings and CPM. Other clinicopathologic variables associated with CPM choice and the pathology found in the contralateral breast are also reported. METHODS: Newly diagnosed breast cancer patients were prospectively enrolled in the University of Iowa Breast Molecular Epidemiology Resource. Patients with stages 0-III breast cancer who underwent mastectomy for the index cancer were eligible for this analysis. Univariate logistic regression and a multivariate model were used to identify factors predictive of CPM. RESULTS: Among 134 patients (mean age 54.9 years), 53 (39.6 %) chose CPM. On univariate analysis, patients undergoing CPM were more likely to have a preoperative breast MRI (64.2 vs. 39.5 %, p = 0.006) and to have follow-up testing recommended for the contralateral breast (28.3 vs. 4.9 %, p = 0.001). Univariate analysis also associated CPM with younger age (p < 0.0001), BRCA testing (p < 0.0001), BRCA mutation (p = 0.034) and reconstruction performed (p = 0.001). Median age of youngest child at diagnosis varied significantly between the CPM (15.9 years) and non-CPM (24.3 years) groups (p = 0.0018). On multivariate analysis, MRI follow-up recommendation, young age, reconstruction and human epidermal growth factor receptor 2 (HER2) positivity of the index cancer were significantly associated with CPM. Of the CPM specimens, one (1.8 %) had ductal carcinoma-in situ, which had not been identified on MRI. CONCLUSIONS: Abnormal findings in the contralateral breast on preoperative MRI, as well as young age, reconstruction and HER2-positive status correlated with CPM choice in this cohort. Occult malignancy was rare.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/prevenção & controle , Carcinoma Intraductal não Infiltrante/diagnóstico , Imageamento por Ressonância Magnética , Mastectomia , Cuidados Pré-Operatórios , Prevenção Primária/métodos , Receptor ErbB-2/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína BRCA1/sangue , Neoplasias da Mama/genética , Neoplasias da Mama/cirurgia , Carcinoma Intraductal não Infiltrante/genética , Carcinoma Intraductal não Infiltrante/cirurgia , Feminino , Seguimentos , Humanos , Mamografia , Pessoa de Meia-Idade , Mutação , Guias de Prática Clínica como Assunto , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Sensibilidade e Especificidade
12.
Carcinogenesis ; 34(8): 1747-55, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23598467

RESUMO

Breast cancer is a large global health burden and the most frequently diagnosed malignancy in women worldwide. Here, we utilize RGS6(-/-) mice to interrogate the role of regulator of G protein signaling 6 (RGS6), localized to the ductal epithelium in mouse and human breast, as a novel tumor suppressor in vivo. RGS6(-/-) mice exhibit accelerated 7,12-dimethylbenza[α]anthracene (DMBA)-induced tumor initiation and progression, as well as decreased overall survival. Analysis of carcinogenic aberrations in the mammary glands of DMBA-treated mice revealed a failure of the DNA damage response concurrent with augmented oncogenesis in RGS6(-/-) animals. Furthermore, RGS6 suppressed cell growth induced by either human epidermal growth factor receptor 2 or estrogen receptor activation in both MCF-7 breast cancer cells and mammary epithelial cells (MECs). MECs isolated from RGS6(-/-) mice also showed a deficit in DMBA-induced ATM/p53 activation, reactive oxygen species generation and apoptosis confirming that RGS6 is required for effective activation of the DNA damage response in these cells, a critical countermeasure against carcinogen-mediated genotoxic stress. The ability of RGS6 to simultaneously enhance DNA-damage-induced apoptotic signaling and suppress oncogenic cell growth likely underlie the accelerated tumorigenesis and cellular transformation observed in DMBA-treated RGS6(-/-) mice and isolated MECs, respectively. Unsurprisingly, spontaneous tumor formation was also seen in old female RGS6(-/-) but not in wild-type mice. Our finding that RGS6 is downregulated in all human breast cancer subtypes independent of their molecular classification indicates that obtaining a means to restore the growth suppressive and pro-apoptotic actions of RGS6 in breast might be a viable means to treat a large spectrum of breast tumors.


Assuntos
Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Carcinogênese/genética , Carcinogênese/patologia , Proteínas RGS/genética , 9,10-Dimetil-1,2-benzantraceno/farmacologia , Animais , Apoptose/genética , Proteínas Mutadas de Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia/metabolismo , Neoplasias da Mama/metabolismo , Carcinogênese/metabolismo , Linhagem Celular Tumoral , Dano ao DNA/genética , Progressão da Doença , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Humanos , Células MCF-7 , Neoplasias Mamárias Experimentais/genética , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Camundongos Endogâmicos C57BL , Proteínas RGS/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Receptores de Estrogênio/genética , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
13.
Ann Surg Oncol ; 20(10): 3317-22, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23975295

RESUMO

BACKGROUND: Detection of a contralateral axillary sentinel lymph node (SLN) during lymphoscintigraphy for breast cancer is rare, and its significance and management are unclear. The purpose of this study was to review our experience and analyze our results together with similar patients in the literature to identify common characteristics and propose a management strategy. METHODS: A PubMed search was performed for articles describing patients in whom contralateral axillary drainage was identified on lymphoscintigraphy. Additionally, a chart review was performed of all patients who had lymphoscintigraphy for breast cancer at our institution. RESULTS: At our institution, two of 988 (0.3 %) consecutive patients were identified with contralateral axillary drainage on lymphoscintigraphy. Twenty-seven publications describing 105 patients with contralateral axillary drainage were found. This comprised our study group of 107 patients. Lymphoscintigraphy patterns varied depending on the history and type of prior surgery. A history of chest/axillary surgery was significantly associated with absence of an ipsilateral SLN (p < 0.05). This was observed in 84.2 % of patients with prior axillary lymph node dissection versus 33.3 % with prior SLN. Contralateral SLN biopsy was attempted in 85 patients (79.4 %); 22 (20.6 %) were positive for tumor. In 17 patients (15.9 %), the contralateral node was the only positive SLN. CONCLUSIONS: These findings suggest that contralateral uptake on lymphoscintigraphy, though rare (0.2 %), is clinically significant and such nodes should undergo excision. Because contralateral uptake is significantly associated with prior chest/axillary surgery, routine lymphoscintigraphy should be considered in this group, as it has potential to change disease stage and management.


Assuntos
Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/cirurgia , Linfonodos/diagnóstico por imagem , Cintilografia , Compostos Radiofarmacêuticos , Adulto , Neoplasias da Mama/patologia , Carcinoma Ductal de Mama/diagnóstico por imagem , Carcinoma Ductal de Mama/patologia , Carcinoma Ductal de Mama/cirurgia , Carcinoma Lobular/diagnóstico por imagem , Carcinoma Lobular/patologia , Carcinoma Lobular/cirurgia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Biópsia de Linfonodo Sentinela
14.
Ann Surg Oncol ; 20(12): 3855-61, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23884753

RESUMO

BACKGROUND: Screening tests for pheochromocytoma involve measuring levels of catecholamines in the urine or plasma, which have significant false-positive rates. We reviewed patients with adrenal masses and elevated levels of catecholamines to determine the value of different preoperative tests in diagnosing pheochromocytomas. METHODS: A retrospective chart review identified patients who underwent adrenalectomy between 1997 and 2011 with elevation of urine or serum catecholamines. A database of clinicopathologic factors was created including preoperative urine and plasma metanephrines, normetanephrines, vanillylmandelic acid, and fractionated catecholamines, and tumor dimensions on imaging and pathology. RESULTS: A total of 70 patients underwent adrenalectomy because of presence of an adrenal mass and elevation of catecholamines or normetanephrines or metanephrines. Of these, 46 had pathologically confirmed pheochromocytomas. To improve our ability to discriminate between pheochromocytoma and other pathology, we examined different combinations of clinicopathologic factors and catecholamine levels and found the best test was a scoring system. Points are awarded for a hierarchy of elevated normetanephrine, norepinephrine, metanephrines, with additional points received for age <50 and size on imaging >3.3 cm. A score of 2 is suggestive of pheochromocytoma, with a positive predictive value of 86-87%, while a score of 4 is diagnostic with positive predictive value of 100%. CONCLUSION: We found that urine/serum normetanephrine levels were the most valuable screening tool; however, a score examining the size of adrenal mass on preoperative CT, age, and either plasma or urine norepinephrine, metanephrine, and normetanephrine values leads to a higher positive predictive value, making this scoring system superior to individual lab tests.


Assuntos
Neoplasias das Glândulas Suprarrenais/diagnóstico , Adrenalectomia , Catecolaminas/sangue , Catecolaminas/urina , Feocromocitoma/diagnóstico , Adolescente , Neoplasias das Glândulas Suprarrenais/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Feocromocitoma/cirurgia , Prognóstico , Curva ROC , Estudos Retrospectivos , Adulto Jovem
15.
Cancer Immunol Immunother ; 61(11): 1917-27, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22476407

RESUMO

The goal of the current study is to determine the effects of blocking phosphatidylserine (PS) on the growth of neuroblastoma in mice. PS, an anionic phospholipid restricted to the cytoplasmic surface of plasma membranes in most cells, is externalized to the surface of apoptotic cells. PS has been shown to induce immune tolerance to self-antigens. PS can also be found on the surface of live cells and in particular tumor cells. Annexin-V (AnV) is a protein that specifically binds and blocks PS. To determine the effects of blocking PS with AnV on tumor growth and immunogenicity, mice were inoculated with AGN2a, a poorly immunogenic murine neuroblastoma that expresses high level of PS on the cell surface. Survival and anti-tumor T cell response were determined. AGN2a were engineered to secrete AnV. Secreted protein effectively blocked tumor PS. 40 % of mice inoculated with AnV-expressing AGN2a cells survived free of tumor, whereas none of the mice inoculated with control cells survived (p = 0.0062). The benefits of AnV were lost when mice were depleted of T cells. The findings suggest that AnV could protect mice from tumor challenge through an immune mediated mechanism. Mice were then immunized with irradiated AnV-secreting or control cells, and challenged with wild-type AGN2a cells. AnV-secreting cell vaccine protected 80 % of mice from AGN2a challenge, while control cell vaccine prevented tumor growth in only 30 % of animals (p = 0.012). ELISPOT analysis demonstrated that AnV-secreting cell vaccine induced a greater frequency of interferon-gamma producing splenic T cells. T cells isolated from mice immunized with AnV-secreting but not control vaccine lysed AGN2a. In summary, AnV blocked PS, enhanced T cell mediated tumor immunity, and inhibited tumor growth.


Assuntos
Anexina A5/imunologia , Neuroblastoma/imunologia , Neuroblastoma/patologia , Fosfatidilserinas/antagonistas & inibidores , Tolerância a Antígenos Próprios , Animais , Anexina A5/genética , Sobrevivência Celular/imunologia , Imunoterapia , Interferon gama/biossíntese , Interferon gama/imunologia , Camundongos , Camundongos Endogâmicos , Neuroblastoma/terapia , Fosfatidilserinas/imunologia , Baço/imunologia , Linfócitos T/imunologia
16.
Ann Surg Oncol ; 19(6): 1887-96, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22227921

RESUMO

PURPOSE: To evaluate the risk of a subsequent primary thyroid cancer (SPTC) in patients with common invasive cancers, with attention to latency trends and histology associations. METHODS: Patients with one of 10 common invasive cancers were followed from 1975 to 2008 in 9 registries participating in the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Standardized incidence ratios (SIRs) for SPTC were determined by the multiple primary-SIR program in SEER*Stat. RESULTS: A total of 2502 SPTCs were observed. Greatly elevated SIRs for SPTC were noted for 9 of 10 evaluated cancers in the 12 months after initial diagnosis. The SIRs remained elevated 12-59 months after diagnosis for all cancers except leukemia, uterine, and bladder cancers. Increased risks persisted 60-119 months beyond diagnosis for renal (SIR 2.56) and breast cancer (SIR 1.16); and 120+ months for renal cancer (SIR 2.46). Increased SPTC risk after renal and female breast cancers was mostly seen in nonirradiated patients. The principal histology association was between papillary thyroid cancer and renal cell carcinomas. CONCLUSIONS: Many common cancers are associated with increased risk of SPTC beyond 12 months of initial diagnosis. Although this can be explained partly by continued surveillance bias, radiation effects, and known rare familial associations for some tumors, these factors alone are unlikely to explain the persistent, significant two-way association with renal and breast cancers. Additional research is needed to further define the biological and environmental mechanisms underlying these associations.


Assuntos
Segunda Neoplasia Primária/epidemiologia , Segunda Neoplasia Primária/etiologia , Neoplasias/complicações , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/etiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Seguimentos , Humanos , Incidência , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias/terapia , Prognóstico , Fatores de Risco , Programa de SEER , Estados Unidos , Adulto Jovem
17.
Am J Surg ; 224(1 Pt B): 315-318, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34863525

RESUMO

BACKGROUND: Work-related injury and musculoskeletal (MSK) symptoms are common among surgeons, however data for endocrine surgeons (ES) are lacking. METHODS: A survey was distributed to American Association of Endocrine Surgeons (AAES) and Endocrine section of American Head and Neck Society (AHNS) members. RESULTS: MSK symptoms were present in 199 (90%) of 220 respondents, most notably pain (91%) and stiffness (81%). The most common locations were neck (87%) and shoulders (55%). Women were more likely to be symptomatic (98.6% versus 86.4%, p = 0.004). Although 67% of respondents reported awareness of ergonomic principles, only 19% had learned about them during training. The most common ergonomic adjustments were stretching, use of microbreaks and headlight/loupe adjustments. CONCLUSION: The vast majority of ES surgeons suffer MSK symptoms that could potentially impact their quality of life and career length. Effective strategies are needed to protect this highly trained workforce.


Assuntos
Doenças Musculoesqueléticas , Dor Musculoesquelética , Doenças Profissionais , Cirurgiões , Feminino , Humanos , Doenças Musculoesqueléticas/epidemiologia , Dor Musculoesquelética/epidemiologia , Dor Musculoesquelética/etiologia , Doenças Profissionais/epidemiologia , Prevalência , Qualidade de Vida , Inquéritos e Questionários
18.
Am J Surg ; 223(1): 76-80, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34303521

RESUMO

BACKGROUND: Multidisciplinary Tumor Boards (MDT) are used to obtain input regarding cancer management. This study assessed the impact of our institutional Endocrine MDT. METHODS: MDT notes on patients with thyroid cancer treated during 2012-2018 were abstracted retrospectively from the electronic medical record. Management change (MC) was prospectively collected by the MDT coordinator. Biannual evaluations reviewed the impact of the MDT as observed by attendees. RESULTS: MC was recommended in 47 (15%) of 286 presentations, with additional imaging being the most frequent (43%). Presentation of recurrences were more likely to result in MC (24% vs. 13% initial, p = 0.03). Overall, 98% of attendees found the conference exceeded educational expectations. About 24% reported intending to use a more evidence/guideline-based approach after attending and this trend increased over time (p = 0.002). CONCLUSION: MDT presentations led to a higher rate of MC particularly in recurrent TC patients and increased evidenced-based practice for attendees.


Assuntos
Tomada de Decisão Clínica/métodos , Equipe de Assistência ao Paciente/normas , Câncer Papilífero da Tireoide/terapia , Neoplasias da Glândula Tireoide/terapia , Adolescente , Endocrinologia/normas , Medicina Baseada em Evidências/normas , Feminino , Humanos , Masculino , Oncologia/normas , Guias de Prática Clínica como Assunto , Estudos Retrospectivos , Câncer Papilífero da Tireoide/diagnóstico , Glândula Tireoide/diagnóstico por imagem , Neoplasias da Glândula Tireoide/diagnóstico , Adulto Jovem
19.
Am J Surg ; 223(1): 94-100, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34325908

RESUMO

INTRODUCTION: Lobular carcinoma in situ (LCIS), atypical ductal and lobular hyperplasia (AH) increase breast cancer risk. We examined risk management recommendations (RMR) and acceptance in AH/LCIS. METHODS: All patients with AH/LCIS on core needle biopsy from 2013 to 2016 at our institution were identified; cancer patients were excluded. Univariate and multivariate analysis examined factors associated with management. RESULTS: 98 % of patients were evaluated by breast surgeons and 53 % underwent risk model calculation (RC). 77 % had new RMR. RMR of MRI screening (MRI), genetic counselling (GC) and medical oncology (MO) referral were 41 %, 18 %, 77 %, respectively. MRI screening was more likely recommended in those with strong family history (p = 0.01), and high RC (p < 0.001). Uptake of at least one RMR did not occur in 84 % of patients. Use of RC correlated with MO acceptance (p = 0.049). CONCLUSIONS: Diagnosis of atypia has the potential to change risk management for most, however only 16 % of patients accepted all RMR.


Assuntos
Carcinoma de Mama in situ/diagnóstico , Neoplasias da Mama/prevenção & controle , Mama/patologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Comportamento de Redução do Risco , Adulto , Mama/diagnóstico por imagem , Mama/cirurgia , Carcinoma de Mama in situ/epidemiologia , Carcinoma de Mama in situ/patologia , Carcinoma de Mama in situ/terapia , Neoplasias da Mama/epidemiologia , Neoplasias da Mama/patologia , Feminino , Aconselhamento Genético/estatística & dados numéricos , Humanos , Hiperplasia/diagnóstico , Hiperplasia/epidemiologia , Hiperplasia/patologia , Hiperplasia/terapia , Imageamento por Ressonância Magnética/estatística & dados numéricos , Programas de Rastreamento/estatística & dados numéricos , Pessoa de Meia-Idade , Medição de Risco/estatística & dados numéricos
20.
Surgery ; 171(1): 245-251, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34362588

RESUMO

BACKGROUND: Tall cell variant of papillary thyroid carcinoma is an aggressive subtype of papillary thyroid carcinoma. We examined expression of cancer stem cell markers in tall cell variant compared with other well-differentiated thyroid cancers. METHODS: Expression of cancer stem cell markers was examined in 572 thyroid tumors from The Cancer Genome Atlas Thyroid Cancer database and tall cell variant and papillary thyroid carcinoma tumors by immunohistochemistry. RESULTS: Expression of the PROM1 gene, encoding the cancer stem cell marker CD133, was elevated in tall cell variant compared to classic papillary thyroid carcinoma in a large cohort of unmatched samples from The Cancer Genome Atlas Thyroid Cancer database (P < .001). By immunohistochemistry in age and stage matched samples, CD133 protein was confirmed to be significantly increased in tall cell variant versus classic papillary thyroid carcinoma (P = .006). Analyzing all thyroid cancers, high PROM1 expression was associated with worse disease-specific survival. Optimal cutoffs were determined to define a tall cell variant-like cancer stem cell signature characterized by high PROM1, high ALDH1A3, and low CD24 expression. Classic papillary thyroid carcinoma with a tall cell variant-like gene signature had worse recurrence disease-free survival compared to classic papillary thyroid carcinoma with a non-tall cell variant signature (P = .02). CONCLUSION: Tall cell variant of papillary thyroid carcinoma has increased expression of cancer stem cell markers compared to classic papillary thyroid carcinoma. The tall cell variant-like cancer stem cell gene signature identified a molecular subtype of classic papillary thyroid carcinoma that has a worse recurrence-free survival.


Assuntos
Biomarcadores Tumorais/metabolismo , Recidiva Local de Neoplasia/epidemiologia , Células-Tronco Neoplásicas/metabolismo , Câncer Papilífero da Tireoide/mortalidade , Glândula Tireoide/patologia , Biomarcadores Tumorais/análise , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/prevenção & controle , Células-Tronco Neoplásicas/patologia , Estudos Retrospectivos , Medição de Risco/métodos , Câncer Papilífero da Tireoide/patologia , Câncer Papilífero da Tireoide/terapia , Glândula Tireoide/citologia , Neoplasias da Glândula Tireoide/patologia
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