Prevalence of Germline Mutations in Genes Engaged in DNA Damage Repair by Homologous Recombination in Patients with Triple-Negative and Hereditary Non-Triple-Negative Breast Cancers.

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Pawel Domagala

Full Text Available This study sought to assess the prevalence of common germline mutations in several genes engaged in the repair of DNA double-strand break by homologous recombination in patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers. Tumors deficient in this type of DNA damage repair are known to be especially sensitive to DNA cross-linking agents (e.g., platinum drugs and to poly(ADP-ribose polymerase (PARP inhibitors.Genetic testing was performed for 36 common germline mutations in genes engaged in the repair of DNA by homologous recombination, i.e., BRCA1, BRCA2, CHEK2, NBN, ATM, PALB2, BARD1, and RAD51D, in 202 consecutive patients with triple-negative breast cancers and hereditary non-triple-negative breast cancers.Thirty five (22.2% of 158 patients in the triple-negative group carried mutations in genes involved in DNA repair by homologous recombination, while 10 (22.7% of the 44 patients in the hereditary non-triple-negative group carried such mutations. Mutations in BRCA1 were most frequent in patients with triple-negative breast cancer (18.4%, and mutations in CHEK2 were most frequent in patients with hereditary non-triple-negative breast cancers (15.9%. In addition, in the triple-negative group, mutations in CHEK2, NBN, and ATM (3.8% combined were found, while mutations in BRCA1, NBN, and PALB2 (6.8% combined were identified in the hereditary non-triple-negative group.Identifying mutations in genes engaged in DNA damage repair by homologous recombination other than BRCA1/2 can substantially increase the proportion of patients with triple-negative breast cancer and hereditary non-triple-negative breast cancer who may be eligible for therapy using PARP inhibitors and platinum drugs.

TNK2 Tyrosine Kinase as a Novel Therapeutic Target in Triple-Negative Breast Cancer

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2017-10-01

Award Number: W81XWH-15-1-0311 TITLE: TNK2 Tyrosine Kinase as a Novel Therapeutic Target in Triple- Negative Breast Cancer PRINCIPAL...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Triple-negative breast cancers (TNBCs) represent only 10%-15% of all breast cancers ; however... cancers (TNBC) represent 10-15% of all breast cancers . While significant advances have been made for targeted therapy of ER and HER2-positive breast

Analysis of the Clinicopathologic Features and Prognosis in Triple-Negative Breast Cancer

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Dehong Yang; Hong Liu; Jing Zhao

2008-01-01

OBJECTIVE To investigate the clinical and pathological features,as well as prognosis in triple-negative breast cancer patients.METHODS A total of 509 cases of operable breast cancer from January,2002 to June,2002 treated in the Cancer Hospital of Tianjin Medical University were analyzed.The Her-2,ER and PR status was determined using immunohistochemistry.Of the total cases,one group was identified as triple negative breast cancer,ie defined as ER,PR and Her-2 negative.The other group was nontriple-negative breast cancer.Clinicopathologic features of the groups were compared and 5-year disease-free survival (DFS)analyzed by the Kaplan-Meier method.RESULTS Of the total cases,21.4% (109/509) of cases were found to be triple- negative while 78.6% (400/509) were non-triplenegative.The triple negative group had higher incidence rates than the non-triple-negative group of the medullary type and Grade Ⅲ tumors (P ＜ 0.05).There was no other difference in the clinicopathologic features between the 2 groups.From follow-up to June,2007,21.1% (23/109) of the triple-negative group and 12.7%(51/400) of the non-triple negative group had a local recurrence or distant metastasis,resulting in a significant difference (P ＜ 0.05).In the triple-negative group and non-triple-negative group,5-year DFS were 78.9% and 87.3% respectively.There was a statistically significant difference between the 2 groups (P = 0.031).CONCLUSION Compared with non-triple-negative breast cancer,triple-negative breast cancer patients have an increased likehood of a local recurrence or distant metastasis and a poorer prognosis.

Targeting Prolyl Peptidases in Triple-Negative Breast Cancer

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2017-02-01

ABSTRACT Triple negative breast cancer (TNBC) is an aggressive sub-type with limited treatment options and poor prognosis. The most life -threatening... negative feedback loops within the pathway limit their effectiveness . For example, AKT inhibitors cause increased expression of IGF1R/ErbB3 and, as a...AWARD NUMBER: W81XWH-16-1-0025 TITLE: Targeting Prolyl Peptidases in Triple- Negative Breast Cancer PRINCIPAL INVESTIGATOR: Carl G. Maki, PhD

Adjuvant trastuzumab with chemotherapy is effective in women with small, node-negative, HER2-positive breast cancer.

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McArthur, Heather L; Mahoney, Kathleen M; Morris, Patrick G; Patil, Sujata; Jacks, Lindsay M; Howard, Jane; Norton, Larry; Hudis, Clifford A

2011-12-15

Several large, randomized trials established the benefits of adjuvant trastuzumab with chemotherapy. However, the benefit for women with small, node-negative HER2-positive (HER2+) disease is unknown, as these patients were largely excluded from these trials. Therefore, a retrospective, single-institution, sequential cohort study of women with small, node-negative, HER2+ breast cancer who did or did not receive adjuvant trastuzumab was conducted. Women with ≤ 2 cm, node-negative, HER2+ (immunohistochemistry 3+ or fluorescence in situ hybridization ≥ 2) breast cancer were identified through an institutional database. A "no-trastuzumab" cohort of 106 trastuzumab-untreated women diagnosed between January 1, 2002 and May 14, 2004 and a "trastuzumab" cohort of 155 trastuzumab-treated women diagnosed between May 16, 2005 and December 31, 2008 were described. Survival and recurrence outcomes were estimated by Kaplan-Meier methods. The cohorts were similar in age, median tumor size, histology, hormone receptor status, hormone therapy, and locoregional therapy. Chemotherapy was administered in 66% and 100% of the "no trastuzumab" and "trastuzumab" cohorts, respectively. The median recurrence-free and survival follow-up was: 6.5 years (0.7-8.5) and 6.8 years (0.7-8.5), respectively, for the "no trastuzumab" cohort and 3.0 years (0.5-5.2) and 3.0 years (0.6-5.2), respectively, for the "trastuzumab" cohort. The 3-year locoregional invasive recurrence-free, distant recurrence-free, invasive disease-free, and overall survival were 92% versus 98% (P = .0137), 95% versus 100% (P = .0072), 82% versus 97% (P < .0001), and 97% versus 99% (P = .18) for the "no trastuzumab" and "trastuzumab" cohorts, respectively. Women with small, node-negative, HER2+ primary breast cancers likely derive significant benefit from adjuvant trastuzumab with chemotherapy. Copyright © 2011 American Cancer Society.

A prognostic model of triple-negative breast cancer based on miR-27b-3p and node status.

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Songjie Shen

Full Text Available Triple-negative breast cancer (TNBC is an aggressive but heterogeneous subtype of breast cancer. This study aimed to identify and validate a prognostic signature for TNBC patients to improve prognostic capability and to guide individualized treatment.We retrospectively analyzed the prognostic performance of clinicopathological characteristics and miRNAs in a training set of 58 patients with invasive ductal TNBC diagnosed between 2002 and 2012. A prediction model was developed based on independent clinicopathological and miRNA covariates. The prognostic value of the model was further validated in a separate set of 41 TNBC patients diagnosed between 2007 and 2008.Only lymph node status was marginally significantly associated with poor prognosis of TNBC (P = 0.054, whereas other clinicopathological factors, including age, tumor size, histological grade, lymphovascular invasion, P53 status, Ki-67 index, and type of surgery, were not. The expression levels of miR-27b-3p, miR-107, and miR-103a-3p were significantly elevated in the metastatic group compared with the disease-free group (P value: 0.008, 0.005, and 0.050, respectively. The Cox proportional hazards regression analysis revealed that lymph node status and miR-27b-3p were independent predictors of poor prognosis (P value: 0.012 and 0.027, respectively. A logistic regression model was developed based on these two independent covariates, and the prognostic value of the model was subsequently confirmed in a separate validation set. The two different risk groups, which were stratified according to the model, showed significant differences in the rates of distant metastasis and breast cancer-related death not only in the training set (P value: 0.001 and 0.040, respectively but also in the validation set (P value: 0.013 and 0.012, respectively.This model based on miRNA and node status covariates may be used to stratify TNBC patients into different prognostic subgroups for potentially

Predicting Likelihood of Having Four or More Positive Nodes in Patient With Sentinel Lymph Node-Positive Breast Cancer: A Nomogram Validation Study

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Unal, Bulent; Gur, Akif Serhat; Beriwal, Sushil; Tang Gong; Johnson, Ronald; Ahrendt, Gretchen; Bonaventura, Marguerite; Soran, Atilla

2009-01-01

Purpose: Katz suggested a nomogram for predicting having four or more positive nodes in sentinel lymph node (SLN)-positive breast cancer patients. The findings from this formula might influence adjuvant radiotherapy decisions. Our goal was to validate the accuracy of the Katz nomogram. Methods and Materials: We reviewed the records of 309 patients with breast cancer who had undergone completion axillary lymph node dissection. The factors associated with the likelihood of having four or more positive axillary nodes were evaluated in patients with one to three positive SLNs. The nomogram developed by Katz was applied to our data set. The area under the curve of the corresponding receiver operating characteristics curve was calculated for the nomogram. Results: Of the 309 patients, 80 (25.9%) had four or more positive axillary lymph nodes. On multivariate analysis, the number of positive SLNs (p < .0001), overall metastasis size (p = .019), primary tumor size (p = .0001), and extracapsular extension (p = .01) were significant factors predicting for four or more positive nodes. For patients with <5% probability, 90.3% had fewer than four positive nodes and 9.7% had four or more positive nodes. The negative predictive value was 91.7%, and sensitivity was 80%. The nomogram was accurate and discriminating (area under the curve, .801). Conclusion: The probability of four or more involved nodes is significantly greater in patients who have an increased number of positive SLNs, increased overall metastasis size, increased tumor size, and extracapsular extension. The Katz nomogram was validated in our patients. This nomogram will be helpful to clinicians making adjuvant treatment recommendations to their patients.

Elaboration of a nomogram to predict nonsentinel node status in breast cancer patients with positive sentinel node, intraoperatively assessed with one step nucleic amplification: Retrospective and validation phase.

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Di Filippo, Franco; Di Filippo, Simona; Ferrari, Anna Maria; Antonetti, Raffaele; Battaglia, Alessandro; Becherini, Francesca; Bernet, Laia; Boldorini, Renzo; Bouteille, Catherine; Buglioni, Simonetta; Burelli, Paolo; Cano, Rafael; Canzonieri, Vincenzo; Chiodera, Pierluigi; Cirilli, Alfredo; Coppola, Luigi; Drago, Stefano; Di Tommaso, Luca; Fenaroli, Privato; Franchini, Roberto; Gianatti, Andrea; Giannarelli, Diana; Giardina, Carmela; Godey, Florence; Grassi, Massimo M; Grassi, Giuseppe B; Laws, Siobhan; Massarut, Samuele; Naccarato, Giuseppe; Natalicchio, Maria Iole; Orefice, Sergio; Palmieri, Fabrizio; Perin, Tiziana; Roncella, Manuela; Roncalli, Massimo G; Rulli, Antonio; Sidoni, Angelo; Tinterri, Corrado; Truglia, Maria C; Sperduti, Isabella

2016-12-08

Tumor-positive sentinel lymph node (SLN) biopsy results in a risk of non sentinel node metastases in micro- and macro-metastases ranging from 20 to 50%, respectively. Therefore, most patients underwent unnecessary axillary lymph node dissections. We have previously developed a mathematical model for predicting patient-specific risk of non sentinel node (NSN) metastases based on 2460 patients. The study reports the results of the validation phase where a total of 1945 patients were enrolled, aimed at identifying a tool that gives the possibility to the surgeon to choose intraoperatively whether to perform or not axillary lymph node dissection (ALND). The following parameters were recorded: Clinical: hospital, age, medical record number; Bio pathological: Tumor (T) size stratified in quartiles, grading (G), histologic type, lymphatic/vascular invasion (LVI), ER-PR status, Ki 67, molecular classification (Luminal A, Luminal B, HER-2 Like, Triple negative); Sentinel and non-sentinel node related: Number of NSNs removed, number of positive NSNs, cytokeratin 19 (CK19) mRNA copy number of positive sentinel nodes stratified in quartiles. A total of 1945 patients were included in the database. All patient data were provided by the authors of this paper. The discrimination of the model quantified with the area under the receiver operating characteristics (ROC) curve (AUC), was 0.65 and 0.71 in the validation and retrospective phase, respectively. The calibration determines the distance between predicted outcome and actual outcome. The mean difference between predicted/observed was 2.3 and 6.3% in the retrospective and in the validation phase, respectively. The two values are quite similar and as a result we can conclude that the nomogram effectiveness was validated. Moreover, the ROC curve identified in the risk category of 31% of positive NSNs, the best compromise between false negative and positive rates i.e. when ALND is unnecessary (31%). The results of the study confirm

Molecular basis of the triple negative breast cancer

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Ayse Feyda Nursal

2015-06-01

Full Text Available Breast cancer is the most common type of cancer in women and more than 1 million breast cancer cases are diagnosed each year all over the world. Breast cancer is a complex and heterogeneous disease in terms of its molecular structure, mutation type, metastase properties, clinical course and therapeutic response. Breast cancer is divided into subtypes based on expression properties of molecular markers as estrogen receptor, progestron receptor, human epidermal growth factor receptor 2. Triple-negative breast cancer is characterized by the lack of tumors that estrogen receptor, progestron receptor, human epidermal growth factor receptor 2 gene expression. These type of tumors lead to agressive clinical course due to unresponsiveness to systemic endocrine therapy and poor prognosis. Triple negative breast cancer constitutes 10-20% of all breast cancers. It affects generally young and African-American women. Triple negative breast cancer have several subtypes based on the gene expression properties. The majority of them are basal-like breast cancers. In this review, current literature is revised and summarized with respect to the molecular basis of triple negative cancers. [Archives Medical Review Journal 2015; 24(2.000: 251-259

Review of the role of the sentinel node biopsy in neoadjuvant chemotherapy in women with breast cancer and negative or positive axillary node at diagnosis.

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Ruano Pérez, R; Rebollo Aguirre, A C; García-Talavera San Miguel, P; Díaz Expósito, R; Vidal-Sicart, S; Cordero García, J M; Carrera Salazar, D; Rioja Martín, M E

The role of the selective sentinel node biopsy (SNB) is increasing in relevance in breast cancer women with indication of neoadjuvant chemotherapy (NAC). The Radiosurgery Working Group of the SEMNIM is aware of the necessity of establishing the need for SNB before or after NAC, and also how to manage patients with axillary node-negative or node-positive. There is sufficient data to assess that the SNB with radioisotope techniques are feasible and safe in all these scenarios. An adequate axilla evaluation prior to surgery and the possibility of marking prior to NAC the nodes infiltrated must be the two main pillars to guarantee the success of the SNB. It has been shown that to incorporate the SNB in breast cancer women with indication of NAC increases the rate of a conservative treatment of the axilla that will be a clear benefit for these patients. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

Evaluation of Sentinel Node Biopsy in Locally Advanced Breast Cancer Patients Who Become Clinically Node-Negative after Neoadjuvant Chemotherapy: A Preliminary Study

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Thomas, Sh.; Prakash, A.; Goyal, V.; Agarwal, Sh.; Choudhury, M.; Popli, M.B.

2011-01-01

Introduction. Controversy continues over the appropriate timing of sentinel lymph node (SLN) biopsy in locally advanced breast cancer (LABC) patients receiving neoadjuvant chemotherapy. We evaluated the feasibility and accuracy of SLN biopsy in LABC patients with cytology-proven axillary nodal metastasis who become clinically node-negative after neoadjuvant chemotherapy. Materials. 30 consecutive patients with LABC, who had become clinically node-negative after 3 cycles of neoadjuvant chemotherapy, were included in the study. They were then subjected to SLN biopsy, axillary lymph node dissection, and breast surgery. Results. Sentinel nodes were successfully identified in 26 of the 30 patients, resulting in an identification rate of 86.67%, sensitivity of 83.33%, false negative rate of 20%, negative predictive value of 72.73%, and an overall accuracy of 88.46%. No complications were observed as a result of dye injection. Conclusions. SLN biopsy is feasible and safe in LABC patients with cytology-positive nodes who become clinically node-negative after neoadjuvant chemotherapy. Our accuracy rate, identification rate, and false negative rate are comparable to those in node-negative LABC patients. SLN biopsy as a therapeutic option in LABC after neoadjuvant chemotherapy is a promising option which should be further investigated

Gastric Metastasis of Triple Negative Invasive Lobular Carcinoma.

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Geredeli, Caglayan; Dogru, Osman; Omeroglu, Ethem; Yilmaz, Farise; Cicekci, Faruk

2015-05-05

Invasive lobular carcinomas are the second most common type (5% to 15%) of invasive breast carcinomas. The most frequent sites of breast cancer metastasis are the local and distant lymph nodes, brain, lung, liver, and bones; metastasis to the gastrointestinal system, especially to the stomach, is rare. When a mass is detected in an unusual place in a patient with invasive lobular carcinoma, it should be kept in mind that such a mass may be either a second primary carcinoma or the metastasis of an invasive lobular carcinoma. In this report, we present a case of gastric metastasis from triple-negative invasive lobular breast cancer. It is important to make an accurate diagnosis by distinguishing gastric metastasis from breast cancer in order to select the best initial treatment for systemic diseases of breast cancer. Considering our case, healthcare professionals should take into account that cases with invasive lobular breast cancer may experience unusual metastases.

A critical reappraisal of false negative sentinel lymph node biopsy in melanoma

International Nuclear Information System (INIS)

Manca, G.; Mazzarri, S.; Boni, G.; Chiacchio, S.; Tredici, M.; Duce, V.; Tardelli, E.; Volterrani, D.; Mariani, G.; Romanini, A.; Rubello, D.

2014-01-01

Lymphatic mapping and sentinel lymph node biopsy (SLNB) have completely changed the clinical management of cutaneous melanoma. This procedure has been accepted worldwide as a recognized method for nodal staging. SLNB is able to accurately determine nodal basin status, providing the most useful prognostic information. However, SLNB is not a perfect diagnostic test. Several large-scale studies have reported a relatively high false-negative rate (5.6-21%), correctly defined as the proportion of false-negative results with respect to the total number of “actual” positive lymph nodes. The main purpose of this review is to address the technical issues that nuclear physicians, surgeons, and pathologists should carefully consider to improve the accuracy of SLNB by minimizing its false-negative rate. In particular, SPECT/CT imaging has demonstrated to be able to identify a greater number of sentinel lymph nodes (SLNs) than those found by planar lymphoscintigraphy. Furthermore, a unique definition in the international guidelines is missing for the operational identification of SLNs, which may be partly responsible for this relatively high false-negative rate of SLNB. Therefore, it is recommended for the scientific community to agree on the radioactive counting rate threshold so that the surgeon can be better radioguided to detect all the lymph nodes which are most likely to harbor metastases. Another possible source of error may be linked to the examination of the harvested SLNs by conventional histopathological methods. A more careful and extensive SLN analysis (e.g. molecular analysis by RT-PCR) is able to find more positive nodes, so that the false-negative rate is reduced. Older age at diagnosis, deeper lesions, histologic ulceration, head-neck anatomical location of primary lesions are the clinical factors associated with false-negative SLNBs in melanoma patients. There is still much controversy about the clinical significance of a false-negative SLNB on the

Triple negative breast cancer: an Indian perspective

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Akhtar M

2015-08-01

Full Text Available Murtaza Akhtar, Subhrajit Dasgupta, Murtuza Rangwala Department of Surgery, NKP Salve Institute of Medical Sciences and Research Centre, Nagpur, Maharashtra, India Introduction: Breast cancer is the most common female cancer in the world. Triple negative breast cancer (TNBC is a recently identified biological variant with aggressive tumor behavior and poor prognosis. Data of hormonal status from the Indian population is scarce due to financial constraints in performing immunohistochemistry evaluation. The present study aims to prospectively analyze receptor status of all breast cancer patients and identify TNBC and compare their clinical profile and short term survival with other non-TNBC group. Materials and methods: All cytologically and histopathologically confirmed cases of carcinoma breast were prospectively enrolled. In a longitudinal study at tertiary care hospital in central India based on the hormonal status, they were further divided into TNBC and other groups. Comparison of risk factors, clinical profile and short-term survival was carried out. Results: A total 85 patients were enrolled and of them 37 (43.7% were TNBC. On comparing risk factors ie, age, age at menarche, total reproductive age, age at first child birth, and menopausal status – no statistical significance was observed between the TNBC and non-TNBC groups. But on comparison of clinical profile TNBC tumors were significantly large with majority of patients presenting as locally advanced breast cancer (83%. No statistical difference was observed in axillary lymph node status between two groups. TNBC tumors were histologically more aggressive (grade 3 compared to other groups. No statistically significant difference was observed in short term overall survival but all three deaths were observed in the TNBC group only and two local recurrences after surgery were observed in the TNBC group. Conclusion: TNBC forms a large proportion of carcinoma breast patients in a central

Clinical and pathological factors influencing survival in a large cohort of triple-negative breast cancer patients.

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Urru, Silvana Anna Maria; Gallus, Silvano; Bosetti, Cristina; Moi, Tiziana; Medda, Ricardo; Sollai, Elisabetta; Murgia, Alma; Sanges, Francesca; Pira, Giovanna; Manca, Alessandra; Palmas, Dolores; Floris, Matteo; Asunis, Anna Maria; Atzori, Francesco; Carru, Ciriaco; D'Incalci, Maurizio; Ghiani, Massimo; Marras, Vincenzo; Onnis, Daniela; Santona, Maria Cristina; Sarobba, Giuseppina; Valle, Enrichetta; Canu, Luisa; Cossu, Sergio; Bulfone, Alessandro; Rocca, Paolo Cossu; De Miglio, Maria Rosaria; Orrù, Sandra

2018-01-08

To provide further information on the clinical and pathological prognostic factors in triple-negative breast cancer (TNBC), for which limited and inconsistent data are available. Pathological characteristics and clinical records of 841 TNBCs diagnosed between 1994 and 2015 in four major oncologic centers from Sardinia, Italy, were reviewed. Multivariate hazard ratios (HRs) for mortality and recurrence according to various clinicopathological factors were estimated using Cox proportional hazards models. After a mean follow-up of 4.3 years, 275 (33.3%) TNBC patients had a progression of the disease and 170 (20.2%) died. After allowance for study center, age at diagnosis, and various clinicopathological factors, all components of the TNM staging system were identified as significant independent prognostic factors for TNBC mortality. The HRs were 3.13, 9.65, and 29.0, for stage II, III and IV, respectively, vs stage I. Necrosis and Ki-67 > 16% were also associated with increased mortality (HR: 1.61 and 1.99, respectively). Patients with tumor histotypes other than ductal invasive/lobular carcinomas had a more favorable prognosis (HR: 0.40 vs ductal invasive carcinoma). No significant associations with mortality were found for histologic grade, tumor infiltrating lymphocytes, and lymphovascular invasion. Among lymph node positive TNBCs, lymph node ratio appeared to be a stronger predictor of mortality than pathological lymph nodes stage (HR: 0.80 for pN3 vs pN1, and 3.05 for >0.65 vs <0.21 lymph node ratio), respectively. Consistent results were observed for cancer recurrence, except for Ki-67 and necrosis that were not found to be significant predictors for recurrence. This uniquely large study of TNBC patients provides further evidence that, besides tumor stage at diagnosis, lymph node ratio among lymph node positive tumors is an additional relevant predictor of survival and tumor recurrence, while Ki-67 seems to be predictive of mortality, but not of recurrence.

Immunohistochemical Characteristics of Triple Negative/Basal-like Breast Cancer

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Emel Ebru PALA; Ümit BAYOL; Süheyla CUMURCU; Elif KESKİN

2012-01-01

Objective: Triple-negative-breast-cancer that accounts for 10-20% of all breast carcinomas is defined by the lack of estrogen receptor, progesterone receptor, HER2 expression, and agressive clinical behavior. Triple-negative-breast-cancer is categorized into basal like and other types. The basal-like subtype is characterized by the expression of myoepithelial/basal markers.Material and Method: We studied 41 immunohistochemically triplenegative- breast-cancer patients to determine EGFR, Cytoke...

Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.

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Paik, Soonmyung; Tang, Gong; Shak, Steven; Kim, Chungyeul; Baker, Joffre; Kim, Wanseop; Cronin, Maureen; Baehner, Frederick L; Watson, Drew; Bryant, John; Costantino, Joseph P; Geyer, Charles E; Wickerham, D Lawrence; Wolmark, Norman

2006-08-10

The 21-gene recurrence score (RS) assay quantifies the likelihood of distant recurrence in women with estrogen receptor-positive, lymph node-negative breast cancer treated with adjuvant tamoxifen. The relationship between the RS and chemotherapy benefit is not known. The RS was measured in tumors from the tamoxifen-treated and tamoxifen plus chemotherapy-treated patients in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B20 trial. Cox proportional hazards models were utilized to test for interaction between chemotherapy treatment and the RS. A total of 651 patients were assessable (227 randomly assigned to tamoxifen and 424 randomly assigned to tamoxifen plus chemotherapy). The test for interaction between chemotherapy treatment and RS was statistically significant (P = .038). Patients with high-RS (> or = 31) tumors (ie, high risk of recurrence) had a large benefit from chemotherapy (relative risk, 0.26; 95% CI, 0.13 to 0.53; absolute decrease in 10-year distant recurrence rate: mean, 27.6%; SE, 8.0%). Patients with low-RS (< 18) tumors derived minimal, if any, benefit from chemotherapy treatment (relative risk, 1.31; 95% CI, 0.46 to 3.78; absolute decrease in distant recurrence rate at 10 years: mean, -1.1%; SE, 2.2%). Patients with intermediate-RS tumors did not appear to have a large benefit, but the uncertainty in the estimate can not exclude a clinically important benefit. The RS assay not only quantifies the likelihood of breast cancer recurrence in women with node-negative, estrogen receptor-positive breast cancer, but also predicts the magnitude of chemotherapy benefit.

Selective androgen receptor modulators (SARMs) negatively regulate triple-negative breast cancer growth and epithelial:mesenchymal stem cell signaling.

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Narayanan, Ramesh; Ahn, Sunjoo; Cheney, Misty D; Yepuru, Muralimohan; Miller, Duane D; Steiner, Mitchell S; Dalton, James T

2014-01-01

The androgen receptor (AR) is the most highly expressed steroid receptor in breast cancer with 75-95% of estrogen receptor (ER)-positive and 40-70% of ER-negative breast cancers expressing AR. Though historically breast cancers were treated with steroidal androgens, their use fell from favor because of their virilizing side effects and the emergence of tamoxifen. Nonsteroidal, tissue selective androgen receptor modulators (SARMs) may provide a novel targeted approach to exploit the therapeutic benefits of androgen therapy in breast cancer. Since MDA-MB-453 triple-negative breast cancer cells express mutated AR, PTEN, and p53, MDA-MB-231 triple-negative breast cancer cells stably expressing wildtype AR (MDA-MB-231-AR) were used to evaluate the in vitro and in vivo anti-proliferative effects of SARMs. Microarray analysis and epithelial:mesenchymal stem cell (MSC) co-culture signaling studies were performed to understand the mechanisms of action. Dihydrotestosterone and SARMs, but not bicalutamide, inhibited the proliferation of MDA-MB-231-AR. The SARMs reduced the MDA-MB-231-AR tumor growth and tumor weight by greater than 90%, compared to vehicle-treated tumors. SARM treatment inhibited the intratumoral expression of genes and pathways that promote breast cancer development through its actions on the AR. SARM treatment also inhibited the metastasis-promoting paracrine factors, IL6 and MMP13, and subsequent migration and invasion of epithelial:MSC co-cultures. 1. AR stimulation inhibits paracrine factors that are important for MSC interactions and breast cancer invasion and metastasis. 2. SARMs may provide promise as novel targeted therapies to treat AR-positive triple-negative breast cancer.

Selective androgen receptor modulators (SARMs negatively regulate triple-negative breast cancer growth and epithelial:mesenchymal stem cell signaling.

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Ramesh Narayanan

Full Text Available The androgen receptor (AR is the most highly expressed steroid receptor in breast cancer with 75-95% of estrogen receptor (ER-positive and 40-70% of ER-negative breast cancers expressing AR. Though historically breast cancers were treated with steroidal androgens, their use fell from favor because of their virilizing side effects and the emergence of tamoxifen. Nonsteroidal, tissue selective androgen receptor modulators (SARMs may provide a novel targeted approach to exploit the therapeutic benefits of androgen therapy in breast cancer.Since MDA-MB-453 triple-negative breast cancer cells express mutated AR, PTEN, and p53, MDA-MB-231 triple-negative breast cancer cells stably expressing wildtype AR (MDA-MB-231-AR were used to evaluate the in vitro and in vivo anti-proliferative effects of SARMs. Microarray analysis and epithelial:mesenchymal stem cell (MSC co-culture signaling studies were performed to understand the mechanisms of action.Dihydrotestosterone and SARMs, but not bicalutamide, inhibited the proliferation of MDA-MB-231-AR. The SARMs reduced the MDA-MB-231-AR tumor growth and tumor weight by greater than 90%, compared to vehicle-treated tumors. SARM treatment inhibited the intratumoral expression of genes and pathways that promote breast cancer development through its actions on the AR. SARM treatment also inhibited the metastasis-promoting paracrine factors, IL6 and MMP13, and subsequent migration and invasion of epithelial:MSC co-cultures.1. AR stimulation inhibits paracrine factors that are important for MSC interactions and breast cancer invasion and metastasis. 2. SARMs may provide promise as novel targeted therapies to treat AR-positive triple-negative breast cancer.

Common breast cancer susceptibility loci are associated with triple negative breast cancer

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Stevens, Kristen N.; Vachon, Celine M.; Lee, Adam M.; Slager, Susan; Lesnick, Timothy; Olswold, Curtis; Fasching, Peter A.; Miron, Penelope; Eccles, Diana; Carpenter, Jane E.; Godwin, Andrew K.; Ambrosone, Christine; Winqvist, Robert; Schmidt, Marjanka K.; Cox, Angela; Cross, Simon S.; Sawyer, Elinor; Hartmann, Arndt; Beckmann, Matthias W.; Schulz-Wendtland, Rüdiger; Ekici, Arif B.; Tapper, William J; Gerty, Susan M; Durcan, Lorraine; Graham, Nikki; Hein, Rebecca; Nickels, Stephan; Flesch-Janys, Dieter; Heinz, Judith; Sinn, Hans-Peter; Konstantopoulou, Irene; Fostira, Florentia; Pectasides, Dimitrios; Dimopoulos, Athanasios M.; Fountzilas, George; Clarke, Christine L.; Balleine, Rosemary; Olson, Janet E.; Fredericksen, Zachary; Diasio, Robert B.; Pathak, Harsh; Ross, Eric; Weaver, JoEllen; Rüdiger, Thomas; Försti, Asta; Dünnebier, Thomas; Ademuyiwa, Foluso; Kulkarni, Swati; Pylkäs, Katri; Jukkola-Vuorinen, Arja; Ko, Yon-Dschun; Van Limbergen, Erik; Janssen, Hilde; Peto, Julian; Fletcher, Olivia; Giles, Graham G.; Baglietto, Laura; Verhoef, Senno; Tomlinson, Ian; Kosma, Veli-Matti; Beesley, Jonathan; Greco, Dario; Blomqvist, Carl; Irwanto, Astrid; Liu, Jianjun; Blows, Fiona M.; Dawson, Sarah-Jane; Margolin, Sara; Mannermaa, Arto; Martin, Nicholas G.; Montgomery, Grant W; Lambrechts, Diether; dos Santos Silva, Isabel; Severi, Gianluca; Hamann, Ute; Pharoah, Paul; Easton, Douglas F.; Chang-Claude, Jenny; Yannoukakos, Drakoulis; Nevanlinna, Heli; Wang, Xianshu; Couch, Fergus J.

2012-01-01

Triple negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiological factors which promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome wide association studies (GWAS) display heterogeneity of effect among breast cancer subtypes as defined by estrogen receptor (ER) and progesterone receptor (PR) status. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple negative breast cancer and 4,978 healthy controls. We identified six single nucleotide polymorphisms (SNPs) significantly associated with risk of triple negative breast cancer, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.11) and rs8100241 (19p13.11). Together, our results provide convincing evidence of genetic susceptibility for triple negative breast cancer. PMID:21844186

S100A14 is a novel independent prognostic biomarker in the triple-negative breast cancer subtype

DEFF Research Database (Denmark)

Ehmsen, Sidse; Hansen, Lea Tykgaard; Bak, Martin

2015-01-01

Triple-negative breast cancer (TNBC) represents a heterogeneous subgroup with generally poor outcome and lack of an effective targeted therapy. Prognostic or predictive biomarkers to guide treatment decisions for this group of patients are needed. To evaluate the potential of S100A14 protein...... as a novel biomarker in TNBC, the protein expression of S100A14 was correlated with clinical outcomes in a Pilot Sample set and a Danish cohort of predominantly TNBC patients. Kaplan-Meier analysis identified a prognostic impact of S100A14 on disease-free survival and overall survival, showing that tumors......-), had equally poor outcomes as those with tumor-positive axillary lymph nodes (N+), while TNBC/N- patients with low S100A14 expression had a significantly better disease free survival (p = 0.013). Multivariate analysis revealed that S100A14 is an independent prognostic factor for TNBC patients (p = 0...

Predictive Factors for Nonsentinel Lymph Node Metastasis in Patients With Positive Sentinel Lymph Nodes After Neoadjuvant Chemotherapy: Nomogram for Predicting Nonsentinel Lymph Node Metastasis.

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Ryu, Jai Min; Lee, Se Kyung; Kim, Ji Young; Yu, Jonghan; Kim, Seok Won; Lee, Jeong Eon; Han, Se Hwan; Jung, Yong Sik; Nam, Seok Jin

2017-11-01

Axillary lymph node (ALN) status is an important prognostic factor for breast cancer patients. With increasing numbers of patients undergoing neoadjuvant chemotherapy (NAC), issues concerning sentinel lymph node biopsy (SLNB) after NAC have emerged. We analyzed the clinicopathologic features and developed a nomogram to predict the possibility of nonsentinel lymph node (NSLN) metastases in patients with positive SLNs after NAC. A retrospective medical record review was performed of 140 patients who had had clinically positive ALNs at presentation, had a positive SLN after NAC on subsequent SLNB, and undergone axillary lymph node dissection (ALND) from 2008 to 2014. On multivariate stepwise logistic regression analysis, pathologic T stage, lymphovascular invasion, SLN metastasis size, and number of positive SLN metastases were independent predictors for NSLN metastases (P Samsung Medical Center NAC nomogram was developed to predict the likelihood of additional positive NSLNs. The Samsung Medical Center NAC nomogram could provide information to surgeons regarding whether to perform additional ALND when the permanent biopsy revealed positive findings, although the intraoperative SLNB findings were negative. Copyright © 2017 Elsevier Inc. All rights reserved.

Isolated perifacial lymph node metastasis in oral squamous cell carcinoma with clinically node-negative neck.

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Agarwal, Sangeet Kumar; Arora, Sowrabh Kumar; Kumar, Gopal; Sarin, Deepak

2016-10-01

The incidence of occult perifacial nodal disease in oral cavity squamous cell carcinoma is not well reported. The purpose of this study was to evaluate the incidence of isolated perifacial lymph node metastasis in patients with oral squamous cell carcinoma with a clinically node-negative neck. The study will shed light on current controversies and will provide valuable clinical and pathological information in the practice of routine comprehensive removal of these lymph node pads in selective neck dissection in the node-negative neck. Prospective analysis. This study was started in August 2011 when intraoperatively we routinely separated the lymph node levels from the main specimen for evaluation of the metastatic rate to different lymph node levels in 231 patients of oral squamous cell cancer with a clinically node-negative neck. The current study demonstrated that 19 (8.22%) out of 231 patients showed ipsilateral isolated perifacial lymph node involvement. The incidence of isolated perifacial nodes did not differ significantly between the oral tongue (7.14%) and buccal mucosa (7.75%). Incidence was statistically significant in cases with lower age group (oral squamous cell carcinoma with a clinically node-negative neck. The incidence of isolated perifacial involvement is high in cases of buccal mucosal and tongue cancers. A meticulous dissection of the perifacial nodes seems prudent when treating the neck in oral cavity squamous cell carcinoma. 4 Laryngoscope, 126:2252-2256, 2016. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma

NARCIS (Netherlands)

Mantel, Hendrik T. J.; Wiggers, Jim K.; Verheij, Joanne; Doff, Jan J.; Sieders, Egbert; van Gulik, Thomas M.; Gouw, Annette S. H.; Porte, Robert J.

2015-01-01

Background. Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The

Lymph Node Micrometastases are Associated with Worse Survival in Patients with Otherwise Node-Negative Hilar Cholangiocarcinoma

NARCIS (Netherlands)

Mantel, Hendrik T. J.; Wiggers, Jim K.; Verheij, Joanne; Doff, Jan J.; Sieders, Egbert; van Gulik, Thomas M.; Gouw, Annette S. H.; Porte, Robert J.

2015-01-01

Lymph node metastases on routine histology are a strong negative predictor for survival after resection of hilar cholangiocarcinoma. Additional immunohistochemistry can detect lymph node micrometastases in patients who are otherwise node negative, but the prognostic value is unsure. The objective of

Triple-negative phenotype of poorly-differentiated metaplastic breast carcinoma in a male: an oncological rarity

International Nuclear Information System (INIS)

Rehman, A.

2013-01-01

Metaplastic breast carcinoma (MBC) is an extremely rare breast malignancy having highly aggressive clinicopathological behaviour and dismal prognosis. A 75 years old man presented with a painless lump on right side of his chest along with two additional lumps in the ipsilateral axillary and inguinal areas. Microscopic evaluation and immunohistochemistry of trucut tissue biopsies of the lumps and that of mastectomy specimen revealed a triple-negative phenotype of poorly differentiated metaplastic breast carcinoma with metastatic deposits to the axillary and inguinal lymph nodes. Exhaustive internet research has revealed only a few case reports of MBC in the men; thus highlighting its absolute oncological rarity. (author)

Male occult triple-negative breast cancer with dermatomyositis: a case report and review of the literature

Directory of Open Access Journals (Sweden)

Zhang L

2017-11-01

Full Text Available Le Zhang,1 Chenghua Zhang,2 Zhaoying Yang,1 Miao He,3 Lijuan Zhang,1 Shereen Ezzat,4 Xi Liang5 1Department of Breast Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, China; 2Endoscopy Department, Jilin Cancer Hospital, Changchun, Jilin,China; 3Department of Anesthesia, The Second Hospital of Jilin University, Changchun, Jilin, China; 4Ontario Cancer Institute and The Endocrine Oncology Site Group, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada; 5Department of Breast Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning, China Abstract: Occult breast cancer is defined by the presence of axillary metastases without an identifiable primary breast tumor. Here, we report a rare case of a male occult breast cancer with dermatomyositis. We performed a modified radical mastectomy consisting of whole breast mastectomy and axillary lymph node dissection. Immunohistochemistry and fluorescent in situ hybridization analyses demonstrated an adenocarcinoma likely of breast origin, which was an occult triple-negative breast cancer. Interestingly, the patient’s previously noted periorbital dermatomyositis resolved promptly following surgical excision. Keywords: male breast cancer, occult breast cancer, triple-negative breast cancer, dermato­myositis 

Nomogram for prediction of level 2 axillary lymph node metastasis in proven level 1 node-positive breast cancer patients.

Science.gov (United States)

Jiang, Yanlin; Xu, Hong; Zhang, Hao; Ou, Xunyan; Xu, Zhen; Ai, Liping; Sun, Lisha; Liu, Caigang

2017-09-22

The current management of the axilla in level 1 node-positive breast cancer patients is axillary lymph node dissection regardless of the status of the level 2 axillary lymph nodes. The goal of this study was to develop a nomogram predicting the probability of level 2 axillary lymph node metastasis (L-2-ALNM) in patients with level 1 axillary node-positive breast cancer. We reviewed the records of 974 patients with pathology-confirmed level 1 node-positive breast cancer between 2010 and 2014 at the Liaoning Cancer Hospital and Institute. The patients were randomized 1:1 and divided into a modeling group and a validation group. Clinical and pathological features of the patients were assessed with uni- and multivariate logistic regression. A nomogram based on independent predictors for the L-2-ALNM identified by multivariate logistic regression was constructed. Independent predictors of L-2-ALNM by the multivariate logistic regression analysis included tumor size, Ki-67 status, histological grade, and number of positive level 1 axillary lymph nodes. The areas under the receiver operating characteristic curve of the modeling set and the validation set were 0.828 and 0.816, respectively. The false-negative rates of the L-2-ALNM nomogram were 1.82% and 7.41% for the predicted probability cut-off points of level 1 axillary lymph node metastasis. Patients with a low probability of L-2-ALNM could be spared level 2 axillary lymph node dissection, thereby reducing postoperative morbidity.

GATA3 expression in triple-negative breast cancers.

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Byrne, David J; Deb, Siddhartha; Takano, Elena A; Fox, Stephen B

2017-07-01

GATA-binding protein 3 (GATA3) is a well-studied transcription factor found to be essential in the development of luminal breast epithelium and has been identified in a variety of tumour types, including breast and urothelial carcinomas, making it a useful immunohistochemistry marker in the diagnosis of both primary and metastatic disease. We investigated GATA3 protein expression in a 106 primary triple-negative breast carcinomas (100 basal-like, six non-basal-like) using Cell Marque mouse monoclonal anti-GATA3 (L50-823). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to quantify mRNA expression in 22 triple-negative breast cancers (TNBCs) (20 primary and two cell lines), four luminal (three primary and one cell line) and five human epidermal growth factor receptor 2 (HER2) (four primary and one cell line) amplified tumours. In 98 TNBCs where IHC was assessable, 47 (48%) had a 1+ or greater staining with 20 (21%) having high GATA3 expression when using a weighted scoring. Our study has demonstrated that GATA3 expression is common in primary triple-negative breast carcinomas. It also suggests that although GATA3 is an oestrogen receptor (ER) regulated gene, it still proves useful in differentiating between primary and metastatic tumours in patients with a history of breast cancer regardless of its molecular subtype. © 2017 John Wiley & Sons Ltd.

Fluorescence-guided surgery of a highly-metastatic variant of human triple-negative breast cancer targeted with a cancer-specific GFP adenovirus prevents recurrence

Science.gov (United States)

Yano, Shuya; Takehara, Kiyoto; Miwa, Shinji; Kishimoto, Hiroyuki; Tazawa, Hiroshi; Urata, Yasuo; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M.

2016-01-01

We have previously developed a genetically-engineered GFP-expressing telomerase-dependent adenovirus, OBP-401, which can selectively illuminate cancer cells. In the present report, we demonstrate that targeting a triple-negative high-invasive human breast cancer, orthotopically-growing in nude mice, with OBP-401 enables curative fluorescence-guided surgery (FGS). OBP-401 enabled complete resection and prevented local recurrence and greatly inhibited lymph-node metastasis due to the ability of the virus to selectively label and subsequently kill cancer cells. In contrast, residual breast cancer cells become more aggressive after bright (white)-light surgery (BLS). OBP-401-based FGS also improved the overall survival compared with conventional BLS. Thus, metastasis from a highly-aggressive triple-negative breast cancer can be prevented by FGS in a clinically-relevant mouse model. PMID:27689331

Outcomes of Post Mastectomy Radiation Therapy in Patients Receiving Axillary Lymph Node Dissection After Positive Sentinel Lymph Node Biopsy

International Nuclear Information System (INIS)

Stauder, Michael C.; Caudle, Abigail S.; Allen, Pamela K.; Shaitelman, Simona F.; Smith, Benjamin D.; Hoffman, Karen E.; Buchholz, Thomas A.; Chavez-Macgregor, Mariana; Hunt, Kelly K.; Meric-Bernstam, Funda; Woodward, Wendy A.

2016-01-01

Purpose: We sought to determine the rate of postmastectomy radiation therapy (PMRT) among women treated with axillary lymph node dissection (ALND) after positive sentinel lymph node (SLN) biopsy results and to establish the effect of negative ALND results and PMRT on locoregional recurrence (LRR) and overall survival (OS). Methods and Materials: All patients were treated with mastectomy and ALND after positive SLN biopsy results. All patients had clinical N0 or NX disease at the time of mastectomy and received no neoadjuvant therapy. The presence of lymphovascular space invasion, presence of multifocality, number of positive SLNs and non-SLNs, clinical and pathologic stage, extranodal extension, age, and use of PMRT were evaluated for significance regarding the rates of OS and LRR. Results: A total of 345 patients were analyzed. ALND after positive SLN biopsy results was negative in 235 patients (68.1%), and a total of 112 patients (32.5%) received radiation therapy. On multivariate analysis, only pathologic stage III predicted for lower OS (hazard ratio, 3.32; P<.001). The rate of 10-year freedom from LRR was 87.9% and 95.3% in patients with positive ALND results and patients with negative ALND results, respectively. In patients with negative ALND results with ≥3 positive SLNs, the rate of freedom from LRR was 74.7% compared with 96.7% in those with <3 positive SLNs (P=.009). In patients with negative ALND results, ≥3 positive SLNs predicted for an increase in LRR on multivariate analysis (hazard ratio, 10.10; P=.034). Conclusions: A low proportion of cT1-2, N0 patients with positive SLNs who undergo mastectomy receive PMRT after ALND. Even in this low-risk cohort, patients with ≥3 positive SLNs and negative ALND results are at increased risk of LRR and may benefit from PMRT.

Outcomes of Post Mastectomy Radiation Therapy in Patients Receiving Axillary Lymph Node Dissection After Positive Sentinel Lymph Node Biopsy

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Stauder, Michael C., E-mail: mstauder@mdanderson.org [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Caudle, Abigail S. [Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Allen, Pamela K.; Shaitelman, Simona F.; Smith, Benjamin D.; Hoffman, Karen E.; Buchholz, Thomas A. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Chavez-Macgregor, Mariana [Department of Breast Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hunt, Kelly K.; Meric-Bernstam, Funda [Department of Breast Surgical Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Woodward, Wendy A. [Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, Texas (United States)

2016-11-01

Purpose: We sought to determine the rate of postmastectomy radiation therapy (PMRT) among women treated with axillary lymph node dissection (ALND) after positive sentinel lymph node (SLN) biopsy results and to establish the effect of negative ALND results and PMRT on locoregional recurrence (LRR) and overall survival (OS). Methods and Materials: All patients were treated with mastectomy and ALND after positive SLN biopsy results. All patients had clinical N0 or NX disease at the time of mastectomy and received no neoadjuvant therapy. The presence of lymphovascular space invasion, presence of multifocality, number of positive SLNs and non-SLNs, clinical and pathologic stage, extranodal extension, age, and use of PMRT were evaluated for significance regarding the rates of OS and LRR. Results: A total of 345 patients were analyzed. ALND after positive SLN biopsy results was negative in 235 patients (68.1%), and a total of 112 patients (32.5%) received radiation therapy. On multivariate analysis, only pathologic stage III predicted for lower OS (hazard ratio, 3.32; P<.001). The rate of 10-year freedom from LRR was 87.9% and 95.3% in patients with positive ALND results and patients with negative ALND results, respectively. In patients with negative ALND results with ≥3 positive SLNs, the rate of freedom from LRR was 74.7% compared with 96.7% in those with <3 positive SLNs (P=.009). In patients with negative ALND results, ≥3 positive SLNs predicted for an increase in LRR on multivariate analysis (hazard ratio, 10.10; P=.034). Conclusions: A low proportion of cT1-2, N0 patients with positive SLNs who undergo mastectomy receive PMRT after ALND. Even in this low-risk cohort, patients with ≥3 positive SLNs and negative ALND results are at increased risk of LRR and may benefit from PMRT.

[Radiotherapy in node-positive prostate cancer].

Science.gov (United States)

Bottke, D; Bartkowiak, D; Bolenz, C; Wiegel, T

2016-03-01

There are numerous randomized trials to guide the management of patients with localized (and metastatic) prostate cancer, but only a few (mostly retrospective) studies have specifically addressed node-positive patients. Therefore, there is uncertainty regarding optimal treatment in this situation. Current guidelines recommend long-term androgen deprivation therapy (ADT) alone or radiotherapy plus long-term ADT as treatment options. This overview summarizes the existing literature on the use of radiotherapy for node-positive prostate cancer as definitive treatment and as adjuvant or salvage therapy after radical prostatectomy. In this context, we also discuss several PET tracers in the imaging evaluation of patients with biochemical recurrence of prostate cancer after radical prostatectomy. As for definitive treatment, retrospective studies suggest that ADT plus radiotherapy improves overall survival compared with ADT alone. These studies also consistently demonstrated that many patients with node-positive prostate cancer can achieve long-term survival - and are likely curable - with aggressive therapy. The beneficial impact of adjuvant radiotherapy on survival in patients with pN1 prostate cancer seems to be highly influenced by tumor characteristics. Men with ≤ 2 positive lymph nodes in the presence of intermediate- to high-grade disease, or positive margins, and those with 3 or 4 positive lymph nodes are the ideal candidates for adjuvant radiotherapy (plus long-term ADT) after surgery. There is a need for randomized trials to further examine the potential role of radiotherapy as either definitive or adjuvant treatment, for patients with node-positive prostate cancer.

A phase II trial of abiraterone acetate plus prednisone in patients with triple-negative androgen receptor positive locally advanced or metastatic breast cancer (UCBG 12-1).

Science.gov (United States)

Bonnefoi, H; Grellety, T; Tredan, O; Saghatchian, M; Dalenc, F; Mailliez, A; L'Haridon, T; Cottu, P; Abadie-Lacourtoisie, S; You, B; Mousseau, M; Dauba, J; Del Piano, F; Desmoulins, I; Coussy, F; Madranges, N; Grenier, J; Bidard, F C; Proudhon, C; MacGrogan, G; Orsini, C; Pulido, M; Gonçalves, A

2016-05-01

Several expression array studies identified molecular apocrine breast cancer (BC) as a subtype that expresses androgen receptor (AR) but not estrogen receptor α. We carried out a multicentre single-arm phase II trial in women with AR-positive, estrogen, progesterone receptor and HER2-negative (triple-negative) metastatic or inoperable locally advanced BC to assess the efficacy and safety of abiraterone acetate (AA) plus prednisone. Patients with a metastatic or locally advanced, centrally reviewed, triple-negative and AR-positive (≥10% by immunohistochemistry, IHC) BC were eligible. Any number of previous lines of chemotherapy was allowed. AA (1000 mg) was administered once a day with prednisone (5 mg) twice a day until disease progression or intolerance. The primary end point was clinical benefit rate (CBR) at 6 months defined as the proportion of patients presenting a complete response (CR), partial response (PR) or stable disease (SD) ≥6 months. Secondary end points were objective response rate (ORR), progression-free survival (PFS) and safety. One hundred and forty-six patients from 27 centres consented for IHC central review. Of the 138 patients with sufficient tissue available, 53 (37.6%) were AR-positive and triple-negative, and 34 of them were included from July 2013 to December 2014. Thirty patients were eligible and evaluable for the primary end point. The 6-month CBR was 20.0% [95% confidence interval (CI) 7.7%-38.6%], including 1 CR and 5 SD ≥6 months, 5 of them still being under treatment at the time of analysis (6.4+, 9.2+, 14.5+, 17.6+, 23.4+ months). The ORR was 6.7% (95% CI 0.8%-22.1%). The median PFS was 2.8 months (95% CI 1.7%-5.4%). Fatigue, hypertension, hypokalaemia and nausea were the most common drug-related adverse events; the majority of them being grade 1 or 2. AA plus prednisone treatment is beneficial for some patients with molecular apocrine tumours and five patients are still on treatment. NCT01842321. © The Author 2016

Adjuvant Chemotherapy and Trastuzumab Is Safe and Effective in Older Women With Small, Node-Negative, HER2-Positive Early-Stage Breast Cancer.

Science.gov (United States)

Cadoo, Karen A; Morris, Patrick G; Cowell, Elizabeth P; Patil, Sujata; Hudis, Clifford A; McArthur, Heather L

2016-12-01

The benefit of adjuvant trastuzumab with chemotherapy is well established for women with higher risk human epidermal growth factor receptor 2-positive (HER2 + ) breast cancer. However, its role in older patients with smaller, node-negative tumors is less clear. We conducted a retrospective, sequential cohort study of this population to describe the impact of trastuzumab on breast cancer outcomes and cardiac safety. Women ≥ 55 years with ≤ 2 cm, node-negative, HER2 + breast cancer were identified and electronic medical records reviewed. A no-trastuzumab cohort of 116 women diagnosed between January 1, 1999 and May 14, 2004 and a trastuzumab cohort of 128 women diagnosed between May 16, 2006 and December 31, 2010 were identified. Overall survival and distant relapse-free survival were estimated by Kaplan-Meier methods. The median ages of the trastuzumab and no-trastuzumab cohorts were 62 and 64 years, respectively. More patients in the trastuzumab cohort had grade III (P = .001), lymphovascular invasion (P = .001), or estrogen receptor-negative (P cancers. The majority of the trastuzumab cohort received chemotherapy versus one-half of the no-trastuzumab cohort (98% vs. 53%; P women in the trastuzumab cohort and 1 in the no-trastuzumab cohort developed symptomatic heart failure. There were no cardiac-related deaths in either arm. Following adjuvant trastuzumab with chemotherapy, selected older women with small, node-negative, HER2 + breast cancers have excellent disease control. The rate of cardiac events is low. Copyright © 2016 Elsevier Inc. All rights reserved.

Medico-economic impact of MSKCC non-sentinel node prediction nomogram for ER-positive HER2-negative breast cancers.

Directory of Open Access Journals (Sweden)

Hélène Bonsang-Kitzis

Full Text Available Avoiding axillary lymph node dissection (ALND for invasive breast cancers with isolated tumor cells or micrometastatic sentinel node biopsy (SNB could decrease morbidity with minimal clinical significance.The aim of this study is to simulate the medico-economic impact of the routine use of the MSKCC non-sentinel node (NSN prediction nomogram for ER+ HER2- breast cancer patients.We studied 1036 ER+ HER2- breast cancer patients with a metastatic SNB. All had a complementary ALND. For each patient, we calculated the probability of the NSN positivity using the MSKCC nomogram. After validation of this nomogram in the population, we described how the patients' characteristics spread as the threshold value changed. Then, we performed an economic simulation study to estimate the total cost of caring for patients treated according to the MSKCC predictive nomogram results.A 0.3 threshold discriminate the type of sentinel node (SN metastases: 98.8% of patients with pN0(i+ and 91.6% of patients with pN1(mic had a MSKCC score under 0.3 (false negative rate = 6.4%. If we use the 0.3 threshold for economic simulation, 43% of ALND could be avoided, reducing the costs of caring by 1 051 980 EUROS among the 1036 patients.We demonstrated the cost-effectiveness of using the MSKCC NSN prediction nomogram by avoiding ALND for the pN0(i+ or pN1(mic ER+ HER2- breast cancer patients with a MSKCC score of less than or equal to 0.3.

Clinical Initial Response of Neoadjuvant Chemotheraphy in Triple Negative, HER-2, and Luminal Types of Breast Cancer in Denpasar (A Preliminary Study

Directory of Open Access Journals (Sweden)

Kristianto Yuli Yarso

2012-01-01

Full Text Available Objectives: Triple Negative, Luminal, HER-2 subtypes of breast cancer are markers to predict behavior, aggressiveness, and response to chemotherapy. The aim of this study is to understand character and response to standard neoadjuvant chemotherapy in different subtypes of breast cancer. Method: This is a descriptive study of breast cancer subtypes. From 687 patients (2003-2010 351 patients have IHC data which divided into 3 groups, Triple negative, Luminal, and HER-2. We used 10% as a cut off point for ER, PR, while 30% & positive 3 for HER-2. We determined initial clinical response after 3 cycles of neoadjuvant chemotherapy although only 77 got standard neoadjuvant chemotherapy and had clinical response data. We used 50% diameters depreciation & no metastasis as cut off point for respond group. Results: There were 116 (33% Triple Negative, 60 (17% HER-2, and 175 (50% Luminal Subtypes. The mean of age for 351 patients are 48.32 (23-82 years. In this study, it was obtained that no significant difference of means of age (p=0.24 in these 3 groups. Triple negative group significantly more advance in grade if compared with the other two groups (p=0.02. HER-2 group had highest response with standard neoadjuvant chemotherapy (50%, Luminal group had (49%, and Triple negative group had only (15% response. One pCR in HER-2 group. There were no difference ages in subtypes. Triple negative has more advances in grade. HER-2 group has highest response to standard neoadjuvant chemotherapy and Triple negative has lowest response to standard neoadjuvant chemotherapy.

Immunohistochemical subtypes predict the clinical outcome in high-risk node-negative breast cancer patients treated with adjuvant FEC regimen: results of a single-center retrospective study

International Nuclear Information System (INIS)

Rahal, S.; Boher, J M; Extra, J M; Tarpin, C.; Charafe-Jauffret, E.; Lambaudie, E.; Sabatier, R.; Thomassin-Piana, J.; Tallet, A.; Resbeut, M.; Houvenaeghel, G.; Laborde, L.; Bertucci, F.; Viens, P.; Gonçalves, A.

2015-01-01

Anthracycline-based adjuvant chemotherapy improves survival in patients with high-risk node-negative breast cancer (BC). In this setting, prognostic factors predicting for treatment failure might help selecting among the different available cytotoxic combinations. Between 1998 and 2008, 757 consecutive patients with node-negative BC treated in our institution with adjuvant FEC (5FU, epirubicin, cyclophosphamide) chemotherapy were identified. Data collection included demographic, clinico-pathological characteristics and treatment information. Molecular subtypes were derived from estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) status and Scarff-Bloom-Richardson (SBR) grade. Disease-free survival (DFS), distant disease-free survival (DDFS) and overall survival (OS) were estimated using the Kaplan-Meier Method, and prognostic factors were examined by multivariate Cox analysis. After a median follow-up of 70 months, the 5-year DFS, DDFS and OS were 90.6 % (95 % confidence interval (CI): 88.2–93.1), 92.8 % (95 % CI: 90.7–95) and 95.1 % (95 % CI, 93.3–96.9), respectively. In the multivariate analysis including classical clinico-pathological parameters, only grade 3 maintained a significant and independent adverse prognostic impact. In an alternative multivariate model where ER, PR and grade were replaced by molecular subtypes, only luminal B/HER2-negative and triple-negative subtypes were associated with reduced DFS and DDFS. Node-negative BC patients receiving adjuvant FEC regimen have a favorable outcome. Luminal B/HER2-negative and triple-negative subtypes identify patients with a higher risk of treatment failure, which might warrant more aggressive systemic treatment. The online version of this article (doi:10.1186/s12885-015-1746-3) contains supplementary material, which is available to authorized users

Targeting histone abnormality in triple negative breast cancer

Science.gov (United States)

2017-08-01

clinical trials for treatment of cancers such as acute myeloid leukemia (AML) and lung cancer (http://clinicaltrials. gov). LSD2 has been linked to...The Cancer Genome Atlas; AML, acute myeloid leukemia ; DNMT, DNA methyltransferase; TNBC, triple-negative breast cancer; BCSC, breast cancer stem cell

The role of postmastectomy radiotherapy in different molecular subtypes of breast cancer patients with T1 - T2 and one to three positive axillary nodes

International Nuclear Information System (INIS)

Wang Hao; Luo Yangkun; Wang Jie; Peng Ying; Wen Hao; Wang Weidong; Lang Jinyi

2011-01-01

Objective: To analyze the role of postmastectomy radiotherapy in different molecular subtypes of breast cancer patients with Stage T 1 -T 2 and one to three positive axillary nodes. Methods: A total of 436 breast cancer patients with T 1 -T 2 and one to three positive axillary lymph nodes treated with mastectomy and axillary dissection were retrospectively analyzed. Patients were grouped as the following four subtypes:Luminal A, Luminal B, Her 2 + and triple-negative. The local recurrence (LR), distant metastasis ( DM ), disease free survival (DFS) and overall survival (OS) rates were compared between patients with or without radiotherapy in univariate analyses. Multivariate analyses for LR were performed. Results: The follow-up rate was 86. 0%. In patients with Luminal A subtype, radiotherapy decreased the 5-year LR rate (4.6% vs 15.8%, χ 2 =5.74, P=0.017) but had no influences on DM, DFS or OS rates (17.2% vs 19.7%, χ 2 =0.17, P=0.682; 77.0% vs 67.1%, χ 2 =1.99, P=0.158 or 87.4% : 85.5%, χ 2 =0.12, P=0.733). In patients with Luminal B subtype, radiotherapy decreased the 5-year LR rate (3.7% vs 12. 1%, χ 2 =4.13, P =0.042), increased DFS and OS (84.0% vs 57.6% (χ 2 =14.61, P =0.000) and 91.4% vs 70. 7% (χ 2 =11.87, P =0.001), but had no influence on DM (12.3% vs 22.2%, χ 2 =2.97, P =0.085). In patients with Her 2 + subtype, radiotherapy decreased the 5-year LR rate (5.6% vs 31.0%, χ 2 =4.31, P=0.035) , increased DFS (61.1% vs 13.8%, χ 2 =11.44, P=0.001) ,but had no influence on DM and OS (27.8% vs 41.4%, χ 2 =0.89, P =0.345 and 66.7% vs 48.3%, χ 2 =1.52, P =0.218). In patients with triple-negative subtype, radiotherapy had no influence in LR, DM, DFS or OS (8.7% vs 26.1%, χ 2 =2.42, P=0.120; 39.1% vs 47.8%, χ 2 =0.35, P=0.552; 52.2% vs 26.1%, χ 2 =3.29, P =0.070 or 65.2% vs 56.5%, χ 2 =0.37, P =0.546). Tumor size and radiotherapy were independent prognostic factors for LR rate in multivariate analyses (χ 2 =4.76, P =0.029 and χ 2 =8.06, P =0

Clinical Significance of CK19 Negative Breast Cancer

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Fujisue, Mamiko, E-mail: nishimura.reiki@cityhosp-kumamoto.jp; Nishimura, Reiki; Okumura, Yasuhiro [Department of Breast and Endocrine Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Tashima, Rumiko [Department of Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Nishiyama, Yasuyuki; Osako, Tomofumi [Department of Breast and Endocrine Surgery, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan); Toyozumi, Yasuo; Arima, Nobuyuki [Department of Pathology, Kumamoto City Hospital, 1-1-60 Kotoh, Kumamoto City, Kumamoto 862-8505 (Japan)

2012-12-21

Analysis of sentinel lymph nodes (SLNs) by means of One-Step Nucleic Acid Amplification (OSNA) is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19) which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis.

Clinical Significance of CK19 Negative Breast Cancer

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Nobuyuki Arima

2012-12-01

Full Text Available Analysis of sentinel lymph nodes (SLNs by means of One-Step Nucleic Acid Amplification (OSNA is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19 which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis.

Clinical Significance of CK19 Negative Breast Cancer

International Nuclear Information System (INIS)

Fujisue, Mamiko; Nishimura, Reiki; Okumura, Yasuhiro; Tashima, Rumiko; Nishiyama, Yasuyuki; Osako, Tomofumi; Toyozumi, Yasuo; Arima, Nobuyuki

2012-01-01

Analysis of sentinel lymph nodes (SLNs) by means of One-Step Nucleic Acid Amplification (OSNA) is gaining widespread use as a quick and accurate method. This assay detects the expression level of cytokeratin 19 (CK19) which is present in some but not all breast tumors. In this study, the clinical significance of negative CK19 was investigated in 219 cases of primary breast cancer. In 179 patients with clinically negative nodes, OSNA and imprint smear cytology of SLN were performed simultaneously. The OSNA revealed a node-positive rate of 24.6%. Negative CK19 correlated significantly with negative ER/PgR and higher Ki-67 values, and marginally with higher nuclear grade and p53 overexpression. The triple negative subtype showed lower CK19 expression. OSNA revealed that one of the negative CK19 cases was actually a false negative but this was corrected with the use of the imprint smear cytology. In conclusion, CK19 negativity reflected the aggressiveness of primary breast cancer. OSNA assay used to analyze SLN was useful, but there is a possibility that it will mistakenly detect false negatives in CK19 negative tumors. Therefore, in tumors with negative CK19, the imprint smear cytology may be more useful in cases with macrometastasis

Triple Negative Breast Cancer in Pregnancy and Postpartum: Two Case Reports in Hispanic Women

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Ruchi Upadhyay

2015-01-01

Full Text Available Objective. Despite studies suggesting that triple negative breast cancer is more often seen in women of African ancestry, we report here two cases of pregnancy associated triple negative breast cancer in Hispanic women. Cases. Case one is a 37-year-old female para 2-0-0-2, who presented with a left breast mass, at 19 weeks of gestation, the biopsy of which reported an invasive ductal carcinoma, found to be triple receptor negative. The patient underwent chemotherapy during the pregnancy and was delivered with a cesarean at 37 weeks for obstetric indication. After delivery, the patient completed her chemotherapy that was followed by radical mastectomy and radiotherapy. Case two is a 28-year-old female para 6-0-1-5, who presented while breast-feeding with signs and symptoms of mastitis, and an engorged and tender right breast, five months postpartum. However, the sonogram revealed a fluid filled cavity. Aspiration and cytology did not reflect an infection and were negative for malignancy. High suspicion and lack of improvement led to biopsy that identified an invasive ductal carcinoma, found to be triple negative. The patient underwent chemotherapy followed by modified radical mastectomy. Conclusions. Triple negative breast cancer, during pregnancy or postpartum, poses a unique challenge and requires a multidisciplinary team to optimize treatment for these women.

Targeting the androgen receptor in triple-negative breast cancer: current perspectives

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Mina A

2017-09-01

Full Text Available Alain Mina,1 Rachel Yoder,2 Priyanka Sharma1 1Division of Medical Oncology, Department of Internal Medicine, University of Kansas Medical Center, Westwood, 2University of Kansas Cancer Center, Kansas City, KS, USA Abstract: Triple-negative breast cancer (TNBC is an aggressive subtype associated with frequent recurrence and metastasis. Unlike hormone receptor-positive subtypes, treatment of TNBC is currently limited by the lack of clinically available targeted therapies. Androgen signaling is necessary for normal breast development, and its dysregulation has been implicated in breast tumorigenesis. In recent years, gene expression studies have identified a subset of TNBC that is enriched for androgen receptor (AR signaling. Interference with androgen signaling in TNBC is promising, and AR-inhibiting drugs have shown antitumorigenic activity in preclinical and proof of concept clinical studies. Recent advances in our understanding of androgenic signaling in TNBC, along with the identification of interacting pathways, are allowing development of the next generation of clinical trials with AR inhibitors. As novel AR-targeting agents are developed and evaluated in clinical trials, it is equally important to establish a robust set of biomarkers for identification of TNBC tumors that are most likely to respond to AR inhibition. Keywords: triple-negative breast cancer, androgen signaling, targeted therapy, biomarkers, prognosis 

Skin invasion and prognosis in node negative breast cancer: a retrospective study

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Horii Rie

2008-01-01

Full Text Available Abstract Background The impact of skin invasion in node negative breast cancer is uncertain. Methods We determined the prognosis in 97 node negative breast cancer patients (case group who had tumors with skin invasion. Then we compared these patients with 4500 node negative invasive breast cancer patients treated surgically in the same period. Results Patients with skin invasion tended to be older, had more invasive lobular carcinoma and larger tumor size, and were less likely to have breast conserving surgery than those in the control group. The 5-year disease-free survival rate in the case group was 94.0%. There was no significant difference in the 10-year disease-specific overall survival rates in terms of skin invasion in node negative patients (90.7% in the case group, 92.9% in the control group; p = 0.2032. Conclusion Results suggest that skin invasion has no impact on survival in node negative invasive breast cancer patients. The adjuvant regimens which the individual institute applies for node negative breast cancer should be used regardless of skin invasion.

Prediction of risk of distant recurrence using the 21-gene recurrence score in node-negative and node-positive postmenopausal patients with breast cancer treated with anastrozole or tamoxifen: a TransATAC study.

Science.gov (United States)

Dowsett, Mitch; Cuzick, Jack; Wale, Christopher; Forbes, John; Mallon, Elizabeth A; Salter, Janine; Quinn, Emma; Dunbier, Anita; Baum, Michael; Buzdar, Aman; Howell, Anthony; Bugarini, Roberto; Baehner, Frederick L; Shak, Steven

2010-04-10

PURPOSE To determine whether the Recurrence Score (RS) provided independent information on risk of distant recurrence (DR) in the tamoxifen and anastrozole arms of the Arimidex, Tamoxifen, Alone or in Combination (ATAC) Trial. PATIENTS AND METHODS RNA was extracted from 1,372 tumor blocks from postmenopausal patients with hormone receptor-positive primary breast cancer in the monotherapy arms of ATAC. Twenty-one genes were assessed by quantitative reverse transcriptase polymerase chain reaction, and the RS was calculated. Cox proportional hazards models assessed the value of adding RS to a model with clinical variables (age, tumor size, grade, and treatment) in node-negative (N0) and node-positive (N+) women. RESULTS Reportable scores were available from 1,231 evaluable patients (N0, n = 872; N+, n = 306; and node status unknown, n = 53); 72, 74, and six DRs occurred in N0, N+, and node status unknown patients, respectively. For both N0 and N+ patients, RS was significantly associated with time to DR in multivariate analyses (P or = 31) groups were 4%, 12%, and 25%, respectively, in N0 patients and 17%, 28%, and 49%, respectively, in N+ patients. The prognostic value of RS was similar in anastrozole- and tamoxifen-treated patients. CONCLUSION This study confirmed the performance of RS in postmenopausal HR+ patients treated with tamoxifen in a large contemporary population and demonstrated that RS is an independent predictor of DR in N0 and N+ hormone receptor-positive patients treated with anastrozole, adding value to estimates with standard clinicopathologic features.

Downregulation of Smurf2, a tumor-suppressive ubiquitin ligase, in triple-negative breast cancers: Involvement of the RB-microRNA axis

International Nuclear Information System (INIS)

Liu, Xianpeng; Gu, Xin; Sun, Limin; Flowers, Ashley B; Rademaker, Alfred W; Zhou, Yiran; Kiyokawa, Hiroaki

2014-01-01

The HECT family ubiquitin ligase Smurf2 regulates cell polarity, migration, division, differentiation and death, by targeting diverse substrates that are critical for receptor signaling, cytoskeleton, chromatin remodeling and transcription. Recent studies suggest that Smurf2 functions as a tumor suppressor in mice. However, no inactivating mutation of SMURF2 has been reported in human, and information about Smurf2 expression in human cancer remains limited or complicated. Here we demonstrate that Smurf2 expression is downregulated in human breast cancer tissues, especially of the triple-negative subtype, and address the mechanism of Smurf2 downregulation in triple-negative breast cancer cells. Human breast cancer tissues (47 samples expressing estrogen receptor (ER) and 43 samples with triple-negative status) were examined by immunohistochemistry for the expression of Smurf2. Ten widely-studied human breast cancer cell lines were examined for the expression of Smurf2. Furthermore, microRNA-mediated regulation of Smurf2 was investigated in triple-negative cancer cell lines. Immunohistochemical analysis showed that benign mammary epithelial cells expressed high levels of Smurf2, so did cells in ductal carcinomas in situ. In contrast, invasive ductal carcinomas showed focal or diffuse decrease in Smurf2 expression, which was observed more frequently in triple-negative tumors than in ER-positive tumors. Consistently, human triple-negative breast cancer cell lines such as BT549, MDA-MB-436, DU-4475 and MDA-MB-468 cells showed significantly lower expression of Smurf2 protein, compared to ER + or HER2+ cell lines. Studies using quantitative PCR and specific microRNA inhibitors indicated that increased expression of miR-15a, miR-15b, miR-16 and miR-128 was involved in Smurf2 downregulation in those triple-negative cancer cell lines, which have mutations in the retinoblastoma (RB) gene. Forced expression of RB increased levels of Smurf2 protein with concomitant decreases in

Pilot Study on MAGE-C2 as a Potential Biomarker for Triple-Negative Breast Cancer

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Qian Zhao

2016-01-01

Full Text Available Objective. In the current study, we measured the expression status of melanoma antigen gene c2 (MAGE-C2 in triple-negative breast cancer (TNBC and analyzed its prognostic with the clinical pathological features of patients with TNBC. Methods. The expressions statuses of MAGE-C2 were detected in TNBC tissues and paracarcinoma tissues by immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR, and western blotting. Then, we investigated the relationship of MAGE-C2 expression status and clinicopathological parameters of TNBC patients by the chi-squared test. Finally, we discussed the relations of MAGE-C2 expression state and prognosis of patients with TNBC by Kaplan-Meier method and Cox proportional hazards model. Results. High MAGE-C2 expression was found in 38.18% (42/110 of TNBC tissues. In adjacent tissues it was 9.09% (10/110. High MAGE-C2 expression in TNBC patients was closely associated with lymph node status, tumor node metastasis (TNM stage, and lymphovascular invasion (P<0.001. TNBC patients with high MAGE-C2 expression had significantly shorter survival time than low expression patients. We also found that age, lymph node status, TNM stage, lymphovascular invasion, and MAGE-C2 expression status were closely associated with overall survival of TNBC patients (P<0.05. Conclusion. High MAGE-C2 expression may serve as an independent prognostic factor for TNBC patients.

Triple-negative breast cancer: present challenges and new perspectives

NARCIS (Netherlands)

Podo, Franca; Buydens, Lutgarde M. C.; Degani, Hadassa; Hilhorst, Riet; Klipp, Edda; Gribbestad, Ingrid S.; van Huffel, Sabine; van Laarhoven, Hanneke W. M.; Luts, Jan; Monleon, Daniel; Postma, Geert J.; Schneiderhan-Marra, Nicole; Santoro, Filippo; Wouters, Hans; Russnes, Hege G.; Sørlie, Therese; Tagliabue, Elda; Børresen-Dale, Anne-Lise

2010-01-01

Triple-negative breast cancers (TNBC), characterized by absence of estrogen receptor (ER), progesterone receptor (PR) and lack of overexpression of human epidermal growth factor receptor 2 (HER2), are typically associated with poor prognosis, due to aggressive tumor phenotype(s), only partial

DETECTION OF OCCULT LYMPH NODE TUMOR CELLS IN NODE-NEGATIVE GASTRIC CANCER PATIENTS.

Science.gov (United States)

Pereira, Marina Alessandra; Ramos, Marcus Fernando Kodama Pertille; Dias, Andre Roncon; Yagi, Osmar Kenji; Faraj, Sheila Friedrich; Zilberstein, Bruno; Cecconello, Ivan; Mello, Evandro Sobroza de; Ribeiro, Ulysses

2017-01-01

The presence of lymph nodes metastasis is one of the most important prognostic indicators in gastric cancer. The micrometastases have been studied as prognostic factor in gastric cancer, which are related to decrease overall survival and increased risk of recurrence. However, their identification is limited by conventional methodology, since they can be overlooked after routine staining. To investigate the presence of occult tumor cells using cytokeratin (CK) AE1/AE3 immunostaining in gastric cancer patients histologically lymph node negative (pN0) by H&E. Forty patients (T1-T4N0) submitted to a potentially curative gastrectomy with D2 lymphadenectomy were evaluated. The results for metastases, micrometastases and isolated tumor cells were also associated to clinicopathological characteristics and their impact on stage grouping. Tumor deposits within lymph nodes were defined according to the tumor-node-metastases guidelines (7th TNM). A total of 1439 lymph nodes were obtained (~36 per patient). Tumor cells were detected by immunohistochemistry in 24 lymph nodes from 12 patients (30%). Neoplasic cells were detected as a single or cluster tumor cells. Tumor (p=0.002), venous (p=0.016), lymphatic (p=0.006) and perineural invasions (p=0.04), as well as peritumoral lymphocytic response (p=0.012) were correlated to CK-positive immunostaining tumor cells in originally negative lymph nodes by H&E. The histologic stage of two patients was upstaged from stage IB to stage IIA. Four of the 28 CK-negative patients (14.3%) and three among 12 CK-positive patients (25%) had disease recurrence (p=0.65). The CK-immunostaining is an effective method for detecting occult tumor cells in lymph nodes and may be recommended to precisely determine tumor stage. It may be useful as supplement to H&E routine to provide better pathological staging. A presença de metástase em linfonodos é um dos indicadores prognósticos mais importantes no câncer gástrico. As micrometástases têm sido

Clinical efficacy of local targeted chemotherapy for triple-negative breast cancer

International Nuclear Information System (INIS)

He, Jinsong; Wang, Xianming; Guan, Hong; Chen, Weicai; Wang, Ming; Wu, Huisheng; Wang, Zun; Zhou, Ruming; Qiu, Shuibo

2011-01-01

The aim of the study was to evaluate the clinical efficacy of superselective intra-arterial targeted neo-adjuvant chemotherapy in the treatment of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and human epidermal growth factor receptor 2 (HER2)-negative (triple-negative) breast cancer. A total of 47 triple-negative breast cancer patients (29 at stage II, 13 at stage III and 5 at stage IV) were randomly assigned to two groups: targeted chemotherapy group (n=24) and control group (n=23). Patients in the targeted chemotherapy group received preoperative superselective intra-arterial chemotherapy with CEF regimen (C: cyclophosphamide [600 mg/m 2 ]; E: epirubicin [90 mg/m 2 ]; F: 5-fluorouracil [600 mg/m 2 ]), and those in the control group received routine neoadjuvant chemotherapy with CEF. The duration of the treatment, changes in lesions and the prognosis were determined. The average course of the treatment was 15 days in the targeted chemotherapy group which was significantly shorter than that in the control group (31 days) (P<0.01). The remission rate of lesions was 91.6% in the targeted chemotherapy group and 60.9% in the control group, respectively. Among these patients, 9 died within two years, including 2 (both at IV stage) in the targeted chemotherapy group and 7 (2 at stage II, 4 at stage III and 1 at stage IV) in the control group. As an neoadjuvant therapy, the superselective intra-arterial chemotherapy is effective for triple-negative breast cancer, with advantages of the short treatment course and favourable remission rates as well as prognoses

Association Between the 21-Gene Recurrence Score Assay and Risk of Locoregional Recurrence in Node-Negative, Estrogen Receptor–Positive Breast Cancer: Results From NSABP B-14 and NSABP B-20

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Mamounas, Eleftherios P.; Tang, Gong; Fisher, Bernard; Paik, Soonmyung; Shak, Steven; Costantino, Joseph P.; Watson, Drew; Geyer, Charles E.; Wickerham, D. Lawrence; Wolmark, Norman

2010-01-01

Purpose The 21-gene OncotypeDX recurrence score (RS) assay quantifies the risk of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor (ER)–positive breast cancer. We investigated the association between RS and risk for locoregional recurrence (LRR) in patients with node-negative, ER-positive breast cancer from two National Surgical Adjuvant Breast and Bowel Project (NSABP) trials (NSABP B-14 and B-20). Patients and Methods RS was available for 895 tamoxifen-treated patients (from both trials), 355 placebo-treated patients (from B-14), and 424 chemotherapy plus tamoxifen-treated patients (from B-20). The primary end point was time to first LRR. Distant metastases, second primary cancers, and deaths before LRR were censored. Results In tamoxifen-treated patients, LRR was significantly associated with RS risk groups (P 30). There were also significant associations between RS and LRR in placebo-treated patients from B-14 (P = .022) and in chemotherapy plus tamoxifen–treated patients from B-20 (P = .028). In multivariate analysis, RS was an independent significant predictor of LRR along with age and type of initial treatment. Conclusion Similar to the association between RS and risk for distant recurrence, a significant association exists between RS and risk for LRR. This information has biologic consequences and potential clinical implications relative to locoregional therapy decisions for patients with node-negative and ER-positive breast cancer. PMID:20065188

Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20.

Science.gov (United States)

Mamounas, Eleftherios P; Tang, Gong; Fisher, Bernard; Paik, Soonmyung; Shak, Steven; Costantino, Joseph P; Watson, Drew; Geyer, Charles E; Wickerham, D Lawrence; Wolmark, Norman

2010-04-01

The 21-gene OncotypeDX recurrence score (RS) assay quantifies the risk of distant recurrence in tamoxifen-treated patients with node-negative, estrogen receptor (ER)-positive breast cancer. We investigated the association between RS and risk for locoregional recurrence (LRR) in patients with node-negative, ER-positive breast cancer from two National Surgical Adjuvant Breast and Bowel Project (NSABP) trials (NSABP B-14 and B-20). RS was available for 895 tamoxifen-treated patients (from both trials), 355 placebo-treated patients (from B-14), and 424 chemotherapy plus tamoxifen-treated patients (from B-20). The primary end point was time to first LRR. Distant metastases, second primary cancers, and deaths before LRR were censored. In tamoxifen-treated patients, LRR was significantly associated with RS risk groups (P 30). There were also significant associations between RS and LRR in placebo-treated patients from B-14 (P = .022) and in chemotherapy plus tamoxifen-treated patients from B-20 (P = .028). In multivariate analysis, RS was an independent significant predictor of LRR along with age and type of initial treatment. Similar to the association between RS and risk for distant recurrence, a significant association exists between RS and risk for LRR. This information has biologic consequences and potential clinical implications relative to locoregional therapy decisions for patients with node-negative and ER-positive breast cancer.

Imbalance of positive and negative links induces regularity

International Nuclear Information System (INIS)

Kamal, Neeraj Kumar; Sinha, Sudeshna

2011-01-01

Research highlights: → We consider the behaviour of a random weighted network with chaotic neuronal dynamics at the nodes. → We investigate the effect of the balance of positive and negative links on dynamical regularity. → We find that when the connections are predominantly excitatory or inhibitory, one obtains a spatiotemporal fixed point. → However, when the links are balanced, the chaotic nature of the nodal dynamics of the uncoupled case is preserved. → Further we observe that larger network size leads to greater spatiotemporal regularity. - Abstract: We investigate the effect of the interplay of positive and negative links, on the dynamical regularity of a random weighted network, with neuronal dynamics at the nodes. We investigate how the mean J-bar and the variance of the weights of links, influence the spatiotemporal regularity of this dynamical network. We find that when the connections are predominantly positive (i.e. the links are mostly excitatory, with J-bar>0) the spatiotemporal fixed point is stable. A similar trend is observed when the connections are predominantly negative (i.e. the links are mostly inhibitory, with J-bar<0). However, when the positive and negative feedback is quite balanced (namely, when the mean of the connection weights is close to zero) one observes spatiotemporal chaos. That is, the balance of excitatory and inhibitory connections preserves the chaotic nature of the uncoupled case. To be brought to an inactive state one needs one type of connection (either excitatory or inhibitory) to dominate. Further we observe that larger network size leads to greater spatiotemporal regularity. We rationalize our observations through mean field analysis of the network dynamics.

Pathway-Enriched Gene Signature Associated with 53BP1 Response to PARP Inhibition in Triple-Negative Breast Cancer.

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Hassan, Saima; Esch, Amanda; Liby, Tiera; Gray, Joe W; Heiser, Laura M

2017-12-01

Effective treatment of patients with triple-negative (ER-negative, PR-negative, HER2-negative) breast cancer remains a challenge. Although PARP inhibitors are being evaluated in clinical trials, biomarkers are needed to identify patients who will most benefit from anti-PARP therapy. We determined the responses of three PARP inhibitors (veliparib, olaparib, and talazoparib) in a panel of eight triple-negative breast cancer cell lines. Therapeutic responses and cellular phenotypes were elucidated using high-content imaging and quantitative immunofluorescence to assess markers of DNA damage (53BP1) and apoptosis (cleaved PARP). We determined the pharmacodynamic changes as percentage of cells positive for 53BP1, mean number of 53BP1 foci per cell, and percentage of cells positive for cleaved PARP. Inspired by traditional dose-response measures of cell viability, an EC 50 value was calculated for each cellular phenotype and each PARP inhibitor. The EC 50 values for both 53BP1 metrics strongly correlated with IC 50 values for each PARP inhibitor. Pathway enrichment analysis identified a set of DNA repair and cell cycle-associated genes that were associated with 53BP1 response following PARP inhibition. The overall accuracy of our 63 gene set in predicting response to olaparib in seven breast cancer patient-derived xenograft tumors was 86%. In triple-negative breast cancer patients who had not received anti-PARP therapy, the predicted response rate of our gene signature was 45%. These results indicate that 53BP1 is a biomarker of response to anti-PARP therapy in the laboratory, and our DNA damage response gene signature may be used to identify patients who are most likely to respond to PARP inhibition. Mol Cancer Ther; 16(12); 2892-901. ©2017 AACR . ©2017 American Association for Cancer Research.

Practical consensus recommendations on management of triple-negative metastatic breast cancer

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R Rangarao

2018-01-01

Full Text Available Patients with breast cancer along with metastatic estrogen and progesterone receptor (ER/PR- and human epidermal growth factor receptor 2 (HER2-negative tumors are referred to as having metastatic triple-negative breast cancer (mTNBC disease. Resistance to current standard therapies such as anthracyclines or taxanes limits the available options for previously treated patients with metastatic TNBC to a small number of non-cross-resistant regimens, and there is currently no preferred standard chemotherapy. Clinical experience suggests that many women with triple-negative metastatic breast cancer (MBC relapse quickly. Expert oncologist discussed about new chemotherapeutic strategies and agents used in treatment of mTNBC and the expert group used data from published literature, practical experience and opinion of a large group of academic oncologists to arrive at this practical consensus recommendations for the benefit of community oncologists.

Does negative retroperitoneal CT in adolescents with paratesticular rhabdomyosarcoma preclude the need of retroperitoneal lymph node dissection?

International Nuclear Information System (INIS)

Damazio, Eulalio; Caran, Eliana; Ortiz, Valdemar; Macedo Junior, Antonio

2011-01-01

We report on a 16-year-old male with paratesticular rhabdomyosarcoma who underwent retroperitoneal lymph node dissection due to a stage I tumor (normal retroperitoneal computed tomography). The surgical finding was three enlarged nodes, positive for metastatic disease. Patient was referred to adjuvant chemotherapy. This case suggests that the Intergroup Rhabdomyosarcoma Study Group IV protocol is subject to questions regarding adolescents with paratesticular rhabdomyosarcoma, and that negative retroperitoneal CT does not preclude the need of lymph node dissection. (author)

Prognostic factors in patients with node-negative gastric cancer: an Indian experience

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Ranganathan Rama

2011-05-01

Full Text Available Abstract Background The status of the regional nodes is the most important prognostic factor in gastric cancer. There are subgroups of patients with different prognosis even in node-negative patients of gastric cancer. The aim of this study is to analyze the factors influencing the prognosis in Indian patients with node-negative gastric cancer. Methods This was a retrospective analysis of patients who underwent radical gastrectomy in a tertiary cancer centre in India between1991 and 2007. The study group included only patients with histologically node-negative disease. Various clinical, pathological and treatment related factors in this group of patients were analyzed to determine their prognostic ability by univariate and multivariate analyses. Results Among the 417 patients who underwent gastrectomy during this period, 122 patients had node-negative disease. A major proportion of the patients had advanced gastric cancer. The 5-year overall survival and disease-free survival in all node-negative gastric cancer patients was 68.2% and 67.5% respectively. The overall recurrence rate in this group was 27.3%. On univariate analysis, the factors found to significantly influence the disease-free survival were the size, location and presence or absence of serosal invasion of the primary tumor. However, on multivariate analysis, only tumor size more than 3 cm and serosal invasion were found to be independently associated with an inferior survival. Conclusion Serosal invasion and primary tumor size more than 3 cm independently predict a poor outcome in patients with node-negative gastric cancer.

Sentinel Node Biopsy Alone versus Completion Axillary Node Dissection in Node Positive Breast Cancer: Systematic Review and Meta-Analysis

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Rachna Ram

2014-01-01

Full Text Available Introduction. There has been recent interest in validity of completion axillary node dissection after a positive sentinel node. This systematic review aims to ascertain if sentinel lymph node dissection alone was noninferior to axillary lymph node dissection for breast cancer patients who have a positive sentinel node. Method. A systematic review of the electronic databases Embase, MEDLINE, and Cochrane Register of Controlled Trials was carried out. Only randomised trials that had patients with positive sentinel node as the study sample were included in the meta-analysis using the reported hazard ratios with a fixed effect model. Results. Three randomised controlled trials and five retrospective studies were identified. The pooled effect for overall survival was HR 0.94, 95% CI [0.79, 1.19], and for disease free survival was HR 0.83, 95% CI [0.60, 1.14]. The reported rates for locoregional recurrence were similar in both groups. The surgical morbidity was found to be significantly more in patients who had underwent axillary dissection. Conclusion. Amongst patients with micrometastasis in the sentinel node, no further axillary dissection is necessary. For patients with macrometastasis in the sentinel node, it is reasonable to consider omitting axillary dissection to avoid the morbidity of the procedure.

ADAM-17: a novel therapeutic target for triple negative breast cancer.

LENUS (Irish Health Repository)

McGowan, P M

2013-02-01

Validated targeted therapy is currently unavailable for patients with invasive breast cancer negative for oestrogen receptors, progesterone receptors and HER2 [i.e., those with triple-negative (TN) disease]. ADAM-17 is a protease involved in the activations of several ligands that bind to and promotes intracellular signalling from the EGFR\\/HER family of receptors.

Outcomes of Node-positive Breast Cancer Patients Treated With Accelerated Partial Breast Irradiation Via Multicatheter Interstitial Brachytherapy: The Pooled Registry of Multicatheter Interstitial Sites (PROMIS) Experience.

Science.gov (United States)

Kamrava, Mitchell; Kuske, Robert R; Anderson, Bethany; Chen, Peter; Hayes, John; Quiet, Coral; Wang, Pin-Chieh; Veruttipong, Darlene; Snyder, Margaret; Demanes, David J

2018-06-01

To report outcomes for breast-conserving therapy using adjuvant accelerated partial breast irradiation (APBI) with interstitial multicatheter brachytherapy in node-positive compared with node-negative patients. From 1992 to 2013, 1351 patients (1369 breast cancers) were treated with breast-conserving surgery and adjuvant APBI using interstitial multicatheter brachytherapy. A total of 907 patients (835 node negative, 59 N1a, and 13 N1mic) had >1 year of data available and nodal status information and are the subject of this analysis. Median age (range) was 59 years old (22 to 90 y). T stage was 90% T1 and ER/PR/Her2 was positive in 87%, 71%, and 7%. Mean number of axillary nodes removed was 12 (SD, 6). Cox multivariate analysis for local/regional control was performed using age, nodal stage, ER/PR/Her2 receptor status, tumor size, grade, margin, and adjuvant chemotherapy/antiestrogen therapy. The mean (SD) follow-up was 7.5 years (4.6). The 5-year actuarial local control (95% confidence interval) in node-negative versus node-positive patients was 96.3% (94.5-97.5) versus 95.8% (87.6-98.6) (P=0.62). The 5-year actuarial regional control in node-negative versus node-positive patients was 98.5% (97.3-99.2) versus 96.7% (87.4-99.2) (P=0.33). The 5-year actuarial freedom from distant metastasis and cause-specific survival were significantly lower in node-positive versus node-negative patients at 92.3% (82.4-96.7) versus 97.8% (96.3-98.7) (P=0.006) and 91.3% (80.2-96.3) versus 98.7% (97.3-99.3) (P=0.0001). Overall survival was not significantly different. On multivariate analysis age 50 years and below, Her2 positive, positive margin status, and not receiving chemotherapy or antiestrogen therapy were associated with a higher risk of local/regional recurrence. Patients who have had an axillary lymph node dissection and limited node-positive disease may be candidates for treatment with APBI. Further research is ultimately needed to better define specific criteria for APBI

Extranodal extension of axillary metastasis of invasive breast carcinoma as a possible predictor for the total number of positive lymph nodes

NARCIS (Netherlands)

Palamba, H. W.; Rombouts, M. C.; Ruers, T. J.; Klinkenbijl, J. H.; Wobbes, T.

2001-01-01

By the implementation of the sentinel node procedure in the treatment of breast carcinoma routine axillary lymph node, dissection can be abandoned in patients with a tumour-negative sentinel node. When the sentinel node is positive there are two options; an axillary dissection or radiotherapy of the

The Prognostic Value of Lymph Nodes Dissection Number on Survival of Patients with Lymph Node-Negative Gastric Cancer

Directory of Open Access Journals (Sweden)

Wu Song

2014-01-01

Full Text Available Objective. The study was designed to explore the prognostic value of examined lymph node (LN number on survival of gastric cancer patients without LN metastasis. Methods. Between August 1995 and January 2011, 300 patients who underwent gastrectomy with D2 lymphadenectomy for LN-negative gastric cancer were reviewed. Patients were assigned to various groups according to LN dissection number or tumor invasion depth. Some clinical outcomes, such as overall survival, operation time, length of stay, and postoperative complications, were compared among all groups. Results. The overall survival time of LN-negative GC patients was 50.2±30.5 months. Multivariate analysis indicated that LN dissection number (P30. Besides, it was not correlated with operation time, transfusion volume, length of postoperative stay, or postoperative complication incidence (P>0.05. Conclusions. The number of examined lymph nodes is an independent prognostic factor of survival for patients with lymph node-negative gastric cancer. Sufficient dissection of lymph nodes is recommended during surgery for such population.

CCR 20th Anniversary Commentary: Triple-Negative Breast Cancer in 2015—Still in the Ballpark.

Science.gov (United States)

Narod, Steven A; Dent, Rebecca A; Foulkes, William D

2015-09-01

The research article by Dent and colleagues, which was published in the August 1, 2007, issue of Clinical Cancer Research, provided a clinical description of metastatic progression of triple-negative breast cancers. Finding successful treatment strategies for women with triple-negative breast cancer remains a challenge. ©2015 American Association for Cancer Research.

Breast cancer-specific survival in patients with lymph node-positive hormone receptor-positive invasive breast cancer and Oncotype DX Recurrence Score results in the SEER database.

Science.gov (United States)

Roberts, Megan C; Miller, Dave P; Shak, Steven; Petkov, Valentina I

2017-06-01

The Oncotype DX ® Breast Recurrence Score™ (RS) assay is validated to predict breast cancer (BC) recurrence and adjuvant chemotherapy benefit in select patients with lymph node-positive (LN+), hormone receptor-positive (HR+), HER2-negative BC. We assessed 5-year BC-specific survival (BCSS) in LN+ patients with RS results in SEER databases. In this population-based study, BC cases in SEER registries (diagnosed 2004-2013) were linked to RS results from assays performed by Genomic Health (2004-2014). The primary analysis included only patients (diagnosed 2004-2012) with LN+ (including micrometastases), HR+ (per SEER), and HER2-negative (per RT-PCR) primary invasive BC (N = 6768). BCSS, assessed by RS category and number of positive lymph nodes, was calculated using the actuarial method. The proportion of patients with RS results and LN+ disease (N = 8782) increased over time between 2004 and 2013, and decreased with increasing lymph node involvement from micrometastases to ≥4 lymph nodes. Five-year BCSS outcomes for those with RS < 18 ranged from 98.9% (95% CI 97.4-99.6) for those with micrometastases to 92.8% (95% CI 73.4-98.2) for those with ≥4 lymph nodes. Similar patterns were found for patients with RS 18-30 and RS ≥ 31. RS group was strongly predictive of BCSS among patients with micrometastases or up to three positive lymph nodes (p < 0.001). Overall, 5-year BCSS is excellent for patients with RS < 18 and micrometastases, one or two positive lymph nodes, and worsens with additionally involved lymph nodes. Further analyses should account for treatment variables, and longitudinal updates will be important to better characterize utilization of Oncotype DX testing and long-term survival outcomes.

Radiographically Negative, Asymptomatic, Sentinel Lymph Node Positive Cutaneous T-Cell Lymphoma in a 3-Year-Old Male: A Case Report

Directory of Open Access Journals (Sweden)

Jeffrey Carson

2012-01-01

Full Text Available We present a case of a 3-year-old male originally diagnosed with a CD30+ anaplastic cutaneous T-cell lymphoma with no evidence of systemic disease after CT scan, PET scan, and bone marrow aspiration. Sentinel lymph node biopsy (SLNB was performed as an additional step in the workup and showed microscopic disease. Current management/recommendations for cutaneous T-cell lymphoma do not include SLNB. Medical and surgical management of cutaneous malignancies is dramatically different for local versus advanced disease. Therefore adequate evaluation is necessary to properly stage patients for specific treatment. Such distinction in extent of disease suggests more extensive therapy including locoregional radiation and systemic chemotherapy versus local excision only. Two international case reports have described SLNB in cutaneous T-cell lymphoma with one demonstrating evidence of node positive microscopic disease despite a negative metastatic disease workup. This case is being presented as a novel case in a child with implications including lymphoscintigraphy and SLNB as a routine procedure for evaluation and staging of cutaneous T-cell lymphoma if the patient does not demonstrate evidence of metastatic disease on routine workup.

An investigation into scalability and compliance for triple patterning with stitches for metal 1 at the 14nm node

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Cork, Christopher; Miloslavsky, Alexander; Friedberg, Paul; Luk-Pat, Gerry

2013-04-01

Lithographers had hoped that single patterning would be enabled at the 20nm node by way of EUV lithography. However, due to delays in EUV readiness, double patterning with 193i lithography is currently relied upon for volume production for the 20nm node's metal 1 layer. At the 14nm and likely at the 10nm node, LE-LE-LE triple patterning technology (TPT) is one of the favored options [1,2] for patterning local interconnect and Metal 1 layers. While previous research has focused on TPT for contact mask, metal layers offer new challenges and opportunities, in particular the ability to decompose design polygons across more than one mask. The extra flexibility offered by the third mask and ability to leverage polygon stitching both serve to improve compliance. However, ensuring TPT compliance - the task of finding a 3-color mask decomposition for a design - is still a difficult task. Moreover, scalability concerns multiply the difficulty of triple patterning decomposition which is an NP-complete problem. Indeed previous work shows that network sizes above a few thousand nodes or polygons start to take significantly longer times to compute [3], making full chip decomposition for arbitrary layouts impractical. In practice Metal 1 layouts can be considered as two separate problem domains, namely: decomposition of standard cells and decomposition of IP blocks. Standard cells typically include only a few 10's of polygons and should be amenable to fast decomposition. Successive design iterations should resolve compliance issues and improve packing density. Density improvements are multiplied repeatedly as standard cells are placed multiple times. IP blocks, on the other hand, may involve very large networks. This paper evaluates multiple approaches to triple patterning decomposition for the Metal 1 layer. The benefits of polygon stitching, in particular, the ability to resolve commonly encountered non-compliant layout configurations and improve packing density, are weighed

Targeting Histone Abnormality in Triple Negative Breast Cancer

Science.gov (United States)

2016-08-01

W81XWH-14-1-0237 Triple-Negative Breast Cancer Davidson, PI U10 CA180844 NCI NCTN-Network Lead 5% 2014- 2019 $11,255 Davidson, Co-PI Academic Site...MD AACR High Tech Strategic Business Meeting, Sunnyvale, CA Medical Oncology Board Review, George Washington University, Washington, DC Great...both ductal car - cinoma in situ and invasive ductal carcinoma of the breast. Oncogene 2003; 22: 2021–2033. 25 Lin T, Ponn A, Hu X, Law BK, Lu J

Reduced risk of axillary lymphatic spread in triple-negative breast cancer

DEFF Research Database (Denmark)

Holm-Rasmussen, Emil Villiam; Jensen, Maj-Britt; Balslev, Eva

2015-01-01

We examined the association between the hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status of women with primary breast cancer and the risk of axillary lymph node (ALN) involvement at the time of diagnosis. Information on 20,009 women diagnosed with primary breast...... cancer between 2008 and 2012 was retrieved from the Danish Breast Cancer Cooperative Group database. The associations between clinical and pathological variables and ALN involvement at the time of diagnosis were evaluated in univariate and multivariate regression analyses, as well as the significance......-negative breast cancer (TNBC) patients showed a significantly reduced risk of ALN involvement at the time of diagnosis compared to patients with HR-positive/HER2-negative tumors (OR 0.55; 95 % CI 0.49-0.62; P

Genetic Analysis of Microglandular Adenosis and Acinic Cell Carcinomas of the Breast Provides Evidence for the Existence of a Low-grade Triple-Negative Breast Neoplasia Family

Science.gov (United States)

Geyer, Felipe C; Berman, Samuel H.; Marchiò, Caterina; Burke, Kathleen A; Guerini-Rocco, Elena; Piscuoglio, Salvatore; Ng, Charlotte K Y; Pareja, Fresia; Wen, Hannah Y; Hodi, Zoltan; Schnitt, Stuart J; Rakha, Emad A; Ellis, Ian O; Norton, Larry; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

Acinic cell carcinoma is an indolent form of invasive breast cancer, whereas microglandular adenosis has been shown to be a neoplastic proliferation. Both entities display a triple-negative phenotype, and may give rise to and display somatic genomic alterations typical of high-grade triple-negative breast cancers. Here we report on a comparison of previously published data on eight carcinoma-associated microglandular adenosis and eight acinic cell carcinomas subjected to targeted massively parallel sequencing targeting all exons of 236 genes recurrently mutated in breast cancer and/or DNA repair-related. Somatic mutations, insertions/deletions and copy number alterations were detected using state-of-the-art bioinformatic algorithms. All cases were of triple-negative phenotype. A median of 4.5 (1–13) and 4.0 (1–7) non-synonymous somatic mutations per carcinoma-associated microglandular adenosis and acinic cell carcinoma were identified, respectively. TP53 was the sole highly recurrently mutated gene (75% in microglandular adenosis versus 88% in acinic cell carcinomas), and TP53 mutations were consistently coupled with loss of heterozygosity of the wild-type allele. Additional somatic mutations shared by both groups included those in BRCA1, PIK3CA and INPP4B. Recurrent (n=2) somatic mutations restricted to microglandular adenosis or acinic cell carcinomas included those affecting PTEN and MED12, or ERBB4, respectively. No significant differences in the repertoire of somatic mutations were detected between microglandular adenosis and acinic cell carcinomas, and between this group of lesions and 77 triple-negative carcinomas from The Cancer Genome Atlas. Microglandular adenosis and acinic cell carcinomas, however, were genetically distinct from estrogen receptor-positive and/or HER2-positive breast cancers from The Cancer Genome Atlas. Our findings support the contention that microglandular adenosis and acinic cell carcinoma are part of the same spectrum of lesions

Wnt signaling in triple-negative breast cancer

Science.gov (United States)

Pohl, SÖ-G; Brook, N; Agostino, M; Arfuso, F; Kumar, A P; Dharmarajan, A

2017-01-01

Wnt signaling regulates a variety of cellular processes, including cell fate, differentiation, proliferation and stem cell pluripotency. Aberrant Wnt signaling is a hallmark of many cancers. An aggressive subtype of breast cancer, known as triple-negative breast cancer (TNBC), demonstrates dysregulation in canonical and non-canonical Wnt signaling. In this review, we summarize regulators of canonical and non-canonical Wnt signaling, as well as Wnt signaling dysfunction that mediates the progression of TNBC. We review the complex molecular nature of TNBC and the emerging therapies that are currently under investigation for the treatment of this disease. PMID:28368389

Triple p-positive parenting program for mothers of ADHD children.

Science.gov (United States)

Aghebati, Asma; Gharraee, Banafsheh; Hakim Shoshtari, Mitra; Gohari, Mahmood Reza

2014-01-01

Attention deficit hyperactivity disorder (ADHD) is a chronic, highly prevalent neurodevelopmental disorder which affects 9% of school-age children. Triple P-Positive Parenting Program is an evidence-based parenting program reported to be useful in the management of this disorder. The aim of this randomized controlled trial was to evaluate the effectiveness of Triple P in mothers of ADHD children. In this study, 30 mothers with ADHD children aged between 6 to 10 were randomly assigned to two groups (15 participants in each group). Parenting style, mother-child relationship, maternal depression, anxiety and stress, and children's behavioral problems were evaluated. The intervention group received 120 minute sessions for 5 weeks and 15-30 minute telephone contacts for 3 weeks while no intervention was done for the control group. Analysis of covariance revealed that mothers of the Triple P group showed significant (p parenting style, mother-child relationship, and considerable decrease in depression, anxiety and stress. Women trained in the Triple P group also reported significantly lower rates of child misbehavior than women of the control group. Triple P-Positive Parenting intervention is effective and acceptable for mothers of ADHD children. None. Clinical Trial Registration-URL: http://www.irct.ir. Unique identifier: IRCT201111288234N1.

19p13.1 is a triple-negative-specific breast cancer susceptibility locus

DEFF Research Database (Denmark)

Stevens, Kristen N; Fredericksen, Zachary; Vachon, Celine M

2012-01-01

(PR), and human epidermal growth factor receptor-2 (HER2) status, using 48,869 breast cancer cases and 49,787 controls from the Breast Cancer Association Consortium (BCAC). Variants from 19p13.1 were not associated with breast cancer overall or with ER-positive breast cancer but were significantly......The 19p13.1 breast cancer susceptibility locus is a modifier of breast cancer risk in BRCA1 mutation carriers and is also associated with the risk of ovarian cancer. Here, we investigated 19p13.1 variation and risk of breast cancer subtypes, defined by estrogen receptor (ER), progesterone receptor...... associated with ER-negative breast cancer risk [rs8170 OR, 1.10; 95% confidence interval (CI), 1.05-1.15; P = 3.49 × 10(-5)] and triple-negative (ER-, PR-, and HER2-negative) breast cancer (rs8170: OR, 1.22; 95% CI, 1.13-1.31; P = 2.22 × 10(-7)). However, rs8170 was no longer associated with ER...

Evidence for the Existence of Triple-Negative Variants in the MCF-7 Breast Cancer Cell Population

Directory of Open Access Journals (Sweden)

Euphemia Leung

2014-01-01

Full Text Available The MCF-7 line, derived in 1973 from a malignant pleural effusion, is one of the most commonly used culture models for human breast cancer. Despite its long history, MCF-7 is a surprisingly heterogeneous line. We previously showed that if MCF-7 cells were cultured for a prolonged period either in the absence of estrogen or in the presence of the antiestrogen tamoxifen, sub-lines were selected that differed from the parental line in ploidy, mean cell volume, signaling pathway usage, and drug sensitivity. This suggests a process of selection of preexisting variants rather than of adaptation of the parental line. All the sublines were estrogen receptor (ER positive, raising the question of whether MCF-7 also contains ER negative variants. Here, we have looked for such variants by culturing for a prolonged period in the presence of fulvestrant, an estrogen antagonist that has no estrogen agonist activity. Three sublines were developed, each of which was ER negative, progesterone receptor (PR negative and expressed only a low level of HER2. Each of the variants differed from the original MCF-7 line in ploidy, modal cell volume, and signaling pathway usage. Control experiments in which cells were cultured for a prolonged period in the absence of estrogen selected for variants that were ER and PR positive. The properties of the triple-negative MCF-7 were compared with those of an existing triple-negative cell line, MDA-MB-231, and human epidermal growth factor receptor 2 (HER2+ SKBr3, as well as from those of the “immortalized” breast epithelial line MCF10A. The results suggest that new variants or phenotypes of MCF-7 might be generated continuously in culture, and by implication this might apply to breast cancer development and even normal breast epithelial development in vivo.

Whole-exome sequencing identifies novel MPL and JAK2 mutations in triple-negative myeloproliferative neoplasms.

Science.gov (United States)

Milosevic Feenstra, Jelena D; Nivarthi, Harini; Gisslinger, Heinz; Leroy, Emilie; Rumi, Elisa; Chachoua, Ilyas; Bagienski, Klaudia; Kubesova, Blanka; Pietra, Daniela; Gisslinger, Bettina; Milanesi, Chiara; Jäger, Roland; Chen, Doris; Berg, Tiina; Schalling, Martin; Schuster, Michael; Bock, Christoph; Constantinescu, Stefan N; Cazzola, Mario; Kralovics, Robert

2016-01-21

Essential thrombocythemia (ET) and primary myelofibrosis (PMF) are chronic diseases characterized by clonal hematopoiesis and hyperproliferation of terminally differentiated myeloid cells. The disease is driven by somatic mutations in exon 9 of CALR or exon 10 of MPL or JAK2-V617F in >90% of the cases, whereas the remaining cases are termed "triple negative." We aimed to identify the disease-causing mutations in the triple-negative cases of ET and PMF by applying whole-exome sequencing (WES) on paired tumor and control samples from 8 patients. We found evidence of clonal hematopoiesis in 5 of 8 studied cases based on clonality analysis and presence of somatic genetic aberrations. WES identified somatic mutations in 3 of 8 cases. We did not detect any novel recurrent somatic mutations. In 3 patients with clonal hematopoiesis analyzed by WES, we identified a somatic MPL-S204P, a germline MPL-V285E mutation, and a germline JAK2-G571S variant. We performed Sanger sequencing of the entire coding region of MPL in 62, and of JAK2 in 49 additional triple-negative cases of ET or PMF. New somatic (T119I, S204F, E230G, Y591D) and 1 germline (R321W) MPL mutation were detected. All of the identified MPL mutations were gain-of-function when analyzed in functional assays. JAK2 variants were identified in 5 of 57 triple-negative cases analyzed by WES and Sanger sequencing combined. We could demonstrate that JAK2-V625F and JAK2-F556V are gain-of-function mutations. Our results suggest that triple-negative cases of ET and PMF do not represent a homogenous disease entity. Cases with polyclonal hematopoiesis might represent hereditary disorders. © 2016 by The American Society of Hematology.

The prevalence of BRCA1 mutations among young women with triple-negative breast cancer

International Nuclear Information System (INIS)

Young, SR; DeSai, Damini; Zandvakili, Inuk; Royer, Robert; Li, Song; Narod, Steven A; Pilarski, Robert T; Donenberg, Talia; Shapiro, Charles; Hammond, Lyn S; Miller, Judith; Brooks, Karen A; Cohen, Stephanie; Tenenholz, Beverly

2009-01-01

Molecular screening for BRCA1 and BRCA2 mutations is now an established component of risk evaluation and management of familial breast cancer. Features of hereditary breast cancer include an early age-of-onset and over-representation of the 'triple-negative' phenotype (negative for estrogen-receptor, progesterone-receptor and HER2). The decision to offer genetic testing to a breast cancer patient is usually based on her family history, but in the absence of a family history of cancer, some women may qualify for testing based on the age-of-onset and/or the pathologic features of the breast cancer. We studied 54 women who were diagnosed with high-grade, triple-negative invasive breast cancer at or before age 40. These women were selected for study because they had little or no family history of breast or ovarian cancer and they did not qualify for genetic testing using conventional family history criteria. BRCA1 screening was performed using a combination of fluorescent multiplexed-PCR analysis, BRCA1 exon-13 6 kb duplication screening, the protein truncation test (PTT) and fluorescent multiplexed denaturing gradient gel electrophoresis (DGGE). All coding exons of BRCA1 were screened. The two large exons of BRCA2 were also screened using PTT. All mutations were confirmed with direct sequencing. Five deleterious BRCA1 mutations and one deleterious BRCA2 mutation were identified in the 54 patients with early-onset, triple-negative breast cancer (11%). Women with early-onset triple-negative breast cancer are candidates for genetic testing for BRCA1, even in the absence of a family history of breast or ovarian cancer

Integrated microRNA and mRNA signatures associated with survival in triple negative breast cancer.

Science.gov (United States)

Cascione, Luciano; Gasparini, Pierluigi; Lovat, Francesca; Carasi, Stefania; Pulvirenti, Alfredo; Ferro, Alfredo; Alder, Hansjuerg; He, Gang; Vecchione, Andrea; Croce, Carlo M; Shapiro, Charles L; Huebner, Kay

2013-01-01

Triple negative breast cancer (TNBC) is a heterogeneous disease at the molecular, pathologic and clinical levels. To stratify TNBCs, we determined microRNA (miRNA) expression profiles, as well as expression profiles of a cancer-focused mRNA panel, in tumor, adjacent non-tumor (normal) and lymph node metastatic lesion (mets) tissues, from 173 women with TNBCs; we linked specific miRNA signatures to patient survival and used miRNA/mRNA anti-correlations to identify clinically and genetically different TNBC subclasses. We also assessed miRNA signatures as potential regulators of TNBC subclass-specific gene expression networks defined by expression of canonical signal pathways.Tissue specific miRNAs and mRNAs were identified for normal vs tumor vs mets comparisons. miRNA signatures correlated with prognosis were identified and predicted anti-correlated targets within the mRNA profile were defined. Two miRNA signatures (miR-16, 155, 125b, 374a and miR-16, 125b, 374a, 374b, 421, 655, 497) predictive of overall survival (P = 0.05) and distant-disease free survival (P = 0.009), respectively, were identified for patients 50 yrs of age or younger. By multivariate analysis the risk signatures were independent predictors for overall survival and distant-disease free survival. mRNA expression profiling, using the cancer-focused mRNA panel, resulted in clustering of TNBCs into 4 molecular subclasses with different expression signatures anti-correlated with the prognostic miRNAs. Our findings suggest that miRNAs play a key role in triple negative breast cancer through their ability to regulate fundamental pathways such as: cellular growth and proliferation, cellular movement and migration, Extra Cellular Matrix degradation. The results define miRNA expression signatures that characterize and contribute to the phenotypic diversity of TNBC and its metastasis.

Survival and local control rates of triple-negative breast cancer patients treated with boost-IOERT during breast-conserving surgery

Energy Technology Data Exchange (ETDEWEB)

Fastner, Gerd; Zehentmayr, Franz; Kopp, Peter; Fussl, Christoph; Sedlmayer, Felix [Landeskrankenhaus, Paracelsus Medical University, Department of Radiotherapy and Radio-Oncology, Salzburg (Austria); Hauser-Kronberger, Cornelia [Landeskrankenhaus, Paracelsus Medical University, Department of Pathology, Salzburg (Austria); Moder, Angelika [Landeskrankenhaus, Paracelsus Medical University, Institute of Inborn Errors in Metabolism, Salzburg (Austria); Reitsamer, Roland; Fischer, Thorsten [Landeskrankenhaus, Paracelsus Medical University, Department of Special Gynecology, Salzburg (Austria); Landeskrankenhaus, Paracelsus Medical University, Department of Gynecology, Salzburg (Austria); Deutschmann, Heinrich [Landeskrankenhaus, Paracelsus Medical University, Department of Radiotherapy and Radio-Oncology, Salzburg (Austria); Paracelsus Medical University, Institute for Research and Development of Advanced Radiation Technologies (radART), Salzburg (Austria)

2016-01-15

The purpose of this work was to retrospectively evaluate survival and local control rates of triple-negative breast cancer subtypes classified as five marker negative (5NP) and core basal (CB), respectively, after breast-conserving surgery and intraoperative boost radiotherapy with electrons (IOERT) followed by whole breast irradiation. A total of 71 patients with triple-negative breast cancer were enrolled, who were treated with lumpectomy, axillary lymph node dissection, and IOERT with 9.6 Gy (median D{sub max}) followed by normofractionated whole breast irradiation to median total doses of 54 Gy. Chemotherapy was applied in a neoadjuvant (12 %), adjuvant (75 %), or combinational setting (7 %). After a median follow-up of 97 months (range 4-170 months), 5 in-breast recurrences were detected (7.0 %). For all patients, 8-year actuarial rates for local control, metastases-free survival, disease-specific survival, and overall survival amounted to 89, 75, 80, and 69 %, respectively. All local recurrences occurred in grade 3 (G3) tumors irrespective of their specific immunohistochemical phenotype; thus, the local control rate for grades 1/2 (G1/2) was 100 % for both 5NP and CB, while for G3 it was 88 % for 5NP and 90 % for CB (p = 0.65 and 0.82, respectively, n.s.). For disease-specific survival, only the difference of the best-prognosis group 5-NP/G3 vs. the worst-prognosis cohort CB/G1/2 was statistically significant: 90 % vs. 54 % (p = 0.03). Boost-IOERT provides acceptable long-term in-breast control in triple negative breast cancer. The best subgroup in terms of disease-specific survival was represented by 5NP in combination with tumor grading G3. (orig.) [German] Ziel der Studie war es, im Rahmen einer retrospektiven Analyse Ueberlebens- und Lokalkontrollraten bei triple-negativen Mammakarzinomen zu untersuchen. Die Tumoren waren in 5NP(5-Marker-negative)- und CB(core basal)-Subtypen klassifiziert und die Patientinnen hatten nach brusterhaltender Operation und

Lymph Node Yield as a Predictor of Survival in Pathologically Node Negative Oral Cavity Carcinoma.

Science.gov (United States)

Lemieux, Aaron; Kedarisetty, Suraj; Raju, Sharat; Orosco, Ryan; Coffey, Charles

2016-03-01

Even after a pathologically node-negative (pN0) neck dissection for oral cavity squamous cell carcinoma (SCC), patients may develop regional recurrence. In this study, we (1) hypothesize that an increased number of lymph nodes removed (lymph node yield) in patients with pN0 oral SCC predicts improved survival and (2) explore predictors of survival in these patients using a multivariable model. Case series with chart review. Administrative database analysis. The SEER database was queried for patients diagnosed with all-stage oral cavity SCC between 1988 and 2009 who were determined to be pN0 after elective lymph node dissection. Demographic and treatment variables were extracted. The association of lymph node yield with 5-year all-cause survival was studied with multivariable survival analyses. A total of 4341 patients with pN0 oral SCC were included in this study. The 2 highest lymph node yield quartiles (representing >22 nodes removed) were found to be significant predictors of overall survival (22-35 nodes: hazard ratio [HR] = 0.854, P = .031; 36-98 nodes: HR = 0.827, P = .010). Each additional lymph node removed during neck dissection was associated with increased survival (HR = 0.995, P = .022). These data suggest that patients with oral SCC undergoing elective neck dissection may experience an overall survival benefit associated with greater lymph node yield. Mechanisms behind the demonstrated survival advantage are unknown. Larger nodal dissections may remove a greater burden of microscopic metastatic disease, diminishing the likelihood of recurrence. Lymph node yield may serve as an objective measure of the adequacy of lymphadenectomy. © American Academy of Otolaryngology—Head and Neck Surgery Foundation 2015.

A Study of Triple Negative Breast Cancer at a Tertiary Cancer Care ...

African Journals Online (AJOL)

cause of cancer deaths worldwide. It is the ... Background: Triple negative breast cancers (TNBCs) are a diverse and heterogeneous group .... nonHispanic black patients with breast cancer, at 24.6%. ... chance of breast conservation rates.

Proposal for the delineation of the nodal CTV in the node-positive and the post-operative neck

International Nuclear Information System (INIS)

Gregoire, Vincent; Eisbruch, Avraham; Hamoir, Marc; Levendag, Peter

2006-01-01

Background and purpose: In 2003, a panel of experts published a set of consensus guidelines regarding the delineation of the neck node levels (Radiother Oncol, 2003; 69: 227-36). These recommendations were applicable for the node-negative and the N1-neck, but were found too restrictive for the node-positive and the post-operative neck. Patients and methods: In this framework, using the previous recommendations as a backbone, new guidelines have been proposed taking into account the specificities of the node-positive and the post-operative neck. Results: Inclusion of the retrostyloid space cranially and the supra-clavicular fossa caudally is proposed in case of neck nodes (defined radiologically or on the surgical specimen) located in levels II, and IV or Vb, respectively. When extra-capsular rupture is suspected (on imaging) or demonstrated on the pathological specimen, adjacent muscles should also be included in the CTV. For node(s) located at the boundary between contiguous levels (e.g. levels II and Ib), these two levels should be delineated. In the post-operative setting, the entire 'surgical bed' should be included. Last, the retropharyngeal space should be delineated in case of positive neck from pharyngeal tumors. Conclusions: The objective of the manuscript is to give a comprehensive description of the new set of guidelines for CTV delineation in the node-positive neck and the post-operative neck, with a complementary atlas of the new anatomical structures to be included

Pre-treatment double- or triple-positive tumor markers are predictive of a poor outcome for patients undergoing radiofrequency ablation for hepatocellular carcinoma.

Science.gov (United States)

Nitta, Hidetoshi; Nakagawa, Shigeki; Kaida, Takayoshi; Arima, Kota; Higashi, Takaaki; Taki, Katsunobu; Okabe, Hirohisa; Hayashi, Hiromitsu; Hashimoto, Daisuke; Chikamoto, Akira; Ishiko, Takatoshi; Beppu, Toru; Baba, Hideo

2017-03-01

We evaluated the therapeutic effect of radiofrequency ablation (RFA) on hepatocellular carcinoma (HCC) according to the number of positive tumor markers. The subjects of this study were 160 patients who underwent percutaneous and surgical RFA for HCC. Patients were divided into negative (n = 51), single- (n = 69), double- (n = 31), and triple-positive (n = 9) tumor marker groups according to the pre-treatment expression of these markers. We looked for any relationships among clinical parameters, outcomes, and tumor markers. The 3-year recurrence-free and overall survival rates of the negative, single-, double-, and triple-positive groups were 30, 19, 16, and 11 % (P = 0.02), and 94, 88, 67, and 37 % (P tumor marker profile was independently associated with local recurrence [hazard ratio (HR) 5.48, 95 % confidence interval (CI) 2.44-12.33, P tumor markers.

Metastatic triple-negative breast cancer is dependent on SphKs/S1P signaling for growth and survival.

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Maiti, Aparna; Takabe, Kazuaki; Hait, Nitai C

2017-04-01

About 40,000 American women die from metastatic breast cancer each year despite advancements in treatment. Approximately, 15% of breast cancers are triple-negative for estrogen receptor, progesterone receptor, and HER2. Triple-negative cancer is characterized by more aggressive, harder to treat with conventional approaches and having a greater possibility of recurrence. Sphingosine-1-phosphate (S1P) is a bioactive sphingolipid signaling mediator has emerged as a key regulatory molecule in breast cancer progression. Therefore, we investigated whether cytosolic sphingosine kinase type 1 (SphK1) and nuclear sphingosine kinase type 2 (SphK2), the enzymes that make S1P are critical for growth and PI3K/AKT, ERK-MAP kinase mediated survival signaling of lung metastatic variant LM2-4 breast cancer cells, generated from the parental triple-negative MDA-MB-231 human breast cancer cell line. Similar with previous report, SphKs/S1P signaling is critical for the growth and survival of estrogen receptor positive MCF-7 human breast cancer cells, was used as our study control. MDA-MB-231 did not show a significant effect of SphKs/S1P signaling on AKT, ERK, and p38 pathways. In contrast, LM2-4 cells that gained lung metastatic phenotype from primary MDA-MB-231 cells show a significant effect of SphKs/S1P signaling requirement on cell growth, survival, and cell motility. PF-543, a selective potent inhibitor of SphK1, attenuated epidermal growth factor (EGF)-mediated cell growth and survival signaling through inhibition of AKT, ERK, and p38 MAP kinase pathways mainly in LM2-4 cells but not in parental MDA-MB-231 human breast cancer cells. Moreover, K-145, a selective inhibitor of SphK2, markedly attenuated EGF-mediated cell growth and survival of LM2-4 cells. We believe this study highlights the importance of SphKs/S1P signaling in metastatic triple-negative breast cancers and targeted therapies. Copyright © 2017 Elsevier Inc. All rights reserved.

Heterogeneity of triple-negative breast cancer: mammographic, US, and MR imaging features according to androgen receptor expression

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Bae, Min Sun; Song, Sung Eun; Kim, Won Hwa; Lee, Su Hyun; Moon, Woo Kyung [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea, Republic of); Park, So Yeon; Park, In-Ae [Seoul National University College of Medicine, Department of Pathology, Seoul (Korea, Republic of); Han, Wonshik; Noh, Dong-Young [Seoul National University College of Medicine, Department of Surgery, Seoul (Korea, Republic of)

2014-09-16

Our aim was to determine whether triple-negative breast cancers (TNBCs) with and without androgen receptor (AR) expression have distinguishing imaging features on mammography, breast ultrasound (US), and magnetic resonance (MR) imaging. AR expression was assessed immunohistochemically in 125 patients with TNBC from a consecutive series of 1,086 operable invasive breast cancers. Two experienced radiologists blinded to clinicopathological findings reviewed all imaging studies in consensus using the BI-RADS lexicon. The imaging and pathological features of 33 AR-positive TNBCs were compared with those of 92 AR-negative TNBCs. The presence of mammographic calcifications with or without a mass (p < 0.001), non-mass enhancement on MR imaging (p < 0.001), and masses with irregular shape or spiculated margins on US (p < 0.001 and p = 0.002) and MR imaging (p = 0.001 and p < 0.001) were significantly associated with AR-positive TNBC. Compared with AR-negative TNBC, AR-positive TNBC was more likely to have a ductal carcinoma in situ component (59.8 % vs. 90.9 %, p = 0.001) and low Ki-67 expression (30.4 % vs. 51.5 %, p = 0.030). AR-positive and AR-negative TNBCs have different imaging features, and certain imaging findings can be useful to predict AR status in TNBC. (orig.)

Long-Term Complete Remission with nab-Paclitaxel, Bevacizumab, and Gemcitabine Combination Therapy in a Patient with Triple-Negative Metastatic Breast Cancer

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Alberto Montero

2012-12-01

Full Text Available This is a case study of a 52-year-old female patient diagnosed in June 2007 with primary metastatic invasive ductal carcinoma of the left breast and synchronous metastases in the bone, lymph nodes, and lung. Biopsy results of the tumor tissue were negative for the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2. In November 2007, she participated in a phase II study of metastatic HER2-negative breast cancer. Treatment consisted of systemic chemotherapy with gemcitabine 1,500 mg/m2, nab-paclitaxel 150 mg/m2, and bevacizumab 10 mg/kg once every other week. The patient experienced pain relief in her sternum after 5 weeks of chemotherapy, and her analgesic therapy was discontinued. After 7 months, the patient achieved a complete radiographic response, which was maintained for nearly 2 additional years. She continued receiving treatment throughout this period, requiring 1 dose reduction due to fatigue. The patient experienced no other adverse events, including neuropathy, and continued working uninterrupted throughout her treatment. The patient was discontinued from the study in May 2010 after disease progression, almost a full 3 years after diagnosis. The patient showed minimal response to subsequent therapies but had disease stabilization and died from her disease in April 2012. Median overall survival for patients with metastatic triple-negative breast cancer is between 12 and 13.3 months. This patient survived nearly 5 years following diagnosis. This case exemplifies how therapy with nab-paclitaxel, bevacizumab, and gemcitabine may prolong survival, with minimal toxicity, in select patients with triple-negative metastatic breast cancer.

A population-based study of tumor gene expression and risk of breast cancer death among lymph node-negative patients.

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Habel, Laurel A; Shak, Steven; Jacobs, Marlena K; Capra, Angela; Alexander, Claire; Pho, Mylan; Baker, Joffre; Walker, Michael; Watson, Drew; Hackett, James; Blick, Noelle T; Greenberg, Deborah; Fehrenbacher, Louis; Langholz, Bryan; Quesenberry, Charles P

2006-01-01

The Oncotype DX assay was recently reported to predict risk for distant recurrence among a clinical trial population of tamoxifen-treated patients with lymph node-negative, estrogen receptor (ER)-positive breast cancer. To confirm and extend these findings, we evaluated the performance of this 21-gene assay among node-negative patients from a community hospital setting. A case-control study was conducted among 4,964 Kaiser Permanente patients diagnosed with node-negative invasive breast cancer from 1985 to 1994 and not treated with adjuvant chemotherapy. Cases (n = 220) were patients who died from breast cancer. Controls (n = 570) were breast cancer patients who were individually matched to cases with respect to age, race, adjuvant tamoxifen, medical facility and diagnosis year, and were alive at the date of death of their matched case. Using an RT-PCR assay, archived tumor tissues were analyzed for expression levels of 16 cancer-related and five reference genes, and a summary risk score (the Recurrence Score) was calculated for each patient. Conditional logistic regression methods were used to estimate the association between risk of breast cancer death and Recurrence Score. After adjusting for tumor size and grade, the Recurrence Score was associated with risk of breast cancer death in ER-positive, tamoxifen-treated and -untreated patients (P = 0.003 and P = 0.03, respectively). At 10 years, the risks for breast cancer death in ER-positive, tamoxifen-treated patients were 2.8% (95% confidence interval [CI] 1.7-3.9%), 10.7% (95% CI 6.3-14.9%), and 15.5% (95% CI 7.6-22.8%) for those in the low, intermediate and high risk Recurrence Score groups, respectively. They were 6.2% (95% CI 4.5-7.9%), 17.8% (95% CI 11.8-23.3%), and 19.9% (95% CI 14.2-25.2%) for ER-positive patients not treated with tamoxifen. In both the tamoxifen-treated and -untreated groups, approximately 50% of patients had low risk Recurrence Score values. In this large, population-based study of lymph

Clinicopathological Characteristics of Triple-negative Breast Cancers in the Northeast Region of Turkey

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Bülent Yıldız

2014-06-01

Full Text Available Background: Triple-negative (TN breast cancer is a subtype of breast cancer characterised by a loss of estrogen receptor (ER, progesterone receptor (PR expression, and the absence of human epidermal growth factor (HER2 overexpression. Aims: To identify the relationships between clinicopathological characteristics of TN breast cancers in the northeast region of Turkey and disease free survival (DFS and overall survival (OS. Study Design: Retrospective clinical study. Methods: Seven hundred and eighty non-metastatic breast cancer patients were enrolled in this study. The relationships between TN breast cancer and other breast cancers with respect to clinicopathological characteristics, as well as DFS and OS, were studied. Results: The triple-negative phenotype was detected in 204 patients (27.1%. Patients with triple-negative breast cancer had more grade 2-3 tumours compared to those with other types of breast cancer (92.5% versus 84.3%, p=0.004. Invasive ductal carcinoma histology, on the other hand, was less prevalent in patients with TN breast cancer (77% versus 84.5%, p=0.016. No significant differences were identified between the groups in other clinicopathological variables. Relapse and mortality rates were higher in the TN group during the follow-up of both groups [57 (27.9% versus 89 (16.2%, p<0.001 for relapse; 27 (13.2% versus 37 (6.8%, p=0.005 for mortality]. The univariate analysis demonstrated shorter DFS and OS for patients with TN breast cancer compared to those with other types of breast cancer. In the multivariate analysis, patients with TN breast cancer were 2.21 times more likely to develop relapse, while the likelihood of death increased 3.21-fold (p<0.001 and p<0.001. Conclusion: Triple-negative breast cancers demonstrate a more aggressive clinical course compared to other breast cancers. More effective strategies should be developed for the treatment of this subgroup of breast cancer.

Inhibition of PKM2 sensitizes triple-negative breast cancer cells to doxorubicin

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Wang, Feng [Department of Gastroenterology, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai 200072 (China); Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Yang, Yong, E-mail: yyang@houstonmethodist.org [Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Department of Medicine, Weill Cornell Medical College, New York, NY 10065 (United States)

2014-11-21

Highlights: • Suppression of PKM2 sensitizes triple-negative breast cancer cells to doxorubicin. • Repression of PKM2 affects the glycolysis and decreases ATP production. • Downregulation of PKM2 increases the intracellular accumulation of doxorubicin. • Inhibition of PKM2 enhances the antitumor efficacy of doxorubicin in vivo. - Abstract: Cancer cells alter regular metabolic pathways in order to sustain rapid proliferation. One example of metabolic remodeling in cancerous tissue is the upregulation of pyruvate kinase isoenzyme M2 (PKM2), which is involved in aerobic glycolysis. Indeed, PKM2 has previously been identified as a tumor biomarker and as a potential target for cancer therapy. Here, we examined the effects of combined treatment with doxorubicin and anti-PKM2 small interfering RNA (siRNA) on triple-negative breast cancer (TNBC). The suppression of PKM2 resulted in changes in glucose metabolism, leading to decreased synthesis of adenosine triphosphate (ATP). Reduced levels of ATP resulted in the intracellular accumulation of doxorubicin, consequently enhancing the therapeutic efficacy of this drug in several triple-negative breast cancer cell lines. Furthermore, the combined effect of PKM2 siRNA and doxorubicin was evaluated in an in vivo MDA-MB-231 orthotopic breast cancer model. The siRNA was systemically administered through a polyethylenimine (PEI)-based delivery system that has been extensively used. We demonstrate that the combination treatment showed superior anticancer efficacy as compared to doxorubicin alone. These findings suggest that targeting PKM2 can increase the efficacy of chemotherapy, potentially providing a new approach for improving the outcome of chemotherapy in patients with TNBC.

Radial displacement of clinical target volume in node negative head and neck cancer

International Nuclear Information System (INIS)

Jeon, Wan; Wu, Hong Gyun; Song, Sang Hyuk; Kim, Jung In

2012-01-01

To evaluate the radial displacement of clinical target volume in the patients with node negative head and neck (H and N) cancer and to quantify the relative positional changes compared to that of normal healthy volunteers. Three node-negative H and N cancer patients and fi ve healthy volunteers were enrolled in this study. For setup accuracy, neck thermoplastic masks and laser alignment were used in each of the acquired computed tomography (CT) images. Both groups had total three sequential CT images in every two weeks. The lymph node (LN) level of the neck was delineated based on the Radiation Therapy Oncology Group (RTOG) consensus guideline by one physician. We use the second cervical vertebra body as a reference point to match each CT image set. Each of the sequential CT images and delineated neck LN levels were fused with the primary image, then maximal radial displacement was measured at 1.5 cm intervals from skull base (SB) to caudal margin of LN level V, and the volume differences at each node level were quantified. The mean radial displacements were 2.26 (±1.03) mm in the control group and 3.05 (±1.97) in the H and N cancer patients. There was a statistically significant difference between the groups in terms of the mean radial displacement (p = 0.03). In addition, the mean radial displacement increased with the distance from SB. As for the mean volume differences, there was no statistical significance between the two groups. This study suggests that a more generous radial margin should be applied to the lower part of the neck LN for better clinical target coverage and dose delivery.

Preoperative F-18-FDG PET for the detection of metastatic cervical lymph nodes in recurrent papillary thyroid carcinoma patients with negative I-131 whole body scans

International Nuclear Information System (INIS)

Byun, Byung Hyun; Urn, Sang Moo; Cheon, Gi Jeong; Choi, Chang Woon; Lee, Byeong Cheol; Lee, Guk Haeng; Lee, Yong Sik; Shim, Youn Sang

2007-01-01

We evaluated the diagnostic performance of FDG-PET for the detection of metastatic cervical lymph nodes in recurrent papillary thyroid carcinoma patients with negative I-131 scan. All patients had total thyroidectomy and following I-131 ablation therapy. In the follow-up period, FDG-PET showed suspected cervical lymph nodes metastases and neck dissection was performed within 3 months after FDG-PET. It had shown for all patients the negative I-131 scan within 3 months before FDG-PET or negative I-131 scan during the period of cervical lymph nodes metastases suspected on the basis of FDG-PET, CT, or ultrasonography until the latest FDG-PET. Preoperative FDG-PET results were compared with the pathologic findings of lymph nodes specimens of 19 papillary thyroid carcinoma patients. Serum Tg, TSH, and Tg antibody levels at the time of latest I-131 scan were reviewed. The size of lymph node was measured by preoperative CT or ultrasonography. In 45 cervical lymph node groups dissected, 31 lymph node groups revealed metastasis. The sensitivity and specificity of FDG-PET for metastasis were 74.2% (23 of 31) and 50.0% (7 of 14), respectively. Except for patients with elevated Tg antibody levels, all patients showed the elevated serum Tg levels than normal limits at the TSH of =30uIU/ml. 8 lesions without suspected metastatic findings on FDG-PET revealed metastasis (false negative), and none of them exceeded 8mm in size (4 to 8mm, median= 6mm). On the other hand, 23 true positive lesions on FDG-PET were variable in size (6 to 17mm, median=9mm). FDG-PET is suitable for the detection of metastatic cervical lymph nodes in patients with recurrent papillary thyroid carcinoma. However, false positive or false negative should be considered according to the size of lymph node

Modulation of the BRCA1 Protein and Induction of Apoptosis in Triple Negative Breast Cancer Cell Lines by the Polyphenolic Compound Curcumin

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Danica L. Rowe

2009-09-01

Full Text Available In the current study, we sought to examine the effects of curcumin in a specific type of breast cancer called triple negative breast cancer. These cancers lack expression of the estrogen and progesterone receptors and do not over-express HER2. Current treatment for triple negative breast cancers is limited to cytotoxic chemotherapy, and upon relapse, there are not any therapies currently available. We demonstrate here that the bioactive food compound curcumin induces DNA damage in triple negative breast cancer cells in association with phosphorylation, increased expression, and cytoplasmic retention of the BRCA1 protein. In addition, curcumin promotes apoptosis and prevents anchorage-independent growth and migration of triple negative breast cancer cells. Apoptosis and BRCA1 modulation were not observed in non-transformed mammary epithelial cells, suggesting curcumin may have limited non-specific toxicity. This study suggests that curcumin and potentially curcumin analogues should be tested further in the context of triple negative breast cancer. These results are novel, having never been previously reported, and suggest that curcumin could provide a novel, non-toxic therapy, which could lead to improved survival for patients with triple negative breast cancer. Curcumin should be studied further in this subset of breast cancer patients, for whom treatment options are severely limited.

Efficacy of Neoadjuvant Cisplatin in Triple-Negative Breast Cancer

DEFF Research Database (Denmark)

Szallasi, Zoltan Imre; Eklund, Aron Charles; Li, Qiyuan

2010-01-01

PURPOSE Cisplatin is a chemotherapeutic agent not used routinely for breast cancer treatment. As a DNA cross-linking agent, cisplatin may be effective treatment for hereditary BRCA1-mutated breast cancers. Because sporadic triple-negative breast cancer (TNBC) and BRCA1-associated breast cancer...... samples were evaluated for selected biomarkers. Results Six (22%) of 28 patients achieved pathologic complete responses, including both patients with BRCA1 germline mutations;18 (64%) patients had a clinical complete or partial response. Fourteen (50%) patients showed good pathologic responses (Miller...

Prognostic and Predictive Value of the 21-Gene Recurrence Score Assay in a Randomized Trial of Chemotherapy for Postmenopausal, Node-Positive, Estrogen Receptor-Positive Breast Cancer

Science.gov (United States)

Albain, Kathy S.; Barlow, William E.; Shak, Steven; Hortobagyi, Gabriel N.; Livingston, Robert B.; Yeh, I-Tien; Ravdin, Peter; Bugarini, Roberto; Baehner, Frederick L.; Davidson, Nancy E.; Sledge, George W.; Winer, Eric P.; Hudis, Clifford; Ingle, James N.; Perez, Edith A.; Pritchard, Kathleen I.; Shepherd, Lois; Gralow, Julie R.; Yoshizawa, Carl; Allred, D. Craig; Osborne, C. Kent; Hayes, Daniel F.

2010-01-01

SUMMARY Background The 21-gene Recurrence Score assay (RS) is prognostic for women with node-negative, estrogen receptor (ER)-positive breast cancer (BC) treated with tamoxifen. A low RS predicts little benefit of chemotherapy. For node-positive BC, we investigated whether RS was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher recurrence risks. Methods The phase III trial S8814 for postmenopausal women with node-positive, ER-positive BC showed that CAF chemotherapy prior to tamoxifen (CAF-T) added survival benefit to tamoxifen alone. Optional tumor banking yielded specimens for RS determination by RT-PCR. We evaluated the effect of RS on disease-free survival (DFS) by treatment group (tamoxifen versus CAF-T) using Cox regression adjusting for number of positive nodes. Findings There were 367 specimens (40% of parent trial) with sufficient RNA (tamoxifen, 148; CAF-T, 219). The RS was prognostic in the tamoxifen arm (p=0.006). There was no CAF benefit in the low RS group (logrank p=0.97; HR=1.02, 95% CI (0.54,1.93)), but major DFS improvement for the high RS subset (logrank p=.03; HR=0.59, 95% CI (0.35, 1.01)), adjusting for number of positive nodes. The RS-by-treatment interaction was significant in the first 5 years (p=0.029), with no additional prediction beyond 5 years (p=0.58), though the cumulative benefit remained at 10 years. Results were similar for overall survival and BC-specific survival. Interpretation In this retrospective analysis, the RS is prognostic for tamoxifen-treated patients with positive nodes and predicts significant CAF benefit in tumors with a high RS. A low RS identifies women who may not benefit from anthracycline-based chemotherapy despite positive nodes. PMID:20005174

Identifying Triple-Negative Breast Cancer Using Background Parenchymal Enhancement Heterogeneity on Dynamic Contrast-Enhanced MRI: A Pilot Radiomics Study.

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Jeff Wang

Full Text Available To determine the added discriminative value of detailed quantitative characterization of background parenchymal enhancement in addition to the tumor itself on dynamic contrast-enhanced (DCE MRI at 3.0 Tesla in identifying "triple-negative" breast cancers.In this Institutional Review Board-approved retrospective study, DCE-MRI of 84 women presenting 88 invasive carcinomas were evaluated by a radiologist and analyzed using quantitative computer-aided techniques. Each tumor and its surrounding parenchyma were segmented semi-automatically in 3-D. A total of 85 imaging features were extracted from the two regions, including morphologic, densitometric, and statistical texture measures of enhancement. A small subset of optimal features was selected using an efficient sequential forward floating search algorithm. To distinguish triple-negative cancers from other subtypes, we built predictive models based on support vector machines. Their classification performance was assessed with the area under receiver operating characteristic curve (AUC using cross-validation.Imaging features based on the tumor region achieved an AUC of 0.782 in differentiating triple-negative cancers from others, in line with the current state of the art. When background parenchymal enhancement features were included, the AUC increased significantly to 0.878 (p<0.01. Similar improvements were seen in nearly all subtype classification tasks undertaken. Notably, amongst the most discriminating features for predicting triple-negative cancers were textures of background parenchymal enhancement.Considering the tumor as well as its surrounding parenchyma on DCE-MRI for radiomic image phenotyping provides useful information for identifying triple-negative breast cancers. Heterogeneity of background parenchymal enhancement, characterized by quantitative texture features on DCE-MRI, adds value to such differentiation models as they are strongly associated with the triple-negative subtype

Prevalence of papillomaviruses, polyomaviruses, and herpesviruses in triple-negative and inflammatory breast tumors from algeria compared with other types of breast cancer tumors.

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Marilys Corbex

Full Text Available The possible role of viruses in breast cancer etiology remains an unresolved question. We hypothesized that if some viruses are involved, it may be in a subgroup of breast cancers only. Epidemiological arguments drove our interest in breast cancer subgroups that are more frequent in Africa, namely inflammatory breast cancer (IBC and triple-negative breast cancer. We tested whether viral prevalence was significantly higher in these subgroups.One hundred fifty-five paraffin-embedded malignant breast tumors were randomly selected at the pathology laboratory of the University Hospital of Annaba (Algeria to include one third of IBC and two thirds of non-IBC. They were tested for the presence of DNA from 61 viral agents (46 human papillomaviruses, 10 polyomaviruses, and 5 herpesviruses using type-specific multiplex genotyping assays, which combine multiplex PCR and bead-based Luminex technology.Viral DNA was found in 22 (17.9% of 123 tumors. The most prevalent viruses were EBV1 and HPV16. IBC tumors carried significantly more viruses (any type than non-IBC tumors (30% vs. 13%, p<0.04. Similarly, triple-negative tumors displayed higher virus-positivity than non-triple-negative tumors (44% vs. 14%, p<0.009.Our results suggest an association between the presence of viral DNA and aggressive breast cancer phenotypes (IBC, triple-negative. While preliminary, they underline the importance of focusing on subgroups when studying viral etiology in breast cancer. Further studies on viruses in breast cancer should be conducted in much larger samples to confirm these initial findings.

ONC201 demonstrates anti-tumor effects in both triple negative and non-triple negative breast cancers through TRAIL-dependent and TRAIL-independent mechanisms

OpenAIRE

Ralff, Marie D.; Kline, Christina L.B.; Küçükkase, Ozan C; Wagner, Jessica; Lim, Bora; Dicker, David T.; Prabhu, Varun V.; Oster, Wolfgang; El-Deiry, Wafik S.

2017-01-01

Breast cancer is a major cause of cancer-related death. TRAIL has been of interest as a cancer therapeutic, but only a subset of triple negative breast cancers (TNBC) is sensitive to TRAIL. The small molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here we show that ONC201 is efficacious against both TNBC and non-TNBC cells (n=13). A subset of TNBC and non-TNBC cells succumb to ONC201-induced cell death. In 2/8 TNBC cell...

21-Gene Recurrence Score and Locoregional Recurrence in Node-Positive/ER-Positive Breast Cancer Treated With Chemo-Endocrine Therapy.

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Mamounas, Eleftherios P; Liu, Qing; Paik, Soonmyung; Baehner, Frederick L; Tang, Gong; Jeong, Jong-Hyeon; Kim, S Rim; Butler, Steven M; Jamshidian, Farid; Cherbavaz, Diana B; Sing, Amy P; Shak, Steven; Julian, Thomas B; Lembersky, Barry C; Wickerham, D Lawrence; Costantino, Joseph P; Wolmark, Norman

2017-01-01

The 21-gene recurrence score (RS) predicts risk of locoregional recurrence (LRR) in node-negative, estrogen receptor (ER)-positive breast cancer. We evaluated the association between RS and LRR in node-positive, ER-positive patients treated with adjuvant chemotherapy plus tamoxifen in National Surgical Adjuvant Breast and Bowel Project B-28. B-28 compared doxorubicin/cyclophosphamide (AC X 4) with AC X 4 followed by paclitaxel X 4. Tamoxifen was given to patients age 50 years or older and those younger than age 50 years with ER-positive and/or progesterone receptor-positive tumors. Lumpectomy patients received breast radiotherapy. Mastectomy patients received no radiotherapy. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Cumulative incidence functions and subdistribution hazard regression models were used for LRR to account for competing risks including distant recurrence, second primary cancers, and death from other causes. Median follow-up was 11.2 years. All statistical tests were one-sided. There were 80 LRRs (7.5%) as first events (68% local/32% regional). RS was low: 36.2%; intermediate: 34.2%; and high: 29.6%. RS was a statistically significant predictor of LRR in univariate analyses (10-year cumulative incidence of LRR = 3.3%, 7.2%, and 12.2% for low, intermediate, and high RS, respectively, P < .001). In multivariable regression analysis, RS remained an independent predictor of LRR (hazard ratio [HR] = 2.59, 95% confidence interval [CI] = 1.28 to 5.26, for a 50-point difference, P = .008) along with pathologic nodal status (HR = 1.91, 95% CI = 1.20 to 3.03, for four or more vs one to three positive nodes, P = .006) and tumor size (HR = 1.28, 95% CI = 1.05 to 1.55, for a 1 cm difference, P = .02). RS statistically significantly predicts risk of LRR in node-positive, ER-positive breast cancer patients after adjuvant chemotherapy plus tamoxifen. These findings can help in the selection of

Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients

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Siggelkow Wulf

2012-11-01

Full Text Available Abstract Background Inhibitors targeting the cell cycle-regulated aurora kinase A (AURKA are currently being developed. Here, we examine the prognostic impact of AURKA in node-negative breast cancer patients without adjuvant systemic therapy (n = 766. Methods AURKA was analyzed using microarray-based gene-expression data from three independent cohorts of node-negative breast cancer patients. In multivariate Cox analyses, the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER, and HER2 were considered. Results Patients with higher AURKA expression had a shorter metastasis-free survival (MFS in the Mainz (HR 1.93; 95% CI 1.34 – 2.78; P Conclusions AURKA is associated with worse prognosis in estrogen receptor positive breast carcinomas. Patients with the highest AURKA expression (>75% percentile have a particularly bad prognosis and may profit from therapy with AURKA inhibitors.

Advancement of mass spectrometry-based proteomics technologies to explore triple negative breast cancer.

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Miah, Sayem; Banks, Charles A S; Adams, Mark K; Florens, Laurence; Lukong, Kiven E; Washburn, Michael P

2016-12-20

Understanding the complexity of cancer biology requires extensive information about the cancer proteome over the course of the disease. The recent advances in mass spectrometry-based proteomics technologies have led to the accumulation of an incredible amount of such proteomic information. This information allows us to identify protein signatures or protein biomarkers, which can be used to improve cancer diagnosis, prognosis and treatment. For example, mass spectrometry-based proteomics has been used in breast cancer research for over two decades to elucidate protein function. Breast cancer is a heterogeneous group of diseases with distinct molecular features that are reflected in tumour characteristics and clinical outcomes. Compared with all other subtypes of breast cancer, triple-negative breast cancer is perhaps the most distinct in nature and heterogeneity. In this review, we provide an introductory overview of the application of advanced proteomic technologies to triple-negative breast cancer research.

Vitamin D compounds inhibit cancer stem-like cells and induce differentiation in triple negative breast cancer.

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Shan, Naing Lin; Wahler, Joseph; Lee, Hong Jin; Bak, Min Ji; Gupta, Soumyasri Das; Maehr, Hubert; Suh, Nanjoo

2017-10-01

Triple-negative breast cancer is one of the least responsive breast cancer subtypes to available targeted therapies due to the absence of hormonal receptors, aggressive phenotypes, and the high rate of relapse. Early breast cancer prevention may therefore play an important role in delaying the progression of triple-negative breast cancer. Cancer stem cells are a subset of cancer cells that are thought to be responsible for tumor progression, treatment resistance, and metastasis. We have previously shown that vitamin D compounds, including a Gemini vitamin D analog BXL0124, suppress progression of ductal carcinoma in situ in vivo and inhibit cancer stem-like cells in MCF10DCIS mammosphere cultures. In the present study, the effects of vitamin D compounds in regulating breast cancer stem-like cells and differentiation in triple-negative breast cancer were assessed. Mammosphere cultures, which enriches for breast cancer cells with stem-like properties, were used to assess the effects of 1α,25(OH) 2 D 3 and BXL0124 on cancer stem cell markers in the triple-negative breast cancer cell line, SUM159. Vitamin D compounds significantly reduced the mammosphere forming efficiency in primary, secondary and tertiary passages of mammospheres compared to control groups. Key markers of cancer stem-like phenotype and pluripotency were analyzed in mammospheres treated with 1α,25(OH) 2 D 3 and BXL0124. As a result, OCT4, CD44 and LAMA5 levels were decreased. The vitamin D compounds also down-regulated the Notch signaling molecules, Notch1, Notch2, Notch3, JAG1, JAG2, HES1 and NFκB, which are involved in breast cancer stem cell maintenance. In addition, the vitamin D compounds up-regulated myoepithelial differentiating markers, cytokeratin 14 and smooth muscle actin, and down-regulated the luminal marker, cytokeratin 18. Cytokeratin 5, a biomarker associated with basal-like breast cancer, was found to be significantly down-regulated by the vitamin D compounds. These results suggest

A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer.

Science.gov (United States)

Paik, Soonmyung; Shak, Steven; Tang, Gong; Kim, Chungyeul; Baker, Joffre; Cronin, Maureen; Baehner, Frederick L; Walker, Michael G; Watson, Drew; Park, Taesung; Hiller, William; Fisher, Edwin R; Wickerham, D Lawrence; Bryant, John; Wolmark, Norman

2004-12-30

The likelihood of distant recurrence in patients with breast cancer who have no involved lymph nodes and estrogen-receptor-positive tumors is poorly defined by clinical and histopathological measures. We tested whether the results of a reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assay of 21 prospectively selected genes in paraffin-embedded tumor tissue would correlate with the likelihood of distant recurrence in patients with node-negative, tamoxifen-treated breast cancer who were enrolled in the National Surgical Adjuvant Breast and Bowel Project clinical trial B-14. The levels of expression of 16 cancer-related genes and 5 reference genes were used in a prospectively defined algorithm to calculate a recurrence score and to determine a risk group (low, intermediate, or high) for each patient. Adequate RT-PCR profiles were obtained in 668 of 675 tumor blocks. The proportions of patients categorized as having a low, intermediate, or high risk by the RT-PCR assay were 51, 22, and 27 percent, respectively. The Kaplan-Meier estimates of the rates of distant recurrence at 10 years in the low-risk, intermediate-risk, and high-risk groups were 6.8 percent (95 percent confidence interval, 4.0 to 9.6), 14.3 percent (95 percent confidence interval, 8.3 to 20.3), and 30.5 percent (95 percent confidence interval, 23.6 to 37.4). The rate in the low-risk group was significantly lower than that in the high-risk group (P<0.001). In a multivariate Cox model, the recurrence score provided significant predictive power that was independent of age and tumor size (P<0.001). The recurrence score was also predictive of overall survival (P<0.001) and could be used as a continuous function to predict distant recurrence in individual patients. The recurrence score has been validated as quantifying the likelihood of distant recurrence in tamoxifen-treated patients with node-negative, estrogen-receptor-positive breast cancer. Copyright 2004 Massachusetts Medical Society.

Genome-wide binding of transcription factor ZEB1 in triple-negative breast cancer cells.

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Maturi, Varun; Enroth, Stefan; Heldin, Carl-Henrik; Moustakas, Aristidis

2018-05-10

Zinc finger E-box binding homeobox 1 (ZEB1) is a transcriptional regulator involved in embryonic development and cancer progression. ZEB1 induces epithelial-mesenchymal transition (EMT). Triple-negative human breast cancers express high ZEB1 mRNA levels and exhibit features of EMT. In the human triple-negative breast cancer cell model Hs578T, ZEB1 associates with almost 2,000 genes, representing many cellular functions, including cell polarity regulation (DLG2 and FAT3). By introducing a CRISPR-Cas9-mediated 30 bp deletion into the ZEB1 second exon, we observed reduced migratory and anchorage-independent growth capacity of these tumor cells. Transcriptomic analysis of control and ZEB1 knockout cells, revealed 1,372 differentially expressed genes. The TIMP metallopeptidase inhibitor 3 and the teneurin transmembrane protein 2 genes showed increased expression upon loss of ZEB1, possibly mediating pro-tumorigenic actions of ZEB1. This work provides a resource for regulators of cancer progression that function under the transcriptional control of ZEB1. The data confirm that removing a single EMT transcription factor, such as ZEB1, is not sufficient for reverting the triple-negative mesenchymal breast cancer cells into more differentiated, epithelial-like clones, but can reduce tumorigenic potential, suggesting that not all pro-tumorigenic actions of ZEB1 are linked to the EMT. © 2018 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

Factors associated with involvement of four or more axillary nodes for sentinel lymph node-positive patients

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Katz, Angela; Niemierko, Andrzej; Gage, Irene; Evans, Sheila; Shaffer, Margaret; Smith, Frederick P.; Taghian, Alphonse; Magnant, Colette

2006-01-01

Purpose: Sentinel lymph node-positive (SLN+) patients who are unlikely to have 4 or more involved axillary nodes might be treated with less extensive regional nodal radiation. The purpose of this study was to define possible predictors of having 4 or more involved axillary nodes. Methods and Materials: The records of 224 patients with breast cancer and 1 to 3 involved SLNs, who underwent completion axillary dissection without neoadjuvant chemotherapy or hormonal therapy were reviewed. Factors associated with the presence of 4 or more involved axillary nodes (SLNs plus non-SLNs) were evaluated by Pearson chi-square test of association and by simple and multiple logistic-regression analysis. Results: Of 224 patients, 42 had involvement of 4 or more axillary nodes. On univariate analysis, the presence of 4 or more involved axillary nodes was positively associated with increased tumor size, lobular histology, lymphovascular space invasion (LVSI), increased number of involved SLNs, decreased number of uninvolved SLNs, and increased size of SLN metastasis. On multivariate analysis, the presence of 4 or more involved axillary nodes was associated with LVSI, increased number of involved SLNs, increased size of SLN metastasis, and lobular histology. Conclusions: Patients with 1 or more involved SLN, LVSI, or SLN macrometastasis should be treated to the supraclavicular fossa/axillary apex if they do not undergo completion axillary dissection. Other SLN+ patients might be adequately treated with less extensive radiation fields

CT-based delineation of lymph node levels and related CTVs in the node-negative neck: DAHANCA, EORTC, GORTEC, NCIC,RTOG consensus guidelines

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Gregoire, Vincent; Levendag, Peter; Ang, Kian K.; Bernier, Jacques; Braaksma, Marijel; Budach, Volker; Chao, Cliff; Coche, Emmanuel; Cooper, Jay S.; Cosnard, Guy; Eisbruch, Avraham; El-Sayed, Samy; Emami, Bahman; Grau, Cai; Hamoir, Marc; Lee, Nancy; Maingon, Philippe; Muller, Karin; Reychler, Herve

2003-01-01

Background and purpose: The appropriate application of 3-D CRT and IMRT for HNSCC requires a standardization of the procedures for the delineation of the target volumes. Over the past few years, two proposals - the so-called Brussels guidelines from Gregoire et al., and the so-called Rotterdam guidelines from Nowak et al. - emerged from the literature for the delineation of the neck node levels. Detailed examination of these proposals however revealed some important discrepancies. Materials and methods: Within this framework, the Brussels and Rotterdam groups decided to review their guidelines and derive a common set of recommendations for delineation of neck node levels. This proposal was then discussed with representatives of major cooperative groups in Europe (DAHANCA, EORTC, GORTEC) and in North America (NCIC, RTOG), which, after some additional refinements, have endorsed them. The objective of the present article is to present the consensus guidelines for the delineation of the node levels in the node-negative neck. Results and conclusions: First a short discussion of the discrepancies between the previous Brussels and the Rotterdam guidelines is presented. The general philosophy of the consensus guidelines and the methodology used to resolve the various discrepancies are then described. The consensus proposal is then presented and representative CTVs that are consistent with these guidelines are illustrated on CT sections. Last, the limitations of the consensus guidelines are discussed and some concerns about the direct applications of these guidelines to the node-positive neck and the post-operative neck are described

The AA genotype of the regulatory BCL2 promoter polymorphism ( 938C>A) is associated with a favorable outcome in lymph node negative invasive breast cancer patients.

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Bachmann, Hagen S; Otterbach, Friedrich; Callies, Rainer; Nückel, Holger; Bau, Maja; Schmid, Kurt W; Siffert, Winfried; Kimmig, Rainer

2007-10-01

Expression of the antiapoptotic and antiproliferative protein Bcl-2 has been repeatedly shown to be associated with better clinical outcome in breast cancer. We recently showed a novel regulatory (-938C>A) single-nucleotide polymorphism (SNP) in the inhibitory P2 BCL2 gene promoter generating significantly different BCL2 promoter activities. Paraffin-embedded neoplastic and nonneoplastic tissues from 274 patients (161 still alive after a follow-up period of at least 80 months) with primary unilateral invasive breast carcinoma were investigated. Bcl-2 expression of tumor cells was shown by immunohistochemistry; nonneoplastic tissues were used for genotyping. Both the Bcl-2 expression and the (-938C>A) genotypes were correlated with the patients' survival. Kaplan-Meier curves revealed a significant association of the AA genotype with increased survival (P = 0.030) in lymph node-negative breast cancer patients, whereas no genotype effect could be observed in lymph node-positive cases. Ten-year survival rates were 88.6% for the AA genotype, 78.4% for the AC genotype, and 65.8% for the CC genotype. Multivariable Cox regression identified the BCL2 (-938CC) genotype as an independent prognostic factor for cancer-related death in lymph node-negative breast carcinoma patients (hazard ratio, 3.59; P = 0.032). Immunohistochemical Bcl-2 expression was significantly associated with the clinical outcome of lymph node-positive but not of lymph node-negative breast cancer patients. In lymph node-negative cases, the (-938C>A) SNP was both significantly related with the immunohistochemically determined level of Bcl-2 expression (P = 0.044) and the survival of patients with Bcl-2-expressing carcinomas (P = 0.006). These results suggest the (-938C>A) polymorphism as a survival prognosticator as well as indicator of a high-risk group within patients with lymph node-negative breast cancer.

Lymphoscintigraphic Identification of Sentinel Nodes in Malignant Melanoma

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Andries, G.; Dindelegan, G.; Ciule, Larisa; Cosgarea, Rodica; Cobzac, Gh.

2006-01-01

Full text: The most important prognostic factor in malignant melanoma is the presence or absence of metastasis in lymph nodes. It has been demonstrated the orderly progression of different types of tumours. Sentinel lymph node identification is done lymphoscintigraphically, followed by surgical excision and morpho pathological exam. Material and methods: We studied 33 patients with malignant melanoma (age 26-84 years) divided in 2 subgroups: group A without gamma probe (18 patients) and group B with gamma probe (15 patients). The lymphoscintigraphy (LS) was performed with a totally dose of 20-30 MBq of 99mTc-nanocoloid (Amersham) injected peritumoral or pericicatriceal in 4-6 points in volume of 0,1-0,2 ml per point. Acquisition was performed dynamic for 10-15 min and static at 30-60 min p.i. on perpendicular projections. Patent blue dye was injected prior surgery. In group A has performed sentinel node excision (13 patients) or ELND (4), one patient has died before surgery. In group B sentinel nodes were surgically excised with gamma probe and ELND was performed in patients with positive lymph nodes. Histopathologically, sentinel nodes were stained with HE and in 6 cases with HMB45. Results: In group A we identified the sentinel nodes scintigraphically in all patients (median 1,83±-1,50 nodes, range 1-7). Surgically with PBD were identified 1,69±1,18 sentinel nodes, in 2 patients the SN lymphadenectomy was negative. All nodes excised were histopathologically negative, but in 4 patients loco-regional recurrence or distant metastasis developed. In group B we identified scintigraphically 33 SNs (median 2,20±1,37 nodes, range 1-5) and 4 in transit nodes in 14 patients, 24 of them being blue dye positive (80%), in 1 patient LS was negative. With gamma probe surgeon excised 39 radioactive nodes and 1 SN blue dye positive only, 10 of them being histopathologically positive (25% node metastasis). No metastasis were identified after ELND in patients with positive SNs

Triple-Frequency GPS Precise Point Positioning Ambiguity Resolution Using Dual-Frequency Based IGS Precise Clock Products

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Fei Liu

2017-01-01

Full Text Available With the availability of the third civil signal in the Global Positioning System, triple-frequency Precise Point Positioning ambiguity resolution methods have drawn increasing attention due to significantly reduced convergence time. However, the corresponding triple-frequency based precise clock products are not widely available and adopted by applications. Currently, most precise products are generated based on ionosphere-free combination of dual-frequency L1/L2 signals, which however are not consistent with the triple-frequency ionosphere-free carrier-phase measurements, resulting in inaccurate positioning and unstable float ambiguities. In this study, a GPS triple-frequency PPP ambiguity resolution method is developed using the widely used dual-frequency based clock products. In this method, the interfrequency clock biases between the triple-frequency and dual-frequency ionosphere-free carrier-phase measurements are first estimated and then applied to triple-frequency ionosphere-free carrier-phase measurements to obtain stable float ambiguities. After this, the wide-lane L2/L5 and wide-lane L1/L2 integer property of ambiguities are recovered by estimating the satellite fractional cycle biases. A test using a sparse network is conducted to verify the effectiveness of the method. The results show that the ambiguity resolution can be achieved in minutes even tens of seconds and the positioning accuracy is in decimeter level.

Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

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Ellsworth, R.E.; Field, L.A.; Kane, J.L.; Love, B.; Hooke, J.A.; Shriver, C.D.

2011-01-01

Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative (n=41) and positive (n=35) lymph node status matched for possible confounding factors were subjected to laser micro dissection and gene expression data generated. Although ANOVA analysis (P 1.5) revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis

Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

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Ellsworth, Rachel E.; Field, Lori A.; Love, Brad; Kane, Jennifer L.; Hooke, Jeffrey A.; Shriver, Craig D.

2011-01-01

Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative (n = 41) and positive (n = 35) lymph node status matched for possible confounding factors were subjected to laser microdissection and gene expression data generated. Although ANOVA analysis (P 1.5) revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis. PMID:22295210

Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

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Rachel E. Ellsworth

2011-01-01

Full Text Available Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative (=41 and positive (=35 lymph node status matched for possible confounding factors were subjected to laser microdissection and gene expression data generated. Although ANOVA analysis (1.5 revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis.

FOXP3 Transcription Factor: A Candidate Marker for Susceptibility and Prognosis in Triple Negative Breast Cancer

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Leandra Fiori Lopes

2014-01-01

Full Text Available Triple negative breast cancer (TNBC is a relevant subgroup of neoplasia which presents negative phenotype of estrogen and progesterone receptors and has no overexpression of the human epidermal growth factor 2 (HER2. FOXP3 (forkhead transcription factor 3 is a marker of regulatory T cells (Tregs, whose expression may be increased in tumor cells. This study aimed to investigate a polymorphism (rs3761548 and the protein expression of FOXP3 for a possible involvement in TNBC susceptibility and prognosis. Genetic polymorphism was evaluated in 50 patients and in 115 controls by allele-specific PCR (polymerase chain reaction. Protein expression was evaluated in 38 patients by immunohistochemistry. It was observed a positive association for homozygous AA (OR = 3.78; 95% CI = 1.02–14.06 in relation to TNBC susceptibility. Most of the patients (83% showed a strong staining for FOXP3 protein in the tumor cells. In relation to FOXP3-positive infiltrate, 47% and 58% of patients had a moderate or intense intratumoral and peritumoral mononuclear infiltrate cells, respectively. Tumor size was positively correlated to intratumoral FOXP3-positive infiltrate (P=0.026. In conclusion, since FOXP3 was positively associated with TNBC susceptibility and prognosis, it seems to be a promising candidate for further investigation in larger TNBC samples.

An Adaptive Connectivity-based Centroid Algorithm for Node Positioning in Wireless Sensor Networks

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Aries Pratiarso

2015-06-01

Full Text Available In wireless sensor network applications, the position of nodes is randomly distributed following the contour of the observation area. A simple solution without any measurement tools is provided by range-free method. However, this method yields the coarse estimating position of the nodes. In this paper, we propose Adaptive Connectivity-based (ACC algorithm. This algorithm is a combination of Centroid as range-free based algorithm, and hop-based connectivity algorithm. Nodes have a possibility to estimate their own position based on the connectivity level between them and their reference nodes. Each node divides its communication range into several regions where each of them has a certain weight depends on the received signal strength. The weighted value is used to obtain the estimated position of nodes. Simulation result shows that the proposed algorithm has up to 3 meter error of estimated position on 100x100 square meter observation area, and up to 3 hop counts for 80 meters' communication range. The proposed algorithm performs an average error positioning up to 10 meters better than Weighted Centroid algorithm. Keywords: adaptive, connectivity, centroid, range-free.

Evaluation of non-genomic, clinical risk and survival results in endocrine-sensitive, HER-2 negative, node negative breast cancer.

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Baena Cañada, José M; Gámez Casado, Salvador; Rodríguez Pérez, Lourdes; Quílez Cutillas, Alicia; Cortés Carmona, Cristina; Rosado Varela, Petra; Estalella Mendoza, Sara; Ramírez Daffós, Patricia; Benítez Rodríguez, Encarnación

2018-02-28

In endocrine-sensitive, HER-2 negative, node negative breast cancer, the presence of a low genomic risk allows treatment with adjuvant endocrine therapy alone, obtaining excellent survival rates. The justification for this study is to show that excellent survival rates are also obtained by treating with adjuvant hormone therapy alone, based on clinical risk assessment. A descriptive, observational and retrospective study was performed between 2006 and 2016 with endocrine-sensitive, HER-2 negative, node negative breast cancer, greater than 1cm or between 0.6 and 1cm with unfavourable features. Retrospective review of health records. Mortality data of the National Registry of Deaths. A total of 203 patients were evaluable for survival. One hundred and twenty-three (60.50%) were treated with adjuvant endocrine therapy alone, 77 (37.90%) with chemotherapy and endocrine therapy, one (0.50%) with chemotherapy alone and 2 (1%) were not treated. The overall survival rate at 5 years was 97% (95% confidence interval [CI] 94-100). Distant recurrence-free interval was 94% (95% CI 90-98). In the subgroup of patients treated with endocrine therapy alone, overall survival and distant recurrence-free interval rates at 5 years were 98% (95% CI 95-100) and 97% (95% CI 93-100), respectively. Patients with endocrine-sensitive, HER-2-negative, node negative breast cancer treated with endocrine therapy alone according to their clinical risk have similar survival outcomes as those treated with endocrine therapy according to their genomic risk. Copyright © 2018 Elsevier España, S.L.U. All rights reserved.

The Influence of Total Nodes Examined, Number of Positive Nodes, and Lymph Node Ratio on Survival After Surgical Resection and Adjuvant Chemoradiation for Pancreatic Cancer: A Secondary Analysis of RTOG 9704

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Showalter, Timothy N. [Department of Radiation Oncology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Winter, Kathryn A. [Radiation Therapy Oncology Group, RTOG Statistical Center, Philadelphia, PA (United States); Berger, Adam C., E-mail: adam.berger@jefferson.edu [Department of Surgery, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA (United States); Regine, William F. [Department of Radiation Oncology, University of Maryland Medical Center, Baltimore, MD (United States); Abrams, Ross A. [Department of Radiation Oncology, Rush University Medical Center, Chicago, IL (United States); Safran, Howard [Department of Medicine, Miriam Hospital, Brown University Oncology Group, Providence, RI (United States); Hoffman, John P. [Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA (United States); Benson, Al B. [Division of Hematology-Oncology, Northwestern University, Chicago, IL (United States); MacDonald, John S. [St. Vincent' s Cancer Care Center, New York, NY (United States); Willett, Christopher G. [Department of Radiation Oncology, Duke University Medical Center, Durham, NC (United States)

2011-12-01

Purpose: Lymph node status is an important predictor of survival in pancreatic cancer. We performed a secondary analysis of Radiation Therapy Oncology Group (RTOG) 9704, an adjuvant chemotherapy and chemoradiation trial, to determine the influence of lymph node factors-number of positive nodes (NPN), total nodes examined (TNE), and lymph node ratio (LNR ratio of NPN to TNE)-on OS and disease-free survival (DFS). Patient and Methods: Eligible patients from RTOG 9704 form the basis of this secondary analysis of lymph node parameters. Actuarial estimates for OS and DFS were calculated using Kaplan-Meier methods. Cox proportional hazards models were performed to evaluate associations of NPN, TNE, and LNR with OS and DFS. Multivariate Cox proportional hazards models were also performed. Results: There were 538 patients enrolled in the RTOG 9704 trial. Of these, 445 patients were eligible with lymph nodes removed. Overall median NPN was 1 (min-max, 0-18). Increased NPN was associated with worse OS (HR = 1.06, p = 0.001) and DFS (HR = 1.05, p = 0.01). In multivariate analyses, both NPN and TNE were associated with OS and DFS. TNE > 12, and >15 were associated with increased OS for all patients, but not for node-negative patients (n = 142). Increased LNR was associated with worse OS (HR = 1.01, p < 0.0001) and DFS (HR = 1.006, p = 0.002). Conclusion: In patients who undergo surgical resection followed by adjuvant chemoradiation, TNE, NPN, and LNR are associated with OS and DFS. This secondary analysis of a prospective, cooperative group trial supports the influence of these lymph node parameters on outcomes after surgery and adjuvant therapy using contemporary techniques.

Ultrasound elastography as an adjuvant to conventional ultrasound in the preoperative assessment of axillary lymph nodes in suspected breast cancer: A pilot study

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Taylor, K., E-mail: kathryn.taylor@addenbrookes.nhs.uk [Department of Radiology, Cambridge Breast Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge (United Kingdom); O' Keeffe, S.; Britton, P.D.; Wallis, M.G. [Department of Radiology, Cambridge Breast Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge (United Kingdom); Treece, G.M.; Housden, J. [Department of Engineering, University of Cambridge, Cambridge (United Kingdom); Parashar, D.; Bond, S. [Cambridge Cancer Trials Centre, Department of Oncology, University of Cambridge, Addenbrookes Hospital, Cambridge (United Kingdom); Cambridge Hub in Trials Methodology Research, MRC Biostatics Unit, University Forvie Site, Cambridge (United Kingdom); Sinnatamby, R. [Department of Radiology, Cambridge Breast Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge (United Kingdom)

2011-11-15

Aims: To compare the performance of ultrasound elastography with conventional ultrasound in the assessment of axillary lymph nodes in suspected breast cancer and whether ultrasound elastography as an adjunct to conventional ultrasound can increase the sensitivity of conventional ultrasound used alone. Materials and methods: Fifty symptomatic women with a sonographic suspicion for breast cancer underwent ultrasound elastography of the ipsilateral axilla concurrent with conventional ultrasound being performed as part of triple assessment. Elastograms were visually scored, strain measurements calculated and node area and perimeter measurements taken. Theoretical biopsy cut points were selected. The sensitivity, specificity, positive predictive value (PPV), and negative predictive values (NPV) were calculated and receiver operating characteristic (ROC) analysis was performed and compared for elastograms and conventional ultrasound images with surgical histology as the reference standard. Results: The mean age of the women was 57 years. Twenty-nine out of 50 of the nodes were histologically negative on surgical histology and 21 were positive. The sensitivity, specificity, PPV, and NPV for conventional ultrasound were 76, 78, 70, and 81%, respectively; 90, 86, 83, and 93%, respectively, for visual ultrasound elastography; and for strain scoring, 100, 48, 58 and 100%, respectively. There was no significant difference between any of the node measurements Conclusions: Initial experience with ultrasound elastography of axillary lymph nodes, showed that it is more sensitive than conventional ultrasound in detecting abnormal nodes in the axilla in cases of suspected breast cancer. The specificity remained acceptable and ultrasound elastography used as an adjunct to conventional ultrasound has the potential to improve the performance of conventional ultrasound alone.

Long-term results of positron emission tomography-directed management of the neck in node-positive head and neck cancer after organ preservation therapy.

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Sjövall, Johanna; Chua, Benjamin; Pryor, David; Burmeister, Elizabeth; Foote, Matthew C; Panizza, Benedict; Burmeister, Bryan H; Porceddu, Sandro V

2015-03-01

The current study presents the long-term results from a study designed to evaluate a restaging positron emission tomography (PET) directed policy whereby neck dissections were omitted in all node positive head and neck squamous cell carcinoma (N+HNSCC) patients with PET-negative lymph nodes after definitive radiotherapy (RT), with or without chemotherapy. A post-therapy nodal response assessment with PET and computed tomography (CT) was performed in patients who achieved a complete response at the primary site after definitive radiotherapy. Patients with PET-negative lymph nodes were observed regardless of residual CT abnormalities. One hundred and twelve patients, the majority of whom (83 patients, 74%) had oropharyngeal primaries, were treated on protocol. Median follow-up was 62months. Negative and positive predictive values for the restaging PET was 97.1% and 77.8% respectively, with only one patient who was PET-negative after treatment experiencing an isolated nodal relapse. PET-guided management of the neck following organ preservation therapy effectively spares neck dissections in patients with N+HNSCC without compromising isolated nodal control or overall survival. Crown Copyright © 2014. Published by Elsevier Ltd. All rights reserved.

Predicting biochemical recurrence-free survival for patients with positive pelvic lymph nodes at radical prostatectomy.

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von Bodman, Christian; Godoy, Guilherme; Chade, Daher C; Cronin, Angel; Tafe, Laura J; Fine, Samson W; Laudone, Vincent; Scardino, Peter T; Eastham, James A

2010-07-01

We evaluated predictors of freedom from biochemical recurrence in patients with pelvic lymph node metastasis at radical prostatectomy. Of 207 patients with lymph node metastasis treated with radical prostatectomy and bilateral pelvic lymph node dissection 45 received adjuvant androgen deprivation therapy and 162 did not. Cox proportional hazards regression models were used to investigate predictors of biochemical recurrence after radical prostatectomy. Recurrence probability was estimated using the Kaplan-Meier method. A median of 13 lymph nodes were removed. Of the patients 122 had 1, 44 had 2 and 41 had 3 or greater positive lymph nodes. Of patients without androgen deprivation therapy 103 had 1, 35 had 2 and 24 had 3 or greater positive lymph nodes while 69 experienced biochemical recurrence. Median time to recurrence in patients with 1, 2 and 3 or greater lymph nodes was 59, 13 and 3 months, respectively. Only specimen Gleason score and the number of positive lymph nodes were independent predictors of biochemical recurrence. Recurrence-free probability 2 years after prostatectomy in men without androgen deprivation with 1 positive lymph node and a prostatectomy Gleason score of 7 or less was 79% vs 29% in those with Gleason score 8 or greater and 2 or more positive lymph nodes. Prognosis in patients with lymph node metastasis depends on the number of positive lymph nodes and primary tumor Gleason grade. Of all patients with lymph node metastasis 80% had 1 or 2 positive nodes. A large subset of those patients had a favorable prognosis. Full bilateral pelvic lymph node dissection should be done in patients with intermediate and high risk cancer to identify those likely to benefit from metastatic node removal. Copyright (c) 2010 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Selecting breast cancer patients with T1-T2 tumors and one to three positive axillary nodes at high postmastectomy locoregional recurrence risk for adjuvant radiotherapy

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Truong, Pauline T.; Olivotto, Ivo A.; Kader, Hosam A.; Panades, Miguel; Speers, Caroline H.; Berthelet, Eric

2005-01-01

Purpose: To define the individual factors and combinations of factors associated with increased risk of locoregional recurrence (LRR) that may justify postmastectomy radiotherapy (PMRT) in patients with T1-T2 breast cancer and one to three positive nodes. Methods and Materials: The study cohort comprised 821 women referred to the British Columbia Cancer Agency between 1989 and 1997 with pathologic T1-T2 breast cancer and one to three positive nodes treated with mastectomy without adjuvant RT. The 10-year Kaplan-Meier estimates of isolated LRR and LRR with or without simultaneous distant recurrence (LRR ± SDR) were analyzed according to age, histologic findings, tumor location, size, and grade, lymphovascular invasion status, estrogen receptor (ER) status, margin status, number of positive nodes, number of nodes removed, percentage of positive nodes, and systemic therapy use. Multivariate analyses were performed using Cox proportional hazards modeling. A risk classification model was developed using combinations of the statistically significant factors identified on multivariate analysis. Results: The median follow-up was 7.7 years. Systemic therapy was used in 94% of patients. Overall, the 10-year Kaplan-Meier isolated LRR and LRR ± SDR rate was 12.7% and 15.9%, respectively. Without PMRT, a 10-year LRR risk of >20% was identified in women with one to three positive nodes plus at least one of the following factors: age 25% of nodes positive (all p 25% of nodes positive, medial tumor location, and ER-negative status were statistically significant predictors of isolated LRR and LRR ± SDR. In the classification model, the first split was according to age ( 25% of nodes positive was associated with a risk of LRR ± SDR of 58.0% compared with 23.8% for those with ≤25% of nodes positive (p = 0.01). Of 698 women >45 years, the presence of >25% of nodes positive also conferred a greater LRR ± SDR risk (26.7%) compared with women with ≤25% of nodes positive (10

Triple-negative breast cancer: the importance of molecular and histologic subtyping, and recognition of low-grade variants.

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Pareja, Fresia; Geyer, Felipe C; Marchiò, Caterina; Burke, Kathleen A; Weigelt, Britta; Reis-Filho, Jorge S

2016-01-01

Triple-negative breast cancers (TNBCs), defined by lack of expression of estrogen receptor, progesterone receptor and HER2, account for 12-17% of breast cancers and are clinically perceived as a discrete breast cancer subgroup. Nonetheless, TNBC has been shown to constitute a vastly heterogeneous disease encompassing a wide spectrum of entities with marked genetic, transcriptional, histological and clinical differences. Although most TNBCs are high-grade tumors, there are well-characterized low-grade TNBCs that have an indolent clinical course, whose natural history, molecular features and optimal therapy vastly differ from those of high-grade TNBCs. Secretory and adenoid cystic carcinomas are two histologic types of TNBCs underpinned by specific fusion genes; these tumors have an indolent clinical behavior and lack all of the cardinal molecular features of high-grade triple-negative disease. Recent studies of rare entities, including lesions once believed to constitute mere benign breast disease (e.g., microglandular adenosis), have resulted in the identification of potential precursors of TNBC and suggested the existence of a family of low-grade triple-negative lesions that, despite having low-grade morphology and indolent clinical behavior, have been shown to harbor the complex genomic landscape of common forms of TNBC, and may progress to high-grade disease. In this review, we describe the heterogeneity of TNBC and focus on the histologic and molecular features of low-grade forms of TNBC. Germane to addressing the challenges posed by the so-called triple-negative disease is the realization that TNBC is merely a descriptive term, and that low-grade types of TNBC may be driven by distinct sets of genetic alterations.

False Positive and False Negative Effects on Network Attacks

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Shang, Yilun

2018-01-01

Robustness against attacks serves as evidence for complex network structures and failure mechanisms that lie behind them. Most often, due to detection capability limitation or good disguises, attacks on networks are subject to false positives and false negatives, meaning that functional nodes may be falsely regarded as compromised by the attacker and vice versa. In this work, we initiate a study of false positive/negative effects on network robustness against three fundamental types of attack strategies, namely, random attacks (RA), localized attacks (LA), and targeted attack (TA). By developing a general mathematical framework based upon the percolation model, we investigate analytically and by numerical simulations of attack robustness with false positive/negative rate (FPR/FNR) on three benchmark models including Erdős-Rényi (ER) networks, random regular (RR) networks, and scale-free (SF) networks. We show that ER networks are equivalently robust against RA and LA only when FPR equals zero or the initial network is intact. We find several interesting crossovers in RR and SF networks when FPR is taken into consideration. By defining the cost of attack, we observe diminishing marginal attack efficiency for RA, LA, and TA. Our finding highlights the potential risk of underestimating or ignoring FPR in understanding attack robustness. The results may provide insights into ways of enhancing robustness of network architecture and improve the level of protection of critical infrastructures.

Artificial neural networks as classification and diagnostic tools for lymph node-negative breast cancers

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Eswari J, Satya; Chandrakar, Neha [National Institute of Technology Raipur, Raipur (India)

2016-04-15

Artificial neural networks (ANNs) can be used to develop a technique to classify lymph node negative breast cancer that is prone to distant metastases based on gene expression signatures. The neural network used is a multilayered feed forward network that employs back propagation algorithm. Once trained with DNA microarraybased gene expression profiles of genes that were predictive of distant metastasis recurrence of lymph node negative breast cancer, the ANNs became capable of correctly classifying all samples and recognizing the genes most appropriate to the classification. To test the ability of the trained ANN models in recognizing lymph node negative breast cancer, we analyzed additional idle samples that were not used beforehand for the training procedure and obtained the correctly classified result in the validation set. For more substantial result, bootstrapping of training and testing dataset was performed as external validation. This study illustrates the potential application of ANN for breast tumor diagnosis and the identification of candidate targets in patients for therapy.

Double-membrane triple-electrolyte redox flow battery design

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Yushan, Yan; Gu, Shuang; Gong, Ke

2018-03-13

A redox flow battery is provided having a double-membrane (one cation exchange membrane and one anion exchange membrane), triple-electrolyte (one electrolyte in contact with the negative electrode, one electrolyte in contact with the positive electrode, and one electrolyte positioned between and in contact with the two membranes). The cation exchange membrane is used to separate the negative or positive electrolyte and the middle electrolyte, and the anion exchange membrane is used to separate the middle electrolyte and the positive or negative electrolyte. This design physically isolates, but ionically connects, the negative electrolyte and positive electrolyte. The physical isolation offers great freedom in choosing redox pairs in the negative electrolyte and positive electrolyte, making high voltage of redox flow batteries possible. The ionic conduction drastically reduces the overall ionic crossover between negative electrolyte and positive one, leading to high columbic efficiency.

Isolated port site recurrence of node-negative clinical stage IB1 cervical adenocarcinoma

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Uma Deshmukh

2017-05-01

Conclusion: This is the first case report describing an isolated port site recurrence in a patient who underwent robotic-assisted laparoscopic surgery for early-stage cervical adenocarcinoma with negative margins and negative lymph nodes. The mechanism underlying this isolated recurrence remains unknown.

Triple-negative breast cancer: new perspectives for targeted therapies

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Tomao F

2015-01-01

Full Text Available Federica Tomao,1 Anselmo Papa,2 Eleonora Zaccarelli,2 Luigi Rossi,2 Davide Caruso,2 Marina Minozzi,2 Patrizia Vici,3 Luigi Frati,4 Silverio Tomao21Department of Gynecology and Obstetrics, “Sapienza” University of Rome, Policlinico “Umberto I”, Rome, 2Department of Medico-Surgical Sciences and Biotechnologies, “Sapienza” University of Rome, Oncology Unit, Istituto Chirurgico Ortopedico Traumatologico, Latina, 3Division of Medical Oncology B, Regina Elena National Cancer Institute, Rome, Italy; 4Department of Molecular Medicine, “Sapienza” University of Rome, Policlinico “Umberto I”, Rome, ItalyAbstract: Breast cancer is a heterogeneous disease, encompassing a large number of entities showing different morphological features and having clinical behaviors. It has became apparent that this diversity may be justified by distinct patterns of genetic, epigenetic, and transcriptomic aberrations. The identification of gene-expression microarray-based characteristics has led to the identification of at least five breast cancer subgroups: luminal A, luminal B, normal breast-like, human epidermal growth factor receptor 2, and basal-like. Triple-negative breast cancer is a complex disease diagnosed by immunohistochemistry, and it is characterized by malignant cells not expressing estrogen receptors or progesterone receptors at all, and human epidermal growth factor receptor 2. Along with this knowledge, recent data show that triple-negative breast cancer has specific molecular features that could be possible targets for new biological targeted drugs. The aim of this article is to explore the use of new drugs in this particular setting, which is still associated with poor prognosis and high risk of distant recurrence and death.Keywords: basal-like breast cancer, estrogen–progesterone receptors, gene-expression microarray, human epidermal growth factor receptor 2, chemotherapy, target therapy

Clinical Characteristics in Patients with Triple Negative Breast Cancer

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Janet Yeh

2017-01-01

Full Text Available Purpose. The purpose of this study was to compare and contrast the clinical characteristics of the triple negative breast cancer (TNBC and non-TNBC patients, with a particular focus on genetic susceptibility and risk factors prior to diagnosis. Methods. Our institutional database was queried for all patients diagnosed with invasive breast cancer between January 2010 and May 2016. Results. Out of a total of 1964 patients, 190 (10% patients had TNBC. The median age for both TNBC and non-TNBC was 59 years. There was a significantly higher proportion of African American and Asian patients with TNBC (p=0.0003 compared to patients with non-TNBC. BRCA1 and BRCA2 were significantly associated with TNBC (p<0.0001, p=0.0007. A prior history of breast cancer was significantly associated with TNBC (p=0.0003. There was no relationship observed between TNBC and a history of chemoprevention or patients who had a history of AH or LCIS. Conclusions. We found that having Asian ancestry, a prior history of breast cancer, and a BRCA1 or BRCA2 mutation all appear to be positively associated with TNBC. In order to develop more effective treatments, better surveillance, and improved prevention strategies, it is necessary to improve our understanding of the population at risk for TNBC.

THE PROGNOSIS SIGNIFICANCE OF CATHEPSIN-D EXPRESSION IN THE DIFFERENT LOCATIONS IN AXILLARY NODES NEGATIVE CARCINOMA

Institute of Scientific and Technical Information of China (English)

无

2001-01-01

Objective: The aim of this study was to investigate Cathepsin-D (Cath-D) expression in different location and its relationship with prognosis in the axillary lymph nodes negative (ANN) breast cancer patients. Methods: Cath-D expression in 192 cases of breast carcinoma were examined by immunohistochemistry. Depending on different parts of expression, three evaluating methods were used, compared and analysed. Results: The positive rate of Cath-D expression in ANN breast cancer with poor prognosis group and axillary nodes positive (ANP) group were significantly higher than that in ANN breast cancer with good prognosis group (x2=23.20, P0.05). Cath-D expression in stromal cells had no statistical difference among the three groups (x2=1.56, P>0.05). When the Cath-D expression in cancer and stromal cells were counted into the positive rate, it was near the same (u1=0.47, u2=1.41, P>0.05). Conclusion: These results suggest that Cath-D expression is one of the powerful prognostic markers in ANN breast cancer. It's a reliable, practical, and convenient method to observe and evaluate Cath-D expression in cancer cells.

The Gαh-PLCδ1 signaling axis drives metastatic progression in triple-negative breast cancer.

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Huang, Shang-Pen; Liu, Pei-Yao; Kuo, Chih-Jung; Chen, Chi-Long; Lee, Wei-Jiunn; Tsai, Yu-Hui; Lin, Yuan-Feng

2017-06-02

Distant metastasis of triple-negative breast cancer (TNBC) to other organs, e.g., the lungs, has been correlated with poor survival rates among breast cancer patients. Therefore, the identification of useful therapeutic targets to prevent metastasis or even inhibit tumor growth of TNBC is urgently needed. Gαh is a novel GTP-binding protein and known as an inactive form of calcium-dependent tissue transglutaminase. However, the functional consequences of transamidating and G-protein activities of tissue transglutaminase in promoting cancer metastasis are still controversial. Kaplan-Meier analyses were performed to estimate the prognostic values of Gαh and PLCδ1 by utilizing public databases and performing immunohistochemical staining experiments. Cell-based invasion assays and in vivo lung colony-forming and orthotropic lung metastasis models were established to evaluate the effectiveness of interrupting the protein-protein interaction (PPI) between Gαh and PLCδ1 in inhibiting the invasive ability and metastatic potential of TNBC cells. Here, we showed that the increased level of cytosolic, not extracellular, Gαh is a poor prognostic marker in breast cancer patients and correlates with the metastatic evolution of TNBC cells. Moreover, clinicopathological analyses revealed that the combined signature of high Gαh/PLCδ1 levels indicates worse prognosis in patients with breast cancer and correlates with lymph node metastasis of ER-negative breast cancer. Blocking the PPI of the Gαh/PLCδ1 complex by synthetically myristoylated PLCδ1 peptide corresponding to the Gαh-binding interface appeared to significantly suppress cellular invasiveness in vitro and inhibit lung metastatic colonies of TNBC cells in vivo. This study establishes Gαh/PLCδ1 as a poor prognostic factor for patients with estrogen receptor-negative breast cancers, including TNBCs, and provides therapeutic value by targeting the PPI of the Gαh/PLCδ1 complex to combat the metastatic progression

Identification of CDC25 as a Common Therapeutic Target for Triple-Negative Breast Cancer

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Jeff C. Liu

2018-04-01

Full Text Available Summary: CDK4/6 inhibitors are effective against cancer cells expressing the tumor suppressor RB1, but not RB1-deficient cells, posing the challenge of how to target RB1 loss. In triple-negative breast cancer (TNBC, RB1 and PTEN are frequently inactivated together with TP53. We performed kinome/phosphatase inhibitor screens on primary mouse Rb/p53-, Pten/p53-, and human RB1/PTEN/TP53-deficient TNBC cell lines and identified CDC25 phosphatase as a common target. Pharmacological or genetic inhibition of CDC25 suppressed growth of RB1-deficient TNBC cells that are resistant to combined CDK4/6 plus CDK2 inhibition. Minimal cooperation was observed in vitro between CDC25 antagonists and CDK1, CDK2, or CDK4/6 inhibitors, but strong synergy with WEE1 inhibition was apparent. In accordance with increased PI3K signaling following long-term CDC25 inhibition, CDC25 and PI3K inhibitors effectively synergized to suppress TNBC growth both in vitro and in xenotransplantation models. These results provide a rationale for the development of CDC25-based therapies for diverse RB1/PTEN/TP53-deficient and -proficient TNBCs. : Liu et al. report that inhibition of the protein phosphatase CDC25 kills diverse triple-negative breast cancer (TNBC cells. Moreover, CDC25 antagonists cooperate with other drugs, such as PI3K inhibitors, to efficiently suppress growth of human TNBC engrafted into mice. Keywords: triple negative breast cancer, basal-like breast cancer, therapy, RB1, PTEN, TP53, CDC25, WEE1, CHK1, checkpoint control

Lymph node size as a simple prognostic factor in node negative colon cancer and an alternative thesis to stage migration.

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Märkl, Bruno; Schaller, Tina; Kokot, Yuriy; Endhardt, Katharina; Kretsinger, Hallie; Hirschbühl, Klaus; Aumann, Georg; Schenkirsch, Gerhard

2016-10-01

Stage migration is an accepted explanation for the association between lymph node (LN) yield and outcome in colon cancer. To investigate whether the alternative thesis of immune response is more likely, we performed a retrospective study. We enrolled 239 cases of node negative cancers, which were categorized according to the number of LNs with diameters larger than 5 mm (LN5) into the groups LN5-very low (0 to 1 LN5), LN5-low (2 to 5 LN5), and LN5-high (≥6 LN5). Significant differences were found in pT3/4 cancers with median survival times of 40, 57, and 71 months (P = .022) in the LN5-very low, LN5-low, and LN5-high groups, respectively. Multivariable analysis revealed that LN5 number and infiltration type were independent prognostic factors. LN size is prognostic in node negative colon cancer. The correct explanation for outcome differences associated with LN harvest is probably the activation status of LNs. Copyright © 2015 Elsevier Inc. All rights reserved.

Overlapping community detection in networks with positive and negative links

International Nuclear Information System (INIS)

Chen, Y; Wang, X L; Yuan, B; Tang, B Z

2014-01-01

Complex networks considering both positive and negative links have gained considerable attention during the past several years. Community detection is one of the main challenges for complex network analysis. Most of the existing algorithms for community detection in a signed network aim at providing a hard-partition of the network where any node should belong to a community or not. However, they cannot detect overlapping communities where a node is allowed to belong to multiple communities. The overlapping communities widely exist in many real-world networks. In this paper, we propose a signed probabilistic mixture (SPM) model for overlapping community detection in signed networks. Compared with the existing models, the advantages of our methodology are (i) providing soft-partition solutions for signed networks; (ii) providing soft memberships of nodes. Experiments on a number of signed networks show that our SPM model: (i) can identify assortative structures or disassortative structures as the same as other state-of-the-art models; (ii) can detect overlapping communities; (iii) outperforms other state-of-the-art models at shedding light on the community detection in synthetic signed networks. (paper)

[Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer. Its relation with molecular subtypes].

Science.gov (United States)

Ruano, R; Ramos, M; García-Talavera, J R; Ramos, T; Rosero, A S; González-Orus, J M; Sancho, M

2014-01-01

To evaluate the influence of the molecular subtype (MS) in the Sentinel Node Biopsy (SNB) technique after neoadjuvant chemotherapy (NAC) in women with locally advanced breast cancer (BC) and a complete axillary response (CR). A prospective study involving 70 patients with BC treated with NAC was carried out. An axillary lymph node dissection was performed in the first 48 patients (validation group: VG), and in case of micro- or macrometastases in the therapeutic application phase (therapy group:TG). Classified according to MS: 14 luminal A; 16 luminal B HER2-, 13 luminal B HER2+, 10HER2+ non-luminal, 17 triple-negative. SNB was carried out in 98.6% of the cases, with only one false negative result in the VG (FN=2%). Molecular subtype did not affect SN detection. Despite the existence of axillary CR, statistically significant differences were found in the proportion of macrometastasis (16.7% vs. 35.7%, p=0.043) on comparing the pre-NAC cN0 and cN+. Breast tumor response to NAC varied among the different MS, this being lowest in luminal A (21.5%) and highest in non-luminal HER2+ group (80%). HER2+ and triple-negative were the groups with the best axillary histological response both when there was prior clinical involvement and when there was not. Molecular subtype is a predictive factor of the degree of tumor response to NAC in breast cancer. However, it does not affect SNB detection and efficiency. SNB can also be used safely in women with prior node involvement as long as a complete clinical and radiological assessment is made of the node response to NAC. Copyright © 2014 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

Low local recurrence rate without postmastectomy radiation in node-negative breast cancer patients with tumors 5 cm and larger

International Nuclear Information System (INIS)

Floyd, Scott R.; Buchholz, Thomas A.; Haffty, Bruce G.; Goldberg, Saveli; Niemierko, Andrzej; Raad, Rita Abi; Oswald, Mary J.; Sullivan, Timothy; Strom, Eric A.; Powell, Simon N.; Katz, Angela; Taghian, Alphonse G.

2006-01-01

Purpose: To assess the need for adjuvant radiotherapy following mastectomy for patients with node-negative breast tumors 5 cm or larger. Methods and Materials: Between 1981 and 2002, a total of 70 patients with node-negative breast cancer and tumors 5 cm or larger were treated with mastectomy and adjuvant systemic therapies but without radiotherapy at three institutions. We retrospectively assessed rates and risk factors for locoregional failure (LRF), overall survival (OS), and disease-free survival (DFS) in these patients. Results: With a median follow-up of 85 months, the 5-year actuarial LRF rate was 7.6% (95% confidence interval, 3%-16%). LRF was primarily in the chest wall (4/5 local failures), and lymphatic-vascular invasion (LVI) was statistically significantly associated with LRF risk by the log-rank test (p = 0.017) and in Cox proportional hazards analysis (p 0.038). The 5-year OS and DFS rates were 83% and 86% respectively. LVI was also significantly associated with OS and DFS in both univariate and multivariate analysis. Conclusions: This series demonstrates a low LRF rate of 7.6% among breast cancer patients with node-negative tumors 5 cm and larger after mastectomy and adjuvant systemic therapy. Our data indicate that further adjuvant radiation therapy to increase local control may not be indicated by tumor size alone in the absence of positive lymph nodes. LVI was significantly associated with LRF in our series, indicating that patients with this risk factor require careful consideration with regard to further local therapy

Gammascintigraphy of metastases of the lymph nodes

International Nuclear Information System (INIS)

Mechev, D.S.; Shishkina, V.V.

1985-01-01

It was indicated that according to the degree of informative value all the methods used in this study can be listed as follows: the method of combined use of positive and negative scintigraphy, the method of positive scintigraphy with Ga 67 -citrate (the tymph nodes above the diagram) and Tc 99 -pertechnate (the lymph nodes below the diaphragm), the method of indirect radionuclide lymphography with colloids. The main indices of radionuclide methods in the diagnosis of the lymph node metastatic involvement are presented

Sentinel node biopsy before neoadjuvant chemotherapy spares breast cancer patients axillary lymph node dissection.

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van Rijk, Maartje C; Nieweg, Omgo E; Rutgers, Emiel J T; Oldenburg, Hester S A; Olmos, Renato Valdés; Hoefnagel, Cornelis A; Kroon, Bin B R

2006-04-01

Neoadjuvant chemotherapy in breast cancer patients is a valuable method to determine the efficacy of chemotherapy and potentially downsize the primary tumor, which facilitates breast-conserving therapy. In 18 studies published about sentinel node biopsy after neoadjuvant chemotherapy, the sentinel node was identified in on average 89%, and the false-negative rate was on average 10%. Because of these mediocre results, no author dares to omit axillary clearance just yet. In our institute, sentinel lymph node biopsy is performed before neoadjuvant chemotherapy. The aim of this study was to evaluate our experience with this approach. Sentinel node biopsy was performed before neoadjuvant chemotherapy in 25 T2N0 patients by using lymphoscintigraphy, a gamma ray detection probe, and patent blue dye. Axillary lymph node dissection was performed after chemotherapy if the sentinel node contained metastases. Ten patients had a tumor-positive axillary sentinel node, and one patient had an involved lateral intramammary node. Four patients had additional involved nodes in the completion lymph node dissection specimen. The other 14 patients (56%) had a tumor-negative sentinel node and did not undergo axillary lymph node dissection. No recurrences have been observed after a median follow-up of 18 months. Fourteen (56%) of the 25 patients were spared axillary lymph node dissection when the sentinel node was found to be disease free. Performing sentinel node biopsy before neoadjuvant chemotherapy seems successful and reliable in patients with T2N0 breast cancer.

Interaction between body mass index and hormone-receptor status as a prognostic factor in lymph-node-positive breast cancer.

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Il Yong Chung

Full Text Available The aim of this study was to determine the relationship between the body mass index (BMI at a breast cancer diagnosis and various factors including the hormone-receptor, menopause, and lymph-node status, and identify if there is a specific patient subgroup for which the BMI has an effect on the breast cancer prognosis. We retrospectively analyzed the data of 8,742 patients with non-metastatic invasive breast cancer from the research database of Asan Medical Center. The overall survival (OS and breast-cancer-specific survival (BCSS outcomes were compared among BMI groups using the Kaplan-Meier method and Cox proportional-hazards regression models with an interaction term. There was a significant interaction between BMI and hormone-receptor status for the OS (P = 0.029, and BCSS (P = 0.013 in lymph-node-positive breast cancers. Obesity in hormone-receptor-positive breast cancer showed a poorer OS (adjusted hazard ratio [HR] = 1.51, 95% confidence interval [CI] = 0.92 to 2.48 and significantly poorer BCSS (HR = 1.80, 95% CI = 1.08 to 2.99. In contrast, a high BMI in hormone-receptor-negative breast cancer revealed a better OS (HR = 0.44, 95% CI = 0.16 to 1.19 and BCSS (HR = 0.53, 95% CI = 0.19 to 1.44. Being underweight (BMI < 18.50 kg/m2 with hormone-receptor-negative breast cancer was associated with a significantly worse OS (HR = 1.98, 95% CI = 1.00-3.95 and BCSS (HR = 2.24, 95% CI = 1.12-4.47. There was no significant interaction found between the BMI and hormone-receptor status in the lymph-node-negative setting, and BMI did not interact with the menopause status in any subgroup. In conclusion, BMI interacts with the hormone-receptor status in a lymph-node-positive setting, thereby playing a role in the prognosis of breast cancer.

What makes dreams positive or negative: relations to fundamental dimensions of positive and negative mood.

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Kallmeyer, R J; Chang, E C

1998-02-01

The present study examined the general emotional content of dreams reported by individuals who typically experience "positive" versus "negative" dreams. Self-reports of the 153 participants indicated that positive versus negative dreamers (ns = 42 and 24, respectively) generally experienced more positive emotions, e.g., joviality, self-assurance, and fewer negative emotions, e.g., fear, sadness. No differences were found in the self-reports of the participants in the experience of surprise, guilt, fatigue, and shyness between the groups, hence, positive and negative dreams do not appear to reflect simply more positive and fewer negative emotions, respectively.

Comparison between ultrasonography and MR imaging for discriminating squamous cell carcinoma nodes with extranodal spread in the neck

International Nuclear Information System (INIS)

Katayama, Ikuo; Sasaki, Miho; Kimura, Yasuo; Hotokezaka, Yuka; Eida, Sato; Tashiro, Shigeki; Sumi, Misa; Nakamura, Takashi

2012-01-01

Objective: To compare the diagnostic ability of ultrasonography (US) and MR imaging for discriminating squamous cell carcinoma (SCC) nodes with extranodal spread (ENS) in the neck. Methods: US and MR imaging was retrospectively evaluated for differentiating ENS-positive (n = 28) from ENS-negative (n = 26) SCC nodes (>10 mm short-axis diameter) in 50 patients with head and neck SCCs. We assessed nodal size on US and MR images; irregular nodal margin on US; and vanishing nodal border, flare, and shaggy nodal margin signs on T1-, fat-suppressed T2-, and contrast-enhanced T1-weighted MR images, respectively. US and MR images were analyzed by 3 radiologists in consensus and the results were compared between ENS-positive and ENS-negative SCC nodes. Results: The nodal sizes of ENS-positive nodes (21 ± 9 mm) were significantly larger than those of ENS-negative SCC nodes (14 ± 4 mm) (p < 0.001). Irregular nodal margins were more frequently observed in ENS-positive SCC nodes (75%) than in ENS-negative SCC nodes (12%). The vanishing nodal margin, flare, and shaggy nodal margin signs were more frequently observed in ENS-positive SCC nodes (93%, 89%, and 82%, respectively) than in ENS-negative nodes (46%, 19%, and 19%, respectively). A combination of size (≥22 mm) and imaging criteria (irregular margin or flare sign) best discriminated ENS-positive SCC nodes with 82% sensitivity, 89% specificity, and 85% accuracy for US and 89% sensitivity, 81% specificity, and 85% accuracy for MR imaging. Conclusion: US discriminated ENS-positive from ENS-negative SCC nodes with comparable accuracy and higher specificity than MR imaging.

Prognostic Value of Molecular Subtypes, Ki67 Expression and Impact of Postmastectomy Radiation Therapy in Breast Cancer Patients With Negative Lymph Nodes After Mastectomy

International Nuclear Information System (INIS)

Selz, Jessica; Stevens, Denise; Jouanneau, Ludivine; Labib, Alain; Le Scodan, Romuald

2012-01-01

Purpose: To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM). Methods and Materials: A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRR associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors. Results: At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (n=191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors. Conclusions: Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies.

Prognostic Value of Molecular Subtypes, Ki67 Expression and Impact of Postmastectomy Radiation Therapy in Breast Cancer Patients With Negative Lymph Nodes After Mastectomy

Energy Technology Data Exchange (ETDEWEB)

Selz, Jessica, E-mail: chaumontjessica@yahoo.fr [Department of Radiation Oncology, Institut Curie, Hopital Rene Huguenin, Saint Cloud (France); Stevens, Denise; Jouanneau, Ludivine [Department of Medical Statistics, Institut Curie, Hopital Rene Huguenin, Saint Cloud (France); Labib, Alain [Department of Radiation Oncology, Institut Curie, Hopital Rene Huguenin, Saint Cloud (France); Le Scodan, Romuald [Department of Radiation Oncology, Centre Hospitalier Prive Saint Gregoire, Saint Gregoire (France)

2012-12-01

Purpose: To determine whether Ki67 expression and breast cancer subtypes could predict locoregional recurrence (LRR) and influence the postmastectomy radiotherapy (PMRT) decision in breast cancer (BC) patients with pathologic negative lymph nodes (pN0) after modified radical mastectomy (MRM). Methods and Materials: A total of 699 BC patients with pN0 status after MRM, treated between 2001 and 2008, were identified from a prospective database in a single institution. Tumors were classified by intrinsic molecular subtype as luminal A or B, HER2+, and triple-negative (TN) using estrogen, progesterone, and HER2 receptors. Multivariate Cox analysis was used to determine the risk of LRR associated with intrinsic subtypes and Ki67 expression, adjusting for known prognostic factors. Results: At a median follow-up of 56 months, 17 patients developed LRR. Five-year LRR-free survival and overall survival in the entire population were 97%, and 94.7%, respectively, with no difference between the PMRT (n=191) and no-PMRT (n=508) subgroups. No constructed subtype was associated with an increased risk of LRR. Ki67 >20% was the only independent prognostic factor associated with increased LRR (hazard ratio, 4.18; 95% CI, 1.11-15.77; P<.0215). However, PMRT was not associated with better locoregional control in patients with proliferative tumors. Conclusions: Ki67 expression but not molecular subtypes are predictors of locoregional recurrence in breast cancer patients with negative lymph nodes after MRM. The benefit of adjuvant RT in patients with proliferative tumors should be further investigated in prospective studies.

Number of evaluated lymph nodes and positive lymph nodes, lymph node ratio, and log odds evaluation in early-stage pancreatic ductal adenocarcinoma: numerology or valid indicators of patient outcome?

Science.gov (United States)

Lahat, G; Lubezky, N; Gerstenhaber, F; Nizri, E; Gysi, M; Rozenek, M; Goichman, Y; Nachmany, I; Nakache, R; Wolf, I; Klausner, J M

2016-09-29

We evaluated the prognostic significance and universal validity of the total number of evaluated lymph nodes (ELN), number of positive lymph nodes (PLN), lymph node ratio (LNR), and log odds of positive lymph nodes (LODDS) in a relatively large and homogenous cohort of surgically treated pancreatic ductal adenocarcinoma (PDAC) patients. Prospectively accrued data were retrospectively analyzed for 282 PDAC patients who had pancreaticoduodenectomy (PD) at our institution. Long-term survival was analyzed according to the ELN, PLN, LNR, and LODDS. Of these patients, 168 patients (59.5 %) had LN metastasis (N1). Mean ELN and PLN were 13.5 and 1.6, respectively. LN positivity correlated with a greater number of evaluated lymph nodes; positive lymph nodes were identified in 61.4 % of the patients with ELN ≥ 13 compared with 44.9 % of the patients with ELN < 13 (p = 0.014). Median overall survival (OS) and 5-year OS rate were higher in N0 than in N1 patients, 22.4 vs. 18.7 months and 35 vs. 11 %, respectively (p = 0.008). Mean LNR was 0.12; 91 patients (54.1 %) had LNR < 0.3. Among the N1 patients, median OS was comparable in those with LNR ≥ 0.3 vs. LNR < 0.3 (16.7 vs. 14.1 months, p = 0.950). Neither LODDS nor various ELN and PLN cutoff values provided more discriminative information within the group of N1 patients. Our data confirms that lymph node positivity strongly reflects PDAC biology and thus patient outcome. While a higher number of evaluated lymph nodes may provide a more accurate nodal staging, it does not have any prognostic value among N1 patients. Similarly, PLN, LNR, and LODDS had limited prognostic relevance.

Implications of a positive sentinel node in oral squamous cell carcinoma

DEFF Research Database (Denmark)

Gurney, Benjamin A S; Schilling, Clare; Putcha, Venkata

2012-01-01

BACKGROUND: The role of sentinel node biopsy in head and neck cancer is currently being explored. Patients with positive sentinel nodes were investigated to establish if additional metastases were present in the neck, their distribution, and their impact on outcome. METHODS: In all, 109 patients ...

Predictors of non-sentinel lymph node metastasis in breast cancer patients with positive sentinel lymph node (Pilot study)

International Nuclear Information System (INIS)

Eldweny, H.; Alkhaldy, Kh.; Alsaleh, N.; Abdulsamad, M.; Abbas, A.; Hamad, A.; Mounib, Sh.; Essam, T.; Kukawski, P.; Bobin, J.; Oteifa, M.; Amangoono, H.; Abulhoda, F.; Usmani, Sh.; Elbasmy, A.

2012-01-01

Background: Sentinel Lymph Node Biopsy [SLNB) procedure was found to be an accurate method of staging the axilla in patients with early stage breast cancer. The standard of care for breast cancer patients with positive SLN metastasis includes complete Axillary Lymph Node Dissection (ALND). Haw ever, in 40-70% of patients, the SLN the only involved axillary node. Factors predicting non SLW metastasis should be identified in order to define subgroups of patient with positive SLN in whom the axilla may be staged by SLNB done. Objective: To identify the factors predicting metastatic involvement of the non-SLNs in breast cancer patients having SLN metastases. Patients and Methods: Data were collected and analyzed from 80 patients with early stage invasive breast cancer (T1, T2, N0, M0) who underwent SLNB at the surgical Oncology Department, Kuwait Cancel control Center (KCCC) between November 2004 and February 2009. SLNB was perfomed using a combined technique (radioactive colloid, and blue dye) in the majority of cases in some cases, only one technique was used. Complete ALND was performed in the case of failure of SLN identification and in patients with positive SLN. Multiple variables (patient, tumor and of SLN identification and in patients with positive SLN. Multiple variables (patient, tumor, and SLN characteristics) with tested as possible predictors of non sentinel lymph node metastasis. Results: The mean age of patients at diagnosis was 46.6 years. The median tumor size was 2 cm. The SLN identification rate was 96.2% (77 out of 80 patients). The SLN was positive in 24 patients(31%), and half of these showed evidence of capsular invasion. The median number of SLNs removed was two. The median number positive SLNs was one. The incidence of non-SLN metatasis associated with positive SLN was 50% (12 out of 24 patients). lymphovascular invasion was found to be the only factor associated with non-SLN metastases. In addition, two trends were observed, though they did

Arm morbidity following sentinel lymph node biopsy or axillary lymph node dissection: a study from the Danish Breast Cancer Cooperative Group

DEFF Research Database (Denmark)

Husted, Madsen A.; Haugaard, K.; Soerensen, J.

2008-01-01

BACKGROUND: Sentinel lymph node biopsy was implemented in the treatment of early breast cancer with the aim of reducing shoulder and arm morbidity. Relatively few prospective studies have been published where the morbidity was assessed by clinical examination. Very few studies have examined...... lymph node biopsy with node negative patients having a lymph node dissection of levels I and II of the axilla, we found significant increase in arm volume among the patients who had an axillary dissection. Only minor, but significant, differences in shoulder mobility were observed comparing the two...... groups of node negative patients. Highly significant difference was found comparing sensibility. Comparing the morbidity in node positive patients who had a one-step axillary dissection with patients having a two-step procedure (sentinel lymph node biopsy followed by delayed axillary dissection) revealed...

Recurrent/metastatic thyroid carcinomas false negative for serum thyroglobulin but positive by posttherapy I-131 whole body scans

International Nuclear Information System (INIS)

Park, Eun-Kyung; Lee, Dong Soo; Lee, Myung Chul; Chung, June-Key; Lim, Il Han; Park, Do Joon; Cho, Bo Youn

2009-01-01

Serum Tg and I-131 WBS have been used to detect recurrent and metastatic thyroid cancers postoperatively. Tg is known to be more sensitive than I-131 WBS, and therefore, false-negative WBS cases with elevated Tg levels are frequently found. However, the clinical characteristics of false-negative Tg cases with positive WBS have not been clarified. The authors evaluated 824 postoperative patients with differentiated thyroid carcinoma who underwent post-ablation/therapy I-131 WBS. Tg negativity was defined as a Tg level of ≤2 ng/mL without TgAb under thyroid-stimulating hormone stimulation. Remission, recurrence, and metastasis were confirmed using pathologic or clinically findings. Fifty-two patients (6.3%) with functioning metastasis and negativity for TgAb were Tg-negative and posttherapy I-131 WBS-positive (TgN group), and 128 patients with functioning metastases were Tg positive and WBS positive (TgP group). The TgN group consisted of 45 cases of cervical/mediastinal lymph node metastases (86.5%) and seven cases of distant metastasis to lung or bone by follow-up WBS. The TgN group demonstrated significantly higher profiles of regional involvement than the TgP group (P < 0.029). In 47 patients in the TgN group, metastatic uptake disappeared in 33, ameliorated in four, and persisted in ten during follow-up. A significant number of differentiated thyroid cancer patients were Tg-/TgAb-negative despite a positive WBS finding. Cervical and mediastinal lymph nodes were predominant sites of metastasis in the TgN group. WBS should be undertaken routinely as a complementary modality to detect functioning recurrence and metastasis regardless of serum Tg results. (orig.)

Presence of atypical thrombopoietin receptor (MPL) mutations in triple-negative essential thrombocythemia patients.

Science.gov (United States)

Cabagnols, Xénia; Favale, Fabrizia; Pasquier, Florence; Messaoudi, Kahia; Defour, Jean Philippe; Ianotto, Jean Christophe; Marzac, Christophe; Le Couédic, Jean Pierre; Droin, Nathalie; Chachoua, Ilyas; Favier, Remi; Diop, M'boyba Khadija; Ugo, Valérie; Casadevall, Nicole; Debili, Najet; Raslova, Hana; Bellanné-Chantelot, Christine; Constantinescu, Stefan N; Bluteau, Olivier; Plo, Isabelle; Vainchenker, William

2016-01-21

Mutations in signaling molecules of the cytokine receptor axis play a central role in myeloproliferative neoplasm (MPN) pathogenesis. Polycythemia vera is mainly related to JAK2 mutations, whereas a wider mutational spectrum is detected in essential thrombocythemia (ET) with mutations in JAK2, the thrombopoietin (TPO) receptor (MPL), and the calreticulin (CALR) genes. Here, we studied the mutational profile of 17 ET patients negative for JAK2V617F, MPLW515K/L, and CALR mutations, using whole-exome sequencing and next-generation sequencing (NGS) targeted on JAK2 and MPL. We found several signaling mutations including JAK2V617F at very low allele frequency, 1 homozygous SH2B3 mutation, 1 MPLS505N, 1 MPLW515R, and 2 MPLS204P mutations. In the remaining patients, 4 presented a clonal and 7 a polyclonal hematopoiesis, suggesting that certain triple-negative ETs are not MPNs. NGS on 26 additional triple-negative ETs detected only 1 MPLY591N mutation. Functional studies on MPLS204P and MPLY591N revealed that they are weak gain-of-function mutants increasing MPL signaling and conferring either TPO hypersensitivity or independence to expressing cells, but with a low efficiency. Further studies should be performed to precisely determine the frequency of MPLS204 and MPLY591 mutants in a bigger cohort of MPN. © 2016 by The American Society of Hematology.

Partial lower axillary dissection for patients with clinically node-negative breast cancer.

Science.gov (United States)

Kodama, H; Mise, K; Kan, N

2012-01-01

To evaluate retrospectively the outcomes of partial lower axillary lymph node dissection caudal to the intercostobrachial nerve in patients with clinically node-negative (N(0)) breast cancer. Numbers of dissected and metastatic nodes, overall and disease-free survival rates, postoperative complication rates, and axillary recurrence were compared between patients who underwent breast cancer surgery with partial axillary node dissection (n = 1043) and historical controls who underwent conventional dissection (n = 1084). The 5-year overall and disease-free survival rates were 95.6% and 89.7%, and 94.9% and 88.4%, respectively, in the partial dissection and conventional dissection groups; the differences were not significant. Mean duration of surgery (41.6 min versus 60.9 min), intraoperative blood loss (28.0 ml versus 51.3 ml), volume of lymphatic drainage at 2 weeks postoperatively (488 ml versus 836 ml), and persistent arm lymphoedema (0.0% versus 11.8%) were significantly different between the partial and conventional dissection groups, respectively. Partial axillary lymph node dissection was associated with similar survival rates (but lower postoperative complication rates) compared with conventional axillary dissection and is recommended in patients with N(0) breast cancer.

Association between obesity with disease-free survival and overall survival in triple-negative breast cancer: A meta-analysis.

Science.gov (United States)

Mei, Lin; He, Lin; Song, Yuhua; Lv, Yang; Zhang, Lijiu; Hao, Fengxi; Xu, Mengmeng

2018-05-01

To investigate the relationship between obesity and disease-free survival (DFS) and overall survival (OS) of triple-negative breast cancer. Citations were searched in PubMed, Cochrane Library, and Web of Science. Random effect model meta-analysis was conducted by using Revman software version 5.0, and publication bias was evaluated by creating Egger regression with STATA software version 12. Nine studies (4412 patients) were included for DFS meta-analysis, 8 studies (4392 patients) include for OS meta-analysis. There were no statistical significances between obesity with DFS (P = .60) and OS (P = .71) in triple-negative breast cancer (TNBC) patients. Obesity has no impact on DFS and OS in patients with TNBC.

Isolation and characterization of a novel catalase-negative, urease-positive Campylobacter from cattle faeces

DEFF Research Database (Denmark)

Atabay, H.I.; Corry, J.E.L.; On, S.L.W.

1997-01-01

characteristics typical for Campylobacter species. However, they were unusual in that they produced urease and copious H2S in triple sugar iron (TSI) medium, but did not produce catalase. They did not grow aerobically. None of the strains grew on modified cefoperazone charcoal deoxycholate agar (m......CCDA). Macrorestriction profiles of chromosomal DNA were prepared for 15 strains using pulsed-field gel electrophoresis (PFGE). Twelve of 15 profiles were identical and all appeared to be closely related. These catalase-negative, urease-positive campylobacters (CNUPC) represent a group not previously reported...

Anticancer and Anti-Inflammatory Properties of Ganoderma lucidum Extract Effects on Melanoma and Triple-Negative Breast Cancer Treatment.

Science.gov (United States)

Barbieri, Antonio; Quagliariello, Vincenzo; Del Vecchio, Vitale; Falco, Michela; Luciano, Antonio; Amruthraj, Nagoth Joseph; Nasti, Guglielmo; Ottaiano, Alessandro; Berretta, Massimiliano; Iaffaioli, Rosario Vincenzo; Arra, Claudio

2017-02-28

Among the most important traditional medicinal fungi, Ganoderma lucidum has been used as a therapeutic agent for the treatment of numerous diseases, including cancer, in Oriental countries. The aim of this study is to investigate the anti-inflammatory, anticancer and anti-metastatic activities of Ganoderma lucidum extracts in melanoma and triple-negative breast cancer cells. Ganoderma lucidum extracts were prepared by using common organic solvents; MDA-MB 231 and B16-F10 cell lines were adopted as cellular models for triple-negative breast cancer and melanoma and characterized for cell viability, wound-healing assay and measurement of cytokines secreted by cancer cells under pro-inflammatory conditions (incubation with lipopolysaccharide, LPS) and pretreatment with Ganoderma lucidum extract at different concentrations. Our study demonstrates, for the first time, how Ganoderma lucidum extracts can significantly inhibit the release of IL-8, IL-6, MMP-2 and MMP-9 in cancer cells under pro-inflammatory condition. Interestingly, Ganoderma lucidum extracts significantly also decrease the viability of both cancer cells in a time- and concentration-dependent manner, with abilities to reduce cell migration over time, which is correlated with a lower release of matrix metalloproteases. Taken together, these results indicate the possible use of Ganoderma lucidum extract for the therapeutic management of melanoma and human triple-negative breast cancer.

Pre-menopausal triple-negative breast cancer at HAM hospital medan

Science.gov (United States)

Betty; Laksmi, L. I.; Siregar, K. B.

2018-03-01

Triple-negative breast cancers (TNBC) are a type of breast cancer that does not have any or lack expression of the three receptors of estrogen (ER), progesterone (PR), and human epidermal growth factor receptor 2 (HER-2). This cross-sectional study was performed on patients TNBC in HAM hospital Medan from 2013 to 2016 by immunohistochemistry stained. A total 60 invasive breast cancer samples with TNBC. The more frequent in TNBC group were 51-60 years (19 cases, 31.66%) and pre-menopause (34 cases, 57%). Tumor size T3 and T4 with staging IIIA and IIIB, histology sub-type IC-NOS and ILC with grade 2 and grade 3 of histologic was more common in TNBC.

Effectiveness of the Triple P Positive Parenting Program on behavioral problems in children: A meta-analysis

NARCIS (Netherlands)

de Graaf, I.; Speetjens, P.; Smit, F.; de Wolff, M.; Tavecchio, L.

2008-01-01

The Triple P Positive Parenting Program is a multilevel parenting program to prevent and offer treatment for severe behavioral, emotional, and developmental problems in children. The aim of this meta-analysis is to assess the effectiveness of Triple P Level 4 interventions in the management of

Adjuvant chemotherapy and radiotherapy in triple-negative breast carcinoma: A prospective randomized controlled multi-center trial

International Nuclear Information System (INIS)

Wang, Jianhua; Shi, Mei; Ling, Rui; Xia Yuesheng; Luo Shanquan; Fu Xuehai; Xiao Feng; Li Jianping; Long Xiaoli; Wang Jianguo; Hou Zengxia; Chen Yunxia; Zhou Bin; Xu, Man

2011-01-01

Background and purpose: Triple-negative breast cancer (TNBC) presents a high risk breast cancer that lacks the benefit from hormone treatment, chemotherapy is the main strategy even though it exists in poor prognosis. Use of adjuvant radiation therapy, which significantly decreases breast cancer mortality, has not been well described among poor TNBC women. The aim of this study was to evaluate whether the combination of chemotherapy and radiotherapy could significantly increase survival outcomes in TNBC women after mastectomy. Patients and methods: A prospective randomized controlled multi-center study was performed between February 2001 and February 2006 and comprised 681 women with triple-negative stage I-II breast cancer received mastectomy, of them, 315 cases received systemic chemotherapy alone, 366 patients received radiation after the course of chemotherapy. Recurrence-free survival (RFS) and overall survival (OS) were estimated. Simultaneously local and systemic toxicity were observed. Results: After a median follow-up of 86.5 months, five-year RFS rates were 88.3% and 74.6% for adjuvant chemotherapy plus radiation and adjuvant chemotherapy alone, respectively, with significant difference between the two groups (HR 0.77 [95% CI 0.72, 0.98]; P = 0.02). Five-year OS significantly improved in adjuvant chemotherapy plus radiation group compared with chemotherapy alone (90.4% and 78.7%) (HR 0.79 [95% CI 0.74, 0.97]; P = 0.03). No severe toxicity was reported. Conclusions: Patients received standard adjuvant chemotherapy plus radiation therapy was more effective than chemotherapy alone in women with triple-negative early-stage breast cancer after mastectomy.

Overexpression of ETV4 protein in triple-negative breast cancer is associated with a higher risk of distant metastasis

Directory of Open Access Journals (Sweden)

Yuan ZY

2014-09-01

Full Text Available Zhong-Yu Yuan,1–3,* Ting Dai,1,2,* Shu-Sen Wang,1–3 Rou-Jun Peng,1–3 Xing-Hua Li,1,2 Tao Qin,1–3 Li-Bing Song,1,2 Xi Wang1,2,41State Key Laboratory of Oncology in South China, Guangzhou, People's Republic of China; 2Collaborative Innovation Center for Cancer Medicine, Guangzhou, People's Republic of China; 3Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China; 4Department of Breast Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, People's Republic of China  *These authors contributed equally to this work Background: Patients with triple-negative breast cancer (TNBC present a higher probability of distant metastasis and lack of effective targeted therapy. ETS translocation variant 4 (ETV4 is an ETS (E-26 transcription factor and has been associated with tumor metastasis. However, the clinical and functional significance of ETV4 in TNBC still remains unclear. Methods: A human tumor metastasis polymerase chain reaction array was used to profile differential expression of tumor metastasis-related genes in TNBC tissue. Real-time reverse transcription and Western blot analyses were performed to verify ETV4 expression in TNBC cells and tissue. Immunohistochemistry was used to detect expression of ETV4 protein in 135 TNBC tissue samples for association between ETV4 protein expression and clinical outcomes. Results: A total total of eight upregulated (CCL7, KISS1, MET, MMP7, NR4A3, ETV4, TIMP3, and TSHR and three downregulated (ITGA7, SSTR, and MMP2 genes were identified between TNBC tissue and the luminal subtype of breast cancer tissue. ETV4 messenger ribonucleic acid was more than five-fold upregulated in TNBC tissue compared with the control tissue. ETV4 overexpression was found in 57.0% of 135 TNBC cases. Overexpression of ETV4 protein was associated with an advanced stage and a higher proportion of positive lymph node and lymphovascular invasion. Patients with an ETV4

Population based study on sentinel node biopsy before or after neoadjuvant chemotherapy in clinically node negative breast cancer patients : Identification rate and influence on axillary treatment

NARCIS (Netherlands)

van der Heiden-van der Loo, M.; de Munck, L.; Sonke, G. S.; van Dalen, T.; van Diest, P. J.; van den Bongard, H. J. G. D.; Peeters, P. H. M.; Rutgers, E. J. T.

The timing of the sentinel lymph node biopsy (SNB) is controversial in clinically node negative patients receiving neoadjuvant chemotherapy (NAC). We studied variation in the timing of axillary staging in breast cancer patients who received NAC and the subsequent axillary treatment in The

Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer

Science.gov (United States)

2017-10-01

AWARD NUMBER: W81XWH-15-1-0268 TITLE: Randomized Trial of Asprin as Adjuvant Therapy for Node-Positive Breast Cancer PRINCIPAL INVESTIGATOR...Eric Winer CONTRACTING ORGANIZATION: Dana-Farber Cancer Institute Boston, MA 02215 REPORT DATE: OCTOBER 2017 TYPE OF REPORT: ANNUAL PREPARED FOR...CONTRACT NUMBER Randomized Trial of Asprin as Adjuvant Therapy for Node- Positive Breast Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR

Modeling triple-negative breast cancer heterogeneity: effects of stromal macrophages, fibroblasts and tumor vasculature.

Science.gov (United States)

Norton, Kerri-Ann; Jin, Kideok; Popel, Aleksander S

2018-05-08

A hallmark of breast tumors is its spatial heterogeneity that includes its distribution of cancer stem cells and progenitor cells, but also heterogeneity in the tumor microenvironment. In this study we focus on the contributions of stromal cells, specifically macrophages, fibroblasts, and endothelial cells on tumor progression. We develop a computational model of triple-negative breast cancer based on our previous work and expand it to include macrophage infiltration, fibroblasts, and angiogenesis. In vitro studies have shown that the secretomes of tumor-educated macrophages and fibroblasts increase both the migration and proliferation rates of triple-negative breast cancer cells. In vivo studies also demonstrated that blocking signaling of selected secreted factors inhibits tumor growth and metastasis in mouse xenograft models. We investigate the influences of increased migration and proliferation rates on tumor growth, the effect of the presence on fibroblasts or macrophages on growth and morphology, and the contributions of macrophage infiltration on tumor growth. We find that while the presence of macrophages increases overall tumor growth, the increase in macrophage infiltration does not substantially increase tumor growth and can even stifle tumor growth at excessive rates. Copyright © 2018. Published by Elsevier Ltd.

Study of metastatic lymph nodes in advanced gastric cancer with spiral computed tomograph

International Nuclear Information System (INIS)

Su Yijuan

2008-01-01

Objective: To study the characteristics of spiral computed tomography (SCT) in the diagnosis of lymph nodes metastases in gastric cancer. Methods: The characteristics of spiral computed tomography (SCT) of metastatic lymph nodes in 35 gastric cancer patients were analyzed and compared with operation and pathology. Results: A total amount of 379 lymph nodes (positive 173, negative 206) were detected by SCT and confirmed by pathology in metastasis-positive or metastasis-negative patients. The positive rate with diameter of lymph nodes ≥ 10 mm is 62.7%. The positive rate with ir- regular shape and uneven enhancement lymph nodes were 96.3% and 89.4%. If the attenuation values, more than or equal to 25 HU in plain scan or 70 HU in arterial phase or 80 HU in venous phase, were used as the threshold to detect the metastasis-positive lymph nodes, the positive rate were 55.7%, 56.3%, 67.8% respectively. Conclusion: SCT is valuable in judging the metastasis in gastric cancer. The reference of diameter ≥ 10mm, combining with the shape and the attenuation values can dramatically improve the diagnosis of lymph node metastasis in gastric cancer. (authors)

Radionavigated detection of sentinel nodes in breast carcinoma--first experiences of our department.

Science.gov (United States)

Duchaj, B; Chvalny, P; Vesely, J; Makaiova, I; Durdik, S; Straka, V; Palaj, J; Procka, V; Aksamitova, K; Skraskova, S; Banki, P; Kovacova, S; Galbavy, S

2010-01-01

Biopsy and histological evaluation of sentinel lymphatic node limits the axillary node dissection only in cases of positive histological finding and decreases the occurrence of postoperative complications related to the axillary node dissection. We used radiotracer SentiScint, Medi-Radiopharma Ltd, Hungary and preoperatively administered blue dye--Blue Patenté V, Guebert, Aulnay-Sous-Bios, France. 11 (18%) patients were subdued to deep peritimorous application of radiotracer, 10 (16.4%) to sub/intradermal application over the lesions and n 40 (65.6%) patients the application was sub/intradermal and periareolar. The patients underwent an operation protocol of corresponding quadrantectomy, radionavigated blue-dye sentinel node biopsy and axillary dissection. From May 2006 to June 2008, we examined 61 patients with breast carcinoma. They underwent radionavigated and blue-dye sentinel node biopsy. We detected 57 (93.4%) sentinel nodes with preoperative scintigraphy, of which only 51 (83.6%) were detected peroperatively and underwent histological evaluation. In six (9.8%) cases, the "frozen cut" histology of the primary lesion had shown a benign lesion; hence no sentinel node biopsy or axillary disection was performed. 12 (19.7%) of 51 histologically evaluated sentinel nodes had metastatic invasion. We retrospectively compared the histological fund in sentinel and axillary nodes in patients with metastatic sentinel nodes. In 6 (16.6%) cases, the sentinel node was positive of metastatic invasion but axillary nodes were histologically negative, in 6 (16.6%) cases the sentinel node and axillary nodes were positive for metastatic invasion. We observed falsely negative findings in 3 (8.3%) patients with negative histological fund in the sentinel node, but positive axillary nodes (Tab. 3, Fig. 2, Ref. 11). Full Text (Free, PDF) www.bmj.sk.

Diagnostic value of HMB-45 and anti-Melan A staining of sentinel lymph nodes with isolated positive cells.

Science.gov (United States)

Mahmood, Muhammad N; Lee, Min W; Linden, Michael D; Nathanson, S D; Hornyak, Thomas J; Zarbo, Richard J

2002-12-01

Numerous immunohistochemical stains have been employed to detect metastatic melanoma in sentinel lymph node (SLN) biopsies. HMB-45 is considered by some as a specific tool to detect early metastatic melanoma (1). Occasionally, one or two isolated HMB-45-positive cells may cause complications in diagnostic interpretation. The goal of this study was to evaluate the reliability of HMB-45 staining of SLNs with sparse isolated positive cells and to compare its staining with anti-Melan A antibody. HMB-45 and anti-Melan A antibody immunostaining was performed on (Group A) 15 histologically negative SLNs excised from patients with malignant melanoma (MM) and on (Group B) 15 histologically negative SLNs excised from patients with breast carcinoma (BC). None of the patients had clinical evidence of systemic metastasis at the time of SLN biopsy. Five cutaneous biopsies with changes of postinflammatory hyperpigmentation (PIHP) were also stained with both antibodies. HMB-45 staining was repeated in all Group B SLNs after blocking endogenous biotins. Electron-microscopic studies were performed on all cases of PIHP. Isolated HMB-45-stained cells were present in 6 of 15 SLNs removed for MM; 8 of 15 for BC; and 3 of 5 cutaneous biopsies of PIHP. HMB-45 reactivity persisted after blocking endogenous biotins in 6 of 8 positive SLNs from Group B. Anti-Melan A antibody was negative in all SLNs of group A and B and in dermal melanophages of all five cases of PIHP. HMB-45 positivity was demonstrated in histologically negative SLNs and cutaneous biopsies, especially in the milieu of aggregated melanophages. Phagocytosis of premelanosomes by macrophages in the draining lymph nodes may account for isolated cell positivity and can hinder correct diagnostic interpretation. HMB-45 may not be a reliable marker for the detection of micro-metastasis of MM and requires correlation with other immunohistochemical markers, such as anti-Melan A antibody, to enhance specificity.

Therapeutic rationale to target highly expressed CDK7 conferring poor outcomes in triple-negative breast cancer

NARCIS (Netherlands)

Li, Bo; Chonghaile, Triona Ni; Fan, Yue; Madden, Stephen F.; Klinger, Rut; O'Connor, Aisling E.; Walsh, Louise; O'Hurley, Gillian; Udupi, Girish Mallya; Joseph, Jesuchristopher; Tarrant, Finbarr; Conroy, Emer; Gaber, Alexander; Chin, Suet-Feung; Bardwell, Helen A; Provenzano, Elena; Crown, John; Dubois, Thierry; Linn, Sabine; Jirstrom, Karin; Caldas, Carlos; O'Connor, Darran P; Gallagher, William M

2017-01-01

Triple-negative breast cancer (TNBC) patients commonly exhibit poor prognosis and high relapse after treatment, but there remains a lack of biomarkers and effective targeted therapies for this disease. Here, we report evidence highlighting the cell-cycle–related kinase CDK7 as a driver and candidate

Prognostic significance of proline, glutamic acid, leucine rich protein 1 (PELP1) in triple-negative breast cancer: a retrospective study on 129 cases

International Nuclear Information System (INIS)

Zhang, Yanzhi; Dai, Jiali; McNamara, Keely M.; Bai, Bing; Shi, Mumu; Chan, Monica S. M.; Liu, Ming; Sasano, Hironobu; Wang, Xiuli; Li, Xiaolei; Liu, Lijuan; Ma, Ying; Cao, Shuwen; Xing, Yanchun; Zhao, Baoshan; Song, Yinli; Wang, Lin

2015-01-01

Triple-negative breast cancer (TNBC) is associated with an aggressive clinical course due to the lack of therapeutic targets. Therefore, identifying reliable prognostic biomarkers and novel therapeutic targets for patients with TNBC is required. Proline, glutamic acid, leucine rich protein 1 (PELP1) is a novel steroidal receptor co-regulator, functioning as an oncogene and its expression is maintained in estrogen receptor (ER) negative breast cancers. PELP1 has been proposed as a prognostic biomarker in hormone-related cancers, including luminal-type breast cancers, but its significance in TNBC has not been studied. PELP1 immunoreactivity was evaluated using immunohistochemistry in 129 patients with TNBC. Results were correlated with clinicopathological variables including patient’s age, tumor size, lymph node stage, tumor grade, clinical stage, histological type, Ki-67 LI, as well as clinical outcome of the patients, including disease-free survival (DFS) and overall survival (OS). PELP1 was localized predominantly in the nuclei of carcinoma cells in TNBC. With the exception of a positive correlation between PELP1 protein expression and lymph node stage (p = 0.027), no significant associations between PELP1 protein expression and other clinicopathological variables, including DFS and OS, were found. However, when PELP1 and Ki-67 LI were grouped together, we found that patients in the PELP1/Ki-67 double high group (n = 48) demonstrated significantly reduced DFS (p = 0.005, log rank test) and OS (p = 0.002, log rank test) than others (n = 81). Multivariable analysis supported PELP1/Ki-67 double high expression as an independent prognostic factor in patients with TNBC, with an adjusted hazard ratio of 2.020 for recurrence (95 % CL, 1.022–3.990; p = 0.043) and of 2.380 for death (95 % CL, 1.138–4.978; p = 0.021). We found that evaluating both PELP1 and Ki-67 expression in TNBC could enhance the prognostic sensitivity of the two biomarkers. Therefore, we propose

G-CSF regulates macrophage phenotype and associates with poor overall survival in human triple-negative breast cancer

Science.gov (United States)

Hollmén, Maija; Karaman, Sinem; Schwager, Simon; Lisibach, Angela; Christiansen, Ailsa J.; Maksimow, Mikael; Varga, Zsuzsanna; Jalkanen, Sirpa; Detmar, Michael

2016-01-01

ABSTRACT Tumor-associated macrophages (TAMs) have been implicated in the promotion of breast cancer growth and metastasis, and a strong infiltration by TAMs has been associated with estrogen receptor (ER)-negative tumors and poor prognosis. However, the molecular mechanisms behind these observations are unclear. We investigated macrophage activation in response to co-culture with several breast cancer cell lines (T47D, MCF-7, BT-474, SKBR-3, Cal-51 and MDA-MB-231) and found that high granulocyte colony-stimulating factor (G-CSF) secretion by the triple-negative breast cancer (TNBC) cell line MDA-MB-231 gave rise to immunosuppressive HLA-DRlo macrophages that promoted migration of breast cancer cells via secretion of TGF-α. In human breast cancer samples (n = 548), G-CSF was highly expressed in TNBC (p CSF blockade in the 4T1 mammary tumor model promoted maturation of MHCIIhi blood monocytes and TAMs and significantly reduced lung metastasis, anti-CSF-1R treatment promoted MHCIIloF4/80hiMRhi anti-inflammatory TAMs and enhanced lung metastasis in the presence of high G-CSF levels. Combined anti-G-CSF and anti-CSF-1R therapy significantly increased lymph node metastases, possibly via depletion of the so-called “gate-keeper” subcapsular sinus macrophages. These results indicate that G-CSF promotes the anti-inflammatory phenotype of tumor-induced macrophages when CSF-1R is inhibited and therefore caution against the use of M-CSF/CSF-1R targeting agents in tumors with high G-CSF expression. PMID:27141367

Cluster synchronization induced by one-node clusters in networks with asymmetric negative couplings

International Nuclear Information System (INIS)

Zhang, Jianbao; Ma, Zhongjun; Zhang, Gang

2013-01-01

This paper deals with the problem of cluster synchronization in networks with asymmetric negative couplings. By decomposing the coupling matrix into three matrices, and employing Lyapunov function method, sufficient conditions are derived for cluster synchronization. The conditions show that the couplings of multi-node clusters from one-node clusters have beneficial effects on cluster synchronization. Based on the effects of the one-node clusters, an effective and universal control scheme is put forward for the first time. The obtained results may help us better understand the relation between cluster synchronization and cluster structures of the networks. The validity of the control scheme is confirmed through two numerical simulations, in a network with no cluster structure and in a scale-free network

Cluster synchronization induced by one-node clusters in networks with asymmetric negative couplings

Science.gov (United States)

Zhang, Jianbao; Ma, Zhongjun; Zhang, Gang

2013-12-01

This paper deals with the problem of cluster synchronization in networks with asymmetric negative couplings. By decomposing the coupling matrix into three matrices, and employing Lyapunov function method, sufficient conditions are derived for cluster synchronization. The conditions show that the couplings of multi-node clusters from one-node clusters have beneficial effects on cluster synchronization. Based on the effects of the one-node clusters, an effective and universal control scheme is put forward for the first time. The obtained results may help us better understand the relation between cluster synchronization and cluster structures of the networks. The validity of the control scheme is confirmed through two numerical simulations, in a network with no cluster structure and in a scale-free network.

The value of level III clearance in patients with axillary and sentinel node positive breast cancer.

LENUS (Irish Health Repository)

Dillon, Mary F

2012-02-01

BACKGROUND: The value of level III axillary clearance is contentious, with great variance worldwide in the extent and levels of clearance performed. OBJECTIVE: To determine rates of level III positivity in patients undergoing level I-III axillary clearance, and identify which patients are at highest risk of involved level III nodes. METHODS: From a database of 2850 patients derived from symptomatic and population-based screening service, 1179 patients who underwent level I-III clearance between the years 1999-2007 were identified. The pathology, surgical details, and prior sentinel nodes biopsies of patients were recorded. RESULTS: Eleven hundred seventy nine patients had level I-III axillary clearance. Of the patients, 63% (n = 747) were node positive. Of patients with node positive disease, 23% (n = 168) were level II positive and 19% (n = 141) were level III positive. Two hundred fifty patients had positive sentinel node biopsies prior to axillary clearance. Of these, 12% (n = 30) and 9% (n = 22) were level II and level III positive, respectively. On multivariate analysis, factors predictive of level III involvement in patients with node positive disease were tumor size (P < 0.001, OR = 1.36; 95% CI: 1.2-1.5), invasive lobular disease (P < 0.001, OR = 3.6; 95% CI: 1.9-6.95), extranodal extension (P < 0.001, OR = 0.27; 95% CI: 0.18-0.4), and lymphovascular invasion (P = 0.04, OR = 0.58; 95% CI: 0.35-1). Lobular invasive disease (P = 0.049, OR = 4.1; 95% CI: 1-16.8), extranodal spread (P = 0.003, OR = 0.18; 95% CI: 0.06-0.57), and having more than one positive sentinel node (P = 0.009, OR = 4.9; 95% CI: 1.5-16.1) were predictive of level III involvement in patients with sentinel node positive disease. CONCLUSION: Level III clearance has a selective but definite role to play in patients who have node positive breast carcinoma. Pathological characteristics of the primary tumor are of particular use in identifying those who are at various risk of level III nodal

False-negative contrast-enhanced spectral mammography: use of more than one imaging modality and application of the triple test avoids misdiagnosis.

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Taylor, Donna; O'Hanlon, Susan; Latham, Bruce

2017-03-31

A 50-year-old woman presented with chest tenderness. On examination, both breasts were lumpy. Bilateral mammography showed heterogeneously dense parenchyma, with possible stromal distortion laterally on the right at the 0900 position. On ultrasound (US), a corresponding 13×9×10 mm irregular hypoechoic mass with internal vascularity was noted and both breasts had a complex heterogeneous fibroglandular background pattern. US-guided core biopsy with marker clip insertion was performed with the diagnosis of a grade 2 invasive ductal carcinoma (IDC). In view of the parenchymal pattern on mammography and US, contrast-enhanced spectral mammography (CESM) was performed for local staging. Mild background enhancement was noted, but there was no enhancement at the lesion site. The patient elected to have bilateral mastectomies and sentinel node biopsies. Final histopathology showed a node negative 11 mm grade 2 oestrogen and progesterone receptor positive, IDC. 2017 BMJ Publishing Group Ltd.

Enhanced Metastatic Recurrence Via Lymphatic Trafficking of a High-Metastatic Variant of Human Triple-Negative Breast Cancer After Surgical Resection in Orthotopic Nude Mouse Models.

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Yano, Shuya; Takehara, Kiyoto; Tazawa, Hiroshi; Kishimoto, Hiroyuki; Kagawa, Shunsuke; Bouvet, Michael; Fujiwara, Toshiyoshi; Hoffman, Robert M

2017-03-01

We previously developed and characterized a highly invasive and metastatic triple-negative breast cancer (TNBC) variant by serial orthotopic implantation of MDA-MB-231 human breast cancer cells in nude mice. Eventually, a highly invasive and metastatic variant of human TNBC was isolated after lymph node metastases was harvested and orthotopically re-implanted into the mammary gland of nude mice for two cycles. The variant thereby isolated is highly invasive in the mammary gland and metastasized to lymph nodes in 10 of 12 mice compared to 2 of 12 of the parental cell line. In the present report, we observed that high-metastatic MDA-MB-231H-RFP cells produced significantly larger subcutaneous tumors compared with parental MDA-MB-231 cells in nude mice. Extensive lymphatic trafficking by high-metastatic MDA-MB-231 cells was also observed. High-metastatic MDA-MB-231 developed larger recurrent tumors 2 weeks after tumor resection compared with tumors that were not resected in orthotopic models. Surgical resection of the MDA-MB-231 high-metastatic variant primary tumor in orthotopic models also resulted in rapid and enhanced lymphatic trafficking of residual cancer cells and extensive lymph node and lung metastasis that did not occur in the non-surgical mice. These results suggest that surgical resection of high metastatic TNBC can greatly increase the malignancy of residual cancer. J. Cell. Biochem. 118: 559-569, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

The external and internal radioimmunodetection of metastatic lymph nodes of breast cancer

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Long Li

1991-01-01

A radiolabeled monoclonal antibody (McAb) 6c6 was used to detect the metastatic lymph nodes of breast cancer externally and internally. 111 In was labeled to 6c6 by DTPA method. Iodogen method was used to label 131 I. The radiolabeled 6c6 was injected into the web space of each hand in seven women with breast cancer and one with benign breast tumor. The scans were positive in two axillae with palpable nodes and four with impalpable nodes. Pathologic examination later confirmed metastases in five of the axillae. Two axillae, one of them with palpable nodes, showed negative result, and here no tumor cells were found pathologically. Intraoperative metastatic lymph node detection with a hand-held gamma probe was carried out in six patients. 24 lymph nodes were measured with 17% (1/6) false negative and no false positive result (0/18), indicating that the result detected by the hand-held gamma probe presents the real radioactivity of the tissues being examined. There were 60 lymph nodes that were removed and detected again by well-shape detector after operation. The false positive rate was 14% (6/42), and the false negative rate was 11% (2/18), indicating that the radiolabeled McAb 6c6 could specifically combine with the metastatic lymph nodes of breast cancer in vivo

Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial.

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Albain, Kathy S; Barlow, William E; Shak, Steven; Hortobagyi, Gabriel N; Livingston, Robert B; Yeh, I-Tien; Ravdin, Peter; Bugarini, Roberto; Baehner, Frederick L; Davidson, Nancy E; Sledge, George W; Winer, Eric P; Hudis, Clifford; Ingle, James N; Perez, Edith A; Pritchard, Kathleen I; Shepherd, Lois; Gralow, Julie R; Yoshizawa, Carl; Allred, D Craig; Osborne, C Kent; Hayes, Daniel F

2010-01-01

The 21-gene recurrence score assay is prognostic for women with node-negative, oestrogen-receptor-positive breast cancer treated with tamoxifen. A low recurrence score predicts little benefit of chemotherapy. For node-positive breast cancer, we investigated whether the recurrence score was prognostic in women treated with tamoxifen alone and whether it identified those who might not benefit from anthracycline-based chemotherapy, despite higher risks of recurrence. The phase 3 trial SWOG-8814 for postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer showed that chemotherapy with cyclophosphamide, doxorubicin, and fluorouracil (CAF) before tamoxifen (CAF-T) added survival benefit to treatment with tamoxifen alone. Optional tumour banking yielded specimens for determination of recurrence score by RT-PCR. In this retrospective analysis, we assessed the effect of recurrence score on disease-free survival by treatment group (tamoxifen vs CAF-T) using Cox regression, adjusting for number of positive nodes. There were 367 specimens (40% of the 927 patients in the tamoxifen and CAF-T groups) with sufficient RNA for analysis (tamoxifen, n=148; CAF-T, n=219). The recurrence score was prognostic in the tamoxifen-alone group (p=0.006; hazard ratio [HR] 2.64, 95% CI 1.33-5.27, for a 50-point difference in recurrence score). There was no benefit of CAF in patients with a low recurrence score (score or =31; log-rank p=0.033; HR 0.59, 0.35-1.01), after adjustment for number of positive nodes. The recurrence score by treatment interaction was significant in the first 5 years (p=0.029), with no additional prediction beyond 5 years (p=0.58), although the cumulative benefit remained at 10 years. Results were similar for overall survival and breast-cancer-specific survival. The recurrence score is prognostic for tamoxifen-treated patients with positive nodes and predicts significant benefit of CAF in tumours with a high recurrence score. A low recurrence

Toxicity and outcome of pelvic IMRT for node-positive prostate cancer

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Mueller, A.C.; Luetjens, J.; Eckert, F.; Bamberg, M.; Alber, M.; Schilling, D.; Belka, C.; Gaswindt, U.

2012-01-01

Background and purpose: This study reports on the treatment techniques, toxicity, and outcome of pelvic intensity-modulated radiotherapy (IMRT) for lymph node-positive prostate cancer (LNPPC, T1-4, c/pN1 cM0). Patients and methods: Pelvic IMRT to 45-50.4 Gy was applied in 39 cases either after previous surgery of involved lymph nodes (n = 18) or with a radiation boost to suspicious nodes (n = 21) with doses of 60-70 Gy, usually combined with androgen deprivation (n = 37). The prostate and seminal vesicles received 70-74 Gy. In cases of previous prostatectomy, prostatic fossa and remnants of seminal vesicles were given 66-70 Gy. Treatment-related acute and late toxicity was graded according to the RTOG criteria. Results: Acute radiation-related toxicity higher than grade 2 occurred in 2 patients (with the need for urinary catheter/subileus related to adhesions after surgery). Late toxicity was mild (grade 1-2) after a median follow-up of 70 months. Over 50% of the patients reported no late morbidity (grade 0). PSA control and cancer-specific survival reached 67% and 97% at over 5 years. Conclusion: Pelvic IMRT after the removal of affected nodes or with a radiation boost to clinically positive nodes led to an acceptable late toxicity (no grade 3/4 events), thus justifying further evaluation of this approach in a larger cohort. (orig.)

Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

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Pistelli, Mirco, E-mail: mirco.pistelli@alice.it; Caramanti, Miriam [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Biscotti, Tommasina; Santinelli, Alfredo [Anatomia Patologica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy); Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano [Clinica di Oncologia Medica, AO Ospedali Riuniti-Ancona, Università Politecnica delle Marche, Ancona 60020 (Italy)

2014-06-27

Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

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Mirco Pistelli

2014-06-01

Full Text Available Background: Triple-negative breast cancers (TNBC are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001 and a lympho-vascular invasion (p = 0.01, but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72 or overall survival (p = 0.93. Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target.

Androgen Receptor Expression in Early Triple-Negative Breast Cancer: Clinical Significance and Prognostic Associations

International Nuclear Information System (INIS)

Pistelli, Mirco; Caramanti, Miriam; Biscotti, Tommasina; Santinelli, Alfredo; Pagliacci, Alessandra; De Lisa, Mariagrazia; Ballatore, Zelmira; Ridolfi, Francesca; Maccaroni, Elena; Bracci, Raffaella; Berardi, Rossana; Battelli, Nicola; Cascinu, Stefano

2014-01-01

Background: Triple-negative breast cancers (TNBC) are characterized by aggressive tumour biology resulting in a poor prognosis. Androgen receptor (AR) is one of newly emerging biomarker in TNBC. In recent years, ARs have been demonstrated to play an important role in the genesis and in the development of breast cancer, although their prognostic role is still debated. In the present study, we explored the correlation of AR expression with clinical, pathological and molecular features and its impact on prognosis in early TNBC. Patients and Methods: ARs were considered positive in case of tumors with >10% nuclear-stained. Survival distribution was estimated by the Kaplan Meier method. The univariate and multivariate analyses were performed. The difference among variables were calculated by chi-square test. Results: 81 TNBC patients diagnosed between January 2006 and December 2011 were included in the analysis. Slides were stained immunohistochemically for estrogen and progesterone receptors, HER-2, Ki-67, ALDH1, e-cadherin and AR. Of the 81 TNBC samples, 18.8% showed positive immunostaining for AR, 23.5% and 44.4% of patients were negative for e-cadherin and ALDH1, respectively. Positive AR immunostaining was inversely correlated with a higher Ki-67 (p < 0.0001) and a lympho-vascular invasion (p = 0.01), but no other variables. Univariate survival analysis revealed that AR expression was not associated with disease-free survival (p = 0.72) or overall survival (p = 0.93). Conclusions: The expression of AR is associated with some biological features of TNBC, such as Ki-67 and lympho-vascular invasion; nevertheless the prognostic significance of AR was not documented in our analysis. However, since ARs are expressed in a significant number of TNBC, prospective studies in order to determine the biological mechanisms and their potential role as novel treatment target

Targeting Tryptophan Catabolism: A Novel Method to Block Triple-Negative Breast Cancer Metastasis

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2017-04-01

Negative Breast Cancer Nicholas C. D’Amato1, Thomas J. Rogers1, Michael A. Gordon1, Lisa I. Greene1, Dawn R. Cochrane1, Nicole S. Spoelstra1, Travis G...cancer progression. Biochim Biophys Acta 2013;1833:3481–98. 10. Kamarajugadda S, Stemboroski L, Cai Q, Simpson NE, Nayak S, Tan M, et al. Glucose...4664. Published OnlineFirst September 11, 2015.Cancer Res Nicholas C. D’Amato, Thomas J. Rogers, Michael A. Gordon, et al. Metastasis in Triple

Comparative analysis of multi-slice spiral CT and positron emission tomography-CT in evaluation of axillary lymph nodes in breast cancer patients

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Sun Xianchang; Zhang Ruyi; Liu Qingwei; Zhao Suhong; Zu Degui; Li Xin

2008-01-01

Objective: To evaluate and compare spiral CT and positron emission tomography-CT (PET-CT) in characterization of of axillary lymph nodes in breast cancer patients. Methods: Forty patients with pathologically proven breast cancer underwent contrast-enhanced spiral CT of the breast and axilla, 13 of them also underwent PET-CT examination. One hundred and fifty-eight axillary lymph nodes were found in the 40 patients through contrast enhanced spiral CT, while 57 lymph nodes were found in the 13 patients through PET-CT. Three radiologists rated the lymph nodes found in CT images on a five-point scale. If the score was equal to or greater than 3, it was defined as positive (metastatic), otherwise negative. Visual observation and semiquantitative analysis were used to classify lymph nodes in PET-CT images. The results of spiral CT observation and PET-CT observation of lymph nodes were compared with pathological results. The relative value of CT and PET-CT was analyzed. Exact probability statistics were employed. Results: One hundred and fifty eight lymph nodes of 40 patients were detected by spiral CT, 91 of them were diagnosed as positive and 67 as negative Among the lymph nodes found in spiral CT, 99 were positive and 59 were negative pathologicall. A total of 57 lymph nodes were found by PET-CT. Thirty-nine of them were defined as positive and 18 as negative. Among the lymph nodes found in PET-CT, 39 were positive and 18 were negative pathologically. The sensitivity, specificity, accuracy, positive and negative predictive values in CT prediction in axillary lymph nodes metastases were 88.89%, 94.91%, 91.14%, 96.70%, and 83.58%, respectively. The sensitivity, specificity, accuracy, positive and negative predictive values in PET-CT prediction in axillary lymph nodes metastases were 97.44%, 94.44%, 96.49%, 97.44%, and 94.44%, respectively. PET-CT had no significant difference with spiral CT in sensitivity, accuracy, positive and negative predictive values for detection

Indications of sentinel node biopsy in thin melanoma

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Fernanda Braga Silva

2010-06-01

Full Text Available Objective: To assess data on survival, recurrence and histological factors in positive and negative sentinel lymph nodes in thin melanoma cases. Methods: A systematic review was conducted on observational studies in four databases (Cochrane Library, Medline, Embase and Lilacs. Positive and negative micrometastases in sentinel lymph node biopsy were compared regarding the clinical outcomes – death and recurrence – and six histological factors – vertical growth phase, Breslow thickness, Clark level, ulceration, regression and mitosis rate. Results: Positive sentinel lymph node is statistically associated with greater risk of death in six studies (OR: 7.2; 95%CI [2.37-21.83]; I2 0% and also to recurrence in three studies (OR: 30.7; 95%CI [12.58-74.92]; I2 36%. Comparing positive and negative groups, the histological factors predicting positive sentinel nodes and poor prognosis were: mitosis rate ≥ 5/mm2 (OR: 16.29; 95%CI [3.64-72.84]; I2 40%; VGP (OR: 2.93; 95%CI [1.08-7.93]; I2 59%; Breslow thickness ≥ 0.75mm (OR: 2.23; 95%CI [1.29-3.86]; I2 0%; and Clark level IV-V (OR: 1.61; 95%CI [1.06-2.44]; I2 34%. Conclusions: The statistically significant results associated with the presence of micrometastases in thin melanomas were Breslow thickness ≥ 0.75 mm, Clark level IV-V and mitoses ≥ 5/mm2, absence of regression. This histological factor of ulceration was associated, but not statistically significant.

Effectiveness of the Triple P Positive Parenting Program on behavioral problems in children: a meta-analysis.

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de Graaf, Ireen; Speetjens, Paula; Smit, Filip; de Wolff, Marianne; Tavecchio, Louis

2008-09-01

The Triple P Positive Parenting Program is a multilevel parenting program to prevent and offer treatment for severe behavioral, emotional, and developmental problems in children. The aim of this meta-analysis is to assess the effectiveness of Triple P Level 4 interventions in the management of behavioral problems in children by pooling the evidence from relevant literature that included Level 4 Triple P interventions. Level 4 intervention is indicated if the child has multiple behavior problems in a variety of settings and there are clear deficits in parenting skills. Results indicate that Level 4 of Triple P interventions reduced disruptive behaviors in children. These improvements were maintained well over time, with further improvements in long-term follow-up. These effects support the widespread adoption and implementation of Triple P that is taking place in an increasing number of countries in quite diverse cultural contexts around the world.

Divergent Synthesis of Chondroitin Sulfate Disaccharides and Identification of Sulfate Motifs that Inhibit Triple Negative Breast Cancer

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Wei Poh, Zhong; Heng Gan, Chin; Lee, Eric J.; Guo, Suxian; Yip, George W.; Lam, Yulin

2015-09-01

Glycosaminoglycans (GAGs) regulate many important physiological processes. A pertinent issue to address is whether GAGs encode important functional information via introduction of position specific sulfate groups in the GAG structure. However, procurement of pure, homogenous GAG motifs to probe the “sulfation code” is a challenging task due to isolation difficulty and structural complexity. To this end, we devised a versatile synthetic strategy to obtain all the 16 theoretically possible sulfation patterns in the chondroitin sulfate (CS) repeating unit; these include rare but potentially important sulfated motifs which have not been isolated earlier. Biological evaluation indicated that CS sulfation patterns had differing effects for different breast cancer cell types, and the greatest inhibitory effect was observed for the most aggressive, triple negative breast cancer cell line MDA-MB-231.

MiR-34b is associated with clinical outcome in triple-negative breast cancer patients

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Svoboda Marek

2012-03-01

Full Text Available Abstract Background Breast cancer is the most common malignancy with the highest incidence rates among women worldwide. Triple-negative breast cancer (TNBC represents the major phenotype of basal-like molecular subtype of breast cancer, characterized by higher incidence in young women and a very poor prognosis. MicroRNAs (miRNAs are small non-coding RNAs playing significant role in the pathogenesis of many cancers including breast cancer. Therefore, miRNAs are also potential prognostic and/or predictive biomarkers in triple-negative breast cancer patients. Methods Thirty-nine TNBC patients with available formalin-fixed paraffin-embedded (FFPE tissues were enrolled in the study. MiR-34a, miR-34b, and miR-34c were analyzed using qRT-PCR and correlated to clinico-pathological features of TNBC patients. Results Expression levels of miR-34b significantly correlate with disease free survival (DFS (p = 0.0020, log-rank test and overall survival (OS (p = 0.0008, log-rank test of TNBC patients. No other significant associations between miR-34a, miR-34b, and miR-34c with available clinical pathological data were observed. Conclusions MiR-34b expression negatively correlates with disease free survival and overall survival in TNBC patients. Thus, miR-34b may present a new promising prognostic biomarker in TNBC patients, but independent validations are necessary.

Prediction of Non-sentinel Node Status in Patients with Melanoma and Positive Sentinel Node Biopsy: An Italian Melanoma Intergroup (IMI) Study.

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Rossi, Carlo Riccardo; Mocellin, Simone; Campana, Luca Giovanni; Borgognoni, Lorenzo; Sestini, Serena; Giudice, Giuseppe; Caracò, Corrado; Cordova, Adriana; Solari, Nicola; Piazzalunga, Dario; Carcoforo, Paolo; Quaglino, Pietro; Caliendo, Virginia; Ribero, Simone

2018-01-01

Approximately 20% of melanoma patients harbor metastases in non-sentinel nodes (NSNs) after a positive sentinel node biopsy (SNB), and recent evidence questions the therapeutic benefit of completion lymph node dissection (CLND). We built a nomogram for prediction of NSN status in melanoma patients with positive SNB. Data on anthropometric and clinicopathological features of patients with cutaneous melanoma who underwent CLND after a positive SNB were collected from nine Italian centers. Multivariate logistic regression was utilized to identify predictors of NSN status in a training set, while model efficiency was validated in a validation set. Data were available for 1220 patients treated from 2000 through 2016. In the training set (n = 810), the risk of NSN involvement was higher when (1) the primary melanoma is thicker or (2) sited in the trunk/head and neck; (3) fewer nodes are excised and (4) more nodes are involved; and (5) the lymph node metastasis is larger or (6) is deeply located. The model showed high discrimination (area under the receiver operating characteristic curve 0.74, 95% confidence interval [CI] 0.70-0.79) and calibration (Brier score 0.16, 95% CI 0.15-0.17) performance in the validation set (n = 410). The nomogram including these six clinicopathological variables performed significantly better than five other previously published models in terms of both discrimination and calibration. Our nomogram could be useful for follow-up personalization in clinical practice, and for patient risk stratification while conducting clinical trials or analyzing their results.

Prospective study of the impact of the Prosigna assay on adjuvant clinical decision-making in unselected patients with estrogen receptor positive, human epidermal growth factor receptor negative, node negative early-stage breast cancer.

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Martín, Miguel; González-Rivera, Milagros; Morales, Serafín; de la Haba-Rodriguez, Juan; González-Cortijo, Lucía; Manso, Luis; Albanell, Joan; González-Martín, Antonio; González, Sónia; Arcusa, Angels; de la Cruz-Merino, Luis; Rojo, Federico; Vidal, María; Galván, Patricia; Aguirre, Elena; Morales, Cristina; Ferree, Sean; Pompilio, Kristen; Casas, Maribel; Caballero, Rosalía; Goicoechea, Uxue; Carrasco, Eva; Michalopoulos, Steven; Hornberger, John; Prat, Aleix

2015-06-01

Improved understanding of risk of recurrence (ROR) is needed to reduce cases of recurrence and more effectively treat breast cancer patients. The purpose of this study was to examine how a gene-expression profile (GEP), identified by Prosigna, influences physician adjuvant treatment selection for early breast cancer (EBC) and the effects of this influence on optimizing adjuvant treatment recommendations in clinical practice. A prospective, observational, multicenter study was carried out in 15 hospitals across Spain. Participating medical oncologists completed pre-assessment, post-assessment, and follow-up questionnaires recording their treatment recommendations and confidence in these recommendations, before and after knowing the patient's ROR. Patients completed questionnaires on decision-making, anxiety, and health status. Between June 2013 and January 2014, 217 patients enrolled and a final 200 were included in the study. Patients were postmenopausal, estrogen receptor positive, human epidermal growth hormone factor negative, and node negative with either stage 1 or stage 2 tumors. After receiving the GEP results, treatment recommendations were changed for 40 patients (20%). The confidence of medical oncologists in their treatment recommendations increased in 41.6% and decreased in 6.5% of total cases. Patients reported lower anxiety after physicians made treatment recommendations based on the GEP results (p anxiety about the selected adjuvant therapy decreased with use of the GEP.

Triple-frequency GPS precise point positioning with rapid ambiguity resolution

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Geng, Jianghui; Bock, Yehuda

2013-05-01

At present, reliable ambiguity resolution in real-time GPS precise point positioning (PPP) can only be achieved after an initial observation period of a few tens of minutes. In this study, we propose a method where the incoming triple-frequency GPS signals are exploited to enable rapid convergences to ambiguity-fixed solutions in real-time PPP. Specifically, extra-wide-lane ambiguity resolution can be first achieved almost instantaneously with the Melbourne-Wübbena combination observable on L2 and L5. Then the resultant unambiguous extra-wide-lane carrier-phase is combined with the wide-lane carrier-phase on L1 and L2 to form an ionosphere-free observable with a wavelength of about 3.4 m. Although the noise of this observable is around 100 times the raw carrier-phase noise, its wide-lane ambiguity can still be resolved very efficiently, and the resultant ambiguity-fixed observable can assist much better than pseudorange in speeding up succeeding narrow-lane ambiguity resolution. To validate this method, we use an advanced hardware simulator to generate triple-frequency signals and a high-grade receiver to collect 1-Hz data. When the carrier-phase precisions on L1, L2 and L5 are as poor as 1.5, 6.3 and 1.5 mm, respectively, wide-lane ambiguity resolution can still reach a correctness rate of over 99 % within 20 s. As a result, the correctness rate of narrow-lane ambiguity resolution achieves 99 % within 65 s, in contrast to only 64 % within 150 s in dual-frequency PPP. In addition, we also simulate a multipath-contaminated data set and introduce new ambiguities for all satellites every 120 s. We find that when multipath effects are strong, ambiguity-fixed solutions are achieved at 78 % of all epochs in triple-frequency PPP whilst almost no ambiguities are resolved in dual-frequency PPP. Therefore, we demonstrate that triple-frequency PPP has the potential to achieve ambiguity-fixed solutions within a few minutes, or even shorter if raw carrier-phase precisions are

Extra-nodal extension is a significant prognostic factor in lymph node positive breast cancer.

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Sura Aziz

Full Text Available Presence of lymph node (LN metastasis is a strong prognostic factor in breast cancer, whereas the importance of extra-nodal extension and other nodal tumor features have not yet been fully recognized. Here, we examined microscopic features of lymph node metastases and their prognostic value in a population-based cohort of node positive breast cancer (n = 218, as part of the prospective Norwegian Breast Cancer Screening Program NBCSP (1996-2009. Sections were reviewed for the largest metastatic tumor diameter (TD-MET, nodal afferent and efferent vascular invasion (AVI and EVI, extra-nodal extension (ENE, number of ENE foci, as well as circumferential (CD-ENE and perpendicular (PD-ENE diameter of extra-nodal growth. Number of positive lymph nodes, EVI, and PD-ENE were significantly increased with larger primary tumor (PT diameter. Univariate survival analysis showed that several features of nodal metastases were associated with disease-free (DFS or breast cancer specific survival (BCSS. Multivariate analysis demonstrated an independent prognostic value of PD-ENE (with 3 mm as cut-off value in predicting DFS and BCSS, along with number of positive nodes and histologic grade of the primary tumor (for DFS: P = 0.01, P = 0.02, P = 0.01, respectively; for BCSS: P = 0.02, P = 0.008, P = 0.02, respectively. To conclude, the extent of ENE by its perpendicular diameter was independently prognostic and should be considered in line with nodal tumor burden in treatment decisions of node positive breast cancer.

Targeting Triple Negative Breast Cancer with a Small-sized Paramagnetic Nanoparticle

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Zhang, Li; Varma, Nadimpalli RS; Gang, Zhang Z.; Ewing, James R.; Arbab, Ali S; Ali, Meser M

2016-01-01

There is no available targeted therapy or imaging agent for triple negative breast cancer (TNBC). We developed a small-sized dendrimer-based nanoparticle containing a clinical relevant MRI contrast agent, GdDOTA and a NIR fluorescent dye, DL680. Systemic delivery of dual-modal nanoparticles led to accumulation of the agents in a flank mouse model of TNBC that were detected by both optical and MR imaging. In-vivo fluorescence images, as well as ex-vivo fluorescence images of individual organs, demonstrated that nanoparticles accumulated into tumor selectively. A dual modal strategy resulted in a selective delivery of a small-sized (GdDOTA)42-G4-DL680 dendrimeric agent to TNBC tumors, avoiding other major organs. PMID:28018751

Cadmium promotes the proliferation of triple-negative breast cancer cells through EGFR-mediated cell cycle regulation

International Nuclear Information System (INIS)

Wei, Zhengxi; Song, Xiulong; Shaikh, Zahir A.

2015-01-01

Cadmium (Cd) is a carcinogenic metal which is implicated in breast cancer by epidemiological studies. It is reported to promote breast cancer cell growth in vitro through membrane receptors. The study described here examined Cd-mediated growth of non-metastatic human breast cancer derived cells that lack receptors for estrogen, progesterone, and HER2. Treatment of triple-negative HCC 1937 cells with 0.1–0.5 μM Cd increased cell growth by activation of AKT and ERK. Accelerated cell cycle progression was achieved by increasing the levels of cyclins A, B, and E, as well as those of CDKs 1 and 2. Although triple negative cells lack estrogen receptor, they express high levels of EGFR. Therefore, further studies on HCC 1937 and another triple-negative cell line, HCC 38, were conducted using specific siRNA and an inhibitor of EGFR to determine whether EGFR was responsible for mediating the effect of Cd. The results revealed that in both cell types EGFR was not only activated upon Cd treatment, but was also essential for the downstream activation of AKT and ERK. Based on these observations, it is concluded that, in breast cancer cells lacking estrogen receptor, sub-micromolar concentration of Cd can promote cell proliferation. Furthermore, that EGFR plays a critical role in this process. - Highlights: • Sub-micromolar concentrations of Cd promote cell growth in breast cancer cells that lack ER, PR, and HER2. • The increase in cell number is not due to reduction in apoptosis. • Growth promotion involves AKT and ERK signaling and downstream stimulation of cell cycle progression. • Initiation of cell growth by Cd occurs at the cell membrane and requires the activation of EGFR.

A case report of locally advanced triple negative breast cancer showing pathological complete response to weekly paclitaxel with bevacizumab treatment following disease progression during anthracycline-based neoadjuvant chemotherapy

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Hideo Shigematsu

2017-01-01

Conclusions: Although the addition of bevacizumab to standard adjuvant chemotherapy is not recommended in unselected triple negative breast cancer, the potent effect on tumor shrinkage should be considered in the treatment of locally advanced triple negative breast cancer showing disease progression during standard NAC.

Neck control after definitive radiochemotherapy without planned neck dissection in node-positive head and neck cancers

International Nuclear Information System (INIS)

Jang, Na Young; Lee, Keun-Wook; Ahn, Soon-Hyun; Kim, Jae-Sung; Ah Kim, In

2012-01-01

The purpose of this study was to evaluate neck control outcomes after definitive radiochemotherapy without planned neck dissection in node-positive head and neck cancer. We retrospectively reviewed medical records of fifty patients with node-positive head and neck cancer who received definitive radiochemotherapy. Twelve patients subsequently underwent neck dissection for suspicious recurrent or persistent disease. A median dose of 70 Gy (range 60-70.6) was delivered to involved nodes. Response evaluation was performed at a median of 5 weeks after completion of radiotherapy. Neck failure was observed in 11 patients and the 3-year regional control (RC) rate was 77.1%. Neck dissection was performed in 10 of the 11 patients; seven of these cases were successfully salvaged, and the ultimate rate of neck control was 92%. The remaining two patients who received neck dissection had negative pathologic results. On univariate analysis, initial nodal size > 2 cm, a less-than-complete response at the primary site, post-radiotherapy nodal size > 1.5 cm, and post-radiotherapy nodal necrosis were associated with RC. On multivariate analysis, less-than-complete primary site response and post-radiotherapy nodal necrosis were identified as independent prognostic factors for RC. The neck failure rate after definitive radiochemotherapy without planned neck dissection was 22%. Two-thirds of these were successfully salvaged with neck dissection and the ultimate neck control rate was 92%. Our results suggest that planned neck dissection might not be necessary in patients with complete response of primary site, no evidence of residual lesion > 1.5 cm, or no necrotic lymph nodes at the 1-2 months follow-up evaluation after radiotherapy

Role of axillary lymph node ultra-sound and large core biopsy in the preoperative assessment of patients selected for sentinel node biopsy

International Nuclear Information System (INIS)

Nori, Jacopo; Boeri, Cecilia; Vanzi, Ermanno; Nori Bufalini, Filippo; Masi, Andrea; Bazzocchi, Massimo; Londero, Viviana; Mangialavori, Giuseppe; Distante, Vito; Simoncini, Roberta

2005-01-01

Purpose: To aim of this study was to evaluate the diagnostic accuracy of axillary lymph node sonography, if necessary in collaboration with US-guided large core biopsy, in the preoperative evaluation of breast cancer patients scheduled for quadrantectomy and sentinel lymph node excision. Materials and methods: From July 2001 to December 2002, we evaluated 117 breast cancer patients with ultrasound and, where indicated, FNAB. Breast lesions has diameters between 4 and 26 mm (mean diameter 11 mm). Fifteen (13%) of the 117 patients were excluded from the series as they did not found fulfil the criteria for preliminary sonography of the axilla: in 9 patients fewer than 4 nodes were detected and in 6 patients the breast lesions were intraoperatively found to be benign. Eleven patients (10.7%) with sonographically suspicious axillary nodes were sampled by US-guided core biopsy using a 14 or 16 Gauge Tru-Cut needle. Results: The ultrasound study aims to evaluate the dimensions and morphology of the breast lesion as well as detect and assess at least 4 axillary nodes. These were evaluated for hilar and cortical thickening and radio between the sinus diameter and the total longitudinal diameter. Lymph nodes with hilar diameters equal to or greater than 50% of the longitudinal diameter were considered normal. Of the 102 patients evaluated, 77 (75.7%) had normal axillary nodes according to the US criteria adopted. Negativity was confirmed by histology in 56 cases (72.7%, true negative); 21 (27.3%, false negative) were found to be positive, in contrast with the sonographic appearance. The false negative cases were due to lymph node micrometastasis which probably did not cause morphologic alterations perceptible at ultrasound. The remaining 25 patients (24.5%) had axillary lymph nodes classified as suspicious. In 13 cases of (52%, true positive) there was agreement with histology, whereas in 12 cases (48%, false positive) the US suspicion was not confirmed at surgery. The most

Quantum-Dot-Based Theranostic Micelles Conjugated with an Anti-EGFR Nanobody for Triple-Negative Breast Cancer Therapy.

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Wang, Yuyuan; Wang, Yidan; Chen, Guojun; Li, Yitong; Xu, Wei; Gong, Shaoqin

2017-09-13

A quantum-dot (QD)-based micelle conjugated with an anti-epidermal growth factor receptor (EGFR) nanobody (Nb) and loaded with an anticancer drug, aminoflavone (AF), has been engineered for EGFR-overexpressing cancer theranostics. The near-infrared (NIR) fluorescence of the indium phosphate core/zinc sulfide shell QDs (InP/ZnS QDs) allowed for in vivo nanoparticle biodistribution studies. The anti-EGFR nanobody 7D12 conjugation improved the cellular uptake and cytotoxicity of the QD-based micelles in EGFR-overexpressing MDA-MB-468 triple-negative breast cancer (TNBC) cells. In comparison with the AF-encapsulated nontargeted (i.e., without Nb conjugation) micelles, the AF-encapsulated Nb-conjugated (i.e., targeted) micelles accumulated in tumors at higher concentrations, leading to more effective tumor regression in an orthotopic triple-negative breast cancer xenograft mouse model. Furthermore, there was no systemic toxicity observed with the treatments. Thus, this QD-based Nb-conjugated micelle may serve as an effective theranostic nanoplatform for EGFR-overexpressing cancers such as TNBCs.

Distinct microbiological signatures associated with triple negative breast cancer.

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Banerjee, Sagarika; Wei, Zhi; Tan, Fei; Peck, Kristen N; Shih, Natalie; Feldman, Michael; Rebbeck, Timothy R; Alwine, James C; Robertson, Erle S

2015-10-15

Infectious agents are the third highest human cancer risk factor and may have a greater role in the origin and/or progression of cancers, and related pathogenesis. Thus, knowing the specific viruses and microbial agents associated with a cancer type may provide insights into cause, diagnosis and treatment. We utilized a pan-pathogen array technology to identify the microbial signatures associated with triple negative breast cancer (TNBC). This technology detects low copy number and fragmented genomes extracted from formalin-fixed paraffin embedded archival tissues. The results, validated by PCR and sequencing, define a microbial signature present in TNBC tissue which was underrepresented in normal tissue. Hierarchical clustering analysis displayed two broad microbial signatures, one prevalent in bacteria and parasites and one prevalent in viruses. These signatures demonstrate a new paradigm in our understanding of the link between microorganisms and cancer, as causative or commensal in the tumor microenvironment and provide new diagnostic potential.

Node-positive cervical cancer: impact of pelvic irradiation and patterns of failure

International Nuclear Information System (INIS)

Stock, Richard G.; Chen, Alex S. J.; Flickinger, John C.; Kalnicki, Shalom; Seski, Jan

1995-01-01

Purpose: The roles of postoperative pelvic and prophylactic paraaortic irradiation in pelvic node positive cervical cancer are currently controversial. A retrospective study was undertaken to examine the effect of pelvic irradiation on pelvic control and survival and to analyze the patterns of recurrence to determine whether indications exist for prophylactic paraaortic irradiation. Methods and Materials: From 1964 to 1991, 143 cases of FIGO Stage I and II cervical cancer undergoing exploratory laparotomy, pelvic lymph node dissection, and radical hysterectomy had positive pelvic lymph nodes. Postoperatively, 108 cases were treated with whole pelvic irradiation while 35 patients were observed. Prophylactic paraaortic irradiation was not given. Results: Patients who received postoperative whole pelvic irradiation compared with those treated with radical hysterectomy alone had a significantly improved pelvic control rate, disease-free survival (DFS), and overall survival. The 5-year actuarial pelvic control rate was 78% vs. 45% (p = <0.0001), respectively. The 5-year actuarial DFS was 65% vs. 41% (p = 0.0004). The 5-year actuarial overall survival was 58% vs. 46% (p 0.02). In multivariate analysis, pelvic irradiation continued to show a positive effect on DFS (p = 0.0001) and overall survival (p = 0.0035). Lymphatic invasion and the total number of positive lymph nodes were the only other independent predictors of overall survival and DFS. The actuarial 5-year pelvic, paraaortic, and distant failure rates were 30%, 10%, and 28%, respectively. An isolated first recurrence in the paraaortic nodes occurred in only three cases. Conclusion: Postoperative pelvic irradiation significantly improves pelvic control, DFS, and overall survival, and should be used in patients with early stage cervical cancer and pathologically proven pelvic nodal metastases. The low incidence of isolated paraaortic nodal failure calls into question the value of routine prophylactic paraaortic

Node-positive cervical cancer: impact of pelvic irradiation and patterns of failure

Energy Technology Data Exchange (ETDEWEB)

Stock, Richard G; Chen, Alex S. J.; Flickinger, John C; Kalnicki, Shalom; Seski, Jan

1995-01-01

Purpose: The roles of postoperative pelvic and prophylactic paraaortic irradiation in pelvic node positive cervical cancer are currently controversial. A retrospective study was undertaken to examine the effect of pelvic irradiation on pelvic control and survival and to analyze the patterns of recurrence to determine whether indications exist for prophylactic paraaortic irradiation. Methods and Materials: From 1964 to 1991, 143 cases of FIGO Stage I and II cervical cancer undergoing exploratory laparotomy, pelvic lymph node dissection, and radical hysterectomy had positive pelvic lymph nodes. Postoperatively, 108 cases were treated with whole pelvic irradiation while 35 patients were observed. Prophylactic paraaortic irradiation was not given. Results: Patients who received postoperative whole pelvic irradiation compared with those treated with radical hysterectomy alone had a significantly improved pelvic control rate, disease-free survival (DFS), and overall survival. The 5-year actuarial pelvic control rate was 78% vs. 45% (p = <0.0001), respectively. The 5-year actuarial DFS was 65% vs. 41% (p = 0.0004). The 5-year actuarial overall survival was 58% vs. 46% (p 0.02). In multivariate analysis, pelvic irradiation continued to show a positive effect on DFS (p = 0.0001) and overall survival (p = 0.0035). Lymphatic invasion and the total number of positive lymph nodes were the only other independent predictors of overall survival and DFS. The actuarial 5-year pelvic, paraaortic, and distant failure rates were 30%, 10%, and 28%, respectively. An isolated first recurrence in the paraaortic nodes occurred in only three cases. Conclusion: Postoperative pelvic irradiation significantly improves pelvic control, DFS, and overall survival, and should be used in patients with early stage cervical cancer and pathologically proven pelvic nodal metastases. The low incidence of isolated paraaortic nodal failure calls into question the value of routine prophylactic paraaortic

Validation of sentinel lymph node biopsy in breast cancer women N1-N2 with complete axillary response after neoadjuvant chemotherapy. Multicentre study in Tarragona.

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Carrera, D; de la Flor, M; Galera, J; Amillano, K; Gomez, M; Izquierdo, V; Aguilar, E; López, S; Martínez, M; Martínez, S; Serra, J M; Pérez, M; Martin, L

2016-01-01

The aim of our study was to evaluate sentinel lymph node biopsy as a diagnostic test for assessing the presence of residual metastatic axillary lymph nodes after neoadjuvant chemotherapy, replacing the need for a lymphadenectomy in negative selective lymph node biopsy patients. A multicentre, diagnostic validation study was conducted in the province of Tarragona, on women with T1-T3, N1-N2 breast cancer, who presented with a complete axillary response after neoadjuvant chemotherapy. Study procedures consisted of performing an selective lymph node biopsy followed by lymphadenectomy. A total of 53 women were included in the study. Surgical detection rate was 90.5% (no sentinel node found in 5 patients). Histopathological analysis of the lymphadenectomy showed complete disease regression of axillary nodes in 35.4% (17/48) of the patients, and residual axillary node involvement in 64.6% (31/48) of them. In lymphadenectomy positive patients, 28 had a positive selective lymph node biopsy (true positive), while 3 had a negative selective lymph node biopsy (false negative). Of the 28 true selective lymph node biopsy positives, the sentinel node was the only positive node in 10 cases. All lymphadenectomy negative cases were selective lymph node biopsy negative. These data yield a sensitivity of 93.5%, a false negative rate of 9.7%, and a global test efficiency of 93.7%. Selective lymph node biopsy after chemotherapy in patients with a complete axillary response provides valid and reliable information regarding axillary status after neoadjuvant treatment, and might prevent lymphadenectomy in cases with negative selective lymph node biopsy. Copyright © 2016 Elsevier España, S.L.U. and SEMNIM. All rights reserved.

LOXL4 knockdown enhances tumor growth and lung metastasis through collagen-dependent extracellular matrix changes in triple-negative breast cancer.

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Choi, Sul Ki; Kim, Hoe Suk; Jin, Tiefeng; Moon, Woo Kyung

2017-02-14

Lysyl oxidase (LOX) family genes catalyze collagen cross-link formation. To determine the effects of lysyl oxidase-like 4 (LOXL4) expression on breast tumor formation and metastasis, we evaluated primary tumor growth and lung metastasis in mice injected with LOXL4-knockdown MDA-MB-231 triple-negative human breast cancer cells. In addition, we analyzed overall survival in breast cancer patients based on LOXL4 expression using a public online database. In the mouse xenograft model, LOXL4 knockdown increased primary tumor growth and lung colonization as well as collagen I and IV, lysine hydroxylase 1 and 2, and prolyl 4-hydroxylase subunit alpha 1 and 2 levels. Second harmonic generation imaging revealed that LOXL4 knockdown resulted in the thickening of collagen bundles within tumors. In addition, weak LOXL4 expression was associated with poor overall survival in breast cancer patients from the BreastMark dataset, and this association was strongest in triple-negative breast cancer patients. These results demonstrate that weak LOXL4 expression leads to remodeling of the extracellular matrix through induction of collagen synthesis, deposition, and structural changes. These alterations in turn promote tumor growth and metastasis and are associated with poor clinical outcomes in triple-negative breast cancer.

Does negative retroperitoneal CT in adolescents with paratesticular rhabdomyosarcoma preclude the need of retroperitoneal lymph node dissection?; A tomografia de retroperitoneo normal em adolescentes com rabdomiossarcoma paratesticular afasta necessidade de linfadenectomia?

Energy Technology Data Exchange (ETDEWEB)

Damazio, Eulalio [Hospital Lucano, Teresina (PI) (Brazil); Caran, Eliana [Instituto de Oncologia Pediatrica, Universidade Federal de Sao Paulo - UNIFESP, Sao Paulo, SP (Brazil); Ortiz, Valdemar; Macedo Junior, Antonio, E-mail: macedo.dcir@epm.br [Departamento de Urologia, Universidade Federal de Sao Paulo - UNIFESP, Sao Paulo, SP (Brazil)

2011-07-01

We report on a 16-year-old male with paratesticular rhabdomyosarcoma who underwent retroperitoneal lymph node dissection due to a stage I tumor (normal retroperitoneal computed tomography). The surgical finding was three enlarged nodes, positive for metastatic disease. Patient was referred to adjuvant chemotherapy. This case suggests that the Intergroup Rhabdomyosarcoma Study Group IV protocol is subject to questions regarding adolescents with paratesticular rhabdomyosarcoma, and that negative retroperitoneal CT does not preclude the need of lymph node dissection. (author)

Abnormal position of lymph nodes in a freemartin sheep

Directory of Open Access Journals (Sweden)

Salazar PA

2012-03-01

Full Text Available Angela M Gonella-Diaza, Luz Zoraya Duarte, Sergio Dominguez, Pedro A SalazarClínica de Grandes Animales, Facultad de Medicina Veterinaria y de Zootecnia, Universidad Cooperativa de Colombia, Bucaramanga, Santander, ColombiaAbstract: In this freemartin case report the authors present the clinical and morphological findings of a freemartin ewe with an abnormal position of two lymph nodes. Freemartins, infertile females from mixed-sex twin pregnancies, are chimeras, having two cell populations: one of their own (XX DNA and one from their male twin (XY DNA. Freemartins can have varying degrees of phenotypic masculinization, including, in some cases, having active male gonads and exhibiting male behaviors such as heat detection and aggressiveness. During the clinical examination of the freemartin ewe, a morphological abnormality of the vulva, the presence of scrotal sacs, and a lack of mammary tissue development were noted. On inspection of the vaginal channel, an extremely enlarged clitoris, resembling a penis, was found. The clinical evidence suggested freemartinism. After the karyotyping diagnosis confirmation, a necropsy was performed and samples were taken for histology and immunohistochemistry. There were two structures found in the scrotal sacs; however, these were found to be lymph nodes, not testicles, and this was confirmed by CD3 lymph protein coloration. On histological study, the phallic structure showed corpus cavernosum and tunica albuginea. The testicles were found retained inside the abdominal cavity, with the presence of atrophic seminiferous tubules. Although the position of the testicles in freemartins has been reported as highly variable, this is the first time, to the best of the authors' knowledge, that a case has been reported where lymph nodes have been found inside the scrotal sacs. It is possible that these were the inguinal lymph nodes, trapped inside the scrotum during fetal growth and development.Keywords: freemartinism

Survival and prognosticators of node-positive cervical cancer patients treated with radical hysterectomy and systematic lymphadenectomy

International Nuclear Information System (INIS)

Hosaka, Masayoshi; Watari, Hidemichi; Mitamura, Takashi; Konno, Yousuke; Odagiri, Tetsuji; Kato, Tatsuya; Takeda, Mahito; Sakuragi, Noriaki

2011-01-01

Lymph node metastasis (LNM) is known to be the most important prognostic factor in cervical cancer. We analyzed the number of positive lymph nodes and other clinicopathological factors as prognostic factors for survival in node-positive patients with cervical cancer. Node-positive cervical cancer patients (n=108) who underwent radical hysterectomy and systematic lymphadenectomy in Hokkaido University Hospital from 1982 to 2002 were enrolled. Clinicopathological data including age, stage, histologic subtype, and the number of LNM sites were collected. The main outcome was the overall survival (OS) rate for Stage Ib-IIb patients treated with surgery and postoperative radiotherapy. The 5-year OS rate of patients with 1 positive node was 93.3%, that for 2 nodes was 77.3%, for 3 nodes it was 33.3%, and for 4 or more it was 13.8%. The OS rate of patients with 1 or 2 LNM sites was significantly better than that for patients with more than 2 LNM sites. The OS rate of patients with adenocarcinoma (Ad) (28.6%) was significantly lower than that for patients with other histologic subtypes (squamous cell carcinoma; 66.7%, adenosquamous carcinoma; 75.0%, p=0.0003). Multivariate analysis revealed that >2 LNM sites and Ad were independent prognostic factors for survival. The 5-year OS rate of patients with 1 or 2 LNM sites was 86.8%, a more favorable prognosis than the OS rates in other reports. More than two LNM sites and adenocarcinoma were independent prognostic factors for node-positive patients with cervical cancer. (author)

Differences in elongation of very long chain fatty acids and fatty acid metabolism between triple-negative and hormone receptor-positive breast cancer.

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Yamashita, Yuji; Nishiumi, Shin; Kono, Seishi; Takao, Shintaro; Azuma, Takeshi; Yoshida, Masaru

2017-08-29

Triple-negative breast cancer (TN) is more aggressive than other subtypes of breast cancer and has a lower survival rate. Furthermore, detailed biological information about the disease is lacking. This study investigated characteristics of metabolic pathways in TN. We performed the metabolome analysis of 74 breast cancer tissues and the corresponding normal breast tissues using LC/MS. Furthermore, we classified the breast cancer tissues into ER-positive, PgR-positive, HER2-negative breast cancer (EP+H-) and TN, and then the differences in their metabolic pathways were investigated. The RT-PCR and immunostaining were carried out to examine the expression of ELOVL1, 2, 3, 4, 5, 6, and 7. We identified 142 of hydrophilic metabolites and 278 of hydrophobic lipid metabolites in breast tissues. We found the differences between breast cancer and normal breast tissues in choline metabolism, glutamine metabolism, lipid metabolism, and so on. Most characteristic of comparison between EP+H- and TN were differences in fatty acid metabolism was which were related to the elongation of very long chain fatty acids were detected between TN and EP+H-. Real-time RT-PCR showed that the mRNA expression levels of ELOVL1, 5, and 6 were significantly upregulated by 8.5-, 4.6- and 7.0-fold, respectively, in the TN tumors compared with their levels in the corresponding normal breast tissue samples. Similarly, the mRNA expression levels of ELOVL1, 5, and 6 were also significantly higher in the EP+H- tissues than in the corresponding normal breast tissues (by 4.9-, 3.4-, and 2.1-fold, respectively). The mRNA expression level of ELOVL6 was 2.6-fold higher in the TN tumors than in the EP+H- tumors. During immunostaining, the TN and EP+H- tumors demonstrated stronger ELOVL1 and 6 staining than the corresponding normal breast tissues, but ELOVL5 was not stained strongly in the TN or EP+H- tumors. Furthermore, the TN tumors exhibited stronger ELOVL1 and 6 staining than the EP+H- tumors. Marked

Neoadjuvant treatments in triple-negative breast cancer patients: where we are now and where we are going

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Omarini C

2018-01-01

Full Text Available Claudia Omarini, Giorgia Guaitoli, Stefania Pipitone, Luca Moscetti, Laura Cortesi, Stefano Cascinu, Federico Piacentini Department of Medical and Surgical Sciences for Children & Adults, Division of Medical Oncology, University Hospital of Modena, Modena, Italy Abstract: Triple-negative breast cancer (TNBC remains the poorest-prognosis breast cancer (BC subtype. Gene expression profiling has identified at least six different triple-negative subtypes with different biology and sensitivity to therapies. The heterogeneous nature of TN tumors may justify the difficulty in treating this BC subtype. Several targeted agents have been investigated in clinical trials without demonstrating a clear survival benefit. Therefore, systemic chemotherapy remains the cornerstone of current clinical practice. Improving the knowledge of tumor biology is mandatory for patient management. In stages II and III, neoadjuvant systemic treatment is an effective option of care. The achievement of a pathological complete response represents an optimal surrogate for survival outcome as well as a test for tumor drug sensitivity. In this review, we provide a brief description of the main predictive biomarkers for tumor response to systemic treatment. Moreover, we review the treatment strategies investigated for TNBCs in neoadjuvant settings focusing on experimental drugs such as immunotherapy and poly [ADP-ribose] polymerase inhibitors that hold promise in the treatment of this aggressive disease. Therefore, the management of TNBC represents an urgent, current, unmet need in daily clinical practice. A key recommendation is to design biology-driven clinical trials wherein TNBC patients may be treated on the basis of tumor molecular profile. Keywords: triple-negative breast cancer, neoadjuvant chemotherapy, BRCA, platinum, immunotherapy, PARP-1 inhibitors

Adjuvant chemotherapy in node negative breast cancer: patterns of use and oncologists' preferences

NARCIS (Netherlands)

Stiggelbout, A. M.; de Haes, J. C.; van de Velde, C. J.

2000-01-01

BACKGROUND: A worldwide variation in policy is seen regarding adjuvant systemic treatment for node negative breast cancer (NNBC). After the first presentations of the 10-year EBCTCG results, a study was carried out in the Netherlands to assess patterns of care and to obtain the views of oncologists

Lack of evidence for KRAS oncogenic mutations in triple-negative breast cancer

International Nuclear Information System (INIS)

Sánchez-Muñoz, Alfonso; Gallego, Elena; Luque, Vanessa de; Pérez-Rivas, Luís G; Vicioso, Luís; Ribelles, Nuria; Lozano, José; Alba, Emilio

2010-01-01

Mutational analysis of the KRAS gene has recently been established as a complementary in vitro diagnostic tool for the identification of patients with colorectal cancer who will not benefit from anti-epidermal growth factor receptor (EGFR) therapies. Assessment of the mutation status of KRAS might also be of potential relevance in other EGFR-overexpressing tumors, such as those occurring in breast cancer. Although KRAS is mutated in only a minor fraction of breast tumors (5%), about 60% of the basal-like subtype express EGFR and, therefore could be targeted by EGFR inhibitors. We aimed to study the mutation frequency of KRAS in that subtype of breast tumors to provide a molecular basis for the evaluation of anti-EGFR therapies. Total, genomic DNA was obtained from a group of 35 formalin-fixed paraffin-embedded, triple-negative breast tumor samples. Among these, 77.1% (27/35) were defined as basal-like by immunostaining specific for the established surrogate markers cytokeratin (CK) 5/6 and/or EGFR. KRAS mutational status was determined in the purified DNA samples by Real Time (RT)-PCR using primers specific for the detection of wild-type KRAS or the following seven oncogenic somatic mutations: Gly12Ala, Gly12Asp, Gly12Arg, Gly12Cys, Gly12Ser, Gly12Val and Gly13Asp. We found no evidence of KRAS oncogenic mutations in all analyzed tumors. This study indicates that KRAS mutations are very infrequent in triple-negative breast tumors and that EGFR inhibitors may be of potential benefit in the treatment of basal-like breast tumors, which overexpress EGFR in about 60% of all cases

Pathologic response after neoadjuvant chemotherapy predicts locoregional control in patients with triple negative breast cancer

OpenAIRE

Chen, Victor E.; Gillespie, Erin F.; Zakeri, Kaveh; Murphy, James D.; Yashar, Catheryn M.; Lu, Sharon; Einck, John P.

2017-01-01

Purpose: Our goal was to determine the impact of pathologic response after neoadjuvant chemotherapy in triple negative breast cancer (TNBC) on the subsequent risk of locoregional recurrence (LRR) and disease-free survival (DFS) in the setting of adjuvant radiation therapy. Methods and materials: This was an institutional review board–approved retrospective chart review of patients with clinical stage I-III breast cancer treated with neoadjuvant chemotherapy, local surgery (breast conservat...

Synchronization unveils the organization of ecological networks with positive and negative interactions

Science.gov (United States)

Girón, Andrea; Saiz, Hugo; Bacelar, Flora S.; Andrade, Roberto F. S.; Gómez-Gardeñes, Jesús

2016-06-01

Network science has helped to understand the organization principles of the interactions among the constituents of large complex systems. However, recently, the high resolution of the data sets collected has allowed to capture the different types of interactions coexisting within the same system. A particularly important example is that of systems with positive and negative interactions, a usual feature appearing in social, neural, and ecological systems. The interplay of links of opposite sign presents natural difficulties for generalizing typical concepts and tools applied to unsigned networks and, moreover, poses some questions intrinsic to the signed nature of the network, such as how are negative interactions balanced by positive ones so to allow the coexistence and survival of competitors/foes within the same system? Here, we show that synchronization phenomenon is an ideal benchmark for uncovering such balance and, as a byproduct, to assess which nodes play a critical role in the overall organization of the system. We illustrate our findings with the analysis of synthetic and real ecological networks in which facilitation and competitive interactions coexist.

Synchronization unveils the organization of ecological networks with positive and negative interactions.

Science.gov (United States)

Girón, Andrea; Saiz, Hugo; Bacelar, Flora S; Andrade, Roberto F S; Gómez-Gardeñes, Jesús

2016-06-01

Network science has helped to understand the organization principles of the interactions among the constituents of large complex systems. However, recently, the high resolution of the data sets collected has allowed to capture the different types of interactions coexisting within the same system. A particularly important example is that of systems with positive and negative interactions, a usual feature appearing in social, neural, and ecological systems. The interplay of links of opposite sign presents natural difficulties for generalizing typical concepts and tools applied to unsigned networks and, moreover, poses some questions intrinsic to the signed nature of the network, such as how are negative interactions balanced by positive ones so to allow the coexistence and survival of competitors/foes within the same system? Here, we show that synchronization phenomenon is an ideal benchmark for uncovering such balance and, as a byproduct, to assess which nodes play a critical role in the overall organization of the system. We illustrate our findings with the analysis of synthetic and real ecological networks in which facilitation and competitive interactions coexist.

Enzalutamide for the Treatment of Androgen Receptor-Expressing Triple-Negative Breast Cancer.

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Traina, Tiffany A; Miller, Kathy; Yardley, Denise A; Eakle, Janice; Schwartzberg, Lee S; O'Shaughnessy, Joyce; Gradishar, William; Schmid, Peter; Winer, Eric; Kelly, Catherine; Nanda, Rita; Gucalp, Ayca; Awada, Ahmad; Garcia-Estevez, Laura; Trudeau, Maureen E; Steinberg, Joyce; Uppal, Hirdesh; Tudor, Iulia Cristina; Peterson, Amy; Cortes, Javier

2018-03-20

Purpose Studies suggest that a subset of patients with triple-negative breast cancer (TNBC) have tumors that express the androgen receptor (AR) and may benefit from an AR inhibitor. This phase II study evaluated the antitumor activity and safety of enzalutamide in patients with locally advanced or metastatic AR-positive TNBC. Patients and Methods Tumors were tested for AR with an immunohistochemistry assay optimized for breast cancer; nuclear AR staining > 0% was considered positive. Patients received enzalutamide 160 mg once per day until disease progression. The primary end point was clinical benefit rate (CBR) at 16 weeks. Secondary end points included CBR at 24 weeks, progression-free survival, and safety. End points were analyzed in all enrolled patients (the intent-to-treat [ITT] population) and in patients with one or more postbaseline assessment whose tumor expressed ≥ 10% nuclear AR (the evaluable subgroup). Results Of 118 patients enrolled, 78 were evaluable. CBR at 16 weeks was 25% (95% CI, 17% to 33%) in the ITT population and 33% (95% CI, 23% to 45%) in the evaluable subgroup. Median progression-free survival was 2.9 months (95% CI, 1.9 to 3.7 months) in the ITT population and 3.3 months (95% CI, 1.9 to 4.1 months) in the evaluable subgroup. Median overall survival was 12.7 months (95% CI, 8.5 months to not yet reached) in the ITT population and 17.6 months (95% CI, 11.6 months to not yet reached) in the evaluable subgroup. Fatigue was the only treatment-related grade 3 or higher adverse event with an incidence of > 2%. Conclusion Enzalutamide demonstrated clinical activity and was well tolerated in patients with advanced AR-positive TNBC. Adverse events related to enzalutamide were consistent with its known safety profile. This study supports additional development of enzalutamide in advanced TNBC.

Benefit of adjuvant chemotherapy with or without trastuzumab in pT1ab node-negative human epidermal growth factor receptor 2-positive breast carcinomas: results of a national multi-institutional study.

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de Nonneville, Alexandre; Gonçalves, Anthony; Zemmour, Christophe; Classe, Jean M; Cohen, Monique; Lambaudie, Eric; Reyal, Fabien; Scherer, Christophe; Muracciole, Xavier; Colombo, Pierre E; Giard, Sylvia; Rouzier, Roman; Villet, Richard; Chopin, Nicolas; Darai, Emile; Garbay, Jean R; Gimbergues, Pierre; Sabiani, Laura; Coutant, Charles; Sabatier, Renaud; Bertucci, François; Boher, Jean M; Houvenaeghel, Gilles

2017-04-01

Benefit of adjuvant trastuzumab-based chemotherapy for node-positive and/or >1 cm human epidermal growth factor receptor 2-positive (HER2+) breast carcinomas has been clearly demonstrated in randomized clinical trials. Yet, evidence that adjuvant chemotherapy with or without trastuzumab is effective in pT1abN0 HER2+ tumors is still limited. The primary objective of this study was to investigate the impact of adjuvant chemotherapy ± trastuzumab on outcome in this subpopulation. A total of 356 cases of pT1abN0M0 HER2 + breast cancers were retrospectively identified from a large cohort of 22,334 patients, including 1248 HER2+ patients who underwent primary surgery at 17 French centers, between December 1994 and January 2014. The primary end point was disease-free survival (DFS). A multivariate Cox model was built, including adjuvant chemotherapy, tumor size, hormone receptor status, and Scarff Bloom Richardson (SBR) grade. A total of 138 cases (39%) were treated with trastuzumab-based chemotherapy, 29 (8%) with chemotherapy alone, and 189 (53%) received neither trastuzumab nor chemotherapy. Adjuvant chemotherapy ± trastuzumab was associated with a significant DFS benefit (3-year 99 vs. 90%, and 5-year 96 vs. 84%, Hazard ratio, HR 0.26 [0.10-0.67]; p = 0.003, logrank test) which was maintained in multivariate analysis (HR 0.19 [0.07-0.52]; p = 0.001). Metastasis-free survival was also increased (HR 0.25 [0.07-0.86]; p = 0.018, logrank test) at 3-year (99 vs. 95%) and 5-year (98 vs. 89%) censoring. Exploratory subgroup analysis found DFS benefit to be significant in hormone receptor-negative, hormone receptor-positive, and pT1b tumors, but not in pT1a tumors. Adjuvant chemotherapy ± trastuzumab is associated with a significantly reduced risk of recurrence in subcentimeter node-negative HER2+ breast cancers. Most of the benefit may be driven by pT1b tumors.

Reasons for failure to identify positive sentinel nodes in breast cancer patients with significant nodal involvement

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de Kanter, A. Y.; Menke-Pluijmers, M. B. E.; Henzen-Logmans, S. C.; van Geel, A. N.; van Eijck, C. J. H.; Wiggers, T.; Eggermont, A. M. M.

Aim: To analyse causes of failure of sentinel node (SN) procedures in breast cancer patients and assess the role of pre-operative ultrasound examination of the axilla. Methods: In 138 consecutive clinically node negative breast cancer patients with the primary turnout in situ a SN procedure with

Loss of PTEN expression is associated with aggressive behavior and poor prognosis in Middle Eastern triple-negative breast cancer.

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Beg, Shaham; Siraj, Abdul K; Prabhakaran, Sarita; Jehan, Zeenath; Ajarim, Dahish; Al-Dayel, Fouad; Tulbah, Asma; Al-Kuraya, Khawla S

2015-06-01

PTEN is a tumor suppressor that negatively regulates the PI3 K-AKT signaling pathway which is involved in the pathogenesis of many different tumor types and serves as a prognostic marker in breast cancer. However, the significance of the role of PTEN in Middle Eastern ethnic breast cancer has not been explored especially with the fact that breast cancer originating from this ethnic population tend to behave more aggressively than breast cancer in the west. In this study, we analyzed PTEN alteration in a tissue microarray format containing more than 1000 primary breast cancers with clinical follow-up data. Tissue Microarray sections were analyzed for protein expression and copy number change using immunohistochemistry and fluorescence in situ hybridization. Loss of PTEN immunostaining was observed in 77 % of the cases. PTEN loss was significantly associated with large tumor size (p = 0.0030), high grade (p = 0.0281), tumor recurrence (p = 0.0333), and triple-negative breast cancers (p = 0.0086). PTEN loss in triple-negative breast cancers was significantly associated with rapid tumor cell proliferation (p = 0.0396) and poor prognosis (p = 0.0408). PTEN deletion was found only in 60 cases (6.4 %). Loss of PTEN protein expression occurs at high frequency in Middle Eastern breast cancer. PTEN inactivation may potentially lead to an aggressive behavior of tumor cells through stimulation of tumor cell proliferation. Furthermore, PTEN signaling pathway might be used as potential therapeutic target in triple-negative breast cancers since loss of its expression is shown to be significantly associated with this aggressive subtype of breast cancer.

Genomic profile of a patient with triple negative essential thrombocythemia, unresponsive to therapy: A case report and literature review

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Uzma Zaidi

2017-07-01

Full Text Available Clonal analysis of patients with triple negative myeloproliferative neoplasm (MPN has provided evidence of additional aberrations, including epigenetic alterations. To discover such novel genetic aberrations, patients were screened through next-generation sequencing using a myeloid sequencing panel of 54 genes using a genetic analyser. Genetic variants in 28 genes, including TET2, BCOR, BCR, and ABL1 were identified in a triple negative essential thrombocythemia (ET patient. The individual role of some of these variants in disease pathogenesis has yet to be studied. Somatic mutations in the same genes have been reported with variable frequencies in myeloid malignancies. However, no pathogenic impact of these variants could be found; therefore, long-term follow up of patients with genetic analysis of a large cohort and the use of whole genome sequencing is required to assess the effects of these variants.

Comparison of 99mTc-MIBI scanning and sentinel node biopsy in the detection of occult melanoma lymph node metastases

International Nuclear Information System (INIS)

Alonso, O.; Lago, G.; Lopes de Amorim, M.C.; Juri, C.; Larre Borges, A.; Martinez, M.; De Boni, D.; Espasandin, J.; Priario, J.

2002-01-01

Aim: Sentinel node biopsy (SNB) is a highly accurate technique for detecting occult metastatic disease in the regional lymph nodes. Our group has reported that 99m Tc-MIBI scintigraphy is an imaging technique that can detect clinically undetectable metastases. This prospective study shows preliminary results on the comparison of both techniques for the detection of lymph node invasion. Material and Methods: Twenty-two consecutive patients (15 women, 7 men; mean age, 55 years) with primary melanoma > 1.0 mm thick were enrolled (mean 2.6 mm). Patients underwent 99m Tc-MIBI scintigraphy of regional lymph nodes 1-2 weeks before surgery, acquiring 10-minute planar images with a LFOV gamma camera. A preoperative lymphoscintigraphy using 99m Tc-colloidal (Re) sulphide was performed the day before surgery, using a dose of 74-93 MBq. Radio guided SNB was performed with a hand-held gamma probe. Lymph nodes were examined histologically and immunostained for S-100 and HMB-45. Results: The sentinel node (SN) was identified in 21/22 patients. An average of 1.6 SN/lesion were harvested from melanomas located in the following regions: head and neck (n=3), trunk (n=6), extremities (n=12). All patients with negative SN (n=11) were also negative with MIBI. In 10 cases the SN demonstrated metastatic involvement, whereas 99m Tc-MIBI was positive in 8 of them (80%). In cases with positive SN/negative 99m Tc-MIBI, the pathology report revealed micro metastatic disease. Conclusion: These preliminary results suggest that 99m Tc-MIBI scanning has the potential of selecting a group of patients who might benefit from a selective complete lymphadenectomy

Identifying logical planes formed of compute nodes of a subcommunicator in a parallel computer

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Davis, Kristan D.; Faraj, Daniel A.

2016-03-01

In a parallel computer, a plurality of logical planes formed of compute nodes of a subcommunicator may be identified by: for each compute node of the subcommunicator and for a number of dimensions beginning with a first dimension: establishing, by a plane building node, in a positive direction of the first dimension, all logical planes that include the plane building node and compute nodes of the subcommunicator in a positive direction of a second dimension, where the second dimension is orthogonal to the first dimension; and establishing, by the plane building node, in a negative direction of the first dimension, all logical planes that include the plane building node and compute nodes of the subcommunicator in the positive direction of the second dimension.

The FDG uptake and glucose transporter(GLUT-1) expression of the mediastinal nodes in the non-small cell lung cancer

International Nuclear Information System (INIS)

Baik, Hee Jong; Jung, Jin Haeng

2000-12-01

The aim of this study was to understand the mechanism of FDG uptake in the mediastinal nodes, and improve the accuracy of mediastinal staging of non-small cell lung cancer by PET. To evaluate factors determining the FDG uptake in mediastinal nodes, FDG-PET was performed preoperatively, and mediastinal dissection with pulmonary resection was done in 20 LSCLC patients. The GLUT-1 expression was studied by immunohistochemistry of paraffin-section from the mediastinal nodes(n=50, true positive 11, true negative 23, false positive 11, false negative 5) using the antiGLUT-1 antibody. The staining intensity of tumor(grade 0-4), percentage of tumor, level of follicular hyperplasia(grade 1-4), and staining intensity of follicle was also studied. The staining intensity of true positive nodes was higher than that of false negative group(Mann-Whitney test, P=0.07) in the metastased nodes. The level of follicular hyperplasia of false positive nodes was higher than that of true negative nodes in non-metastased nodes(P=0.02). This finding indicates that FN interpretation of mediastinal nodes by FDG-PET might be associated with low uptake of FDG due to low expression of GLUT-1, and that FP might be associated with high level of follicular hyperplasia as a reactive change to inflammatory and/or immune reaction

LYMPHOCYTIC THYROIDITIS IS ASSOCIATED WITH INCREASED NUMBER OF BENIGN CERVICAL NODES AND FEWER CENTRAL NECK COMPARTMENT METASTATIC LYMPH NODES IN PATIENTS WITH DIFFERENTIATED THYROID CANCER.

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Donangelo, Ines; Walts, Ann E; Bresee, Catherine; Braunstein, Glenn D

2016-10-01

Whether or not autoimmune thyroid disease influences the progression of differentiated thyroid cancer (DTC) remains controversial. Findings of previous studies are influenced by lead time bias and/or procedure bias selection. These biases can be reduced by studying a single-institution patient population that underwent a similar extent of surgical resection. From a cohort of 660 patients with DTC who underwent thyroidectomy, we retrospectively studied 357 patients who underwent total thyroidectomy and central compartment node dissection (CCND) for DTC between 2003 and 2013. Forty-one percent (140/345) of study patients had lymphocytic thyroiditis (LT), and 30% (91/301) had serum positive for thyroglobulin antibody (TgAb). LT was reported in 78% of the TgAb-positive cases. Sixty percent (213/357) of cases had metastatic thyroid carcinoma in 1 or more neck lymph nodes (55% [198/357] central compartment, and 22% [77/356] lateral compartment). Patients with LT had fewer metastatic cervical lymph nodes than those with no LT (2.7 ± 4.7 vs 3.5 ± 4.8, respectively, P = .0285). Patients with positive TgAb and thyroiditis had a larger number of benign cervical lymph nodes removed than those with negative TgAb or no LT. No significant difference was observed in age, tumor size, multifocality, extrathyroidal extension, vascular invasion, or frequency of cervical lymph node metastasis between TgAb-negative and -positive cases or between cases with and without LT. Lymphocytic thyroiditis is associated with fewer central neck compartment metastatic lymph nodes and a larger number of excised reactive benign cervical lymph nodes. Whether this association indicates a protective role of thyroid autoimmunity in lymph node spreading remains unclear. CCND = central compartment node dissection DTC = differentiated thyroid cancer HT = Hashimoto thyroiditis LT = lymphocytic thyroiditis TgAb = thyroglobulin antibody TPO = thyroid peroxidase.

Age-Related Frequency of Triple Negative Breast Cancer in Women

International Nuclear Information System (INIS)

Sajid, M. T.; Ahmad, M.; Mustafa, Q.; Shukr, I.; Azhar, M.

2014-01-01

Objective: To determine frequency of triple negative breast cancer (TNBC) in Pakistani women with respect to age. Study Design: Observational study. Place and Duration of Study: Armed Forces Institute of Pathology (AFIP), Rawalpindi, from July 2005 to July 2010. Methodology: Pathological records of all specimens of breast cancer were reviewed and data was obtained for estrogen receptor (ER), progesterone receptor (PR) and HER-2 neu receptor proteins. Specimens having complete record of all three proteins were included for analysis. TNBC was defined as those who were ER, PR and HER-2 neu negative. Overall frequency as well as frequency with respect to age was calculated. Descriptive and categorical variables were analyzed using SPSS version 17. Results: Eight hundred and fifteen patients out of 4715 (17.28%) were found to be TNBC. Mean age of diagnosis of TNBC was found to be 46.26 A +- 12.22 years of age while other breast cancers had a mean age 52.90 A +- 9.78 years (p 50 years while majority of patients with other breast cancers were elderly females (p < 0.001). Conclusion: TNBC comprised 17.28% of the breast cancers in Pakistani women diagnosed at the studied centre. A higher frequency of TNBC was noted in significantly younger patients. (author)

CLINICOPATHOLOGICAL FACTORS ASSOCIATED WITH POSITIVE PREOPERATIVE AXILLARY ULTRASOUND SCANNING IN BREAST CANCER PATIENTS

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Lona Jalini

2016-01-01

Full Text Available Background: Axillary lymph node status is the most important breast cancer prognostic factor. Preoperative axillary ultrasound examination (PAUS is used to triage patients for sentinel lymph node biopsy (SLNB or axillary lymph node dissection (ALND. We assessed the detection rate of lymph node metastases by PAUS in a screening unit and evaluated associations between clinicopathological factors and PAUS positivity. Patients and Methods: This was a single-centre retrospective analysis of data extracted from a hospital breast cancer database and clinical records. Clinical, radiological, and pathological and prognostic indices were compared between PAUS-positive and PAUS-negative patients subsequently found to have lymph node metastases on histopathological analysis. Results: Two hundred and two patients were eligible for analysis. 50.5% of lymph node-positive patients were correctly identified as PAUS positive. Patients with PAUS-positive lymph nodes had less favorable disease characteristics, namely clinically palpable lymph nodes, higher Nottingham prognostic (NPI index, high lymph node burden according to the European Society of Medical Oncology (ESMO group classification, and larger, grade 3 tumors with lymphovascular invasion and extranodal spread. Moreover, PAUS-positive patients had more macrometastases and lymph node involvement than PAUS-negative patients. Conclusion: PAUS-positive patients and PAUS-negative (SLNB-positive patients have different clinicopathological characteristics. The presence of LVI, extranodal spread, grade 3 histology, or large tumors with poor prognostic indices in PAUS-negative patients should be regarded with caution and perhaps prompt second-look ultrasound examination.

Cellular uptake mechanism and comparative evaluation of antineoplastic effects of paclitaxel–cholesterol lipid emulsion on triple-negative and non-triple-negative breast cancer cell lines

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Ye J

2016-08-01

Full Text Available Jun Ye,1,2 Xuejun Xia,1,2 Wujun Dong,1,2 Huazhen Hao,1,2 Luhua Meng,1,2 Yanfang Yang,1,2 Renyun Wang,1,2 Yuanfeng Lyu,3 Yuling Liu1,2 1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, 2Beijing Key Laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, 3School of Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: There is no effective clinical therapy for triple-negative breast cancers (TNBCs, which have high low-density lipoprotein (LDL requirements and express relatively high levels of LDL receptors (LDLRs on their membranes. In our previous study, a novel lipid emulsion based on a paclitaxel–cholesterol complex (PTX-CH Emul was developed, which exhibited improved safety and efficacy for the treatment of TNBC. To date, however, the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul have not been investigated. In order to offer powerful proof for the therapeutic effects of PTX-CH Emul, we systematically studied the cellular uptake mechanism and intracellular trafficking of PTX-CH Emul and made a comparative evaluation of antineoplastic effects on TNBC (MDA-MB-231 and non-TNBC (MCF7 cell lines through in vitro and in vivo experiments. The in vitro antineoplastic effects and in vivo tumor-targeting efficiency of PTX-CH Emul were significantly more enhanced in MDA-MB-231-based models than those in MCF7-based models, which was associated with the more abundant expression profile of LDLR in MDA-MB-231 cells. The results of the cellular uptake mechanism indicated that PTX-CH Emul was internalized into breast cancer cells through the LDLR-mediated internalization pathway via clathrin-coated pits, localized in lysosomes, and then released into the cytoplasm, which was consistent with the internalization pathway and intracellular trafficking of native

Combined calcitriol and menadione reduces experimental murine triple negative breast tumor.

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Bohl, Luciana; Guizzardi, Solange; Rodríguez, Valeria; Hinrichsen, Lucila; Rozados, Viviana; Cremonezzi, David; Tolosa de Talamoni, Nori; Picotto, Gabriela

2017-10-01

Calcitriol (D) or 1,25(OH) 2 D 3 inhibits the growth of several tumor cells including breast cancer cells, by activating cell death pathways. Menadione (MEN), a glutathione-depleting compound, may be used to potentiate the antiproliferative actions of D on cancer cells. We have previously shown in vitro that MEN improved D-induced growth arrest on breast cancer cell lines, inducing oxidative stress and DNA damage via ROS generation. Treatment with MEN+D resulted more effective than D or MEN alone. To study the in vivo effect of calcitriol, MEN or their combination on the development of murine transplantable triple negative breast tumor M-406 in its syngeneic host. Tumor M-406 was inoculated s.c., and when tumors reached the desired size, animals were randomly assigned to one of four groups receiving daily i.p. injections of either sterile saline solution (controls, C), MEN, D, or both (MEN+D). Body weight and tumor volume were recorded three times a week. Serum calcium was determined before and at the end of the treatment, at which time tumor samples were obtained for histological examination. None of the drugs, alone or in combination, affected mice body weight in the period studied. The combined treatment reduced tumor growth rate (C vs. MEN+D, P<0.05) and the corresponding histological sections exhibited small remaining areas of viable tumor only in the periphery. A concomitant DNA fragmentation was observed in all treated groups and MEN potentiated the calcitriol effect on tumor growth. As previously observed in vitro, treatment with MEN and D delayed tumor growth in vivo more efficiently than the individual drugs, with evident signals of apoptosis induction. Our results propose an alternative protocol to treat triple negative breast cancer, using GSH depleting drugs together with calcitriol, which would allow lower doses of the steroid to maintain the antitumor effect while diminishing its adverse pharmacological effects. Copyright © 2017. Published by

Sentinel Lymph Node Dissection to Select Clinically Node-negative Prostate Cancer Patients for Pelvic Radiation Therapy: Effect on Biochemical Recurrence and Systemic Progression

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Grivas, Nikolaos, E-mail: n.grivas@nki.nl [Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Wit, Esther [Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Pos, Floris [Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Jong, Jeroen de [Department of Pathology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Vegt, Erik [Department of Nuclear Medicine, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Bex, Axel; Hendricksen, Kees; Horenblas, Simon [Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); KleinJan, Gijs [Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Interventional Molecular Imaging Laboratory, Department of Radiology, Leiden University Medical Center, Leiden (Netherlands); Rhijn, Bas van; Poel, Henk van der [Department of Urology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands)

2017-02-01

Purpose: To assess the efficacy of robotic-assisted laparoscopic sentinel lymph node (SLN) dissection (SLND) to select those patients with prostate cancer (PCa) who would benefit from additional pelvic external beam radiation therapy and long-term androgen deprivation therapy (ADT). Methods and Materials: Radioisotope-guided SLND was performed in 224 clinically node-negative patients scheduled to undergo external beam radiation therapy. Patients with histologically positive SLNs (pN1) were also offered radiation therapy to the pelvic lymph nodes, combined with 3 years of ADT. Biochemical recurrence (BCR), overall survival, and metastasis-free (including pelvic and nonregional lymph nodes) survival (MFS) rates were retrospectively calculated. The Briganti and Kattan nomogram predictions were compared with the observed pN status and BCR. Results: The median prostate-specific antigen (PSA) value was 15.4 ng/mL (interquartile range [IQR] 8-29). A total number of 834 SLNs (median 3 per patient; IQR 2-5) were removed. Nodal metastases were diagnosed in 42% of the patients, with 150 SLNs affected (median 1; IQR 1-2). The 5-year BCR-free and MFS rates for pN0 patients were 67.9% and 87.8%, respectively. The corresponding values for pN1 patients were 43% and 66.6%. The PSA level and number of removed SLNs were independent predictors of BCR and MFS, and pN status was an additional independent predictor of BCR. The 5-year overall survival rate was 97.6% and correlated only with pN status. The predictive accuracy of the Briganti nomogram was 0.665. Patients in the higher quartiles of Kattan nomogram prediction of BCR had better than expected outcomes. The complication rate from SLND was 8.9%. Conclusions: For radioisotope-guided SLND, the high staging accuracy is accompanied by low morbidity. The better than expected outcomes observed in the lower quartiles of BCR prediction suggest a role for SLN biopsy as a potential selection tool for the addition of pelvic radiation

Triple-negative breast cancer with brain metastases: a comparison between basal-like and non-basal-like biological subtypes

NARCIS (Netherlands)

A. Niwińska (Anna); W. Olszewski (Wojciech); M. Murawska (Magdalena); K. Pogoda (Katarzyna)

2011-01-01

textabstractThe aim of this study was to divide the group of triple-negative breast cancer patients with brain metastases into basal-like and non-basal-like biological subtypes in order to compare clinical features and survival rates in those two groups. A comprehensive analysis of 111 consecutive

Pretreatment Hematocrit Is Superior to Hemoglobin as a Prognostic Factor for Triple Negative Breast Cancer.

Science.gov (United States)

Chen, Bo; Dai, Danian; Tang, Hailin; Ai, Xiaohong; Chen, Xi; Zhang, Xiaoyan; Li, Zhiyan; Xie, Xiaoming

2016-01-01

Anemia usually refers to low hemoglobin (Hb) levels. Previous studies indicated that anemia negatively influence the survival in various cancers. Hematocrit (HCT) is the volume percentage of red blood cells in blood, which could indicate anemia in both individuals and populations. This study compared the value of HCT with that of Hb for predicting outcomes of patients who underwent treatment for triple negative breast cancer (TNBC). A retrospective study of 293 triple negative breast cancer patients, accepting treatment from January 2004 to December 2009 at Sun Yat-sen University Cancer Center, was conducted. Kaplan-Meier curves and multivariate Cox proportional models were used to calculate disease free survival (DFS) and overall survival (OS). The cut-off value of HCT was 35.9% determined by X-tile software analysis. The cut-off value of Hb was 12.0 g/dl based on the World Health Organization (WHO) criteria. In univariate analysis, low HCT and low Hb were both significantly associated with decreased DFS and OS. In multivariate analysis, HCT (HR: 0.570; 95% CI: 0.331-0.981, P = 0.042 for DFS; HR: 0.456; 95% CI: 0.256-0.813, P = 0.008 for OS) was still identified as independent predictor of outcome, but not Hb. Pretreatment low HCT is independently associated with poor prognosis in TNBC patients. However, HCT was found to be superior to Hb in terms of predicting breast cancer mortality. In the future, large-scale prospective studies or validation studies are needed to verify our findings.

Chasing down the triple-negative myeloproliferative neoplasms: Implications for molecular diagnostics.

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Langabeer, Stephen E

2016-01-01

The majority of patients with classical myeloproliferative neoplasms (MPN) of polycythemia vera, essential thrombocythemia, and primary myelofibrosis harbor distinct disease-driving mutations within the JAK2 , CALR , or MPL genes. The term triple-negative has been recently applied to those MPN without evidence of these consistent mutations, prompting whole or targeted exome sequencing approaches to determine the driver mutational status of this subgroup. These strategies have identified numerous novel mutations that occur in alternative exons of both JAK2 and MPL , the majority of which result in functional activation. Current molecular diagnostic approaches may possess insufficient coverage to detect these alternative mutations, prompting further consideration of targeted exon sequencing into routine diagnostic practice. How to incorporate these illuminating findings into the expanding molecular diagnostic algorithm for MPN requires continual attention.

Tumor gene expression and prognosis in breast cancer patients with 10 or more positive lymph nodes.

Science.gov (United States)

Cobleigh, Melody A; Tabesh, Bita; Bitterman, Pincas; Baker, Joffre; Cronin, Maureen; Liu, Mei-Lan; Borchik, Russell; Mosquera, Juan-Miguel; Walker, Michael G; Shak, Steven

2005-12-15

This study, along with two others, was done to develop the 21-gene Recurrence Score assay (Oncotype DX) that was validated in a subsequent independent study and is used to aid decision making about chemotherapy in estrogen receptor (ER)-positive, node-negative breast cancer patients. Patients with >or=10 nodes diagnosed from 1979 to 1999 were identified. RNA was extracted from paraffin blocks, and expression of 203 candidate genes was quantified using reverse transcription-PCR (RT-PCR). Seventy-eight patients were studied. As of August 2002, 77% of patients had distant recurrence or breast cancer death. Univariate Cox analysis of clinical and immunohistochemistry variables indicated that HER2/immunohistochemistry, number of involved nodes, progesterone receptor (PR)/immunohistochemistry (% cells), and ER/immunohistochemistry (% cells) were significantly associated with distant recurrence-free survival (DRFS). Univariate Cox analysis identified 22 genes associated with DRFS. Higher expression correlated with shorter DRFS for the HER2 adaptor GRB7 and the macrophage marker CD68. Higher expression correlated with longer DRFS for tumor protein p53-binding protein 2 (TP53BP2) and the ER axis genes PR and Bcl2. Multivariate methods, including stepwise variable selection and bootstrap resampling of the Cox proportional hazards regression model, identified several genes, including TP53BP2 and Bcl2, as significant predictors of DRFS. Tumor gene expression profiles of archival tissues, some more than 20 years old, provide significant information about risk of distant recurrence even among patients with 10 or more nodes.

Sequential 18F-FDG PET/CT for early prediction of complete pathological response in breast and axilla during neoadjuvant chemotherapy

International Nuclear Information System (INIS)

Koolen, Bas B.; Pengel, Kenneth E.; Wesseling, Jelle; Vogel, Wouter V.; Valdes Olmos, Renato A.; Vrancken Peeters, Marie-Jeanne T.F.D.; Rutgers, Emiel J.T.; Vincent, Andrew D.; Gilhuijs, Kenneth G.A.; Rodenhuis, Sjoerd

2014-01-01

To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account. In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 - 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 - 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis. A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively. In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR. (orig.)

Sequential {sup 18}F-FDG PET/CT for early prediction of complete pathological response in breast and axilla during neoadjuvant chemotherapy

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Koolen, Bas B. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Pengel, Kenneth E. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); Wesseling, Jelle [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Pathology, Amsterdam (Netherlands); Vogel, Wouter V.; Valdes Olmos, Renato A. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Nuclear Medicine, Amsterdam (Netherlands); Vrancken Peeters, Marie-Jeanne T.F.D.; Rutgers, Emiel J.T. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Surgical Oncology, Amsterdam (Netherlands); Vincent, Andrew D. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Biometrics, Amsterdam (Netherlands); Gilhuijs, Kenneth G.A. [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Radiology, Amsterdam (Netherlands); University Medical Center Utrecht, Department of Radiology, Utrecht (Netherlands); Rodenhuis, Sjoerd [Netherlands Cancer Institute - Antoni van Leeuwenhoek Hospital, Department of Medical Oncology, Amsterdam (Netherlands)

2014-01-15

To investigate the value of response monitoring in both the primary tumour and axillary nodes on sequential PET/CT scans during neoadjuvant chemotherapy (NAC) for predicting complete pathological response (pCR), taking the breast cancer subtype into account. In 107 consecutive patients 290 PET/CT scans were performed at baseline (PET/CT1, 107 patients), after 2 - 3 weeks of chemotherapy (PET/CT2, 85 patients), and after 6 - 8 weeks (PET/CT3, 98 patients). The relative changes in SUVmax (from baseline) of the tumour and the lymph nodes and in both combined (after logistic regression), and the changes in the highest SUVmax between scans (either tumour or lymph node) were determined and their associations with pCR of the tumour and lymph nodes after completion of NAC were assessed using receiver operating characteristic (ROC) analysis. A pCR was seen in 17 HER2-positive tumours (65 %), 1 ER-positive/HER2-negative tumour (2 %), and 16 triple-negative tumours (52 %). The areas under the ROC curves (ROC-AUC) for the prediction of pCR in HER2-positive tumours after 3 weeks were 0.61 for the relative change in tumours, 0.67 for the combined change in tumour and nodes, and 0.72 for the changes in the highest SUVmax between scans. After 8 weeks equivalent values were 0.59, 0.42 and 0.64, respectively. In triple-negative tumours the ROC-AUCs were 0.76, 0.84 and 0.76 after 2 weeks, and 0.87, 0.93 and 0.88 after 6 weeks, respectively. In triple-negative tumours a PET/CT scan after 6 weeks (three cycles) appears to be optimally predictive of pCR. In HER2-positive tumours neither a PET/CT scan after 3 weeks nor after 8 weeks seems to be useful. The changes in SUVmax of both the tumour and axillary nodes combined correlates best with pCR. (orig.)

Podoplanin-positive Cancer-associated Stromal Fibroblasts in Primary Tumor and Synchronous Lymph Node Metastases of HER2-overexpressing Breast Carcinomas.

Science.gov (United States)

Niemiec, Joanna; Adamczyk, Agnieszka; Harazin-Lechowska, Agnieszka; Ambicka, Aleksandra; Grela-Wojewoda, Aleksandra; Majchrzyk, Kaja; Kruczak, Anna; Sas-Korczyńska, Beata; Ryś, Janusz

2018-04-01

We compared the status of stromal podoplanin-positive cancer-associated fibroblasts (ppCAFs) between primary tumors and paired synchronous lymph node metastases (LNMs) and analyzed the prognostic significance of tumoral ppCAFs in 203 patients with human epidermal growth factor receptor 2-positive breast carcinoma. ppCAFs were found in 167/203 and in 35/87 tumors and LNM, respectively. ppCAFs were most frequently found in tumors and corresponding LNM (n=52, 59.8%; p=0.001). However, for all LNMs (n=12) without ppCAFs, their paired tumors also lacked ppCAFs. In both tumors and LNMs, ppCAFs were α-smooth muscle actin-positive and cluster of differentiation 21 protein-negative, suggesting them not to be resident lymph node cells. Moreover, in our series, the presence of ppCAFs in tumors was borderline related to poor disease-free survival (p=0.058). These results speak in favor of a hypothesis suggesting ppCAFs accompany metastatic cancer cells migrating from tumor to LNMs. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Imaging and histologic prognostic factors in triple-negative breast cancer and carcinoma in situ as a prognostic factor.

Science.gov (United States)

Sebastián Sebastián, C; García Mur, C; Cruz Ciria, S; Rosero Cuesta, D S; Gros Bañeres, B

2016-01-01

To analyze what factors in magnetic resonance imaging (MRI) and histological study of triple-negative breast cancers are related to tumor recurrence and to shorter disease-free survival. To analyze survival and recurrence in function of the presence of an in situ component. This was a retrospective study of MRI staging examinations in 122 women with triple-negative breast cancer done from 2007 through 2014. In the MRI, we evaluated morphological variables (size, margins, morphology, internal signal in T2-weighted sequences) and dynamic variables (perfusion and diffusion). In the histological study, we evaluated Ki67, p53, CK5/6, nuclear grade, and Scarff-Bloom grade, as well as the presence of an in situ component and tumor grade (high grade or not high grade). We compared the variables between patients with tumor recurrence and those without, and we conducted a survival analysis. Non-nodular enhancement was more common in patients with tumor recurrence (p=0.038) and was associated with shorter disease-free survival (p=0.023). Neither diffusion restriction (p=0.079) nor ki67 (p=0.052) was associated with a worse prognosis. An in situ component was detected in 44% of triple-negative tumors, and a greater proportion of patients in the group with tumor recurrence had an in situ component; however, the presence of an in situ component was not associated with shorter survival (p = 0.185). Non-nodular enhancement was associated with a worse prognosis. Diffusion restriction, ki67, and the presence of an in situ component were not associated with shorter disease-free survival. Copyright © 2016 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Reoperative sentinel lymph node biopsy after previous mastectomy.

Science.gov (United States)

Karam, Amer; Stempel, Michelle; Cody, Hiram S; Port, Elisa R

2008-10-01

Sentinel lymph node (SLN) biopsy is the standard of care for axillary staging in breast cancer, but many clinical scenarios questioning the validity of SLN biopsy remain. Here we describe our experience with reoperative-SLN (re-SLN) biopsy after previous mastectomy. Review of the SLN database from September 1996 to December 2007 yielded 20 procedures done in the setting of previous mastectomy. SLN biopsy was performed using radioisotope with or without blue dye injection superior to the mastectomy incision, in the skin flap in all patients. In 17 of 20 patients (85%), re-SLN biopsy was performed for local or regional recurrence after mastectomy. Re-SLN biopsy was successful in 13 of 20 patients (65%) after previous mastectomy. Of the 13 patients, 2 had positive re-SLN, and completion axillary dissection was performed, with 1 having additional positive nodes. In the 11 patients with negative re-SLN, 2 patients underwent completion axillary dissection demonstrating additional negative nodes. One patient with a negative re-SLN experienced chest wall recurrence combined with axillary recurrence 11 months after re-SLN biopsy. All others remained free of local or axillary recurrence. Re-SLN biopsy was unsuccessful in 7 of 20 patients (35%). In three of seven patients, axillary dissection was performed, yielding positive nodes in two of the three. The remaining four of seven patients all had previous modified radical mastectomy, so underwent no additional axillary surgery. In this small series, re-SLN was successful after previous mastectomy, and this procedure may play some role when axillary staging is warranted after mastectomy.

The sigma-2 receptor as a therapeutic target for drug delivery in triple negative breast cancer

International Nuclear Information System (INIS)

Makvandi, Mehran; Tilahun, Estifanos D.; Lieberman, Brian P.; Anderson, Redmond-Craig; Zeng, Chenbo; Xu, Kuiying; Hou, Catherine; McDonald, Elizabeth S.; Pryma, Daniel A.; Mach, Robert H.

2015-01-01

Background: Triple-negative breast cancer (TNBC) is associated with high relapse rates and increased mortality when compared with other breast cancer subtypes. In contrast to receptor positive breast cancers, there are no approved targeted therapies for TNBC. Identifying biomarkers for TNBC is of high importance for the advancement of patient care. The sigma-2 receptor has been shown to be overexpressed in triple negative breast cancer in vivo and has been characterized as a marker of proliferation. The aim of the present study was to define the sigma-2 receptor as a target for therapeutic drug delivery and biomarker in TNBC. Methods: Three TNBC cell lines were evaluated: MDA-MB-231, HCC1937 and HCC1806. Sigma-2 compounds were tested for pharmacological properties specific to the sigma-2 receptor through competitive inhibition assays. Sigma-2 receptor expression was measured through radioligand receptor saturation studies. Drug sensitivity for taxol was compared to a sigma-2 targeting compound conjugated to a cytotoxic payload, SW IV-134. Cell viability was assessed after treatments for 2 or 48 h. Sigma-2 blockade was assessed to define sigma-2 mediated cytotoxicity of SW IV-134. Caspase 3/7 activation induced by SW IV-134 was measured at corresponding treatment time points. Results: SW IV-134 was the most potent compound tested in two of the three cell lines and was similarly effective in all three. MDA-MB-231 displayed a statistically significant higher sigma-2 receptor expression and also was the most sensitive cell line evaluated to SW IV-134. Conclusion: Targeting the sigma-2 receptor with a cytotoxic payload was effective in all the three cell lines evaluated and provides the proof of concept for future development of a therapeutic platform for the treatment of TNBC. - Highlights: • TNBC cells are sensitive to sigma-2 receptor targeted drug conjugate SW IV-134. • MDA-MB-231 displayed the highest amount of sigma-2 receptors and corresponded well with

The sigma-2 receptor as a therapeutic target for drug delivery in triple negative breast cancer

Energy Technology Data Exchange (ETDEWEB)

Makvandi, Mehran; Tilahun, Estifanos D.; Lieberman, Brian P.; Anderson, Redmond-Craig; Zeng, Chenbo; Xu, Kuiying; Hou, Catherine; McDonald, Elizabeth S.; Pryma, Daniel A.; Mach, Robert H., E-mail: rmach@mail.med.upenn.edu

2015-11-27

Background: Triple-negative breast cancer (TNBC) is associated with high relapse rates and increased mortality when compared with other breast cancer subtypes. In contrast to receptor positive breast cancers, there are no approved targeted therapies for TNBC. Identifying biomarkers for TNBC is of high importance for the advancement of patient care. The sigma-2 receptor has been shown to be overexpressed in triple negative breast cancer in vivo and has been characterized as a marker of proliferation. The aim of the present study was to define the sigma-2 receptor as a target for therapeutic drug delivery and biomarker in TNBC. Methods: Three TNBC cell lines were evaluated: MDA-MB-231, HCC1937 and HCC1806. Sigma-2 compounds were tested for pharmacological properties specific to the sigma-2 receptor through competitive inhibition assays. Sigma-2 receptor expression was measured through radioligand receptor saturation studies. Drug sensitivity for taxol was compared to a sigma-2 targeting compound conjugated to a cytotoxic payload, SW IV-134. Cell viability was assessed after treatments for 2 or 48 h. Sigma-2 blockade was assessed to define sigma-2 mediated cytotoxicity of SW IV-134. Caspase 3/7 activation induced by SW IV-134 was measured at corresponding treatment time points. Results: SW IV-134 was the most potent compound tested in two of the three cell lines and was similarly effective in all three. MDA-MB-231 displayed a statistically significant higher sigma-2 receptor expression and also was the most sensitive cell line evaluated to SW IV-134. Conclusion: Targeting the sigma-2 receptor with a cytotoxic payload was effective in all the three cell lines evaluated and provides the proof of concept for future development of a therapeutic platform for the treatment of TNBC. - Highlights: • TNBC cells are sensitive to sigma-2 receptor targeted drug conjugate SW IV-134. • MDA-MB-231 displayed the highest amount of sigma-2 receptors and corresponded well with

Skin irritation, false positives and the local lymph node assay: a guideline issue?

Science.gov (United States)

Basketter, David A; Kimber, Ian

2011-10-01

Since the formal validation and regulatory acceptance of the local lymph node assay (LLNA) there have been commentaries suggesting that the irritant properties of substances can give rise to false positives. As toxicology aspires to progress rapidly towards the age of in vitro alternatives, it is of increasing importance that issues relating to assay selectivity and performance are understood fully, and that true false positive responses are distinguished clearly from those that are simply unpalatable. In the present review, we have focused on whether skin irritation per se is actually a direct cause of true false positive results in the LLNA. The body of published work has been examined critically and considered in relation to our current understanding of the mechanisms of skin irritation and skin sensitisation. From these analyses it is very clear that, of itself, skin irritation is not a cause of false positive results. The corollary is, therefore, that limiting test concentrations in the LLNA for the purpose of avoiding skin irritation may lead, unintentionally, to false negatives. Where a substance is a true false positive in the LLNA, the classic example being sodium lauryl sulphate, explanations for that positivity will have to reach beyond the seductive, but incorrect, recourse to its skin irritation potential. Copyright © 2011 Elsevier Inc. All rights reserved.

Metabolomics Analysis of Hormone-Responsive and Triple-Negative Breast Cancer Cell Responses to Paclitaxel Identify Key Metabolic Differences.

Science.gov (United States)

Stewart, Delisha A; Winnike, Jason H; McRitchie, Susan L; Clark, Robert F; Pathmasiri, Wimal W; Sumner, Susan J

2016-09-02

To date, no targeted therapies are available to treat triple negative breast cancer (TNBC), while other breast cancer subtypes are responsive to current therapeutic treatment. Metabolomics was conducted to reveal differences in two hormone receptor-negative TNBC cell lines and two hormone receptor-positive Luminal A cell lines. Studies were conducted in the presence and absence of paclitaxel (Taxol). TNBC cell lines had higher levels of amino acids, branched-chain amino acids, nucleotides, and nucleotide sugars and lower levels of proliferation-related metabolites like choline compared with Luminal A cell lines. In the presence of paclitaxel, each cell line showed unique metabolic responses, with some similarities by type. For example, in the Luminal A cell lines, levels of lactate and creatine decreased while certain choline metabolites and myo-inositol increased with paclitaxel. In the TNBC cell lines levels of glutamine, glutamate, and glutathione increased, whereas lysine, proline, and valine decreased in the presence of drug. Profiling secreted inflammatory cytokines in the conditioned media demonstrated a greater response to paclitaxel in the hormone-positive Luminal cells compared with a secretion profile that suggested greater drug resistance in the TNBC cells. The most significant differences distinguishing the cell types based on pathway enrichment analyses were related to amino acid, lipid and carbohydrate metabolism pathways, whereas several biological pathways were differentiated between the cell lines following treatment.

Person-centred positive emotions, object-centred negative emotions: 2-year-olds generalize negative but not positive emotions across individuals.

Science.gov (United States)

Vaish, Amrisha; Grossmann, Tobias; Woodward, Amanda

2015-09-01

Prior work suggests that young children do not generalize others' preferences to new individuals. We hypothesized (following Vaish et al., 2008, Psychol. Bull., 134, 383-403) that this may only hold for positive emotions, which inform the child about the person's attitude towards the object but not about the positivity of the object itself. It may not hold for negative emotions, which additionally inform the child about the negativity of the object itself. Two-year-old children saw one individual (the emoter) emoting positively or negatively towards one and neutrally towards a second novel object. When a second individual then requested an object, children generalized the emoter's negative but not her positive emotion to the second individual. Children thus draw different inferences from others' positive versus negative emotions: Whereas they view others' positive emotions as person centred, they may view others' negative emotions as object centred and thus generalizable across people. The results are discussed with relation to the functions and implications of the negativity bias. © 2015 The British Psychological Society.

Management of the clinically node negative neck in squamous cell carcinoma of the maxilla

NARCIS (Netherlands)

Joosten, Michiel H M A; de Bree, Remco; Van Cann, Ellen M.

Objective: The management of the clinically node negative (N0) neck in patients with squamous cell carcinoma of the maxilla (MSCC) is a matter of debate. In this retrospective cohort study the incidence of occult metastases is determined in clinically N0 MSCCs, as well as histopathological factors

The clinical value of 99mTc-MIBI imaging for axillary lymph node metastasis of breast cancer

International Nuclear Information System (INIS)

Song Bangkun; Yang Jisheng; Shen Dawei; Zuo Lei; Jiang Ling; Zhou Ya

2001-01-01

Objective: To observe the clinical value of 99m Tc-MIBI imaging for axillary lymph node metastasis of breast cancer. Methods: 56 patients with breast cancer proven by pathology were imaged with 99m Tc-MIBI. Images were taken at 5, 30, 60 minutes. The axillary area of affected side was included in imaging field. Results: The primary foci in 55 cases were positive and one case was negative in uptake. Of the 56 cases, 35 had histologically proven axillary lymph node metastases. MIBI uptake was seen in 30 cases and negative in 5 cases. The sensitivity was 85.7% (30/35 cases). In 21 cases who had no metastasis, 3 cases showed false positive uptake and 18 cases were true negative, making the specificity 85.7%. In the case who had negative imaging for primary focus, which was non-palpable, had an enlarged axillary lymphatic node. Positive MIBI uptake of the node area was seen in this case. Conclusion: 99m Tc-MIBI imaging is valuable for the diagnosis of axillary nodal metastasis of breast cancer. Even though there is no palpable primary focus, if there is an enlarged axillary lymphatic node and positive MIBI uptake, metastasis should be considered

Pregnancy failure in patients with obstetric antiphospholipid syndrome with conventional treatment: the influence of a triple positive antibody profile.

Science.gov (United States)

Latino, J O; Udry, S; Aranda, F M; Perés Wingeyer, S D A; Fernández Romero, D S; de Larrañaga, G F

2017-08-01

Conventional treatment of obstetric antiphospholipid syndrome fails in approximately 20-30% of pregnant women without any clearly identified risk factor. It is important to identify risk factors that are associated with these treatment failures. This study aimed to assess the impact of risk factors on pregnancy outcomes in women with obstetric antiphospholipid syndrome treated with conventional treatment. We carefully retrospectively selected 106 pregnancies in women with obstetric antiphospholipid syndrome treated with heparin + aspirin. Pregnancy outcomes were evaluated according to the following associated risk factors: triple positivity profile, double positivity profile, single positivity profile, history of thrombosis, autoimmune disease, more than four pregnancy losses, and high titers of anticardiolipin antibodies and/or anti-βeta-2-glycoprotein-I (aβ2GPI) antibodies. To establish the association between pregnancy outcomes and risk factors, a single binary logistic regressions analysis was performed. Risk factors associated with pregnancy loss with conventional treatment were: the presence of triple positivity (OR = 5.0, CI = 1.4-16.9, p = 0.01), high titers of aβ2GPI (OR = 4.4, CI = 1.2-16.1, p = 0.023) and a history of more than four pregnancy losses (OR = 3.5, CI = 1.2-10.0, p = 0.018). The presence of triple positivity was an independent risk factor associated with gestational complications (OR = 4.1, CI = 1.2-13.9, p = 0.02). Our findings reinforce the idea that triple positivity is a categorical risk factor for poor response to conventional treatment.

Sentinel lymph node biopsy in breast cancer--the Aarhus experience

DEFF Research Database (Denmark)

Lauridsen, M C; Garne, J P; Hessov, I

2000-01-01

Eighty patients, with newly diagnosed unifocal breast cancer and with no axillary metastases verified by ultrasonography, underwent sentinel lymph node (SLN) and subsequent axillary lymph node dissection. To identify the SLN, we used a combination of Tc-99m labelled colloid (Albures) and blue dye...... (Patent Blue V) injected peritumorally. Lymphoscintigraphy was not performed. The SLN was successfully identified in 78 out of 80 patients (97.5%); 43 patients (54%) were found to have metastatic disease. In 33 patients (77%) the SLN was the only node involved. No false-negative nodes were found, defined...... as SLNs that tested negative but with higher nodes that tested positive. If SLN biopsy is accepted as a routine procedure and when the exact indications are defined, the method described probably could be offered to the majority of breast cancer patients....

Scintigraphic study of palpable breast nodes with 99m Tc-tetrofosmin

International Nuclear Information System (INIS)

Pellini, Marcos Pinto; Fonseca, Lea Mirian Barbosa da; Amarante Junior, Jose Luiz de Medeiros; Fabricio, Maria Ines Menescal

1998-01-01

In Brazil, breast carcinoma has the greater incidence among women. In 1996, about 31,210 new cases were diagnosed. The purpose of this study is to determine if 99m technetium-tetrofosmin preferentially concentrates within malignant palpable breast nodes, distinguishing them from the benign lumps. Fifth-four consecutive and unsolicited women, mean age 47.5 +- 10.7 years, with palpable nodes in breast, underwent breast scintigraphy with 99m technetium-tetrofosmin and excisional biopsy or fine needle puncture within interval eight weeks. Histopathologic studies demonstrated 13 cysts, 1 cyst with local inflammation, 11 fibroadenoma, 2 fibrodysplasias, 3 fibroadenomas with high cellularity, 1 fibrocystic change with local inflammation, 23 invasive intraductal carcinomas and 1 invasive lobular carcinoma. The nodes ranged from 10 to 100 mm in greater diameter. The scintigraphic study yielded 30 true-negative cases, 24 true-positives, no false-negative and 1 false-positive. This case was a fibrocystic lump with local inflammation. Two patients had metastases in axillary lymph nodes, well detected in scintigraphy. The statistic analysis showed: sensitivity, 100%; specificity, 96.8%; accuracy, 98.2%; negative predictive value, 100%; positive predictive value, 96.0%. Nonparametric tests of Fisher and Chi-square rejected the antithesis at a confidence interval of 99.9% (p 99m technetium-tetrofosmin preferentially concentrates in malignant palpable breast nodes and can help to distinguish them from the benign tumors with with very high accuracy. (author)

Expression of aurora kinase A is associated with metastasis-free survival in node-negative breast cancer patients

International Nuclear Information System (INIS)

Siggelkow, Wulf; Koelbl, Heinz; Gehrmann, Mathias; Marchan, Rosemarie; Cadenas, Cristina; Hengstler, Jan G; Schmidt, Marcus; Boehm, Daniel; Gebhard, Susanne; Battista, Marco; Sicking, Isabel; Lebrecht, Antje; Solbach, Christine; Hellwig, Birte; Rahnenführer, Jörg

2012-01-01

Inhibitors targeting the cell cycle-regulated aurora kinase A (AURKA) are currently being developed. Here, we examine the prognostic impact of AURKA in node-negative breast cancer patients without adjuvant systemic therapy (n = 766). AURKA was analyzed using microarray-based gene-expression data from three independent cohorts of node-negative breast cancer patients. In multivariate Cox analyses, the prognostic impact of age, histological grade, tumor size, estrogen receptor (ER), and HER2 were considered. Patients with higher AURKA expression had a shorter metastasis-free survival (MFS) in the Mainz (HR 1.93; 95% CI 1.34 – 2.78; P < 0.001), Rotterdam (HR 1.95; 95% CI 1.45– 2.63; P<0.001) and Transbig (HR 1.52; 95% CI 1.14–2.04; P=0.005) cohorts. AURKA was also associated with MFS in the molecular subtype ER+/HER2- carcinomas (HR 2.10; 95% CI 1.70–2.59; P<0.001), but not in ER-/HER2- nor in HER2+ carcinomas. In the multivariate Cox regression adjusted to age, grade and tumor size, AURKA showed independent prognostic significance in the ER+/HER2- subtype (HR 1.73; 95% CI 1.24–2.42; P=0.001). Prognosis of patients in the highest quartile of AURKA expression was particularly poor. In addition, AURKA correlated with the proliferation metagene (R=0.880; P<0.001), showed a positive association with grade (P<0.001), tumor size (P<0.001) and HER2 (P<0.001), and was inversely associated with ER status (P<0.001). AURKA is associated with worse prognosis in estrogen receptor positive breast carcinomas. Patients with the highest AURKA expression (>75% percentile) have a particularly bad prognosis and may profit from therapy with AURKA inhibitors

Metabolic Syndrome and Triple-Negative Breast Cancer: A New Paradigm

International Nuclear Information System (INIS)

Davis, A.A.; Kaklamani, V.G.

2012-01-01

Triple-negative breast cancers (TNBCs) are aggressive tumors with poor prognosis compared to other breast cancer subtypes. The evidence linking TNBC with the metabolic syndrome, which consists of central obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension, has emerged from clinical studies and experiments using cell lines and mouse models. Epidemiological studies have associated abdominal obesity with increased incidence of TNBC. Additionally, insulin resistance, dyslipidemia, and hypertension are associated with increased incidence of breast cancer across all subtypes. The insulin-leptin-adiponectin axis has been implicated mechanistically in breast cancer tumorigenesis. Specifically, increased leptin and decreased adiponectin levels disrupt homeostatic signaling pathways involved in cell proliferation, survival, cell-cycle regulation, and angio genesis. Insulin, insulin-like growth factor I (IGF-I), and epidermal growth factor receptor (EGFR) may mediate interactions between these two hormones. Further research will facilitate the development of targeted therapeutics and programs to modify lifestyle factors to modulate the insulin-leptin-adiponectin axis for TNBC

Metabolic Syndrome and Triple-Negative Breast Cancer: A New Paradigm

Energy Technology Data Exchange (ETDEWEB)

Davis, A A; Kaklamani, V G [Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611 (Ukraine)

2012-07-01

Triple-negative breast cancers (TNBCs) are aggressive tumors with poor prognosis compared to other breast cancer subtypes. The evidence linking TNBC with the metabolic syndrome, which consists of central obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension, has emerged from clinical studies and experiments using cell lines and mouse models. Epidemiological studies have associated abdominal obesity with increased incidence of TNBC. Additionally, insulin resistance, dyslipidemia, and hypertension are associated with increased incidence of breast cancer across all subtypes. The insulin-leptin-adiponectin axis has been implicated mechanistically in breast cancer tumorigenesis. Specifically, increased leptin and decreased adiponectin levels disrupt homeostatic signaling pathways involved in cell proliferation, survival, cell-cycle regulation, and angio genesis. Insulin, insulin-like growth factor I (IGF-I), and epidermal growth factor receptor (EGFR) may mediate interactions between these two hormones. Further research will facilitate the development of targeted therapeutics and programs to modify lifestyle factors to modulate the insulin-leptin-adiponectin axis for TNBC

The local lymph node assay: current position in the regulatory classification of skin sensitizing chemicals.

Science.gov (United States)

Basketter, David A; Gerberick, G Frank; Kimber, Ian

2007-01-01

The local lymph node assay (LLNA) is being used increasingly in the identification of skin sensitizing chemicals for regulatory purposes. In the context of new chemicals legislation (REACH) in Europe, it is the preferred assay. The rationale for this is that the LLNA quantitative and objective approach to skin sensitization testing allied with the important animal welfare benefits that the method offers. However, as with certain guinea pig sensitization tests before it, this increasing use also brings experience with an increasingly wide range of industrial and other chemicals where the outcome of the assay does not always necessarily meet with the expectations of those conducting it. Sometimes, the result appears to be a false negative, but rather more commonly, the complaint is that the chemical represents a false positive. Against this background we have here reviewed a number of instances where false positive and false negative results have been described and have sought to reconcile science with expectation. Based on these analyses, it is our conclusion that false positives and false negatives do occur in the LLNA, as they do with any other skin sensitization assay (and indeed with all tests used for hazard identification), and that this occurs for a number of reasons. We further conclude, however, that false positive results in the LLNA, as with the guinea pig maximization test, arise most commonly via failure to distinguish what is scientifically correct from that which is unpalatable. The consequences of this confusion are discussed in the article, particularly in relation to the need to integrate both potency measurement and risk assessments into classification and labelling schemes that aim to manage potential risks to human health.

The role of ultrasound and ultrasound-guided fine needle aspiration biopsy of lymph nodes in patients with skin tumours

International Nuclear Information System (INIS)

Solivetti, Francesco Maria; Elia, Fulvia; Santaguida, Maria Giulia; Guerrisi, Antonino; Visca, Paolo; Cercato, Maria Cecilia; Di Carlo, Aldo

2014-01-01

The primary aim of this study was to evaluate the diagnostic accuracy of ultrasound (US) in the study of superficial lymph nodes during the follow-up of patients surgically treated for skin tumours. The secondary objective was to compare positive cytological results with histological reports. From 2004 to 2011, 480 patients (male/female: 285/195; median age 57 years; prevalent skin tumour: melanoma) underwent US-guided fine-needle aspiration biopsy (FNAB) of suspicious recurrent lymph nodes. An expert radiologist first performed US testing of the lymph nodes, expressing either a negative or positive outcome of the test. Subsequently, US-guided FNAB was performed. FNAB positive patients were subjected to lymphadenectomy; the patients who tested negative underwent the follow-up. The size of lymph nodes was ≤ 2 cm in 90% of cases. Out of the 336 (70%) US “positive” patients, 231 (68.8%) were FNAB positives. Out of the 144 (30%) US “negatives”, 132 (91.7%) were FNAB negatives. The sensitivity and specificity of the US were 95% and 55.7%, respectively; the negative predictive value was 91.7% and the positive predictive value was 68.8%. Definitive histological results confirmed FNAB positivity in 97.5% of lymphadenectomies. US is a sensitive method in the evaluation of superficial lymph nodes during the follow-up of patients with skin tumours. High positive predictive value of cytology was confirmed

[The lymph nodes imprint for the diagnosis of lymphoid neoplasms].

Science.gov (United States)

Peniche-Alvarado, Carolina; Ramos-Peñafiel, Christian Omar; Martínez-Murillo, Carlos; Romero-Guadarrama, Mónica; Olarte-Carrillo, Irma; Rozen-Fuller, Etta; Martínez-Tovar, Adolfo; Collazo-Jaloma, Juan; Mendoza-García, Carlos Alberto

2013-01-01

lymphoma is the most frequent lymphoid neoplasm in our country. Its diagnosis is based on histopathological findings. The lymph node imprint has been used for more than 40 years. The aim was to establish the sensitivity, specificity, positive predictive value and negative predictive value of lymph node imprint and estimate the inter-observer rate. we did an observational, retrospective, prolective study, based on the lymph node imprint obtained by excisional biopsies over a period of 6 years. the inclusion criteria was met on 199 samples, 27.1 % were considered as reactive (n = 54), 16.1 % Hodgkin lymphoma (n = 32), 40.2 % (n = 80) non-Hodgkin lymphoma and 16.6 % (n = 33) as metastatic carcinoma. Comparing with the final histopathology report, the sensitivity and specificity of lymph node imprint were 88 % (0.81-0.95) and 64 % (0.55-0.73) respectively, the positive predictive value was 67 % (0.59-0.76) and the negative predictive value was 86 % (0.79-0.94). The interobserver kappa index was 0.467. the lymph node imprint remains as a useful tool for the diagnosis of lymphoid neoplasm. The agreement between observers was acceptable.

Tumor-initiating CD49f cells are a hallmark of chemoresistant triple negative breast cancer.

Science.gov (United States)

Gomez-Miragaya, Jorge; González-Suárez, Eva

2017-01-01

Taxanes are mainstay treatment of triple negative breast cancer (TNBC) patients but resistance often develops. Using TNBC patient-derived orthoxenografts (PDX) we have recently discovered that a CD49f+ chemoresistant population with tumor-initiating ability is present in sensitive tumors and expands in tumors that have acquired resistance. Importantly, sensitivity to taxanes is recovered after long-term drug interruption. The characterization of this chemoresistant CD49f+ cells provides a unique opportunity to identify novel targets for the treatment of chemoresistant TNBC.

Influence of internal mammary node irradiation on long-term outcome and contralateral breast cancer incidence in node-negative breast cancer patients

International Nuclear Information System (INIS)

Courdi, Adel; Chamorey, Emmanuel; Ferrero, Jean-Marc; Hannoun-Lévi, Jean-Michel

2013-01-01

Background and purpose: There is no general consensus concerning irradiation (RT) of internal mammary nodes (IMN) in axillary node-negative breast cancer. Based on a large series of patients treated in a single institute and followed up for a long period of time, we looked at the influence of IMN RT on late outcome of these patients as well as the development of contralateral breast cancer (CBC). Patients and methods: The study was based on 1630 node-negative breast cancer patients treated in our institution between 1975 and 2008 with primary conservative surgery and axillary dissection or sentinel node examination. All patients received post-operative breast RT. IMN RT was more frequent in inner or central tumours. Kaplan–Meier (K–M) overall survival (OS), cancer-specific survival (CSS), and disease-free survival (DFS) according to IMN RT were calculated for all patients and for patients with inner/central tumours. The K–M rate of contralateral breast cancer (CBC) was also analysed and correlated with IMN RT. Results: Prognostic variables such as tumour size, histological grade, and hormone receptors were not significantly different in the groups having received IMN RT or not. Considering all patients, OS was strictly comparable in the 2 groups: 10-year values were 85% (IMN RT) and 86% (no IMN RT), respective values at 20 years were 66.6% and 61.0% (p = 0.95). However, in patients presenting with inner/central tumours, OS was significantly improved in the IMN RT group with respective values of 92.5% and 87.2% at 10 years, and 80.2% and 63.3% at 20 years: Hazard ratio (HR) = 0.56 (0.37–0.85); p = 0.0052. Again, CSS was improved in patients with inner/central tumours having received IMN RT, with 20-year rates of 89.5% versus 79.1% in patients not receiving IMN RT (p = 0.047). No difference in DFS was noticed. The actuarial rate of CBC development was comparable between patients having received IMN RT and other patients. However, considering only patients

The value of STIR sequence in the characterization of mediastinal lymph nodes

Directory of Open Access Journals (Sweden)

Aylin Okur

2013-12-01

Full Text Available INTRODUCTION: To investigate availability of Short Time Inversion Recovery Turbo Spin Echo Magnetic Resonance imaging (STIR TSE MRI in the detection of mediastinal lymph nodes and in the distinguishing malign and benign lymph nodes detected in cases with pulmonary lesions. METHODS: Overall, 46 patients having mediastinal lymph nodes with confirmed or suspected lung cancer were included to the study. All patients underwent STIR TSE MR imaging before mediastinoscopy. Lymph nodes were assessed by signal characteristics on STIR TSE MRI. The results of histopathological evaluation and STIR TSE MRI were compared after mediastinoscopy. As data were qualitative, distributions were expressed as percentage and chi-square test was used to determine the difference between variables. RESULTS: Overall, 92 lymph nodes were analyzed. When a comparison was made between malign and benign lymph nodes, a significant difference was found between STIR MRI signal properties of lymph nodes and lymph node size. The specificity, sensitivity, positive predictive value and negative predictive value of STIR TSE MRI were estimated as 75.0%, 75.0%, 61.5% and 83.3%, respectively. DISCUSSION AND CONCLUSION: Although the negative predictive value is high in STIR TSE MRI, it has a low positive predictive value. Thus, the case may directly undergo surgery without performing mediastinoscopy when no malign lymph node is detected in STIR TSE MRI, while mediastinoscopy is warranted when a malign lymph node is detected.

Localization studies of metastatic axillary lymph node by radioimmunoimmaging with monoclonal antibody C50 in breast cancer

International Nuclear Information System (INIS)

Feng Jue; Gao Yougong

1993-01-01

Eleven patients with breast cancer and 2 normal controls (26 axillary lymph-nodes) were studied by the radio immunoimaging with 131 I labelled anti-CEA monoclonal antibody C 50 . Among them, the imaging was positive in 8 patients and negative in 3 patients. 7 of the 8 positive patients were proven by the pathological examination of postoperative lymph nodes. Other one had proved with the presence of CEA-antigen and antigen-antibody immuno complexes in the lymphoid sinus by immuno histochemistry. Cancer cell was not found by pathology in the axillary lymph node of 3 negative imaging patients. 2 normal controls was also negative

Selective sentinel lymph node biopsy in papillary thyroid carcinoma in patients with no preoperative evidence of lymph node metastasis.

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González, Óscar; Zafon, Carles; Caubet, Enric; García-Burillo, Amparo; Serres, Xavier; Fort, José Manuel; Mesa, Jordi; Castell, Joan; Roca, Isabel; Ramón Y Cajal, Santiago; Iglesias, Carmela

2017-10-01

Lymphadenectomy is recommended during surgery for papillary thyroid carcinoma when there is evidence of cervical lymph node metastasis (therapeutic) or in high-risk patients (prophylactic) such as those with T3 and T4 tumors of the TNM classification. Selective sentinel lymph node biopsy may improve preoperative diagnosis of nodal metastases. To analyze the results of selective sentinel lymph node biopsy in a group of patients with papillary thyroid carcinoma and no evidence of nodal involvement before surgery. A retrospective, single-center study in patients with papillary thyroid carcinoma and no clinical evidence of lymph node involvement who underwent surgery between 2011 and 2013. The sentinel node was identified by scintigraphy. When the sentinel node was positive, the affected compartment was removed, and when sentinel node was negative, central lymph node dissection was performed. Forty-three patients, 34 females, with a mean age of 52.3 (±17) years, were enrolled. Forty-six (27%) of the 170 SNs resected from 24 (55.8%) patients were positive for metastasis. In addition, 94 (15.6%) out of the 612 lymph nodes removed in the lymphadenectomies were positive for metastases. Twelve of the 30 (40%) low risk patients (cT1N0 and cT2N0) changed their stage to pN1, whereas 12 of 13 (92%) high risk patients (cT3N0 and cT4N0) changed to pN1 stage. Selective sentinel lymph node biopsy changes the stage of more than 50% of patients from cN0 to pN1. This confirms the need for lymph node resection in T3 and T4 tumors, but reveals the presence of lymph node metastases in 40% of T1-T2 tumors. Copyright © 2017 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

Circulating tumor DNA for triple-negative breast cancer diagnosis and treatment decisions.

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Saliou, Adrien; Bidard, François-Clément; Lantz, Olivier; Stern, Marc-Henri; Vincent-Salomon, Anne; Proudhon, Charlotte; Pierga, Jean-Yves

2016-01-01

Triple-negative breast cancer (TNBC) is a highly aggressive disease characterized by a high number of relapses and poor overall survival. The heterogeneity of the disease and the limited treatment options compared to other breast cancer subtypes mainly explain these clinical outcomes. New biomarkers are urgently needed to improve the management of TNBC. Circulating tumor DNA, identified by tumor-related molecular alterations, could be used in the context of non-invasive "liquid biopsy" and help in TNBC diagnosis and treatment decisions. In this review, we discuss the key issues related to the potential of circulating tumor DNA to improve the management of this disease and the future steps to overcome before its implementation into clinical routine within the next 5 years.

Effects of salience-network-node neurofeedback training on affective biases in major depressive disorder.

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Hamilton, J Paul; Glover, Gary H; Bagarinao, Epifanio; Chang, Catie; Mackey, Sean; Sacchet, Matthew D; Gotlib, Ian H

2016-03-30

Neural models of major depressive disorder (MDD) posit that over-response of components of the brain's salience network (SN) to negative stimuli plays a crucial role in the pathophysiology of MDD. In the present proof-of-concept study, we tested this formulation directly by examining the affective consequences of training depressed persons to down-regulate response of SN nodes to negative material. Ten participants in the real neurofeedback group saw, and attempted to learn to down-regulate, activity from an empirically identified node of the SN. Ten other participants engaged in an equivalent procedure with the exception that they saw SN-node neurofeedback indices from participants in the real neurofeedback group. Before and after scanning, all participants completed tasks assessing emotional responses to negative scenes and to negative and positive self-descriptive adjectives. Compared to participants in the sham-neurofeedback group, from pre- to post-training, participants in the real-neurofeedback group showed a greater decrease in SN-node response to negative stimuli, a greater decrease in self-reported emotional response to negative scenes, and a greater decrease in self-reported emotional response to negative self-descriptive adjectives. Our findings provide support for a neural formulation in which the SN plays a primary role in contributing to negative cognitive biases in MDD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Exercise and dietary advice intervention for survivors of triple-negative breast cancer: effects on body fat, physical function, quality of life, and adipokine profile.

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Swisher, Anne K; Abraham, Jame; Bonner, Daniel; Gilleland, Diana; Hobbs, Gerald; Kurian, Sobha; Yanosik, Mary Anne; Vona-Davis, Linda

2015-10-01

Regular exercise and healthy eating are routinely recommended for breast cancer survivors, and past studies show benefits in quality of life and decreased inflammation. However, this has not been tested specifically in triple-negative breast cancer survivors. Increasing physical activity and losing body fat are thought to positively affect inflammatory biomarkers that have been associated with breast cancer. Therefore, the primary purpose of this study was to determine if participation in an exercise and dietary counseling program can improve body fat, physical function, and quality of life in survivors of this aggressive breast cancer. Secondarily, we sought to determine if participation in the program had beneficial effects on obesity-related markers of the adipokine profile. Sixty-six survivors of triple-negative breast cancer with BMI >25 were invited to participate. Twenty-eight enrolled and 23 completed the randomized, controlled trial (13 intervention, 10 control). Moderate-intensity aerobic exercise (150 min per week, for 12 weeks) and diet counseling were compared to usual care, education only. The primary outcome of interest was weight loss (body mass, BMI, % fat), and secondary outcomes included physical function (exercise capacity), quality of life (Function After Cancer Therapy-Breast (FACT-B)), cytokines (C-reactive protein (CRP), TNF-α, IL-6), and adipokine profile (leptin, adiponectin, insulin). Participants in the program lost more body fat (2.4 % loss vs. 0.4 % gain, p life (FACT-B total score +14 pts) and decreased sedentary time but did not improve peak exercise capacity. The intervention had no effect on serum cytokines and adipokines after 12 weeks in the program. However, serum leptin and adiponectin and their ratio were significantly correlated with BMI in the intervention group (p life in survivors of triple-negative breast cancer. BMI was associated with favorable changes in leptin and adiponectin which may reflect a change in adiposity

ONC201 activates ER stress to inhibit the growth of triple-negative breast cancer cells

OpenAIRE

Yuan, Xun; Kho, Dhonghyo; Xu, Jing; Gajan, Ambikai; Wu, Kongming; Wu, Gen Sheng

2017-01-01

ONC201 was previously identified as a first-in-class antitumor agent and small-molecule inducer of the TRAIL (tumor necrosis factor-related apoptosis-inducing ligand) gene that induces apoptosis in cancer cells. ONC201 has a safety profile and is currently in phase II clinical trials for the treatment of various malignancies. In the current study, we examine the effect of ONC201 on triple-negative breast cancer cells (TNBC), a subtype of breast cancer that is sensitive to TRAIL. We find that ...

Number of negative lymph nodes as a prognostic factor in esophageal squamous cell carcinoma.

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Ma, Mingquan; Tang, Peng; Jiang, Hongjing; Gong, Lei; Duan, Xiaofeng; Shang, Xiaobin; Yu, Zhentao

2017-10-01

The aim of this study is to investigate the number of negative lymph nodes (NLNs) as a prognostic factor for survival in patients with resected esophageal squamous cell carcinoma. A total of 381 esophageal squamous cell carcinoma patients who had underwent surgical resection as the primary treatment was enrolled into this retrospective study. The impact of number of NLNs on patient's overall survival was assessed and compared with the factors among the current tumor-nodes-metastasis (TNM) staging system. The number of NLNs was closely related to the overall survival, and the 5-year survival rate was 45.4% for number of NLNs of >20 (142 cases) and 26.4% for NLNs ≤ 20 (239 cases) (P = 0.001). In multivariate survival analysis, the number of NLNs remained an independent prognostic factor (P = 0.002) as did the other current TNM factors. For subgroup analysis, the predictive value of number of NLNs was significant in patients with T3 or T4 disease (P = 0.001) and patients with N1 and N2-3 disease (P = 0.025, 0.043), but not in patients with T1 or T2 disease or patients with N0 disease. The number of NLNs, which represents the extent of lymphadenectomy for esophageal squamous cell carcinoma, could impact the overall survival of patients with resected esophageal squamous cell carcinoma, especially among those with nodal-positive disease and advanced T-stage tumor. © 2016 John Wiley & Sons Australia, Ltd.

The spreading of opposite opinions on online social networks with authoritative nodes

Science.gov (United States)

Yan, Shu; Tang, Shaoting; Pei, Sen; Jiang, Shijin; Zhang, Xiao; Ding, Wenrui; Zheng, Zhiming

2013-09-01

The study of opinion dynamics, such as spreading and controlling of rumors, has become an important issue on social networks. Numerous models have been devised to describe this process, including epidemic models and spin models, which mainly focus on how opinions spread and interact with each other, respectively. In this paper, we propose a model that combines the spreading stage and the interaction stage for opinions to illustrate the process of dispelling a rumor. Moreover, we set up authoritative nodes, which disseminate positive opinion to counterbalance the negative opinion prevailing on online social networking sites. With analysis of the relationship among positive opinion proportion, opinion strength and the density of authoritative nodes in networks with different topologies, we demonstrate that the positive opinion proportion grows with the density of authoritative nodes until the positive opinion prevails in the entire network. In particular, the relationship is linear in homogeneous topologies. Besides, it is also noteworthy that initial locations of the negative opinion source and authoritative nodes do not influence positive opinion proportion in homogeneous networks but have a significant impact on heterogeneous networks. The results are verified by numerical simulations and are helpful to understand the mechanism of two different opinions interacting with each other on online social networking sites.

Clinical outcomes in ER+ HER2 -node-positive breast cancer patients who were treated according to the Recurrence Score results: evidence from a large prospectively designed registry.

Science.gov (United States)

Stemmer, Salomon M; Steiner, Mariana; Rizel, Shulamith; Geffen, David B; Nisenbaum, Bella; Peretz, Tamar; Soussan-Gutman, Lior; Bareket-Samish, Avital; Isaacs, Kevin; Rosengarten, Ora; Fried, Georgeta; McCullough, Debbie; Svedman, Christer; Shak, Steven; Liebermann, Nicky; Ben-Baruch, Noa

2017-01-01

The Recurrence Score® is increasingly used in node-positive ER+ HER2-negative breast cancer. This retrospective analysis of a prospectively designed registry evaluated treatments/outcomes in node-positive breast cancer patients who were Recurrence Score-tested through Clalit Health Services from 1/2006 through 12/2011 ( N  = 709). Medical records were reviewed to verify treatments/recurrences/survival. Median follow-up, 5.9 years; median age, 62 years; 53.9% grade 2; 69.8% tumors ≤ 2 cm; 84.5% invasive ductal carcinoma; 42.0% N1mi, and 37.2%/15.5%/5.2% with 1/2/3 positive nodes; 53.4% Recurrence Score < 18, 36.4% Recurrence Score 18-30, and 10.2% Recurrence Score ≥ 31. Overall, 26.9% received adjuvant chemotherapy: 7.1%, 39.5%, and 86.1% in the Recurrence Score < 18, 18-30, and ≥ 31 group, respectively. The 5-year Kaplan-Meier estimates for distant recurrence were 3.2%, 6.3%, and 16.9% for these respective groups and the corresponding 5-year breast cancer death estimates were 0.5%, 3.4%, and 5.7%. In Recurrence Score < 18 patients, 5-year distant-recurrence rates for N1mi/1 positive node/2-3 positive nodes were 1.2%/4.4%/5.4%. As patients were not randomized to treatment and treatment decision is heavily influenced by Recurrence Score, analysis of 5-year distant recurrence by chemotherapy use was exploratory and should be interpreted cautiously: In Recurrence Score < 18, recurrence rate was 7.7% in chemotherapy-treated ( n  = 27) and 2.9% in chemotherapy-untreated patients ( n  = 352); P  = 0.245. In Recurrence Score 18-30, recurrence rate in chemotherapy-treated patients ( n  = 102) was significantly lower than in untreated patients ( n  = 156) (1.0% vs. 9.7% P  = 0.019); in Recurrence Score ≤ 25 (the RxPONDER study cutoff), recurrence rate was 2.3% in chemotherapy-treated ( n  = 89) and 4.4% in chemotherapy-untreated patients ( n  = 488); P  = 0.521. In conclusion, our findings

Positive and negative gain exceeding unity magnitude in silicon quantum well metal-oxide-semiconductor transistors

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Hu, Gangyi; Wijesinghe, Udumbara; Naquin, Clint; Maggio, Ken; Edwards, H. L.; Lee, Mark

2017-10-01

Intrinsic gain (AV) measurements on Si quantum well (QW) n-channel metal-oxide-semiconductor (NMOS) transistors show that these devices can have |AV| > 1 in quantum transport negative transconductance (NTC) operation at room temperature. QW NMOS devices were fabricated using an industrial 45 nm technology node process incorporating ion implanted potential barriers to define a lateral QW in the conduction channel under the gate. While NTC at room temperature arising from transport through gate-controlled QW bound states has been previously established, it was unknown whether the quantum NTC mechanism could support gain magnitude exceeding unity. Bias conditions were found giving both positive and negative AV with |AV| > 1 at room temperature. This result means that QW NMOS devices could be useful in amplifier and oscillator applications.

The PIKfyve–ArPIKfyve–Sac3 triad in human breast cancer: Functional link between elevated Sac3 phosphatase and enhanced proliferation of triple negative cell lines

International Nuclear Information System (INIS)

Ikonomov, Ognian C.; Filios, Catherine; Sbrissa, Diego; Chen, Xuequn; Shisheva, Assia

2013-01-01

Highlights: •We assess PAS complex proteins and phosphoinositide levels in breast cancer cells. •Sac3 and ArPIKfyve are markedly elevated in triple-negative breast cancer cells. •Sac3 silencing inhibits proliferation in triple-negative breast cancer cell lines. •Phosphoinositide profiles are altered in breast cancer cells. •This is the first evidence linking high Sac3 with breast cancer cell proliferation. -- Abstract: The phosphoinositide 5-kinase PIKfyve and 5-phosphatase Sac3 are scaffolded by ArPIKfyve in the PIKfyve–ArPIKfyve–Sac3 (PAS) regulatory complex to trigger a unique loop of PtdIns3P–PtdIns(3,5)P 2 synthesis and turnover. Whereas the metabolizing enzymes of the other 3-phosphoinositides have already been implicated in breast cancer, the role of the PAS proteins and the PtdIns3P–PtdIns(3,5)P 2 conversion is unknown. To begin elucidating their roles, in this study we monitored the endogenous levels of the PAS complex proteins in cell lines derived from hormone-receptor positive (MCF7 and T47D) or triple-negative breast cancers (TNBC) (BT20, BT549 and MDA-MB-231) as well as in MCF10A cells derived from non-tumorigenic mastectomy. We report profound upregulation of Sac3 and ArPIKfyve in the triple negative vs. hormone-sensitive breast cancer or non-tumorigenic cells, with BT cell lines showing the highest levels. siRNA-mediated knockdown of Sac3, but not that of PIKfyve, significantly inhibited proliferation of BT20 and BT549 cells. In these cells, knockdown of ArPIKfyve had only a minor effect, consistent with a primary role for Sac3 in TNBC cell proliferation. Intriguingly, steady-state levels of PtdIns(3,5)P 2 in BT20 and T47D cells were similar despite the 6-fold difference in Sac3 levels between these cell lines. However, steady-state levels of PtdIns3P and PtdIns5P, both regulated by the PAS complex, were significantly reduced in BT20 vs. T47D or MCF10A cell lines, consistent with elevated Sac3 affecting directly or indirectly the

The efficacy of the Triple P-Positive Parenting Program in improving parenting and child behavior: a comparison with two other treatment conditions.

Science.gov (United States)

Bodenmann, Guy; Cina, Annette; Ledermann, Thomas; Sanders, Matthew R

2008-04-01

The aim of this randomized controlled trial was to evaluate the efficacy of an evidence-based parenting program (the Triple P-Positive Parenting Program), intending to improve parenting skills and children's well-being. Parents participating in a Group Triple P program (n=50 couples) were compared with parents of a non-treated control group (n=50 couples) and parents participating in a marital distress prevention program (couples coping enhancement training (CCET)) (n=50 couples). The two major goals of this study were (a) to evaluate the efficacy of Triple P compared with the two other treatment conditions over a time-span of 1 year and (b) to answer the question whether this program that was developed in Australia is culturally accepted by Swiss parents. Results revealed that Triple P was effective with Swiss families. Mothers of the Triple P group showed significant improvements in parenting, parenting self-esteem, and a decrease in stressors related to parenting. Women trained in Triple P also reported significantly lower rates of child's misbehavior than women of the two other conditions. However, in men only a few significant results were found. Positive effects of the relationship training (CCET) were somewhat lower than those for the Triple P. These findings are further discussed.

Risk Factors for Regional Nodal Relapse in Breast Cancer Patients With One to Three Positive Axillary Nodes

Energy Technology Data Exchange (ETDEWEB)

Yates, Lucy, E-mail: lucy.yates@gstt.nhs.uk [Guy' s, King' s, St Thomas' Cancer Centre, Guy' s Hospital, London (United Kingdom); Kirby, Anna [Guy' s, King' s, St Thomas' Cancer Centre, Guy' s Hospital, London (United Kingdom); Department of Clinical Oncology, Royal Marsden Hospital, Sutton (United Kingdom); Crichton, Siobhan [Department of Statistics, Kings College London (United Kingdom); Gillett, Cheryl [Breast Pathology, Kings College London (United Kingdom); Cane, Paul [Department of Histopathology, Guy' s and St Thomas' Foundation Trust, London (United Kingdom); Fentiman, Ian; Sawyer, Elinor [Guy' s, King' s, St Thomas' Cancer Centre, Guy' s Hospital, London (United Kingdom)

2012-04-01

Purpose: In many centers, supraclavicular fossa radiotherapy (SCF RT) is not routinely offered to breast cancer patients with one to three positive lymph nodes. We aimed to identify a subgroup of these patients who are at high risk of supra or infraclavicular fossa relapse (SCFR) such that they can be offered SCFRT at the time of diagnosis to improve long term locoregional control. Methods and Materials: We performed a retrospective analysis of the pathological features of 1,065 cases of invasive breast cancer with one to three positive axillary lymph nodes. Patients underwent radical breast conserving surgery or mastectomy. A total of 45% of patients received adjuvant chest wall/breast RT. No patients received adjuvant SCFRT. The primary outcome was SCFR. Secondary outcomes were chest wall/breast recurrence, distant metastasis, all death, and breast-cancer specific death. Kaplan-Meier estimates were used to calculate actuarial event rates and survival functions compared using log-rank tests. Multivariate analyses (MVA) of factors associated with outcome were conducted using Cox proportional hazards models. Results: Median follow-up was 9.7 years. SCFR rate was 9.2%. Median time from primary diagnosis to SCFR was 3.4 years (range, 0.7-14.4 years). SCFR was associated with significantly lower 10-year survival (18% vs. 65%; p < 0.001). Higher grade and number of positive lymph nodes were the most significant predictors of SCFR on MVA (p < 0.001). 10 year SCFR rates were less than 1% in all patients with Grade 1 cancers compared with 30% in those having Grade 3 cancers with three positive lymph nodes. Additional factors associated with SCFR on univariate analysis but not on MVA included larger nodal deposits (p = 0.002) and proportion of positive nodes (p = 0.003). Conclusions: Breast cancer patients with one to three positive lymph nodes have a heterogenous risk of SCFR. Patients with two to three positive axillary nodes and/or high-grade disease may warrant

Intratumoral bidirectional transitions between epithelial and mesenchymal cells in triple-negative breast cancer.

Science.gov (United States)

Yamamoto, Mizuki; Sakane, Kota; Tominaga, Kana; Gotoh, Noriko; Niwa, Takayoshi; Kikuchi, Yasuko; Tada, Keiichiro; Goshima, Naoki; Semba, Kentaro; Inoue, Jun-Ichiro

2017-06-01

Epithelial-mesenchymal transition (EMT) and its reverse process, mesenchymal-epithelial transition MET, are crucial in several stages of cancer metastasis. Epithelial-mesenchymal transition allows cancer cells to move to proximal blood vessels for intravasation. However, because EMT and MET processes are dynamic, mesenchymal cancer cells are likely to undergo MET transiently and subsequently re-undergo EMT to restart the metastatic process. Therefore, spatiotemporally coordinated mutual regulation between EMT and MET could occur during metastasis. To elucidate such regulation, we chose HCC38, a human triple-negative breast cancer cell line, because HCC38 is composed of epithelial and mesenchymal populations at a fixed ratio even though mesenchymal cells proliferate significantly more slowly than epithelial cells. We purified epithelial and mesenchymal cells from Venus-labeled and unlabeled HCC38 cells and mixed them at various ratios to follow EMT and MET. Using this system, we found that the efficiency of EMT is approximately an order of magnitude higher than that of MET and that the two populations significantly enhance the transition of cells from the other population to their own. In addition, knockdown of Zinc finger E-box-binding homeobox 1 (ZEB1) or Zinc finger protein SNAI2 (SLUG) significantly suppressed EMT but promoted partial MET, indicating that ZEB1 and SLUG are crucial to EMT and MET. We also show that primary breast cancer cells underwent EMT that correlated with changes in expression profiles of genes determining EMT status and breast cancer subtype. These changes were very similar to those observed in EMT in HCC38 cells. Consequently, we propose HCC38 as a suitable model to analyze EMT-MET dynamics that could affect the development of triple-negative breast cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Histologic heterogeneity of triple negative breast cancer: A National Cancer Centre Database analysis.

Science.gov (United States)

Mills, Matthew N; Yang, George Q; Oliver, Daniel E; Liveringhouse, Casey L; Ahmed, Kamran A; Orman, Amber G; Laronga, Christine; Hoover, Susan J; Khakpour, Nazanin; Costa, Ricardo L B; Diaz, Roberto

2018-06-02

Triple negative breast cancer (TNBC) is an aggressive disease, but recent studies have identified heterogeneity in patient outcomes. However, the utility of histologic subtyping in TNBC has not yet been well-characterised. This study utilises data from the National Cancer Center Database (NCDB) to complete the largest series to date investigating the prognostic importance of histology within TNBC. A total of 729,920 patients (pts) with invasive ductal carcinoma (IDC), metaplastic breast carcinoma (MBC), medullary breast carcinoma (MedBC), adenoid cystic carcinoma (ACC), invasive lobular carcinoma (ILC) or apocrine breast carcinoma (ABC) treated between 2004 and 2012 were identified in the NCDB. Of these, 89,222 pts with TNBC that received surgery were analysed. Kaplan-Meier analysis, log-rank testing and multivariate Cox proportional hazards regression were utilised with overall survival (OS) as the primary outcome. MBC (74.1%), MedBC (60.6%), ACC (75.7%), ABC (50.1%) and ILC (1.8%) had significantly different proportions of triple negativity when compared to IDC (14.0%, p < 0.001). TNBC predicted an inferior OS in IDC (p < 0.001) and ILC (p < 0.001). Lumpectomy and radiation (RT) were more common in MedBC (51.7%) and ACC (51.5%) and less common in MBC (33.1%) and ILC (25.4%), when compared to IDC (42.5%, p < 0.001). TNBC patients with MBC (HR 1.39, p < 0.001), MedBC (HR 0.42, p < 0.001) and ACC (HR 0.32, p = 0.003) differed significantly in OS when compared to IDC. Our results indicate that histologic heterogeneity in TNBC significantly informs patient outcomes and thus, has the potential to aid in the development of optimum personalised treatments. Copyright © 2018 Elsevier Ltd. All rights reserved.

Axillary lymph node metastases in patients with breast carcinomas: assessment with nonenhanced versus uspio-enhanced MR imaging.

Science.gov (United States)

Memarsadeghi, Mazda; Riedl, Christopher C; Kaneider, Andreas; Galid, Arik; Rudas, Margaretha; Matzek, Wolfgang; Helbich, Thomas H

2006-11-01

To prospectively assess the accuracy of nonenhanced versus ultrasmall superparamagnetic iron oxide (USPIO)-enhanced magnetic resonance (MR) imaging for depiction of axillary lymph node metastases in patients with breast carcinoma, with histopathologic findings as reference standard. The study was approved by the university ethics committee; written informed consent was obtained. Twenty-two women (mean age, 60 years; range, 40-79 years) with breast carcinomas underwent nonenhanced and USPIO-enhanced (2.6 mg of iron per kilogram of body weight intravenously administered) transverse T1-weighted and transverse and sagittal T2-weighted and T2*-weighted MR imaging in adducted and elevated arm positions. Two experienced radiologists, blinded to the histopathologic findings, analyzed images of axillary lymph nodes with regard to size, morphologic features, and USPIO uptake. A third independent radiologist served as a tiebreaker if consensus between two readers could not be reached. Visual and quantitative analyses of MR images were performed. Sensitivity, specificity, and accuracy values were calculated. To assess the effect of USPIO after administration, signal-to-noise ratio (SNR) changes were statistically analyzed with repeated-measurements analysis of variance (mixed model) for MR sequences. At nonenhanced MR imaging, of 133 lymph nodes, six were rated as true-positive, 99 as true-negative, 23 as false-positive, and five as false-negative. At USPIO-enhanced MR imaging, 11 lymph nodes were rated as true-positive, 120 as true-negative, two as false-positive, and none as false-negative. In two metastatic lymph nodes in two patients with more than one metastatic lymph node, a consensus was not reached. USPIO-enhanced MR imaging revealed a node-by-node sensitivity, specificity, and accuracy of 100%, 98%, and 98%, respectively. At USPIO-enhanced MR imaging, no metastatic lymph nodes were missed on a patient-by-patient basis. Significant interactions indicating differences

Define the Twist ATX LPAR1 Signaling Axis in Promoting Obesity Associated Triple Negative Breast Cancer

Science.gov (United States)

2017-05-01

with the research as presented in the original proposal and as defined in the statement of work . 6. Products We have generated mice with tissue...University of Kentucky College of Medicine 5e. TASK NUMBER E-Mail: a.j.morris@uky.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES...14. ABSTRACT Breast cancer remains the second leading cause of cancer‐related death in women worldwide. Triple negative breast cancer (TNBC) carries a

Define the Twist-ATX-LPAR1 Signaling Axis in Promoting Obesity Associated Triple Negative Breast Cancer

Science.gov (United States)

2017-05-01

original proposal and as defined in the statement of work . 6. Products We have generated mice with tissue specific inactivation of the ENPP2 gene in...Kentucky College of Medicine 5e. TASK NUMBER E-Mail: yiwei.lin@uky.edu 5f. WORK UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8...ABSTRACT Breast cancer remains the second leading cause of cancer‐related death in women worldwide. Triple negative breast cancer (TNBC) carries a poorer

Carnosol induces ROS-mediated beclin1-independent autophagy and apoptosis in triple negative breast cancer.

Directory of Open Access Journals (Sweden)

Yusra Al Dhaheri

Full Text Available In this study we investigated the in vitro and in vivo anticancer effect of carnosol, a naturally occurring polyphenol, in triple negative breast cancer.We found that carnosol significantly inhibited the viability and colony growth induced G2 arrest in the triple negative MDA-MB-231. Blockade of the cell cycle was associated with increased p21/WAF1 expression and downregulation of p27. Interestingly, carnosol was found to induce beclin1-independent autophagy and apoptosis in MDA-MB-231 cells. The coexistence of both events, autophagy and apoptosis, was confirmed by electron micrography. Induction of autophagy was found to be an early event, detected within 3 h post-treatment, which subsequently led to apoptosis. Carnosol treatment also caused a dose-dependent increase in the levels of phosphorylated extracellular signal-regulated kinase 1 and 2 (pERK1/2. Moreover, we show that carnosol induced DNA damage, reduced the mitochondrial potential and triggered the activation of the intrinsic and extrinsic apoptotic pathway. Furthermore, we found that carnosol induced a dose-dependent generation of reactive oxygen species (ROS and inhibition of ROS by tiron, a ROS scavenger, blocked the induction of autophagy and apoptosis and attenuated DNA damage. To our knowledge, this is the first report to identify the induction of autophagy by carnosol.In conclusion our findings provide strong evidence that carnosol may be an alternative therapeutic candidate against the aggressive form of breast cancer and hence deserves more exploration.

Comparison of systematic mediastinal lymph node dissection versus systematic sampling for lung cancer staging and completeness of surgery.

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Wu, Nan; Yan, Shi; Lv, Chao; Feng, Yuan; Wang, Yuzhao; Zhang, Lijian; Yang, Yue

2011-12-01

This self-controlled prospective study was designed to investigate the efficacy of systematic sampling (SS), compared with systematic mediastinal lymph node dissection (SMLD), for pathologic staging and completeness of surgery. Over a period of 11 mo, 110 patients with lung cancer were enlisted and treated by pulmonary resection. Surgeons systematically sampled mediastinal lymph nodes prior to pulmonary resection, and after pulmonary resection SMLD was performed to each patient using Mountain's procedure [1]. After SMLD, pN status was classified as N0 in 57 cases, N1 in 27, and N2 in 26. SS detected 38.3% of pooled nodes and 37.6% of pooled positive nodes collected from SMLD. Pathologic diagnosis after SS was understaged in nine cases (8.2%) compared with staging after SMLD. However, surgery was incomplete in 24 cases (21.8%) if SMLD was not performed after sampling. Negative predictive value for SS was 86.8% on the right side, and 95.0% on the left. Three categories were generated according to pN status: negative nodes in SS and additional negative nodes from SMLD [S(-)D(-)], negative nodes in SS but additional positive nodes from SMLD [S(-)D(+)], and positive nodes in SS [S(+)D(+)]. cN2 (P=0.000) and CEA level (P=0.001) were correlated with pN status. There was significant overall survival difference between non-N2 group and N2 group (P=0.002). SMLD may harvest about three times of mediastinal lymph nodes compared with SS. SS is more likely to affect the completeness of surgery instead of underrating pathologic stage. Copyright © 2011 Elsevier Inc. All rights reserved.

Concomitant Mycobacterium avium infection and Hodgkin's disease in a lymph node from an HIV-negative child.

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de Armas, Yaxsier; Capó, Virginia; González, Ida; Mederos, Lilian; Díaz, Raúl; de Waard, Jacobus H; Rodríguez, Alberto; García, Yarmila; Cabanas, Ricardo

2011-03-01

We report a case of an immunocompetent child with simultaneously an infection with Mycobacterium avium and Hodgkin's disease in a cervical lymph node. A positive PCR result for M. avium on a biopsy of the lymph node directed the definitive diagnosis for both etiologies and avoided a possible dissemination of this infection after chemotherapy was started.

Instantaneous Real-Time Kinematic Decimeter-Level Positioning with BeiDou Triple-Frequency Signals over Medium Baselines.

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He, Xiyang; Zhang, Xiaohong; Tang, Long; Liu, Wanke

2015-12-22

Many applications, such as marine navigation, land vehicles location, etc., require real time precise positioning under medium or long baseline conditions. In this contribution, we develop a model of real-time kinematic decimeter-level positioning with BeiDou Navigation Satellite System (BDS) triple-frequency signals over medium distances. The ambiguities of two extra-wide-lane (EWL) combinations are fixed first, and then a wide lane (WL) combination is reformed based on the two EWL combinations for positioning. Theoretical analysis and empirical analysis is given of the ambiguity fixing rate and the positioning accuracy of the presented method. The results indicate that the ambiguity fixing rate can be up to more than 98% when using BDS medium baseline observations, which is much higher than that of dual-frequency Hatch-Melbourne-Wübbena (HMW) method. As for positioning accuracy, decimeter level accuracy can be achieved with this method, which is comparable to that of carrier-smoothed code differential positioning method. Signal interruption simulation experiment indicates that the proposed method can realize fast high-precision positioning whereas the carrier-smoothed code differential positioning method needs several hundreds of seconds for obtaining high precision results. We can conclude that a relatively high accuracy and high fixing rate can be achieved for triple-frequency WL method with single-epoch observations, displaying significant advantage comparing to traditional carrier-smoothed code differential positioning method.

Instantaneous Real-Time Kinematic Decimeter-Level Positioning with BeiDou Triple-Frequency Signals over Medium Baselines

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Xiyang He

2015-12-01

Full Text Available Many applications, such as marine navigation, land vehicles location, etc., require real time precise positioning under medium or long baseline conditions. In this contribution, we develop a model of real-time kinematic decimeter-level positioning with BeiDou Navigation Satellite System (BDS triple-frequency signals over medium distances. The ambiguities of two extra-wide-lane (EWL combinations are fixed first, and then a wide lane (WL combination is reformed based on the two EWL combinations for positioning. Theoretical analysis and empirical analysis is given of the ambiguity fixing rate and the positioning accuracy of the presented method. The results indicate that the ambiguity fixing rate can be up to more than 98% when using BDS medium baseline observations, which is much higher than that of dual-frequency Hatch-Melbourne-Wübbena (HMW method. As for positioning accuracy, decimeter level accuracy can be achieved with this method, which is comparable to that of carrier-smoothed code differential positioning method. Signal interruption simulation experiment indicates that the proposed method can realize fast high-precision positioning whereas the carrier-smoothed code differential positioning method needs several hundreds of seconds for obtaining high precision results. We can conclude that a relatively high accuracy and high fixing rate can be achieved for triple-frequency WL method with single-epoch observations, displaying significant advantage comparing to traditional carrier-smoothed code differential positioning method.

Positive and Negative Peer Influence in Residential Care.

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Huefner, Jonathan C; Smith, Gail L; Stevens, Amy L

2017-10-13

The potential for negative peer influence has been well established in research, and there is a growing interest in how positive peer influence also impacts youth. No research, however, has concurrently examined positive and negative peer influence in the context of residential care. Clinical records for 886 residential care youth were used in a Hierarchical Linear Model analysis to examine the impact of negative and positive peer influence on naturally occurring patterns of serious problem behavior over time. Negative peer influence, where the majority of youth in a home manifested above the average number of serious behavior problems, occurred 13.7% of the time. Positive peer influence, where the majority of youth manifested no serious problem behaviors for the month, occurred 47.7% of the time. Overall, youth problem behavior improved over time. There were significantly lower rates of serious problem behavior in target youth during positive peer influence months. Conversely, there were significantly higher rates of serious problem behaviors in target youth during negative peer influence months. Negative peer influence had a relatively greater impact on target peers' serious behavior problems than did positive peer influence. Caregiver experience significantly reduced the impact of negative peer influence, but did not significantly augment positive peer influence. Months where negative peer influence was combined with inexperienced caregivers produced the highest rates of serious problem behavior. Our results support the view that residential programs for troubled youth need to create circumstances that promote positive and control for negative peer influence.

Triple Test in Carcinoma Breast

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Sameer; Mukherjee, Arindam

2014-01-01

Introduction: The commonest clinical presentation in majority of breast pathology is a lump. A definite diagnosis of breast lump is very important for the surgeon to decide on the final course of treatment and also saves the patient from unnecessary physical, emotional and psychological trauma if there is a definite preoperative diagnosis of benign lesion. The present study was done to evaluate the effectiveness and relevance of “TRIPLE TEST”in diagnosis of carcinoma breast in rural labour class population. Materials and Methods: The present study was a prospective study conducted on patients over 35 years of age having palpable breast lumps presenting in the out patient department of general surgery, ESI Hospital Basaidarapur New Delhi, India. The duration of study was from May 2007 to June 2009 and a total of 100 cases were studied. Each patient was subjected to a detailed history, clinical breast examination ,diagnostic mammography and FNAC. In this study, the results of each modality was divided in three groups: benign, suspicious and malignant. The sensitivity, specificity, positive predictive value, negative predictive value and diagnostic accuracy of each test was calculated individually and as combined. Result: Out of 100 patients enrolled in this study, 60 cases were benign and 40 cases were of malignant breast disease. The age of patients with carcinoma breast in the series varied from 35 years to 70 years. The highest incidence of malignancy noted was 30% in 41-50 years age group (4th decade) followed by 27.5% in 51-60 years age group (5th decade). The sensitivity of clinical examination was found to be 75%, specificity was 83.3%, positive predictive value (PPV) of 75% and diagnostic accuracy of 80%. The sensitivity, specificity, positive predictive value and diagnostic accuracy of mammography was calculated and was found to be 94.9% , 90% , 86% and 92% respectively. The sensitivity, specificity, positive predictive value and diagnostic accuracy of

Clinicopathologic features of sentinel node metastases predictive of positive axillary clearance in grade 1 invasive breast carcinoma.

LENUS (Irish Health Repository)

Hayes, B

2012-02-01

BACKGROUND: Sentinel node (SN) biopsy is widely used to stage breast carcinoma and, when positive, typically leads to axillary clearance (AC). AIMS: This study assesses clinicopathologic features of grade 1 breast carcinoma SNs with the aim of identifying a group of patients, who are likely to have a negative AC and can, therefore, safely be spared further surgery. RESULTS: Two hundred and forty-seven patients with grade 1 invasive carcinoma were identified, of whom 29 had a positive SN. Four patients (13.8%) had a positive AC. Positive AC occurred in 3 of 6 (50%) patients whose SN showed extranodal extension (EE), but in only 1 of 23 (4.3%) patients without EE. All patients were staged as pN1(sn) following SN biopsy: only one, who had a 5.27 mm metastasis with EE, was pN2 following AC. CONCLUSIONS: Extranodal extension is a significant predictor of a positive AC in this group. In its absence, AC did not alter the post-SN biopsy pN stage.

Sentinel node concept in breast cancer

International Nuclear Information System (INIS)

Kiricuta, I.C.

2000-01-01

Background/purpose: It seems that there exists a specific lymph node center called sentinel node (SN) which appears to be the primary site of metastases. The sentinel node concept (SNC) is fundamentally based on the orderly progression of tumor cells within the lymphatic system. It is the most important new concept in surgical and radiation oncology. The purpose is to present the biological significance, the diagnostic and clinical basis of the sentinel node concept in breast cancer patients. Material and methods: Lymphoscintigraphy and gamma probe biopsy is necessary to show predictable lymph flow to the regional sentinel node, to multiple sentinel nodes or unpredictable lymph flow to extra-regional sentinel nodes and for performing sentinel node procedure. The standard protocol for the evaluation of the sentinel node metastases consists of extensive histopathological investigation including step Hematoxylin and Eosin (H and E) stained sections and immunohistochemistry. Results: A high rate of success of the identification of the sentinel node for breast cancer was reported. The presence or absence of metastasis in this node is a very accurate predictor of overall nodal status. The temptation to examine the sentinel node with the greatest possible degree of accuracy highlights one of the major problems related to sentinel node biopsy. The success of the sentinel node procedure depends primarily on the adequate functional capacity necessary for sufficient uptake to ensure the accurate identification. In negative sentinel-node patients a complete axillary lymph node dissection is avoidable. In sentinel-node positive patients and clinically negative patients a postoperative radiotherapy would permit an adequate tumor control. The last 2-procedures permit a low morbidity. In the actual TNM classification it was recently introduced a definition of a 'pN0' patient based on sentinel node biopsy. New target volumes are defined for adjuvant radiotherapy or lymphatic basins

Does a Negative Triple Test Reduce the Rate of Negative Appendectomy in Adults?

Directory of Open Access Journals (Sweden)

Mahmoud F. Sakr

2012-08-01

Results: Sixty-seven patients (65.9% were female and 35 (34.1% were male. Their ages ranged between 16 and 49 years (mean 27.5 years. Most patients (87.3% had their symptoms for 12-36 hours before hospital admission. The mean values for TLC, NP, and CRP were 7,573/ and micro;L, 54.53%, and 0.61 mg/L, respectively. Of the 102 patients with NTT, 101 (99% proved not to have appendiceal inflammation (NPV=99%. Only 39 patients were operated upon, of whom 38 (97.4% had a normal appendix, and the remaining 63 patients were either discharged (n=47 or referred to other specialties (n=16. There were significantly more women (76.3%, 29/38 with negative appendectomy than men (24.7%, 9/38 (X2= 21.1, p=0.0001. Gynecological causes were the most common (60.5%, 23/38 and in 11 cases, the exact etiology could not be identified. Conclusions: From the data presented, it may be concluded that TLC, NP and CRP blood levels (triple test should be measured upon hospital admission of adult patients with clinically suspected acute appendicitis. If used judiciously, they may spare the group of patients with an NTT an unnecessary surgical operation, hence markedly reducing the NAR with its potential risks. [Arch Clin Exp Surg 2012; 1(4.000: 229-236

Positive Effects of Negative Publicity: When Negative Reviews Increase Sales

OpenAIRE

Jonah Berger; Alan T. Sorensen; Scott J. Rasmussen

2010-01-01

Can negative information about a product increase sales, and if so, when? Although popular wisdom suggests that "any publicity is good publicity," prior research has demonstrated only downsides to negative press. Negative reviews or word of mouth, for example, have been found to hurt product evaluation and sales. Using a combination of econometric analysis and experimental methods, we unify these perspectives to delineate contexts under which negative publicity about a product will have posit...

Temozolomide Enhances Triple-Negative Breast Cancer Virotherapy In Vitro

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Rodolfo Garza-Morales

2018-05-01

Full Text Available Triple-negative breast cancer (TNBC is one of the most aggressive types of cancer, and treatment is limited to chemotherapy and radiation. Oncolytic virotherapy may be a promising approach to treat TNBC. However, oncolytic adenovirus (OAd-based mono-therapeutic clinical trials have resulted in modest outcomes. The OAd potency could be increased by chemotherapy-induced autophagy, an intracellular degradation system that delivers cytoplasmic constituents to the lysosome. In this study, the ability of alkylating agent temozolomide (TMZ-induced autophagy to increase OAd replication and oncolysis in TNBC cells was evaluated. Human TNBC MDA-MB-231 and HCC1937 cells and mouse 4T1 cells were infected with an OAd expressing the red fluorescent protein mCherry on the virus capsid (OAdmCherry alone or in combination with TMZ. TNBC cells treated with OAdmCherry/TMZ displayed greater mCherry and adenovirus (Ad early region 1A (E1A expression and enhanced cancer-cell killing compared to OAdmCherry or TMZ alone. The combined therapy-mediated cell death was associated with virus replication and accumulation of the autophagy marker light chain 3 (LC3-II. Overall, this study provides experimental evidence of TMZ’s ability to increase oncolytic virotherapy in both human and murine TNBC cells.

Transcriptome analysis of Wnt3a-treated triple-negative breast cancer cells.

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Sylvie Maubant

Full Text Available The canonical Wnt/β-catenin pathway is activated in triple-negative breast cancer (TNBC. The activation of this pathway leads to the expression of specific target genes depending on the cell/tissue context. Here, we analyzed the transcriptome of two different TNBC cell lines to define a comprehensive list of Wnt target genes. The treatment of cells with Wnt3a for 6h up-regulated the expression (fold change > 1.3 of 59 genes in MDA-MB-468 cells and 241 genes in HCC38 cells. Thirty genes were common to both cell lines. Beta-catenin may also be a transcriptional repressor and we found that 18 and 166 genes were down-regulated in response to Wnt3a treatment for 6h in MDA-MB-468 and HCC38 cells, respectively, of which six were common to both cell lines. Only half of the activated and the repressed transcripts have been previously described as Wnt target genes. Therefore, our study reveals 137 novel genes that may be positively regulated by Wnt3a and 104 novel genes that may be negatively regulated by Wnt3a. These genes are involved in the Wnt pathway itself, and also in TGFβ, p53 and Hedgehog pathways. Thorough characterization of these novel potential Wnt target genes may reveal new regulators of the canonical Wnt pathway. The comparison of our list of Wnt target genes with those published in other cellular contexts confirms the notion that Wnt target genes are tissue-, cell line- and treatment-specific. Genes up-regulated in Wnt3a-stimulated cell lines were more strongly expressed in TNBC than in luminal A breast cancer samples. These genes were also overexpressed, but to a much lesser extent, in HER2+ and luminal B tumors. We identified 72 Wnt target genes higher expressed in TNBCs (17 with a fold change >1.3 which may reflect the chronic activation of the canonical Wnt pathway that occurs in TNBC tumors.

A mathematical prediction model incorporating molecular subtype for risk of non-sentinel lymph node metastasis in sentinel lymph node-positive breast cancer patients: a retrospective analysis and nomogram development.

Science.gov (United States)

Wang, Na-Na; Yang, Zheng-Jun; Wang, Xue; Chen, Li-Xuan; Zhao, Hong-Meng; Cao, Wen-Feng; Zhang, Bin

2018-04-25

Molecular subtype of breast cancer is associated with sentinel lymph node status. We sought to establish a mathematical prediction model that included breast cancer molecular subtype for risk of positive non-sentinel lymph nodes in breast cancer patients with sentinel lymph node metastasis and further validate the model in a separate validation cohort. We reviewed the clinicopathologic data of breast cancer patients with sentinel lymph node metastasis who underwent axillary lymph node dissection between June 16, 2014 and November 16, 2017 at our hospital. Sentinel lymph node biopsy was performed and patients with pathologically proven sentinel lymph node metastasis underwent axillary lymph node dissection. Independent risks for non-sentinel lymph node metastasis were assessed in a training cohort by multivariate analysis and incorporated into a mathematical prediction model. The model was further validated in a separate validation cohort, and a nomogram was developed and evaluated for diagnostic performance in predicting the risk of non-sentinel lymph node metastasis. Moreover, we assessed the performance of five different models in predicting non-sentinel lymph node metastasis in training cohort. Totally, 495 cases were eligible for the study, including 291 patients in the training cohort and 204 in the validation cohort. Non-sentinel lymph node metastasis was observed in 33.3% (97/291) patients in the training cohort. The AUC of MSKCC, Tenon, MDA, Ljubljana, and Louisville models in training cohort were 0.7613, 0.7142, 0.7076, 0.7483, and 0.671, respectively. Multivariate regression analysis indicated that tumor size (OR = 1.439; 95% CI 1.025-2.021; P = 0.036), sentinel lymph node macro-metastasis versus micro-metastasis (OR = 5.063; 95% CI 1.111-23.074; P = 0.036), the number of positive sentinel lymph nodes (OR = 2.583, 95% CI 1.714-3.892; P model based on the results of multivariate analysis was established to predict the risk of non

Del-1 Expression as a Potential Biomarker in Triple-Negative Early Breast Cancer.

Science.gov (United States)

Lee, Soo Jung; Lee, Jeeyeon; Kim, Wan Wook; Jung, Jin Hyang; Park, Ho Yong; Park, Ji-Young; Chae, Yee Soo

2018-01-01

A differential diagnostic role for plasma Del-1 was proposed for early breast cancer (EBC) in our previous study. We examined tumoral Del-1 expression and analyzed its prognostic impact among patients with EBC. Del-1 mRNA expression was assessed in breast epithelial and cancer cells. Meanwhile, the tumoral expression of Del-1 was determined based on tissue microarrays and immunohistochemistry results from 440 patients. While a high Del-1 mRNA expression was found in all the breast cancer cell lines, the expression was significantly higher in MDA-MB-231. Tumoral expression of Del-1 was also significantly associated with a negative expression of estrogen receptor or progesterone receptor, and low expression of Ki-67, particularly in the case of triple-negative breast cancer (TNBC) (p breast cancer cell lines exhibited Del-1 expression, the expression rate and intensity were specifically prominent in TNBC. In addition, based on its relationship to an unfavorable histology and worse survival trend, Del-1 could act as a molecular target in TNBC patients. © 2018 S. Karger AG, Basel.

Sentinel lymph node biopsy in breast cancer--the Aarhus experience

DEFF Research Database (Denmark)

Lauridsen, M C; Garne, J P; Hessov, I

2000-01-01

Eighty patients, with newly diagnosed unifocal breast cancer and with no axillary metastases verified by ultrasonography, underwent sentinel lymph node (SLN) and subsequent axillary lymph node dissection. To identify the SLN, we used a combination of Tc-99m labelled colloid (Albures) and blue dye...... as SLNs that tested negative but with higher nodes that tested positive. If SLN biopsy is accepted as a routine procedure and when the exact indications are defined, the method described probably could be offered to the majority of breast cancer patients....

BioBenchmark Toyama 2012: an evaluation of the performance of triple stores on biological data

Science.gov (United States)

2014-01-01

Background Biological databases vary enormously in size and data complexity, from small databases that contain a few million Resource Description Framework (RDF) triples to large databases that contain billions of triples. In this paper, we evaluate whether RDF native stores can be used to meet the needs of a biological database provider. Prior evaluations have used synthetic data with a limited database size. For example, the largest BSBM benchmark uses 1 billion synthetic e-commerce knowledge RDF triples on a single node. However, real world biological data differs from the simple synthetic data much. It is difficult to determine whether the synthetic e-commerce data is efficient enough to represent biological databases. Therefore, for this evaluation, we used five real data sets from biological databases. Results We evaluated five triple stores, 4store, Bigdata, Mulgara, Virtuoso, and OWLIM-SE, with five biological data sets, Cell Cycle Ontology, Allie, PDBj, UniProt, and DDBJ, ranging in size from approximately 10 million to 8 billion triples. For each database, we loaded all the data into our single node and prepared the database for use in a classical data warehouse scenario. Then, we ran a series of SPARQL queries against each endpoint and recorded the execution time and the accuracy of the query response. Conclusions Our paper shows that with appropriate configuration Virtuoso and OWLIM-SE can satisfy the basic requirements to load and query biological data less than 8 billion or so on a single node, for the simultaneous access of 64 clients. OWLIM-SE performs best for databases with approximately 11 million triples; For data sets that contain 94 million and 590 million triples, OWLIM-SE and Virtuoso perform best. They do not show overwhelming advantage over each other; For data over 4 billion Virtuoso works best. 4store performs well on small data sets with limited features when the number of triples is less than 100 million, and our test shows its

BioBenchmark Toyama 2012: an evaluation of the performance of triple stores on biological data.

Science.gov (United States)

Wu, Hongyan; Fujiwara, Toyofumi; Yamamoto, Yasunori; Bolleman, Jerven; Yamaguchi, Atsuko

2014-01-01

Biological databases vary enormously in size and data complexity, from small databases that contain a few million Resource Description Framework (RDF) triples to large databases that contain billions of triples. In this paper, we evaluate whether RDF native stores can be used to meet the needs of a biological database provider. Prior evaluations have used synthetic data with a limited database size. For example, the largest BSBM benchmark uses 1 billion synthetic e-commerce knowledge RDF triples on a single node. However, real world biological data differs from the simple synthetic data much. It is difficult to determine whether the synthetic e-commerce data is efficient enough to represent biological databases. Therefore, for this evaluation, we used five real data sets from biological databases. We evaluated five triple stores, 4store, Bigdata, Mulgara, Virtuoso, and OWLIM-SE, with five biological data sets, Cell Cycle Ontology, Allie, PDBj, UniProt, and DDBJ, ranging in size from approximately 10 million to 8 billion triples. For each database, we loaded all the data into our single node and prepared the database for use in a classical data warehouse scenario. Then, we ran a series of SPARQL queries against each endpoint and recorded the execution time and the accuracy of the query response. Our paper shows that with appropriate configuration Virtuoso and OWLIM-SE can satisfy the basic requirements to load and query biological data less than 8 billion or so on a single node, for the simultaneous access of 64 clients. OWLIM-SE performs best for databases with approximately 11 million triples; For data sets that contain 94 million and 590 million triples, OWLIM-SE and Virtuoso perform best. They do not show overwhelming advantage over each other; For data over 4 billion Virtuoso works best. 4store performs well on small data sets with limited features when the number of triples is less than 100 million, and our test shows its scalability is poor; Bigdata

Significant difference in p53 and p21 protein immunoreactivity in HPV 16 positive and HPV negative breast carcinomas

International Nuclear Information System (INIS)

Hennig, E.M.; Norwegian Radium Hospital, Oslo; Kvinnsland, S.; Holm, R.; Nesland, J.M.

1999-01-01

Human papillomavirus (HPV) 16 has previously been found in 19/41 breast carcinomas (46%) in women with a history of HPV 16 positive CIN III lesions. There was no significant difference in distribution of histological subtypes, mean or median tumour diameter or number of regional lymph node metastases in the HPV positive and HPV negative breast carcinoma groups. P53, p21 and c-erbB-2 proteins were analyzed by immunohistochemistry in the HPV 16 positive and HPV negative breast carcinomas. There was a significant difference in p53 and p21 protein immunoreactivity between HPV 16 positive and HPV negative breast carcinomas (p=0.0091 and p=0.0040), with a significant less detectable p53 and p21 protein immunoreactivity in the HPV 16 positive cases. There was also a significant difference in the coexpression of p53/p21 between the HPV 16 positive and HPV 16 negative breast carcinomas (p=0.002). No significant difference in immunostaining for c-erbB-2 protein in the two groups was found (p=0.15), or for the coexpression of p53/c-erbB-2 (p=0.19). The significantly lower expression of p53 and p21 proteins in HPV 16 positive than in HPV 16 negative breast carcinomas supports the hypothesis of inactivation and degradation of wild-type p53 proteins by HPV 16 E6 and that p53 mutation is not necessary for transformation in the HPV 16 positive cases. (orig.)

Triple composite tumor of stomach: A rare combination of alpha fetoprotein positive hepatoid adenocarcinoma, tubular adenocarcinoma and large cell neuroendocrine carcinoma

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Lipika Lipi

2014-01-01

Full Text Available A 50-year-old male patient presented with pain abdomen of 6 months duration. Computed tomography scan revealed a large mass in the stomach occluding the lumen. Histopathology revealed a triple composite tumor comprising of tubular adenocarcinoma arising on a background of high-grade dysplasia, hepatoid adenocarcinoma (positive for Hep Par-1 and alpha fetoprotein and large cell neuroendocrine carcinoma (positive for synaptophysin and chromogranin with nodal metastasis.Triple composite tumors are distinctly rare with few reports in literature.

Gene expression variation to predict 10-year survival in lymph-node-negative breast cancer

International Nuclear Information System (INIS)

Karlsson, Elin; Delle, Ulla; Danielsson, Anna; Olsson, Björn; Abel, Frida; Karlsson, Per; Helou, Khalil

2008-01-01

It is of great significance to find better markers to correctly distinguish between high-risk and low-risk breast cancer patients since the majority of breast cancer cases are at present being overtreated. 46 tumours from node-negative breast cancer patients were studied with gene expression microarrays. A t-test was carried out in order to find a set of genes where the expression might predict clinical outcome. Two classifiers were used for evaluation of the gene lists, a correlation-based classifier and a Voting Features Interval (VFI) classifier. We then evaluated the predictive accuracy of this expression signature on tumour sets from two similar studies on lymph-node negative patients. They had both developed gene expression signatures superior to current methods in classifying node-negative breast tumours. These two signatures were also tested on our material. A list of 51 genes whose expression profiles could predict clinical outcome with high accuracy in our material (96% or 89% accuracy in cross-validation, depending on type of classifier) was developed. When tested on two independent data sets, the expression signature based on the 51 identified genes had good predictive qualities in one of the data sets (74% accuracy), whereas their predictive value on the other data set were poor, presumably due to the fact that only 23 of the 51 genes were found in that material. We also found that previously developed expression signatures could predict clinical outcome well to moderately well in our material (72% and 61%, respectively). The list of 51 genes derived in this study might have potential for clinical utility as a prognostic gene set, and may include candidate genes of potential relevance for clinical outcome in breast cancer. According to the predictions by this expression signature, 30 of the 46 patients may have benefited from different adjuvant treatment than they recieved. The research on these tumours was approved by the Medical Faculty Research

Selumetinib suppresses cell proliferation, migration and trigger apoptosis, G1 arrest in triple-negative breast cancer cells.

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Zhou, Yan; Lin, Shuchen; Tseng, Kuo-Fu; Han, Kun; Wang, Yaling; Gan, Zhi-Hua; Min, Da-Liu; Hu, Hai-Yan

2016-10-21

Triple-negative breast cancer (TNBC) has aggressive progression with poor prognosis and ineffective treatments. Selumetinib is an allosteric, ATP-noncompetitive inhibitor of MEK1/2, which has benn known as effective antineoplastic drugs for several malignant tumors. We hypothesized that Selumetinib might be potential drug for TNBC and explore the mechanism. After treated with Selumetinib, the viability and mobility of HCC1937 and MDA-MB-231 were detected by MTT, tunnel, wound-healing assay, transwell assay and FCM methods. MiR array was used to analysis the change of miRs. We predicted and verified CUL1 is the target of miR-302a using Luciferase reporter assay. We also silenced the CUL1 by siRNA, to clarify whether CUL1 take part in the cell proliferation, migration and regulated its substrate TIMP1 and TRAF2. Moreover, after transfection, the antagomir of miR-302a and CUL1 over-expressed plasmid into HCC1937 and MDA-MB-231 cell accompanied with the Selumetinib treatment, we detected the proliferation and migration again. Selumetinib reduce the proliferation, migration, triggered apoptosis and G1 arrest in TNBC cell lines. In this process, the miR-302a was up-regulated and inhibited the CUL1 expression. The later negatively regulated the TIMP1 and TRAF2. As soon as we knockdown miR-302a and over-expression CUL1 in TNBC cells, the cytotoxicity of Selumetinib was reversed. MiR-302a targeted regulated the CUL1 expression and mediated the Selumetinib-induced cytotoxicity of triple-negative breast cancer.

Outcomes of Breast Cancer Patients With Triple Negative Receptor Status Treated With Accelerated Partial Breast Irradiation

International Nuclear Information System (INIS)

Wilkinson, J. Ben; Reid, Robert E.; Shaitelman, Simona F.; Chen, Peter Y.; Mitchell, Christine K.; Wallace, Michelle F.; Marvin, Kimberly S.; Grills, Inga S.; Margolis, Jeffrey M.; Vicini, Frank A.

2011-01-01

Purpose: Triple negative receptor status (TNRS) of patients undergoing breast-conserving therapy treated with whole-breast irradiation has been associated with increased distant metastasis and decreased disease-free and overall survival. This paper reports the outcomes of TNRS patients treated with accelerated partial breast irradiation (APBI). Methods and Materials: We studied 455 patients who received APBI at our institution, using interstitial, intracavitary, and three-dimensional conformal radiation therapy. TNRS was assigned if a patient tested negative for all three (ER [estrogen receptor], PR [progesterone receptor], and HER2/neu) receptors. Of 202 patients with all receptor results available, 20 patients were designated TNRS, and 182 patients had at least one receptor positive (RP). We analyzed ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), distant metastasis (DM), and overall survival (OS). Results: Mean follow-up was 4.1 years for the TNRS group and 5.1 years for the RP cohort (p = 0.11). TNRS patients had a higher histologic grade (59% TNRS vs. 13% RP; p 0.52). OS for the RP cohort was 93% at 5 years (p > 0.28). Conclusions: In our patient population, TNRS conferred a clinical outcome similar to that of patients with RP disease treated with APBI. Further investigation with larger patient populations and longer follow-up periods is warranted to confirm that APBI is a safe and effective treatment for patients with localized TNRS breast cancer.

Outcomes of breast cancer patients with triple negative receptor status treated with accelerated partial breast irradiation.

Science.gov (United States)

Wilkinson, J Ben; Reid, Robert E; Shaitelman, Simona F; Chen, Peter Y; Mitchell, Christine K; Wallace, Michelle F; Marvin, Kimberly S; Grills, Inga S; Margolis, Jeffrey M; Vicini, Frank A

2011-11-01

Triple negative receptor status (TNRS) of patients undergoing breast-conserving therapy treated with whole-breast irradiation has been associated with increased distant metastasis and decreased disease-free and overall survival. This paper reports the outcomes of TNRS patients treated with accelerated partial breast irradiation (APBI). We studied 455 patients who received APBI at our institution, using interstitial, intracavitary, and three-dimensional conformal radiation therapy. TNRS was assigned if a patient tested negative for all three (ER [estrogen receptor], PR [progesterone receptor], and HER2/neu) receptors. Of 202 patients with all receptor results available, 20 patients were designated TNRS, and 182 patients had at least one receptor positive (RP). We analyzed ipsilateral breast tumor recurrence (IBTR), regional nodal failure (RNF), distant metastasis (DM), and overall survival (OS). Mean follow-up was 4.1 years for the TNRS group and 5.1 years for the RP cohort (p = 0.11). TNRS patients had a higher histologic grade (59% TNRS vs. 13% RP; p 0.52). OS for the RP cohort was 93% at 5 years (p > 0.28). In our patient population, TNRS conferred a clinical outcome similar to that of patients with RP disease treated with APBI. Further investigation with larger patient populations and longer follow-up periods is warranted to confirm that APBI is a safe and effective treatment for patients with localized TNRS breast cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

Bridging disparate symptoms of schizophrenia: a Triple network dysfunction theory

Directory of Open Access Journals (Sweden)

Tereza eNekovarova

2014-05-01

Full Text Available Schizophrenia is a complex neuropsychiatric disorder with variable symptomatology, traditionally divided into positive and negative symptoms, and cognitive deficits. Yet, the etiology of this disorder has yet to be fully understood.Recent findings suggest that alteration of the basic sense of self-awareness may be an essential distortion of schizophrenia spectrum disorders. In addition, extensive research of social and mentalizing abilities has stressed the role of distortion of social skills in schizophrenia.This article aims to propose and support a concept of triple brain network model of the dysfunctional switching between default mode and central executive network related to the aberrant activity of salience network. This model could represent a unitary mechanism of a wide array of symptom domains present in schizophrenia including the deficit of SELF (self-awareness and self-representation and theory of mind (ToM dysfunctions along with the traditional positive, negative and cognitive domains. We review previous studies which document the dysfunctions of SELF and ToM in schizophrenia together with neuroimaging data elucidating the triple brain network model as a common neuronal substrate of this dysfunction.

Three-year follow-up of sentinel node-negative patients with early oral cavity squamous cell carcinoma

DEFF Research Database (Denmark)

Sebbesen, Lars; Bilde, Anders; Therkildsen, Marianne

2014-01-01

2009, 53 consecutive SNB-negative patients with oral cavity squamous cell carcinoma (SCC) T1 to T2 were accrued. Follow-up was done continuously with the most recent examination in October 2011. The location of the sentinel lymph nodes was determined using dynamic and planar lymphoscintigraphy...

The hidden sentinel node in breast cancer

International Nuclear Information System (INIS)

Tanis, P.J.; Sandick, J.W. van; Nieweg, O.E.; Rutgers, E.J.T.; Kroon, B.B.R.; Valdes Olmos, R.A.; Hoefnagel, C.A.

2002-01-01

The purpose of this study was to analyse the occurrence of non-visualisation during preoperative lymphoscintigraphy for sentinel node identification in breast cancer. Preoperative lymphoscintigraphy was performed in 495 clinically node-negative breast cancer patients (501 sentinel node procedures) after injection of technetium-99m nanocolloid. Anterior and prone lateral (hanging breast) planar images were obtained a few minutes and 4 h after injection. The sentinel node was intraoperatively identified with the aid of patent blue dye and a gamma-ray detection probe. A sentinel node was visualised on the 4-h images in 449 of 501 procedures (90%). This visualisation rate improved from 76% to 94% during the study period. Delayed imaging (5-23 h) in 19 patients whose sentinel nodes failed to show, resulted in visualisation in four of them. A repeat injection of radiocolloid in 11 patients revealed a sentinel node in six. In the end, the visualisation rate was 92%. The sentinel node was surgically retrieved in 24 of the remaining 42 patients with non-visualisation (57%). Sentinel nodes that were visualised were tumour-positive in 38% and non-visualised sentinel nodes were involved in 50% (χ 2 , P=0.17). In a multivariate regression analysis, scintigraphic non-visualisation was independently associated with increased patient age (P<0.001), decreased tracer dose (P<0.001) and increased number of tumour-positive lymph nodes (P=0.013). The use of a sufficient amount of radioactivity (at least 100 MBq) is recommended for lymphatic mapping in breast cancer, especially in elderly women. Delayed imaging and re-injection of the radioactive tracer increase the visualisation rate. The non-visualised sentinel node can be identified intraoperatively in more than half of the patients. (orig.)

The hidden sentinel node in breast cancer

Energy Technology Data Exchange (ETDEWEB)

Tanis, P.J.; Sandick, J.W. van; Nieweg, O.E.; Rutgers, E.J.T.; Kroon, B.B.R. [Department of Surgery, Netherlands Cancer Institute, Amsterdam (Netherlands); Valdes Olmos, R.A.; Hoefnagel, C.A. [Department of Nuclear Medicine, Netherlands Cancer Institute, Amsterdam (Netherlands)

2002-03-01

The purpose of this study was to analyse the occurrence of non-visualisation during preoperative lymphoscintigraphy for sentinel node identification in breast cancer. Preoperative lymphoscintigraphy was performed in 495 clinically node-negative breast cancer patients (501 sentinel node procedures) after injection of technetium-99m nanocolloid. Anterior and prone lateral (hanging breast) planar images were obtained a few minutes and 4 h after injection. The sentinel node was intraoperatively identified with the aid of patent blue dye and a gamma-ray detection probe. A sentinel node was visualised on the 4-h images in 449 of 501 procedures (90%). This visualisation rate improved from 76% to 94% during the study period. Delayed imaging (5-23 h) in 19 patients whose sentinel nodes failed to show, resulted in visualisation in four of them. A repeat injection of radiocolloid in 11 patients revealed a sentinel node in six. In the end, the visualisation rate was 92%. The sentinel node was surgically retrieved in 24 of the remaining 42 patients with non-visualisation (57%). Sentinel nodes that were visualised were tumour-positive in 38% and non-visualised sentinel nodes were involved in 50% ({chi}{sup 2}, P=0.17). In a multivariate regression analysis, scintigraphic non-visualisation was independently associated with increased patient age (P<0.001), decreased tracer dose (P<0.001) and increased number of tumour-positive lymph nodes (P=0.013). The use of a sufficient amount of radioactivity (at least 100 MBq) is recommended for lymphatic mapping in breast cancer, especially in elderly women. Delayed imaging and re-injection of the radioactive tracer increase the visualisation rate. The non-visualised sentinel node can be identified intraoperatively in more than half of the patients. (orig.)

Age and axillary lymph node ratio in postmenopausal women with T1-T2 node positive breast cancer.

Science.gov (United States)

Vinh-Hung, Vincent; Joseph, Sue A; Coutty, Nadege; Ly, Bevan Hong; Vlastos, Georges; Nguyen, Nam Phong

2010-01-01

The purpose of this article was to examine the relationship between age and lymph node ratio (LNR, number of positive nodes divided by number of examined nodes), and to determine their effects on breast cancer (BC) and overall mortality. Women aged ≥50 years, diagnosed in 1988-1997 with a unilateral histologically confirmed T1-T2 node positive surgically treated primary nonmetastatic BC, were selected from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER). Generalized Additive Models for Location Scale and Shape (GAMLSS) were used to evaluate the age-LNR relationship. Cumulative incidence functions and multivariate competing risks analysis based on model selection by the Bayesian Information Criterion (BIC) were used to examine the effect of age and LNR on mortality. Low LNR was defined as ≤0.20, mid-LNR 0.21-0.65, and high LNR >0.65. GAMLSS showed a nonlinear LNR-age relationship, increasing from mean LNR 0.26-0.28 at age 50-70 years to 0.30 at 80 years and 0.40 at 90 years. Compared with a 9.8% [95% confidence interval (CI) 8.8%-10.8%] risk of BC death at 5 years in women aged 50-59 years with low LNR, the risk in women ≥80 years with low LNR was 12.6% [95% CI 10.1%-15.0%], mid-LNR 18.1% [13.9%-22.1%], high LNR 29.8% [22.7%-36.1%]. Five-years overall risk of death increased from 40.8% [37.5%-43.9%] by low LNR to 67.4% [61.4%-72.4%] by high LNR. The overall mortality hazard ratio for age ≥80 years with high LNR was 7.49 [6.54-8.59], as compared with women aged 50-59 years with low LNR. High LNR combined with older age was associated with a threefold increased risk of BC death and a sevenfold increased hazard ratio of overall mortality.

Definitive radiotherapy for head-and-neck cancer with radiographically positive retropharyngeal nodes: Incomplete radiographic response does not necessarily indicate failure

International Nuclear Information System (INIS)

Liauw, Stanley L.; Mancuso, Anthony A.; Morris, Christopher G. M.S.; Amdur, Robert J.; Mendenhall, William M.

2006-01-01

Purpose: Our aim was to report the control rate of radiographically positive retropharyngeal (RP) nodes with radiation therapy (RT) and to correlate posttreatment imaging with clinical outcome. Methods and Materials: Sixteen patients treated with definitive RT for head-and-neck cancer had radiographically positive RP nodes (size >1 cm in largest axial dimension, or presence of focal enhancement, lucency, or calcification), and both pre-RT and post-RT image sets available for review. An additional 21 patients with unconfirmed radiographically positive RP nodes had post-RT imaging, which consisted of computed tomography (CT) at a median of 4 weeks after completing RT. Patients with positive post-RT RP nodes underwent observation with serial imaging. Results: Of 16 patients with pre-RT and post-RT images available for review, 9 (56%) had a radiographic complete response, and of 21 patients with unconfirmed positive RP nodes with post-RT images available for review, 14 (67%) had a radiographic complete response. In all, 14 patients with incomplete response on post-RT imaging experienced control of their disease with no further therapy, and no RP node or neck failures were noted during a median follow-up of 2.8 years. Six patients with positive post-RT RP nodes had serial imaging available for review, and none demonstrated radiographic progression of disease. Conclusions: Radiographic response at 4 weeks may not accurately reflect long-term locoregional control, as RP nodes may continue to resolve over time. The highest index of suspicion should be reserved for patients with progressive changes in size, focal lucency, or focal enhancement on serial imaging after RT

Clinical value of detection of intrathoracic metastatic lymph nodes with radioguided technique in patients with non-small cell lung carcinoma

International Nuclear Information System (INIS)

Lu Ming; Hu Yongxiao

2008-01-01

Objective: To study the possible clinical feasibility of intraoperative detection of metastatic lymph node with radioguided technique after labeling with 99m Tc-MIBI in patients with non-small cell lung carcinoma. Methods: Gamma-detecting probe was used intra-operatively to examine the radioactivity of lungs, regional and mediastinal nodes in 30 patients with non-small cell lung carcinoma after intravenous injection of 99m Tc-MIBI (740MBq) 30 minutes before operation for radio-labeling of the nodes. Postoperatively, the radiologically positive but conventionally pathologically negative as well as all the other nodes judged to be negative with conventional standard (altogether 201 groups) were all meticulously examined with serial sections and immunohistologic staining for detection of the presence of micro-metastasis. Results: Altogether 41 groups of nodes specimens were radiologically positive (over twofolds of normal radio-activity measured with γ probe), of which conventional pathological examination revealed metastasis in 32 groups. The remaining 9 groups of specimens were examined further with serial sections and IHC studies and micro-metastasis was found in 3 of them. Thus, the sensitivity of the radioguided technique was 100%, specificity 96.9% and accuracy rate 97.42%. In the remaining 192 radiologically negative groups of lymph nodes studied, no false negative cases (i. e. micrometastasis positive) were demonstrated. Conclusion: The radio-guided technique is very sensitive (100%), highly specific and accurate (98.9%), and 97.4% respectively), without false negativity demonstrated. Its practical clinical application seems to be feasible. (authors)

Post-mastectomy radiation in large node-negative breast tumors: Does size really matter?

International Nuclear Information System (INIS)

Floyd, Scott R.; Taghian, Alphonse G.

2009-01-01

Treatment decisions regarding local control can be particularly challenging for T3N0 breast tumors because of difficulty in estimating rates of local failure after mastectomy. Reports in the literature detailing the rates of local failure vary widely, likely owing to the uncommon incidence of this clinical situation. The literature regarding this clinical scenario is reviewed, including recent reports that specifically address the issue of local failure rates after mastectomy in the absence of radiation for large node-negative breast tumors.

Melanin-originated carbonaceous dots for triple negative breast cancer diagnosis by fluorescence and photoacoustic dual-mode imaging.

Science.gov (United States)

Xiao, Wei; Li, Yuan; Hu, Chuan; Huang, Yuan; He, Qin; Gao, Huile

2017-07-01

Carbonaceous dots exhibit increasing applications in diagnosis and drug delivery due to excellent photostability and biocompatibility properties. However, relative short excitation and emission of melanin carbonaceous dots (MCDs) limit the applicability in fluorescence bioimaging. Furthermore, the generally poor spatial resolution of fluorescence imaging limits potential in vivo applications. Due to a variety of beneficial properties, in this study, MCDs were prepared exhibiting great potential in fluorescence and photoacoustic dual-mode bioimaging. The MCDs exhibited a long excitation peak at 615nm and emission peak at 650nm, further highlighting the applicability in fluorescence imaging, while the absorbance peak at 633nm renders MCDs suitable for photoacoustic imaging. In vivo, the photoacoustic signal of MCDs was linearly correlated with the concentration of MCDs. Moreover, the MCDs were shown to be taken up into triple negative breast cancer cell line 4T1 in both a time- and concentration-dependent manner. In vivo fluorescence and photoacoustic imaging of subcutaneous 4T1 tumor demonstrated that MCDs could passively target triple negative breast cancer tissue by enhanced permeability and retention effects and may therefore be used for tumor dual-mode imaging. Furthermore, fluorescence distribution in tissue slices suggested that MCDs may distribute in 4T1 tumor with high efficacy. In conclusion, the MCDs studied offer potential application in fluorescence and photoacoustic dual-mode imaging. Copyright © 2017 Elsevier Inc. All rights reserved.

Sentinel Lymph Node Biopsy in Breast Cancer: A Clinical Review and Update.

Science.gov (United States)

Zahoor, Sheikh; Haji, Altaf; Battoo, Azhar; Qurieshi, Mariya; Mir, Wahid; Shah, Mudasir

2017-09-01

Sentinel lymph node biopsy has become a standard staging tool in the surgical management of breast cancer. The positive impact of sentinel lymph node biopsy on postoperative negative outcomes in breast cancer patients, without compromising the oncological outcomes, is its major advantage. It has evolved over the last few decades and has proven its utility beyond early breast cancer. Its applicability and efficacy in patients with clinically positive axilla who have had a complete clinical response after neoadjuvant chemotherapy is being aggressively evaluated at present. This article discusses how sentinel lymph node biopsy has evolved and is becoming a useful tool in new clinical scenarios of breast cancer management.

High Ki-67 score is indicative of a greater benefit from adjuvant chemotherapy when added to endocrine therapy in luminal B HER2 negative and node-positive breast cancer.

Science.gov (United States)

Criscitiello, Carmen; Disalvatore, Davide; De Laurentiis, Michele; Gelao, Lucia; Fumagalli, Luca; Locatelli, Marzia; Bagnardi, Vincenzo; Rotmensz, Nicole; Esposito, Angela; Minchella, Ida; De Placido, Sabino; Santangelo, Michele; Viale, Giuseppe; Goldhirsch, Aron; Curigliano, Giuseppe

2014-02-01

The indication of adjuvant chemotherapy for patients with highly proliferative estrogen receptor-positive breast cancer is controversial. We analyzed the predictive value of Ki67 for the efficacy of adjuvant chemotherapy in patients with estrogen receptor-positive, node-positive breast cancer. We identified 1241 patients with Luminal B early stage breast cancer with 1-3 axillary positive nodes who underwent surgery between 1995 and 2005 at the European Institute of Oncology and received adjuvant hormonotherapy and/or chemotherapy. Differences in the distribution of characteristics according to treatment were evaluated by the Chi-square test. To evaluate the effect of adding chemotherapy to hormonotherapy, the propensity score method was used to match patients' characteristics minimizing bias related to the non-random assignment of treatment. The probability of receiving chemotherapy was significantly associated with age, tumor grade, degree of hormone responsiveness, tumor size and peripheral vascular invasion. The propensity score distribution was statistically different between the two treatment groups (p chemotherapy group (log-rank test p-value 0.663). The 5-year DFS percentages were 84.6% (95% CI, 81.0-87.6%) in the hormonotherapy group and 84.2% (95% CI, 81.3-86.7%) in the hormonotherapy/chemotherapy group (log-rank test p-value 0.388). However, when analyzing the 5-year DFS by Ki-67 distribution, Subpopulation Treatment Effect Pattern Plot (STEPP) analysis showed a beneficial effect of chemotherapy in patients with highly proliferative tumor (Ki-67 ≥ 32%). The interaction between Ki-67 and treatment was statistically significant (p = 0.027). Ki67 expression identifies a subset of patients with Luminal B and node-positive breast cancer who could benefit from addition of adjuvant chemotherapy to hormonotherapy. Dichotomy was observed for Ki67 at 32% level. Copyright © 2013 Elsevier Ltd. All rights reserved.

Identification of a rhodium(iii) complex as a Wee1 inhibitor against TP53-mutated triple-negative breast cancer cells.

Science.gov (United States)

Yang, Guan-Jun; Zhong, Hai-Jing; Ko, Chung-Nga; Wong, Suk-Yu; Vellaisamy, Kasipandi; Ye, Min; Ma, Dik-Lung; Leung, Chung-Hang

2018-03-06

The rhodium(iii) complex 1 was identified as a potent Wee1 inhibitor in vitro and in cellulo. It decreased Wee1 activity and unscheduled mitotic entry, and induced cell damage and death in TP53-mutated triple-negative breast cancer cells. 1 represents a promising scaffold for further development of more potent metal-based Wee1 antagonists.

The diagnostic value of thyroglobulin concentration in fine-needle aspiration of the cervical lymph nodes in patients with differentiated thyroid cancer

International Nuclear Information System (INIS)

Mikosinski, S.; Oszukowska, L.; Makarewicz, J.; Adamczewski, Z.; Lewinski, A.; Pomorski, L.; Sporny, S.

2006-01-01

Introduction: Recurrent differentiated thyroid cancer generally occurs first in the neck. Ultrasound is sensitive in detecting enlarged cervical lymph nodes but is not specific enough. Ultrasound-guided fine-needle biopsy increases the specificity but still may fail to detect a recurrence of the disease in the cystic metastatic lymph nodes. The aim of the study was to estimate the value of Tg concentration in the needle washout after fine-needle aspiration of suspicious lymph nodes. Material and methods: The 105 patients studied had presented one or more enlarged suspicious cervical lymph nodes. All had undergone total thyroidectomy and 131I ablative therapy. Serum thyroglobulin (Tg) concentration was within the 0.15 - 711.5 ng/ml range (mean 22.24 ng/ml) and Tg recovery range 94 - 100%. The positive Tg washout concentration cut-off value was established as equal to the mean plus two standard deviations of the Tg washout concentration of patients with negative cytology. Results: Lymph node involvement was diagnosed by cytology in 15 patients and in 28 lymph nodes. Positive Tg washout concentration was found in 22 patients and in 48 lymph nodes. All the lymph nodes which turned out to have positive cytology had a positive Tg washout concentration. All lymph nodes with positive cytology were positive in pathology. Seven patients and 20 lymph nodes with negative cytology were positive in the Tg washout concentration test. All but one patients and all but two lymph nodes with a positive Tg washout concentration had positive pathology. Conclusions: 1. Ultrasound-guided fine-needle biopsy is not sensitive enough to detect all metastatic lymph nodes. 2. The Tg washout concentration test is 100% sensitive in the detection of metastatic lymph nodes. 3. Cytology in ultrasound- guided fine-needle biopsy is 100% specific. 4. The Tg washout concentration test carries a risk of false-positive results. 5. Both methods should be used for early detection of metastatic lymph nodes

A systematic review of tests for lymph node status in primary endometrial cancer.

Science.gov (United States)

Selman, Tara J; Mann, Christopher H; Zamora, Javier; Khan, Khalid S

2008-05-05

The lymph node status of a patient is a key determinate in staging, prognosis and adjuvant treatment of endometrial cancer. Despite this, the potential additional morbidity associated with lymphadenectomy makes its role controversial. This study systematically reviews the accuracy literature on sentinel node biopsy; ultra sound scanning, magnetic resonance imaging (MRI) and computer tomography (CT) for determining lymph node status in endometrial cancer. Relevant articles were identified form MEDLINE (1966-2006), EMBASE (1980-2006), MEDION, the Cochrane library, hand searching of reference lists from primary articles and reviews, conference abstracts and contact with experts in the field. The review included 18 relevant primary studies (693 women). Data was extracted for study characteristics and quality. Bivariate random-effect model meta-analysis was used to estimate diagnostic accuracy of the various index tests. MRI (pooled positive LR 26.7, 95% CI 10.6 - 67.6 and negative LR 0.29 95% CI 0.17 - 0.49) and successful sentinel node biopsy (pooled positive LR 18.9 95% CI 6.7 - 53.2 and negative LR 0.22, 95% CI 0.1 - 0.48) were the most accurate tests. CT was not as accurate a test (pooled positive LR 3.8, 95% CI 2.0 - 7.3 and negative LR of 0.62, 95% CI 0.45 - 0.86. There was only one study that reported the use of ultrasound scanning. MRI and sentinel node biopsy have shown similar diagnostic accuracy in confirming lymph node status among women with primary endometrial cancer than CT scanning, although the comparisons made are indirect and hence subject to bias. MRI should be used in preference, in light of the ASTEC trial, because of its non invasive nature.

A systematic review of tests for lymph node status in primary endometrial cancer

Directory of Open Access Journals (Sweden)

Zamora Javier

2008-05-01

Full Text Available Abstract Background The lymph node status of a patient is a key determinate in staging, prognosis and adjuvant treatment of endometrial cancer. Despite this, the potential additional morbidity associated with lymphadenectomy makes its role controversial. This study systematically reviews the accuracy literature on sentinel node biopsy; ultra sound scanning, magnetic resonance imaging (MRI and computer tomography (CT for determining lymph node status in endometrial cancer. Methods Relevant articles were identified form MEDLINE (1966–2006, EMBASE (1980–2006, MEDION, the Cochrane library, hand searching of reference lists from primary articles and reviews, conference abstracts and contact with experts in the field. The review included 18 relevant primary studies (693 women. Data was extracted for study characteristics and quality. Bivariate random-effect model meta-analysis was used to estimate diagnostic accuracy of the various index tests. Results MRI (pooled positive LR 26.7, 95% CI 10.6 – 67.6 and negative LR 0.29 95% CI 0.17 – 0.49 and successful sentinel node biopsy (pooled positive LR 18.9 95% CI 6.7 – 53.2 and negative LR 0.22, 95% CI 0.1 – 0.48 were the most accurate tests. CT was not as accurate a test (pooled positive LR 3.8, 95% CI 2.0 – 7.3 and negative LR of 0.62, 95% CI 0.45 – 0.86. There was only one study that reported the use of ultrasound scanning. Conclusion MRI and sentinel node biopsy have shown similar diagnostic accuracy in confirming lymph node status among women with primary endometrial cancer than CT scanning, although the comparisons made are indirect and hence subject to bias. MRI should be used in preference, in light of the ASTEC trial, because of its non invasive nature.

Incidence and Outcome of BRCA Mutations in Unselected Patients with Triple Receptor-Negative Breast Cancer.

LENUS (Irish Health Repository)

Gonzalez-Angulo, Ana M

2011-03-01

To investigate the incidence of germline and somatic BRCA1\\/2 mutations in unselected patients with triple-negative breast cancer (TNBC) and determine the prognostic significance of carrying a mutation. Methods: DNA was obtained from 77 TNBC and normal tissues. BRCA1\\/2 exons\\/flanking regions were sequenced from tumor and patients classified as mutant or wild type (WT). Sequencing was repeated from normal tissue to identify germline and somatic mutations. Patient characteristics were compared with chi-square. Survival was estimated by Kaplan-Meier method and compared with log-rank. Cox proportional hazards models were fit to determine the independent association of mutation status with outcome.

Clinical impact of sentinel lymph node biopsy in patients with thick (>4 mm) melanomas.

Science.gov (United States)

White, Ian; Fortino, Jeanine; Curti, Brendan; Vetto, John

2014-05-01

The role of sentinel lymph node status (SLNS) in thick melanoma is evolving. The purpose of this study was to determine the prognostic value of SLNS in thick melanoma. A retrospective analysis of 120 prospectively collected clinically node-negative thick melanomas over 5 years was performed. Patient (age/sex) and tumor (thickness, ulceration, SLNS, mitoses, metastases, and recurrence) features were collected. Multivariate analysis was performed using Cox proportional hazard model. Factors predictive of positive SLN included male sex, ulceration, and high mitoses. Factors associated with positive SLN had higher local-regional recurrence and metastases than negative SLN. SLNS and tumor thickness impacted 5-year disease-free survival (DFS) and overall survival (OS). Positive SLN, ulceration, age, and mitoses were independent predictors of DFS/OS. Nonulcerated/lower mitoses thick melanomas had lower positive SLN rates. Positive SLN develop recurrence and metastases and have worse OS/DFS. SLNS is an important prognosticator for OS/DFS. Sentinel lymph node biopsy delineates prognostic groups in thick melanomas and can impact management. Copyright © 2014 Elsevier Inc. All rights reserved.

Urine-Based Nested PCR for the Diagnosis of Mycobacterium tuberculosis: A Comparative Study Between HIV-Positive and HIV-Negative Patients.

Science.gov (United States)

Jamshidi Makiani, Mahin; Davoodian, Parivash; Baghershiroodi, Mahnaz; Nejatizadeh, Abdol Azim; Fakkhar, Farideh; Zangeneh, Mehrangiz; Jahangiri, Nadia

2016-08-01

While tuberculosis (TB) can be diagnosed by microscopy and culture, the sensitivity of Ziehl-Neelsen staining is variable and culture results require 4 - 8 weeks to be determined. Polymerase chain reaction (PCR) and its modifications, including nested PCR, might be promising methods for the rapid diagnosis of TB. This study aimed to evaluate the performance of nested PCR on urine samples of human immunodeficiency virus (HIV)-positive and -negative patients with different manifestations of clinical TB. In a prospective study, three early-morning urine samples from 100 patients with pulmonary TB (PTB) or extrapulmonary TB (EPTB) were evaluated using a molecular target with insertion element IS6110, specific to the Mycobacterium tuberculosis genome, and nested PCR was performed. The results were analyzed with SPSS version 22. A total of 100 patients, including 74 (74%) with PTB and 26 (26%) with EPTB, were enrolled. Positive smears were seen in 38 patients (38%). Lymph nodes were the most commonly involved organ in 14 of the 26 (53.8%) EPTB patients (13.5%). Seven (23.1%) of the EPTB patients were HIV-positive. Urine PCR was positive in only 28 patients (28%). Seven HIV-positive patients with PTB showed positive urine PCR results. Moreover, PCR results were positive in only one of the seven HIV-positive subjects with EPTB. Positive PCR results were found in 20 of the 73 HIV-negative patients (27.4%) and in 8 of the 27 HIV-positive patients (29.6%). Therefore, there was no significant difference between the HIV-negative and HIV-positive patients for urine PCR (sensitivity 29.6%, specificity 72.6%; positive and negative predictive values 28% and 72%, respectively; P = 0.138). Nested PCR showed the same sensitivity in HIV-positive and HIV-negative patients. It can be applied as a rapid technique for the diagnosis of TB.

Risk of Recurrence and Chemotherapy Benefit for Patients With Node-Negative, Estrogen Receptor–Positive Breast Cancer: Recurrence Score Alone and Integrated With Pathologic and Clinical Factors

Science.gov (United States)

Tang, Gong; Cuzick, Jack; Costantino, Joseph P.; Dowsett, Mitch; Forbes, John F.; Crager, Michael; Mamounas, Eleftherios P.; Shak, Steven; Wolmark, Norman

2011-01-01

Purpose The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) –positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value. Patients and Methods From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20. Results RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037). Conclusion RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit. PMID:22010013

Risk of recurrence and chemotherapy benefit for patients with node-negative, estrogen receptor-positive breast cancer: recurrence score alone and integrated with pathologic and clinical factors.

Science.gov (United States)

Tang, Gong; Cuzick, Jack; Costantino, Joseph P; Dowsett, Mitch; Forbes, John F; Crager, Michael; Mamounas, Eleftherios P; Shak, Steven; Wolmark, Norman

2011-11-20

The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) -positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value. From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were compared in node-negative (N0) patients. RSPC was compared with RS for predicting chemotherapy benefit in NSABP B-20. RSPC had significantly more prognostic value for distant recurrence than did RS (P < .001) and showed better separation of risk in the study population. RSPC classified fewer patients as intermediate risk (17.8% v 26.7%, P < .001) and more patients as lower risk (63.8% v 54.2%, P < .001) than did RS among 1,444 N0 ER-positive patients. In B-20, the interaction of RSPC with chemotherapy was not statistically significant (P = .10), in contrast to the previously reported significant interaction of RS with chemotherapy (P = .037). RSPC refines the assessment of distant recurrence risk and reduces the number of patients classified as intermediate risk. Adding clinicopathologic measures did not seem to enhance the value of RS alone nor the individual biology RS identifies in predicting chemotherapy benefit.

Renal lymph nodes for tumor staging: appraisal of 871 nephrectomies with examination of hilar fat.

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Mehta, Vikas; Mudaliar, Kumaran; Ghai, Ritu; Quek, Marcus L; Milner, John; Flanigan, Robert C; Picken, Maria M

2013-11-01

Despite decades of research, the role of lymphadenectomy in the management of renal cell carcinoma (RCC) is still not clearly defined. Before the implementation of targeted therapies, lymph node metastases were considered to be a portent of markedly decreased survival, regardless of the tumor stage. However, the role of lymphadenectomy and the relative benefit of retroperitoneal lymph node dissection in the context of modern adjunctive therapies have not been conclusively addressed in the clinical literature. The current pathologic literature does not offer clear recommendations with regard to the minimum number of lymph nodes that should be examined in order to accurately stage the pN in renal cell carcinoma. Although gross examination of the hilar fat to assess the nodal status is performed routinely, it has not yet been determined whether this approach is adequate. To evaluate the status of lymph nodes and their rate of identification in the pathologic examination of nephrectomy specimens in adult renal malignancies. We reviewed the operative and pathology reports of 871 patients with renal malignancies treated by nephrectomy. All tumors were classified according to the seventh edition of the Tumor-Nodes-Metastasis classification. Patients were divided into 3 groups: Nx, no lymph nodes recovered; N0, negative; and N1, with positive lymph nodes. Grossly visible lymph nodes were submitted separately; as per grossing protocol, hilar fatty tissue was submitted for microscopic examination. We evaluated the factors that affected the number of lymph nodes identified and the variables that allowed the prediction of nodal involvement. Lymph nodes were recovered in 333 of 871 patients (38%): hilar in 125 patients, nonhilar in 137 patients, and hilar and nonhilar in 71 patients. Patients with positive lymph nodes (n = 87) were younger, had larger primary tumors, and had lymph nodes of average size, as well as a higher pT stage, nuclear grade, and rate of metastases

Triple negative breast cancers have a reduced expression of DNA repair genes.

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Enilze Ribeiro

Full Text Available DNA repair is a key determinant in the cellular response to therapy and tumor repair status could play an important role in tailoring patient therapy. Our goal was to evaluate the mRNA of 13 genes involved in different DNA repair pathways (base excision, nucleotide excision, homologous recombination, and Fanconi anemia in paraffin embedded samples of triple negative breast cancer (TNBC compared to luminal A breast cancer (LABC. Most of the genes involved in nucleotide excision repair and Fanconi Anemia pathways, and CHK1 gene were significantly less expressed in TNBC than in LABC. PARP1 levels were higher in TNBC than in LABC. In univariate analysis high level of FANCA correlated with an increased overall survival and event free survival in TNBC; however multivariate analyses using Cox regression did not confirm FANCA as independent prognostic factor. These data support the evidence that TNBCs compared to LABCs harbour DNA repair defects.

CXCR4 Protein Epitope Mimetic Antagonist POL5551 Disrupts Metastasis and Enhances Chemotherapy Effect in Triple-Negative Breast Cancer.

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Xiang, Jingyu; Hurchla, Michelle A; Fontana, Francesca; Su, Xinming; Amend, Sarah R; Esser, Alison K; Douglas, Garry J; Mudalagiriyappa, Chidananda; Luker, Kathryn E; Pluard, Timothy; Ademuyiwa, Foluso O; Romagnoli, Barbara; Tuffin, Gérald; Chevalier, Eric; Luker, Gary D; Bauer, Michael; Zimmermann, Johann; Aft, Rebecca L; Dembowsky, Klaus; Weilbaecher, Katherine N

2015-11-01

The SDF-1 receptor CXCR4 has been associated with early metastasis and poorer prognosis in breast cancers, especially the most aggressive triple-negative subtype. In line with previous reports, we found that tumoral CXCR4 expression in patients with locally advanced breast cancer was associated with increased metastases and rapid tumor progression. Moreover, high CXCR4 expression identified a group of bone marrow-disseminated tumor cells (DTC)-negative patients at high risk for metastasis and death. The protein epitope mimetic (PEM) POL5551, a novel CXCR4 antagonist, inhibited binding of SDF-1 to CXCR4, had no direct effects on tumor cell viability, but reduced migration of breast cancer cells in vitro. In two orthotopic models of triple-negative breast cancer, POL5551 had little inhibitory effect on primary tumor growth, but significantly reduced distant metastasis. When combined with eribulin, a chemotherapeutic microtubule inhibitor, POL5551 additively reduced metastasis and prolonged survival in mice after resection of the primary tumor compared with single-agent eribulin. Hypothesizing that POL5551 may mobilize tumor cells from their microenvironment and sensitize them to chemotherapy, we used a "chemotherapy framing" dosing strategy. When administered shortly before and after eribulin treatment, three doses of POL5551 with eribulin reduced bone and liver tumor burden more effectively than chemotherapy alone. These data suggest that sequenced administration of CXCR4 antagonists with cytotoxic chemotherapy synergize to reduce distant metastases. ©2015 American Association for Cancer Research.

Family Caregivers' Patterns of Positive and Negative Affect

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Robertson, Suzanne M.; Zarit, Steven H.; Duncan, Larissa G.; Rovine, Michael J.; Femia, Elia E.

2007-01-01

Stressful and positive family caregiving experiences were examined as predictors of caregivers' patterns of positive and negative affect in a sample of families providing care for a relative with dementia (N = 234). Four affect pattern groups were identified: (a) Well Adjusted (i.e., high positive affect, low negative affect); (b) Ambiguous (i.e.,…

A Novel Differentiation Therapy Approach to Reduce the Metastatic Potential of Basal, Highly Metastatic, Triple-Negative Breast Cancers

Science.gov (United States)

2012-05-01

metastatic process (Condeelis and Pollard 2006), we quantitated macrophage recruitment in the lungs of mice injected with 231-Empty or 231-GATA3 cells by...image quantitation of Ki-67 expression and H&E staining of metastatic lung lesions using Apirio Image Analysis software (Figure 9) which demonstrated...expression in MD A-MB-231 and in another triple negative breast cancer cell line, Hs578T Transient knock down of GATA3 in the lum inal GATA3 positiv

Positive rights, negative rights and health care.

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Bradley, Andrew

2010-12-01

In the current debate about healthcare reform in the USA, advocates for government-ensured universal coverage assume that health care is a right. Although this position is politically popular, it is sometimes challenged by a restricted view of rights popular with libertarians and individualists. The restricted view of rights only accepts 'negative' rights as legitimate rights. Negative rights, the argument goes, place no obligations on you to provide goods to other people and thus respect your right to keep the fruits of your labour. A classic enumeration of negative rights includes life, liberty, and the pursuit of happiness. Positive rights, by contrast, obligate you either to provide goods to others, or pay taxes that are used for redistributive purposes. Health care falls into the category of positive rights since its provision by the government requires taxation and therefore redistribution. Therefore, the libertarian or individualist might argue that health care cannot be a true right. This paper rejects the distinction between positive and negative rights. In fact, the protection of both positive and negative rights can place obligations on others. Furthermore, because of its role in helping protect equality of opportunity, health care can be tied to the rights to life, liberty, and the pursuit of happiness. There is, therefore, good reason to believe that health care is a human right and that universal access should be guaranteed. The practical application, by governments and non-governmental organisations, of several of the arguments presented in this paper is also discussed.

Cotargeting the lncRNA-PIP3 Interaction and AKT/PI3K Signaling Axis: A Novel Paradigm for Treating Triple-Negative Breast Cancer

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2017-10-01

Negative Breast Cancer PRINCIPAL INVESTIGATOR: Dr. Liuqing Yang CONTRACTING ORGANIZATION: University of Texas MD Anderson Cancer Center Houston, TX...Signaling Axis: A Novel Paradigm for Treating Triple-Negative Breast Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Liuqing Yang 5d...ORGANIZATION REPORT NUMBER UNIVERSITY OF TEXAS M D ANDERSON CANCER HOUSTON TX 77030-0417 9. SPONSORING / MONITORING AGENCY NAME(S) AND ADDRESS(ES

Positive and Negative Affect More Concurrent among Blacks than Whites.

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Lankarani, Maryam Moghani; Assari, Shervin

2017-08-01

While positive and negative affect are inversely linked, people may experience and report both positive and negative emotions simultaneously. However, it is unknown if race alters the magnitude of the association between positive and negative affect. The current study compared Black and White Americans for the association between positive and negative affect. We used data from MIDUS (Midlife in the United States), a national study of Americans with an age range of 25 to 75. A total number of 7108 individuals were followed for 10 years from 1995 to 2004. Positive and negative affect was measured at baseline (1995) and follow-up (2004). Demographic (age and gender), socioeconomic (education and income) as well as health (self-rated health, chronic medical conditions, and body mass index) factors measured at baseline were covariates. A series of linear regressions were used to test the moderating effect of race on the reciprocal association between positive and negative affect at baseline and over time, net of covariates. In the pooled sample, positive and negative affect showed inverse correlation at baseline and over time, net of covariates. Blacks and Whites differed in the magnitude of the association between positive and negative affect, with weaker inverse associations among Blacks compared to Whites, beyond all covariates. Weaker reciprocal association between positive and negative affect in Blacks compared to Whites has implications for cross-racial measurement of affect and mood, including depression. Depression screening programs should be aware that race alters the concordance between positive and negative affect domains and that Blacks endorse higher levels of positive affect compared to Whites in the presence of high negative affect.

Triple negative breast cancer: new therapeutic approaches and BRCA status.

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Guney Eskiler, Gamze; Cecener, Gulsah; Egeli, Unal; Tunca, Berrin

2018-05-01

Treatment of triple negative breast cancer (TNBC) is a clinically challenging problem due to intriguing clinical and pathologic features of TNBC and natural or induced resistance to existing therapies. However, a great understanding of features of TNBC particularly associated with BRCA mutations has led to the development of different therapeutic approaches. Besides, identification of TNBC subtypes contribute to investigation of the underlying molecular differences and development of new strategies for the treatment of TNBC patients. In this review, we discussed the definition and characteristic properties of TNBC. We summarized an up-to-date description of the reported clinical trials of novel targeted strategies especially PARP inhibitors (PARPi) due to novel and highly potent for the treatment of TNBC. Additionally, we reviewed published studies which investigated the prevalence and types of BRCA1/2 mutation in breast cancer patients to assess and draw attention of association of BRCA status with TNBC. Consequently, the definition subtype of TNBC has important predictive value for the development of new therapeutic agents in the treatment of TNBC. Additionally, the incidence and types of mutations in BRCA-related pathways may be affected by ethnic origin and contribute to the risk of developing TNBC. © 2018 APMIS. Published by John Wiley & Sons Ltd.

MENA Confers Resistance to Paclitaxel in Triple-Negative Breast Cancer.

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Oudin, Madeleine J; Barbier, Lucie; Schäfer, Claudia; Kosciuk, Tatsiana; Miller, Miles A; Han, Sangyoon; Jonas, Oliver; Lauffenburger, Douglas A; Gertler, Frank B

2017-01-01

Taxane therapy remains the standard of care for triple-negative breast cancer. However, high frequencies of recurrence and progression in treated patients indicate that metastatic breast cancer cells can acquire resistance to this drug. The actin regulatory protein MENA and particularly its invasive isoform, MENA INV , are established drivers of metastasis. MENA INV expression is significantly correlated with metastasis and poor outcome in human patients with breast cancer. We investigated whether MENA isoforms might play a role in driving resistance to chemotherapeutics. We find that both MENA and MENA INV confer resistance to the taxane paclitaxel, but not to the widely used DNA-damaging agents doxorubicin or cisplatin. Furthermore, paclitaxel treatment does not attenuate growth of MENA INV -driven metastatic lesions. Mechanistically, MENA isoform expression alters the ratio of dynamic and stable microtubule populations in paclitaxel-treated cells. MENA expression also increases MAPK signaling in response to paclitaxel treatment. Decreasing ERK phosphorylation by co-treatment with MEK inhibitor restored paclitaxel sensitivity by driving microtubule stabilization in MENA isoform-expressing cells. Our results reveal a novel mechanism of taxane resistance in highly metastatic breast cancer cells and identify a combination therapy to overcome such resistance. Mol Cancer Ther; 16(1); 143-55. ©2016 AACR. ©2016 American Association for Cancer Research.

Prognostic role of a multigene reverse transcriptase-PCR assay in patients with node-negative breast cancer not receiving adjuvant systemic therapy.

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Esteva, Francisco J; Sahin, Aysegul A; Cristofanilli, Massimo; Coombes, Kevin; Lee, Sang-Joon; Baker, Joffre; Cronin, Maureen; Walker, Michael; Watson, Drew; Shak, Steven; Hortobagyi, Gabriel N

2005-05-01

To test the ability of a reverse transcriptase-PCR (RT-PCR) assay, based on gene expression profiles, to accurately determine the risk of recurrence in patients with node-negative breast cancer who did not receive systemic therapy using formalin-fixed, paraffin-embedded tissue. A secondary objective was to determine whether the quantitative RT-PCR data correlated with immunohistochemistry assay data regarding estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status. We obtained archival paraffin-embedded tissue from patients with invasive breast cancer but no axillary lymph node involvement who had received no adjuvant systemic therapy and been followed for at least 5 years. RNA was extracted from three 10-microm-thick sections. The expression of 16 cancer-related genes and 5 reference genes was quantified using RT-PCR. A gene expression algorithm was used to calculate a recurrence score for each patient. We then assessed the ability of the test to accurately predict distant recurrence-free survival in this population. We identified 149 eligible patients. Median age at diagnosis was 59 years; mean tumor diameter was 2 cm; and 69% of tumors were estrogen receptor positive. Median follow-up was 18 years. The 5-year disease-free survival rate for the group was 80%. The 21 gene-based recurrence score was not predictive of distant disease recurrence. However, a high concordance between RT-PCR and immunohistochemical assays for estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 status was noted. RT-PCR can be done on paraffin-embedded tissue to validate the large numbers of genes associated with breast cancer recurrence. However, further work needs to be done to develop an assay to identify the likelihood of recurrent disease in patients with node-negative breast cancer who do not receive adjuvant tamoxifen or chemotherapy.

Relationship Between Quantitative GRB7 RNA Expression and Recurrence after Adjuvant Anthracycline Chemotherapy in Triple Negative Breast Cancer

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Sparano, Joseph A.; Goldstein, Lori J.; Childs, Barrett H.; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L.; Bugarini, Roberto; Rowley, Steve; Perez, Edith; Shulman, Lawrence N.; Martino, Silvana; Davidson, Nancy E.; Kenny, Paraic A.; Sledge, George W.; Gray, Robert

2012-01-01

Purpose To perform an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. Experimental design RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative RT-PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Results GRB7 was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn’s adjusted p value=0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR 2.31, p=0.04 using the median as the split). The 5-year recurrence rates were 10.5% (95% confidence intervals [CI] 7.8%, 14.1%) in the low and 20.4% (95% CI 16.5%, 25.0%) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. Conclusions GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered. PMID:21933890

Relationship between quantitative GRB7 RNA expression and recurrence after adjuvant anthracycline chemotherapy in triple-negative breast cancer.

Science.gov (United States)

Sparano, Joseph A; Goldstein, Lori J; Childs, Barrett H; Shak, Steven; Brassard, Diana; Badve, Sunil; Baehner, Frederick L; Bugarini, Roberto; Rowley, Steve; Perez, Edith A; Shulman, Lawrence N; Martino, Silvana; Davidson, Nancy E; Kenny, Paraic A; Sledge, George W; Gray, Robert

2011-11-15

To conduct an exploratory analysis of the relationship between gene expression and recurrence in patients with operable triple-negative breast cancer (TNBC) treated with adjuvant doxorubicin-containing chemotherapy. RNA was extracted from archived tumor samples derived from 246 patients with stage I-III TNBC treated with adjuvant doxorubicin-containing chemotherapy, and was analyzed by quantitative reverse transcriptase PCR for a panel of 374 genes. The relationship between gene expression and recurrence was evaluated using weighted Cox proportional hazards model score tests. Growth factor receptor bound protein 7 (GRB7) was the only gene for which higher expression was significantly associated with increased recurrence in TNBC (Korn's adjusted P value = 0.04). In a Cox proportional hazards model adjusted for clinicopathologic features, higher GRB7 expression was associated with an increased recurrence risk (HR = 2.31; P = 0.04 using the median as the split). The 5-year recurrence rates were 10.5% [95% confidence intervals (CI), 7.8-14.1] in the low and 20.4% (95% CI, 16.5-25.0) in the high GRB7 groups. External validation in other datasets indicated that GRB7 expression was not prognostic in two adjuvant trials including variable systemic therapy, but in two other trials showed that high GBR7 expression was associated with resistance to neoadjuvant doxorubicin and taxane therapy. GRB7 was associated with an increased risk of recurrence in TNBC, suggesting that GRB7 or GRB7-dependent pathways may serve as potential biomarkers for therapeutic targets. Therapeutic targeting of one or more factors identified which function as interaction nodes or effectors should also be considered.

Ratios of involved nodes in early breast cancer

International Nuclear Information System (INIS)

Vinh-Hung, Vincent; Royce, Melanie; Verschraegen, Claire; Promish, Donald I; Cserni, Gábor; Van de Steene, Jan; Tai, Patricia; Vlastos, Georges; Voordeckers, Mia; Storme, Guy

2004-01-01

The number of lymph nodes found to be involved in an axillary dissection is among the most powerful prognostic factors in breast cancer, but it is confounded by the number of lymph nodes that have been examined. We investigate an idea that has surfaced recently in the literature (since 1999), namely that the proportion of node-positive lymph nodes (or a function thereof) is a much better predictor of survival than the number of excised and node-positive lymph nodes, alone or together. The data were abstracted from 83,686 cases registered in the Surveillance, Epidemiology, and End Results (SEER) program of women diagnosed with nonmetastatic T1–T2 primary breast carcinoma between 1988 and 1997, in whom axillary node dissection was performed. The end-point was death from breast cancer. Cox models based on different expressions of nodal involvement were compared using the Nagelkerke R 2 index (R 2 N ). Ratios were modeled as percentage and as log odds of involved nodes. Log odds were estimated in a way that avoids singularities (zero values) by using the empirical logistic transform. In node-negative cases both the number of nodes excised and the log odds were significant, with hazard ratios of 0.991 (95% confidence interval 0.986–0.997) and 1.150 (1.058–1.249), respectively, but without improving R 2 N . In node-positive cases the hazard ratios were 1.003–1.088 for the number of involved nodes, 0.966–1.005 for the number of excised nodes, 1.015–1.017 for the percentage, and 1.344–1.381 for the log odds. R 2 N improved from 0.067 (no nodal covariate) to 0.102 (models based on counts only) and to 0.108 (models based on ratios). Ratios are simple optimal predictors, in that they provide at least the same prognostic value as the more traditional staging based on counting of involved nodes, without replacing them with a needlessly complicated alternative. They can be viewed as a per patient standardization in which the number of involved nodes is standardized

Evaluation of MR lymphography with positive lymphotropic contrast agent in diagnosing lymph node lesions

International Nuclear Information System (INIS)

Zhou Zhengyang; Yu Haiping; Chen Junkun; Zhu Bin

2010-01-01

Objective: To evaluate the interstital MR lymphography using positive lymphotropic contrast agent for differentiation of metastatic lymph nodes from inflammatory lymph nodes hyperplasm. Methods: Eighteen New Zealand white rabbits weighted at 2. 0-2. 5 kg were used. Inflammatory hyperplastic popliteal lymph node model was established in 9 rabbits by injection of complete freund adjuvant into the interdigitial skin of the dorsal aspect of one hind leg, and tumor-bearing popliteal lymph node model was established in another 9 rabbits by injection of VX2 tumor cell suspension. The popliteal lymph nodes of another hind leg of all 18 rabbits were assigned to the normal contral group. In each group, every rabbit underwent MR lymphography examination before and after the inoculation. Volumes of 0.2 ml of Gd [ DTPA-bis ( 2-aminoethoxy ) ethane ] polymeric contrast agent ( Gd-poly-DTPA-EOEA ) injection were injected subcutaneously into the dorsal feet of both hind legs of two groups of rabbits. T 1 -weighted 3D gradient-echo images were obtained, and source images were used to reconstruct images of MIP before and after the administration of agent. The maximum short-axis diameter (MSAD) of each popliteal lymph node was measured on the enhanced 3D MIP images, and the signal-to-noise ratio (SNR) measurement was performed in the largest popliteal node of each rabbit at each time point in delayed scan. Independent- samples t test was used to compare the sizes of popliteal nodes in MSADs between inflammatorily hyperplastic and tumor-bearing nodes after the inoculation, and the values of SNRs of popliteal nodes at each time point between inflammatorily hyperplastic, tumor-bearing and normal popliteal lymph nodes. Imaging results of the popliteal nodes were analyzed and correlated with pathological findings. Results: All of the rabbits were successfully inoculated except of the 2 rabbits in tumor-bearing nodal group. The size in MSAD of 13 inflammatorily hyperplastic and 11 tumor

Retrieval of past and future positive and negative autobiographical experiences.

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García-Bajos, Elvira; Migueles, Malen

2017-09-01

We studied retrieval-induced forgetting for past or future autobiographical experiences. In the study phase, participants were given cues to remember past autobiographical experiences or to think about experiences that may occur in the future. In both conditions, half of the experiences were positive and half negative. In the retrieval-practice phase, for past and future experiences, participants retrieved either half of the positive or negative experiences using cued recall, or capitals of the world (control groups). Retrieval practice produced recall facilitation and enhanced memory for the practised positive and negative past and future experiences. While retrieval practice on positive experiences did not impair the recall of other positive experiences, we found inhibition for negative past and future experiences when participants practised negative experiences. Furthermore, retrieval practice on positive future experiences inhibited negative future experiences. These positivity biases for autobiographical memory may have practical implications for treatment of emotional disorders.

Lymph node yield during radical prostatectomy does not impact rate of biochemical recurrence in patients with seminal vesicle invasion and node-negative disease.

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Badani, Ketan K; Reddy, Balaji N; Moskowitz, Eric J; Paulucci, David J; Beksac, Alp Tuna; Martini, Alberto; Whalen, Michael J; Skarecky, Douglas W; Huynh, Linda My; Ahlering, Thomas E

2018-06-01

Seminal vesicle invasion (SVI) is a risk factor for poor oncologic outcome in patients with prostate cancer. Modifications to the pelvic lymph node dissection (PLND) during radical prostatectomy (RP) have been reported to have a therapeutic benefit. The present study is the first to determine if lymph node yield (LNY) is associated with a lower risk of biochemical recurrence (BCR) for men with SVI. A total of 220 patients from 2 high-volume institutions who underwent RP without adjuvant treatment between 1990 and 2015 and had prostate cancer with SVI (i.e., pT3b) were identified, and 21 patients did not undergo lymph node dissection. BCR was defined as a postoperative PSA>0.2ng/mL, or use of salvage androgen deprivation therapy (ADT) or radiation. Multivariable Cox proportional hazards models were used to determine whether LNY was predictive of BCR, controlling for PSA, pathologic Gleason Score, pathologic lymph node status, NCCN risk category, etc. The Kaplan-Meier method was used to determine 3-year freedom from BCR. Median number of lymph nodes sampled were 7 (IQR: 3-12; range: 0-35) and 90.5% underwent PLND. The estimated 3-year BCR rate was 43.9%. Results from multivariable analysis demonstrated that LNY was not significantly associated with risk of BCR overall (HR = 1.00, 95% CI: 0.98-1.03; P = 0.848) for pN0 (HR = 0.99, 95% CI: 0.97-1.03; P = 0.916) or pN1 patients (HR = 0.96, 95% CI: 0.88-1.06; P = 0.468). Overall, PSA (HR = 1.02, P2 positive lymph nodes (OR = 1.27, 95% CI: 1.06-1.65, P = 0.023). Seminal vesicle invasion is associated with an increased risk of BCR at 3 years, primarily due to pathologic Gleason score and PSA. Although greater lymph node yield is diagnostic and facilitates more accurate pathologic staging, our data do not show a therapeutic benefit in reducing BCR. Copyright © 2018 Elsevier Inc. All rights reserved.

High Frequency of CD8 Positive Lymphocyte Infiltration Correlates with Lack of Lymph Node Involvement in Early Rectal Cancer

Directory of Open Access Journals (Sweden)

Silvio Däster

2014-01-01

Full Text Available Aims. A trend towards local excision of early rectal cancers has prompted us to investigate if immunoprofiling might help in predicting lymph node involvement in this subgroup. Methods. A tissue microarray of 126 biopsies of early rectal cancer (T1 and T2 was stained for several immunomarkers of the innate and the adaptive immune response. Patients’ survival and nodal status were analyzed and correlated with infiltration of the different immune cells. Results. Of all tested markers, only CD8 (P=0.005 and TIA-1 (P=0.05 were significantly more frequently detectable in early rectal cancer biopsies of node negative as compared to node positive patients. Although these two immunomarkers did not display prognostic effect “per se,” CD8+ and, marginally, TIA-1 T cell infiltration could predict nodal involvement in univariate logistic regression analysis (OR 0.994; 95% CI 0.992–0.996; P=0.009 and OR 0.988; 95% CI 0.984–0.994; P=0.05, resp.. An algorithm significantly predicting the nodal status in early rectal cancer based on CD8 together with vascular invasion and tumor border configuration could be calculated (P<0.00001. Conclusion. Our data indicate that in early rectal cancers absence of CD8+ T-cell infiltration helps in predicting patients’ nodal involvement.

Sentinel lymph node biopsy: is it possible to reduce false negative rates by excluding patients with nodular melanoma?

LENUS (Irish Health Repository)

Corrigan, M A

2012-02-03

OBJECTIVE: The aim of this study was to review the outcome of sentinel lymph node biopsy (SLNB) in patients with melanoma and to delineate whether patients with nodular melanoma are more likely to develop nodal recurrence despite negative SLNB. METHODS: Consecutive patients with cutaneous melanoma undergoing SLNB were identified from a departmental database between 1997 and 2005. Factors including demographic data, site, histological subtype, depth and outcome were examined. RESULTS: Of 131 patients, 103 were node negative and eligible for study. The median age was 53 (16-82) years with 46 patients being male (45%) and 57 female (55%). Primary melanoma sites included lower limb (49; 48%), upper limb (29; 28%), head (12; 11%), trunk (7; 7%) and back (6; 6%). The median Breslow thickness was 2mm. Superficial spreading accounted for 43% of melanoma with nodular accounting for 42%. Median follow-up was 40 (3-90) months. Of 20 relapses, seven recurred in the same nodal basin, three were satellite recurrences, one recurred with both satellite and nodal lesions simultaneously, and nine experienced haematogenous spread. Of the eight patients who developed recurrence in the same nodal basin, four were of nodular histological subtype (p=NS). All of the three patients with satellite lesions had nodular melanoma histologically (p=0.02). When nodal and satellite recurrences were combined, eight of 11 were histologically nodular (p=0.01). CONCLUSIONS: This study indicates that lymphatic recurrence occurs more often in SLNB negative patients with nodular melanoma. Further evaluation of the inclusion criteria for sentinel node biopsy is warranted.

Experience with local lymph node assay performance standards using standard radioactivity and nonradioactive cell count measurements.

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Basketter, David; Kolle, Susanne N; Schrage, Arnhild; Honarvar, Naveed; Gamer, Armin O; van Ravenzwaay, Bennard; Landsiedel, Robert

2012-08-01

The local lymph node assay (LLNA) is the preferred test for identification of skin-sensitizing substances by measuring radioactive thymidine incorporation into the lymph node. To facilitate acceptance of nonradioactive variants, validation authorities have published harmonized minimum performance standards (PS) that the alternative endpoint assay must meet. In the present work, these standards were applied to a variant of the LLNA based on lymph node cell counts (LNCC) run in parallel as a control with the standard LLNA with radioactivity measurements, with threshold concentrations (EC3) being determined for the sensitizers. Of the 22 PS chemicals tested in this study, 21 yielded the same results from standard radioactivity and cell count measurements; only 2-mercaptobenzothiazole was positive by LLNA but negative by LNCC. Of the 16 PS positives, 15 were positive by LLNA and 14 by LNCC; methylmethacrylate was not identified as sensitizer by either of the measurements. Two of the six PS negatives tested negative in our study by both LLNA and LNCC. Of the four PS negatives which were positive in our study, chlorobenzene and methyl salicylate were tested at higher concentrations than the published PS, whereas the corresponding concentrations resulted in consistent negative results. Methylmethacrylate and nickel chloride tested positive within the concentration range used for the published PS. The results indicate cell counts and radioactive measurements are in good accordance within the same LLNA using the 22 PS test substances. Comparisons with the published PS results may, however, require balanced analysis rather than a simple checklist approach. Copyright © 2011 John Wiley & Sons, Ltd.

A Phenotypic Cell-Binding Screen Identifies a Novel Compound Targeting Triple-Negative Breast Cancer.

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Chen, Luxi; Long, Chao; Youn, Jonghae; Lee, Jiyong

2018-06-11

We describe a "phenotypic cell-binding screen" by which therapeutic candidate targeting cancer cells of a particular phenotype can be isolated without knowledge of drug targets. Chemical library beads are incubated with cancer cells of the phenotype of interest in the presence of cancer cells lacking the phenotype of interest, and then the beads bound to only cancer cells of the phenotype of interest are selected as hits. We have applied this screening strategy in discovering a novel compound (LC129-8) targeting triple-negative breast cancer (TNBC). LC129-8 displayed highly specific binding to TNBC in cancer cell lines and patient-derived tumor tissues. LC129-8 exerted anti-TNBC activity by inducing apoptosis, inhibiting proliferation, reversing epithelial-mesenchymal transition, downregulating cancer stem cell activity and blocking in vivo tumor growth.

Early stage cost-effectiveness analysis of a BRCA1-like test to detect triple negative breast cancers responsive to high dose alkylating chemotherapy

NARCIS (Netherlands)

Miquel-Cases, Anna; Steuten, Lotte Maria Gertruda; Retel, Valesca P.; van Harten, Willem H.

2015-01-01

Purpose Triple negative breast cancers (TNBC) with a BRCA1-like profile may benefit from high dose alkylating chemotherapy (HDAC). This study examines whether BRCA1-like testing to target effective HDAC in TNBC patients can be more cost-effective than treating all patients with standard

The 21-gene Recurrence Score® assay predicts distant recurrence in lymph node-positive, hormone receptor-positive, breast cancer patients treated with adjuvant sequential epirubicin- and docetaxel-based or epirubicin-based chemotherapy (PACS-01 trial).

Science.gov (United States)

Penault-Llorca, Frédérique; Filleron, Thomas; Asselain, Bernard; Baehner, Frederick L; Fumoleau, Pierre; Lacroix-Triki, Magali; Anderson, Joseph M; Yoshizawa, Carl; Cherbavaz, Diana B; Shak, Steven; Roca, Lise; Sagan, Christine; Lemonnier, Jérôme; Martin, Anne-Laure; Roché, Henri

2018-05-04

The 21-gene Recurrence Score (RS) result predicts outcome and chemotherapy benefit in node-negative and node-positive (N+), estrogen receptor-positive (ER+) patients treated with endocrine therapy. The purpose of this study was to evaluate the prognostic impact of RS results in N+, hormone receptor-positive (HR+) patients treated with adjuvant chemotherapy (6 cycles of FEC100 vs. 3 cycles of FEC100 followed by 3 cycles of docetaxel 100 mg/m 2 ) plus endocrine therapy (ET) in the PACS-01 trial (J Clin Oncol 2006;24:5664-5671). The current study included 530 HR+/N+ patients from the PACS-01 parent trial for whom specimens were available. The primary objective was to evaluate the relationship between the RS result and distant recurrence (DR). There were 209 (39.4%) patients with low RS (< 18), 159 (30%) with intermediate RS (18-30) and 162 (30.6%) with high RS (≥ 31). The continuous RS result was associated with DR (hazard ratio = 4.14; 95% confidence interval: 2.67-6.43; p <  0.001), adjusting for treatment. In multivariable analysis, the RS result remained a significant predictor of DR (p <  0.001) after adjustment for number of positive nodes, tumor size, tumor grade, Ki-67 (immunohistochemical status), and chemotherapy regimen. There was no statistically significant interaction between RS result and treatment in predicting DR (p = 0.79). After adjustment for clinical covariates, the 21-gene RS result is a significant prognostic factor in N+/HR+ patients receiving adjuvant chemoendocrine therapy. Not applicable.

The sentinel node concept in breast cancer: A commentary

International Nuclear Information System (INIS)

Canizales, A.L. . E-mail A.L.Canizales@qmul.ac.uk; Al-Yasi, A.; Gambhir, S.; Morris, G.; Granowska, M.; Britton, K.E.

2004-01-01

As there are multiple lymphatic pathways from the breast to the axilla with multiple possible choices for a cancer cell or a colloid, it appears intuitively unusual that one node is preferentially 'chosen'. The intuitive response would be that there is an equal chance for a breast cancer cell to travel by any lymphatic pathway to any axillary node at level 1. If this were true, then after a colloid injection into the peritumoural lymphatics or the periareolar lymphatic plexus, such a colloid has a similar chance to travel to any level 1 axillary node, be it an involved node or an uninvolved node. We have tried to resolve this conflict between intuition and practice. It was tested by identifying and measuring the activity of the radiolabelled colloid in the nodes removed in an axillary clearance and in the sentinel node or nodes after applying a sentinel node technique similar to that of Veronesi et al. The histology of all the nodes that were counted was analysed so that the colloid activity in each node was able to be correlated with its histology, whether it was involved with cancer or not involved. Measurements were obtained in those patients, in whom there were both involved and uninvolved nodes in the axillae. The colloid counts in cpm/g of each node were compared with the related sentinel node findings either involved with cancer or not involved. These were calculated either as the involved to uninvolved that is a 'positive' to 'negative' ratio. The results were that the activity ratio of all involved axillary nodes to uninvolved axillary nodes was about 4:1. The involved Sentinel nodes had on average over 25 times the uptake of the uninvolved Sentinel nodes. P value was <0.009 for a significant difference between colloid uptake in sentinel nodes with positive histology and those with negative histology. It is a new observation that involved axillary nodes show greater uptake of the colloid than uninvolved nodes in all patients where there are both involved

Formation of thin film of negative and positive ions

Energy Technology Data Exchange (ETDEWEB)

Horino, Yuji; Tsubouchi, Nobuteru [Osaka National Research Inst., AIST, Ikeda (Japan)

1997-02-01

Positive and negative ions deposition apparatus (PANDA) was developed by us as new synthesis method of materials. This apparatus is able to form simultaneously or independently the positive and negative ion beams to separate the mass and to control the energy from 10 eV to 3 KeV. It consists of positive beam line, negative beam line and a film formation room. Microwave discharge ion source and plasma sputtering source are used as the positive ion and the negative ion source, respectably. The beam generation test was carried out. The negative ion beams were generated from silicon wafer (target) and measured by MS. The mass spectrum of extracted negative silicon beams showed mass number 28, 29, and 30 of Si{sup -} and Si{sub 2}{sup -}. It proved that ions were separated in the isotope level. Therefore, film, it`s purity is isotope level, may be formed by such ion beams. (S.Y.)

Local behavior and lymph node metastases of Wilms' tumor: accuracy of computed tomography; Comportamento local e metastases linfonodais do tumor de Wilms: acuracia da tomografia computadorizada

Energy Technology Data Exchange (ETDEWEB)

Silva, Eduardo Just da Costa e, E-mail: eduardojust@oi.com.br [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil); Instituto Materno Infantil de Pernambuco (IMIP), Recife, PE (Brazil); Silva, Giselia Alves Pontes da [Universidade Federal de Pernambuco (UFPE), Recife, PE (Brazil). Dept. Maternal Infantil

2014-01-15

Objective: to evaluate the accuracy of computed tomography for local and lymph node staging of Wilms' tumor. Materials and methods: each case of Wilms' tumor was evaluated for the presence of abdominal lymph nodes by a radiologist. Signs of capsule and adjacent organ invasion were analyzed. Surgical and histopathological results were taken as the gold standard. Results: sensitivity was 100% for both mesenteric and retroperitoneal lymph nodes detection, and specificity was, respectively, 12% and 33%, with positive predictive value of 8% and 11% and negative predictive value of 100%. Signs of capsular invasion presented sensitivity of 87%, specificity of 77%, positive predictive value of 63% and negative predictive value of 93%. Signs of adjacent organ invasion presented sensitivity of 100%, specificity of 78%, positive predictive value of 37% and negative predictive value of 100%. Conclusion: computed tomography tumor showed low specificity and low positive predictive value in the detection of lymph node dissemination. The absence of detectable lymph nodes makes their presence unlikely, and likewise regarding the evaluation of local behavior of tumors. (author)

Irregular echogenic foci representing coagulation necrosis: a useful but perhaps under-recognized EUS echo feature of malignant lymph node invasion.

Science.gov (United States)

Bhutani, Manoop S; Saftoiu, Adrian; Chaya, Charles; Gupta, Parantap; Markowitz, Avi B; Willis, Maurice; Kessel, Ivan; Sharma, Gulshan; Zwischenberger, Joseph B

2009-06-01

Coagulation necrosis has been described in malignant lymph nodes. Our aim was to determine if coagulation necrosis in mediastinal lymph nodes imaged by EUS could be used as a useful echo feature for predicting malignant invasion. Patients with known or suspected lung cancer who had undergone mediastinal lymph node staging by EUS. Tertiary Care university hospital. An expert endosonographer blinded to the final diagnosis, reviewed the archived digital EUS images of lymph nodes prior to being sampled by FNA. LNs positive for malignancy by FNA were included. The benign group included lymph node images with either negative EUS-FNA or lymph nodes imaged by EUS but not subjected to EUS-FNA, with surgical correlation of their benign nature. 24 patients were included. 8 patients were found to have coagulation necrosis. 7/8 patients had positive result for malignancy by EUS-FNA. One patient determined to have coagulation necrosis had a non-malignant diagnosis indicating a false positive result. 16 patients had no coagulation necrosis. In 6 patients with no coagulation necrosis, the final diagnosis was malignant and in the remaining 10 cases, the final diagnosis was benign. For coagulation necrosis as an echo feature for malignant invasion, sensitivity was 54%, specificity was 91%, positive predictive value was 88%, negative predictive value was 63% and accuracy was 71%. Coagulation necrosis is a useful echo feature for mediastinal lymph node staging by EUS.

The predictive value of single-photon emission computed tomography/computed tomography for sentinel lymph node localization in head and neck cutaneous malignancy.

Science.gov (United States)

Remenschneider, Aaron K; Dilger, Amanda E; Wang, Yingbing; Palmer, Edwin L; Scott, James A; Emerick, Kevin S

2015-04-01

Preoperative localization of sentinel lymph nodes in head and neck cutaneous malignancies can be aided by single-photon emission computed tomography/computed tomography (SPECT/CT); however, its true predictive value for identifying lymph nodes intraoperatively remains unquantified. This study aims to understand the sensitivity, specificity, and positive and negative predictive values of SPECT/CT in sentinel lymph node biopsy for cutaneous malignancies of the head and neck. Blinded retrospective imaging review with comparison to intraoperative gamma probe confirmed sentinel lymph nodes. A consecutive series of patients with a head and neck cutaneous malignancy underwent preoperative SPECT/CT followed by sentinel lymph node biopsy with a gamma probe. Two nuclear medicine physicians, blinded to clinical data, independently reviewed each SPECT/CT. Activity within radiographically defined nodal basins was recorded and compared to intraoperative gamma probe findings. Sensitivity, specificity, and negative and positive predictive values were calculated with subgroup stratification by primary tumor site. Ninety-two imaging reads were performed on 47 patients with cutaneous malignancy who underwent SPECT/CT followed by sentinel lymph node biopsy. Overall sensitivity was 73%, specificity 92%, positive predictive value 54%, and negative predictive value 96%. The predictive ability of SPECT/CT to identify the basin or an adjacent basin containing the single hottest node was 92%. SPECT/CT overestimated uptake by an average of one nodal basin. In the head and neck, SPECT/CT has higher reliability for primary lesions of the eyelid, scalp, and cheek. SPECT/CT has high sensitivity, specificity, and negative predictive value, but may overestimate relevant nodal basins in sentinel lymph node biopsy. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

Positive and Negative Affect More Concurrent among Blacks than Whites

OpenAIRE

Lankarani, Maryam Moghani; Assari, Shervin

2017-01-01

Background: While positive and negative affect are inversely linked, people may experience and report both positive and negative emotions simultaneously. However, it is unknown if race alters the magnitude of the association between positive and negative affect. The current study compared Black and White Americans for the association between positive and negative affect. Methods: We used data from MIDUS (Midlife in the United States), a national study of Americans with an age range of 25 to 7...

Neoadjuvant letrozole for postmenopausal estrogen receptor-positive, HER2-negative breast cancer patients, a study from the Danish Breast Cancer Cooperative Group (DBCG)

DEFF Research Database (Denmark)

Skriver, Signe Korsgaard; Laenkholm, Anne-Vibeke; Rasmussen, Birgitte Bruun

2018-01-01

response and 55% of patients had partial pathological response. ER at 100%, ductal subtype, tumor size below 2 cm and lymph node-negative status was significantly associated with a better response to NET and malignancy grade 3 with a poorer response to NET. One patient progressed during treatment......INTRODUCTION: Neoadjuvant endocrine treatment (NET) is a low-toxicity approach to achieve operability in locally advanced breast cancer, and to facilitate breast conservation in early breast cancer, particular in patients with highly estrogen receptor (ER) positive and HER2-negative disease. Here......, we report the results obtained by neoadjuvant letrozole in patients with early breast cancer in a phase-II design. MATERIAL AND METHODS: A total of 119 postmenopausal women with ER-positive, HER2-negative operable breast cancer were assigned to four months of neoadjuvant letrozole before definitive...

Impact on regional recurrence and survival of axillary surgery in women with node-negative primary breast cancer

DEFF Research Database (Denmark)

Axelsson, C K; Düring, M; Christiansen, P M

2009-01-01

-negative primary breast cancer treated solely by surgery. Median follow-up was 9 years. RESULTS: The number of lymph nodes removed correlated with a reduction in the rate of subsequent axillary recurrence (from 2.1 to 0.4 per cent; P = 0.037), local recurrence (from 7.4 to 3.8 per cent; P

Case Report: Intramammary lymph node metastasis of an unknown primary, probably occult breast, undifferentiated carcinoma [version 1; referees: 2 approved, 1 approved with reservations

Directory of Open Access Journals (Sweden)

Zacharoula Sidiropoulou

2017-03-01

Full Text Available Little is known about the clinical importance of intramammary lymph node metastasis of breast cancer, even though it is not rare. In the present paper, the authors present an unusual, rare case of an intramammary lymph node metastasis of an unknown primary, probably occult breast cancer, and its management. The patient was submitted to various staging exams and surgical procedures and a definitive diagnosis was not established. From a multidisciplinary context, it was assumed that the patient had a breast triple negative primary with axillary involvement. This decision lead to adjuvant chemo and radiotherapy. Challenging cases like the one described here, should always be managed within the multidisciplinary team context and recorded in the institution’s database.

Positive versus negative priming of older adults' generative value: do negative messages impair memory?

Science.gov (United States)

Hagood, Elizabeth W; Gruenewald, Tara L

2018-02-01

A considerable volume of experimental evidence demonstrates that exposure to aging stereotypes can strongly influence cognitive performance among older individuals. However, whether such effects extend to stereotypes regarding older adults' generative (i.e. contributory) worth is not yet known. The present investigation sought to evaluate the effect of exposure to positive versus negative generative value primes on an important aspect of later life functioning, memory. Participants of age 55 and older (n = 51) were randomly assigned to read a mock news article portraying older individuals as either an asset (positive prime) or a burden (negative prime) to society. Upon reading their assigned article, participants completed a post-priming memory assessment in which they were asked to recall a list of 30 words. Those exposed to the negative prime showed significantly poorer memory performance relative to those exposed to the positive prime (d = 0.75), even when controlling for baseline memory performance and sociodemographic covariates. These findings suggest that negative messages regarding older adults' generative social value impair memory relative to positive ones. Though demonstrated in the short term, these results also point to the potential consequences of long-term exposure to such negative ideologies and may indicate a need to promote more positive societal conceptualizations of older adults' generative worth.

Lymphoscintigraphic sentinel node identification in patients with breast cancer: the role of SPECT-CT

International Nuclear Information System (INIS)

Lerman, H.; Metser, U.; Lievshitz, G.; Sperber, F.; Shneebaum, S.; Even-Sapir, E.

2006-01-01

Lymph node status is a major factor in determining the stage, appropriate therapy and outcome in patients with breast cancer. It is therefore of clinical importance to accurately identify all sentinel nodes (SNs) for each individual tumour before surgery. The purpose of this study was to assess the role of SPECT-CT lymphoscintigraphy in SN identification in patients with breast cancer. Lymphoscintigraphy comprising planar and SPECT-CT acquisition was performed in 157 consecutive patients with breast cancer (mean age 54.7±10.6, range 27-81 years) with a palpable mass (n=100), with a non-palpable mass (n=52) or post lumpectomy (n=5). Planar and SPECT-CT images were interpreted separately and the two imaging techniques were compared with respect to their ability to identify hot nodes. Planar imaging alone was negative for identification of hot nodes in 15% of the patients. SPECT-CT alone was negative in 10% and both techniques were negative in 9% of the patients. Forty-six of the total of 361 (13%) hot nodes identified by lymphoscintigraphy were detected only on SPECT-CT, including 21 nodes obscured by the scattered radiation from the injection site, nine adjacent nodes misinterpreted on planar images as a single node and 16 nodes which were missed on planar images and detected on SPECT data. SPECT-CT detected additional sites of drainage unexpected on planar images, including axillary (n=23 patients), internal mammary (n=5 patients), interpectoral (n=3 patients) and intramammary (n=2 patients) lymph node sites. Fourteen of the 329 (4%) hot lesions seen on planar images were false positive non-nodal sites of uptake that were accurately assessed by SPECT-CT and further validated by surgery. In a single patient, SPECT-CT was negative while planar images identified the SN. (orig.)

Technetium-99m-sestamibi scintigraphy in breast nodes; Estudo cintilografico de nodulos mamarios com tecnecio-99m-sestamibi

Energy Technology Data Exchange (ETDEWEB)

Pellini, Marcos Pinto; Fonseca, Lea Mirian Barbosa da [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina; Balen, Jacir Luiz; Fabricio, Maria Ines Menescal [Universidade Federal, Rio de Janeiro, RJ (Brazil). Faculdade de Medicina. Inst. de Ginecologia; Amarante Junior, Jose Luiz de Medeiros

1997-01-01

The purpose was to was to determine if technetium-99m-sestamibi accumulates preferentially within the malignant palpable nodes of breast. Twenty-five patients, mean age 36.16 ({+-} 9.34) year, and without any other additional information, underwent breast scintigraphy and excisional biopsy. We had nineteen true-negative cases, four true-positive, two false-positive and none false-negative. Sensitivity, 100% specificity, 90.5%, accuracy, 92%; PPV, 66.7%, NPV, 100%. The four true positive were invasive intraductal carcinomas and one of them metastases in auxiliary lymph-nodes, confirmed in biopsy and well defined in scintigraphy. The two false-positives were a fibroadenoma with high cellularity and a fibrodisplasy surrounded by chronic inflammatory process. Two statistical tests were applied: chi-square and Fisher. Both rejected the antithesis at a confidence interval of 99% (p , 0.01) We concluded that technetium-99-sestamibi accumulates preferentially within the malignant nodes of breast. (author) 17 refs., 3 figs., 2 tabs.

A simplified CT-based definition of the lymph node levels in the node negative neck

International Nuclear Information System (INIS)

Wijers, O.B.; Levendag, P.C.; Tan, T.; Dieren, E.B. van; Sornsen de Koste, J. van; Est, H. van der; Senan, S.; Nowak, P.J.C.M.

1999-01-01

Using three dimensional (3D) conformal radiotherapy (CRT) techniques for elective neck irradiation (ENI) may allow for local disease control to be maintained while diminishing xerostomia by eliminating major salivary glands (or parts thereof) from the treatment portals. The standardization of CT based target volumes for the clinically negative (elective) neck is a prerequisite for 3DCRT. The aim of the present study was to substantially modify an existing ('original') CT-based protocol for the delineation of the neck tar-et volume, into a more practical ('simplified') protocol. This will allow for rapid contouring and the implementation of conformal ENI in routine clinical procedures. An earlier ('original') version of the CT-based definition for elective neck node re-ions 2-5 was re-evaluated, using 15 planning CT scans of previously treated patients. The contouring guidelines were simplified by (1) using a smaller number of easily identifiable soft tissue- and bony anatomical landmarks, which in turn had to be identified in only a limited number of CT slices, and (2) by subsequently interpolating the contoured lymph node regions. The adequacy of target coverage and the sparing using both 'original' and 'simplified' delineation protocols was evaluated by DVH analysis after contouring the primary tumor, the neck and the major salivary glands in a patient with supraglottic laryngeal (SGL) carcinoma who was treated using a 3DCRT technique. The BEV projections of the 'original' and the 'simplified' versions of the 3D elective neck target showed good agreement and were found to be reproducible. The DVH's of the target and parotid glands were not significantly different using both contouring protocols. The 'simplified' protocol for the delineation of the 3D elective neck target produced both comparable target coverage and sparing of the major salivary glands. When used together with an interpolation program, this 'simplified' protocol substantial reduced the contouring

Influence of Lymphatic Invasion on Locoregional Recurrence Following Mastectomy: Indication for Postmastectomy Radiotherapy for Breast Cancer Patients With One to Three Positive Nodes

International Nuclear Information System (INIS)

Matsunuma, Ryoichi; Oguchi, Masahiko; Fujikane, Tomoko; Matsuura, Masaaki; Sakai, Takehiko; Kimura, Kiyomi; Morizono, Hidetomo; Iijima, Kotaro; Izumori, Ayumi; Miyagi, Yumi; Nishimura, Seiichiro; Makita, Masujiro; Gomi, Naoya; Horii, Rie; Akiyama, Futoshi; Iwase, Takuji

2012-01-01

Purpose: The indication for postmastectomy radiotherapy (PMRT) in breast cancer patients with one to three positive lymph nodes has been in discussion. The purpose of this study was to identify patient groups for whom PMRT may be indicated, focusing on varied locoregional recurrence rates depending on lymphatic invasion (ly) status. Methods and Materials: Retrospective analysis of 1,994 node-positive patients who had undergone mastectomy without postoperative radiotherapy between January 1990 and December 2000 at our hospital was performed. Patient groups for whom PMRT should be indicated were assessed using statistical tests based on the relationship between locoregional recurrence rate and ly status. Results: Multivariate analysis showed that the ly status affected the locoregional recurrence rate to as great a degree as the number of positive lymph nodes (p < 0.001). Especially for patients with one to three positive nodes, extensive ly was a more significant factor than stage T3 in the TNM staging system for locoregional recurrence (p < 0.001 vs. p = 0.295). Conclusion: Among postmastectomy patients with one to three positive lymph nodes, patients with extensive ly seem to require local therapy regimens similar to those used for patients with four or more positive nodes and also seem to require consideration of the use of PMRT.

Intra-operative rapid diagnostic method based on CK19 mRNA expression for the detection of lymph node metastases in breast cancer

NARCIS (Netherlands)

Visser, Mike; Jiwa, Mehdi; Horstman, Anja; Brink, Antoinette A. T. P.; Pol, Rene P.; van Diest, Paul; Snijders, Peter J. F.; Meijer, Chris J. L. M.

2008-01-01

Staging by sentinel node (SN) biopsy is the standard procedure for clinically node-negative breast cancer patients. Intra-operative analysis of the SN allows immediate axillary lymph node (ALN) dissection in SN positive patients, but a quick, reliable and reproducible method is lacking. We tested

Treatment of triple-negative breast cancer with Chinese herbal medicine

Science.gov (United States)

Meng, Hui; Peng, Nan; Yu, Mingwei; Sun, Xu; Ma, Yunfei; Yang, Guowang; Wang, Xiaomin

2017-01-01

Abstract Introduction: Triple-negative breast cancer (TNBC) is featured with the biological properties of strong aggressive behaviors, rapid disease progression, high risk of recurrence and metastasis, and low disease free survival. Patients with this tumor are insensitive to the endocrine therapy and target treatment for HER-2; therefore, chemotherapy is often used as routine treatment in clinical. Because of the fact that a considerable number of patients seek for Chinese herbal medicine (CHM) treatment after operation and chemotherapy and (or) radiotherapy, it is thus need to evaluate the correlation between Chinese herbal medicine treatment and prognosis. Methods and analysis: This is a multicenter, prospective cohort study started in March 2016 in Beijing. A simple of 220 participants diagnosed with TNBC were recruited from nine hospitals and are followed up every 3 to 6 months till March 2020. Detailed information of participants includes personal information, history of cancer, quality of life, symptoms of traditional Chinese medicine and fatigue status is taken face-to-face at baseline. Ethics and dissemination: The study has received ethical approval from the Research Ethical Committee of Beijing Hospital of Traditional Chinese Medicine affiliated to Capital Medical University (No.2016BL-014-01). Articles summarizing the primary results and ancillary analyses will be published in peer-reviewed journals. Trial registration: Chinese Clinical Trial Registry: ChiCTR-OOC-16008246. PMID:29095272

Motivation enhances control of positive and negative emotional distractions.

Science.gov (United States)

Walsh, Amy T; Carmel, David; Harper, David; Grimshaw, Gina M

2018-01-03

Using cognitive control to ignore distractions is essential for successfully achieving our goals. In emotionally-neutral contexts, motivation can reduce interference from irrelevant stimuli by enhancing cognitive control. However, attention is commonly biased towards emotional stimuli, making them potent distractors. Can motivation aid control of emotional distractions, and does it do so similarly for positive and negative stimuli? Here, we examined how task motivation influences control of distraction from positive, negative, and neutral scenes. Participants completed a simple perceptual task while attempting to ignore task-irrelevant images. One group received monetary reward for fast and accurate task performance; another (control) group did not. Overall, both negative (mutilation) and positive (erotic) images caused greater slowing of responses than neutral images of people, but emotional distraction was reduced with reward. Crucially, despite the different motivational directions associated with negative and positive stimuli, reward reduced negative and positive distraction equally. Our findings suggest that motivation may encourage the use of a sustained proactive control strategy that can effectively reduce the impact of emotional distraction.

TMEPAI genome editing in triple negative breast cancer cells

Directory of Open Access Journals (Sweden)

Bantari W.K. Wardhani

2017-05-01

Full Text Available Background: Clustered regularly interspaced short palindromic repeats/CRISPR-associated 9 (CRISPR/Cas9 is a powerful genome editing technique. It consists of RNA-guided DNA endonuclease Cas9 and single guide RNA (gRNA. By combining their expressions, high efficiency cleavage of the target gene can be achieved, leading to the formation of DNA double-strand break (DSB at the genomic locus of interest which will be repaired via NHEJ (non-homologous end joining or HDR (homology-directed repair and mediate DNA alteration. We aimed to apply the CRISPR/Cas9 technique to knock-out the transmembrane prostate androgen-induced protein (TMEPAI gene in the triple negative breast cancer cell line.Methods: Designed gRNA which targets the TMEPAI gene was synthesized, annealed, and cloned into gRNA expression vector. It was co-transfected into the TNBC cell line using polyethylenimine (PEI together with Cas9-GFP and puromycin resistant gene vector. At 24-hours post-transfection, cells were selected by puromycin for 3 days before they were cloned. Selected knock-out clones were subsequently checked on their protein levels by western blotting.Results: CRISPR/Cas9, a genome engineering technique successfully knocked-out TMEPAI in the Hs578T TNBC cell line. Sequencing shows a frameshift mutation in TMEPAI. Western blot shows the absence of TMEPAI band on Hs578T KO cells.Conclusion: TMEPAI gene was deleted in the TNBC cell line using the genomic editing technique CRISPR/Cas9. The deletion was confirmed by genome and protein analysis.

Positive and negative dimensions of weight control motivation.

Science.gov (United States)

Stotland, S; Larocque, M; Sadikaj, G

2012-01-01

This study examined weight control motivation among patients (N=5460 females and 547 males) who sought weight loss treatment with family physicians. An eight-item measure assessed the frequency of thoughts and feelings related to weight control "outcome" (e.g. expected physical and psychological benefits) and "process" (e.g. resentment and doubt). Factor analysis supported the existence of two factors, labeled Positive and Negative motivation. Positive motivation was high (average frequency of thoughts about benefits was 'every day') and stable throughout treatment, while Negative motivation declined rapidly and then stabilized. The determinants of changes in the Positive and Negative dimensions during treatment were examined within 3 time frames: first month, months 2-6, and 6-12. Maintenance of high scores on Positive motivation was associated with higher BMI and more disturbed eating habits. Early reductions in Negative motivation were greater for those starting treatment with higher weight and more disturbed eating habits, but less depression and stress, while later reductions in Negative motivation were predicted by improvements in eating habits, weight, stress and perfectionism. Clinicians treating obesity should be sensitive to fluctuations in both motivational dimensions, as they are likely to play a central role in determining long-term behavior and weight change. Copyright © 2011 Elsevier Ltd. All rights reserved.

Detection of axillary lymph node metastases in breast carcinoma by technetium-99m sestamibi breast scintigraphy, ultrasound and conventional mammography

International Nuclear Information System (INIS)

Lam, W.W.M.; Yang, W.T.; Chan, Y.L.; Stewart, I.E.T.; Metreweli, C.; King, W.

1996-01-01

Axillary lymph node status is important in the staging of breast carcinoma. To evaluate the accuracy of technetium-99m sestamibi breast scintigraphy in detecting metastatic axillary lymph nodes as compared with other accepted imaging modalities, we performed 99m Tc-sestamibi breast scintigraphy, conventional mammography and ultrasound in 36 patients with primary untreated breast cardinoma. With histopathology as the gold standard, 99m Tc-sestamibi breast scintigraphy was found to yield true-positive results in 7 of 11 cases (64%) of axillary lymph nodes metastases and true-negative results in 18 of 20 cases (90%); it has an accuracy of 81%, a positive predictive value of 77.8% and a negative predicive value of 81.8%. (orig.)

Locally advanced pancreatic cancer: association between prolonged preoperative treatment and lymph-node negativity and overall survival.

Science.gov (United States)

Kadera, Brian E; Sunjaya, Dharma B; Isacoff, William H; Li, Luyi; Hines, O Joe; Tomlinson, James S; Dawson, David W; Rochefort, Matthew M; Donald, Graham W; Clerkin, Barbara M; Reber, Howard A; Donahue, Timothy R

2014-02-01

Treatment of patients with locally advanced/borderline resectable (LA/BR) pancreatic ductal adenocarcinoma (PDAC) is not standardized. To (1) perform a detailed survival analysis of our institution's experience with patients with LA/BR PDAC who were downstaged and underwent surgical resection and (2) identify prognostic biomarkers that may help to guide a decision for the use of adjuvant therapy in this patient subgroup. Retrospective observational study of 49 consecutive patients from a single institution during 1992-2011 with American Joint Committee on Cancer stage III LA/BR PDAC who were initially unresectable, as determined by staging computed tomography and/or surgical exploration, and who were treated and then surgically resected. Clinicopathologic variables and prognostic biomarkers SMAD4, S100A2, and microRNA-21 were correlated with survival by univariate and multivariate Cox proportional hazard modeling. All 49 patients were deemed initially unresectable owing to vascular involvement. After completing preoperative chemotherapy for a median of 7.1 months (range, 5.4-9.6 months), most (75.5%) underwent a pylorus-preserving Whipple operation; 3 patients (6.1%) had a vascular resection. Strikingly, 37 of 49 patients were lymph-node (LN) negative (75.5%) and 42 (85.7%) had negative margins; 45.8% of evaluable patients achieved a complete histopathologic (HP) response. The median overall survival (OS) was 40.1 months (range, 22.7-65.9 months). A univariate analysis of HP prognostic biomarkers revealed that perineural invasion (hazard ratio, 5.5; P=.007) and HP treatment response (hazard ratio, 9.0; P=.009) were most significant. Lymph-node involvement, as a marker of systemic disease, was also significant on univariate analysis (P=.05). Patients with no LN involvement had longer OS (44.4 vs 23.2 months, P=.04) than LN-positive patients. The candidate prognostic biomarkers, SMAD4 protein loss (P=.01) in tumor cells and microRNA-21 expression in the stroma (P=.05

Negative cognitive errors and positive illusions for negative divorce events: predictors of children's psychological adjustment.

Science.gov (United States)

Mazur, E; Wolchik, S A; Sandler, I N

1992-12-01

This study examined the relations among negative cognitive errors regarding hypothetical negative divorce events, positive illusions about those same events, actual divorce events, and psychological adjustment in 38 8- to 12-year-old children whose parents had divorced within the previous 2 years. Children's scores on a scale of negative cognitive errors (catastrophizing, overgeneralizing, and personalizing) correlated significantly with self-reported symptoms of anxiety and self-esteem, and with maternal reports of behavior problems. Children's scores on a scale measuring positive illusions (high self-regard, illusion of personal control, and optimism for the future) correlated significantly with less self-reported aggression. Both appraisal types accounted for variance in some measures of symptomatology beyond that explained by actual events. There was no significant association between children's negative cognitive errors and positive illusions. The implications of these results for theories of negative cognitive errors and of positive illusions, as well as for future research, are discussed.

Interest of the technical detection of the sentinel node applied to uterine cancers: about three cases

International Nuclear Information System (INIS)

Ech charraq, I.; Ben Rais, N.; Ech charra, I.; Albertini, A.F.

2009-01-01

Introduction The sentinel node technique (S.N.) was proposed in cervical cancers in order to optimise the diagnosis of metastases and the lymphatic micrometastases in the early stages while avoiding useless wide clearings out. The identification of this node is done by injection of a dye and/or a radioactive colloid and its ablation for pathological examination. Patients and methods We report the case of three patients followed for a uterine cancer having benefited from a lymphoscintigraphy before surgery. During the surgical procedure, the detection of the sentinel node was carried out after cervical injection of blue dye and using a gamma detection probe. Results The lymphoscintigraphy was positive for two cases with a positive detection for the three cases during the operation. The pathological study revealed a node metastasis for one case. The technical of the sentinel node applied to uterine cancers appears realizable essentially for uterine cancers of early stage (I). However the risk of false negative can be observed in advanced cancer (III), as it is the case of our patient having a negative lymphoscintigraphy. Conclusion The nuclear medicine is important in the detection of the sentinel node of various cancers, uterine cancer included, thus allowing an appropriate cardiologic management. (authors)

Value of sonomammography utilizing color Doppler technique in qualification of breast cancer patients for sentinel node identification

International Nuclear Information System (INIS)

Basta, P.; Wadowska-Jaszczynska, K.; Krysztopowicz, W.; Przybylska, P.; Wisniowski, Z.

2007-01-01

Sentinel node identification has become a standard procedure in the management of breast cancer. This procedure requires involvement of a multidisciplinary team and is rather costly. Ultrasonography (USG) of axillary lymph nodes is a method that gives hope for improving the quality of qualification of patients for the procedure. Eighty patients with grade I and II breast cancers underwent sentinel node identification followed by axillary lymphadenectomy. Pre-operative ultrasonography was employed to assess axillary lymph nodes, using the morphological and vascular characteristics as predictors of the presence of lymph node metastases. Sensitivity of sentinel node identification reached 89.3%, specificity - 100%, positive predictive value - 100%, negative predictive value - 93.5%, percentage of false negative results - 10.7%. Sensitivity of USG reached 68.75 %, and specificity - 70.31%. In the group of patients in whom the sentinel node was identified, the sensitivity of the method was 69.23 %, and specificity - 72.41%. Preoperative axillary lymph node ultrasonography in breast cancer patients, utilizing color Doppler technique, allows better selection of patients for sentinel node identification procedure. (author)

Using quantitative image analysis to classify axillary lymph nodes on breast MRI: A new application for the Z 0011 Era

Energy Technology Data Exchange (ETDEWEB)

Schacht, David V., E-mail: dschacht@radiology.bsd.uchicago.edu; Drukker, Karen, E-mail: kdrukker@uchicago.edu; Pak, Iris, E-mail: irisgpak@gmail.com; Abe, Hiroyuki, E-mail: habe@radiology.bsd.uchicago.edu; Giger, Maryellen L., E-mail: m-giger@uchicago.edu

2015-03-15

Highlights: •Quantitative image analysis showed promise in evaluating axillary lymph nodes. •13 of 28 features performed better than guessing at metastatic status. •When all features were used in together, a considerably higher AUC was obtained. -- Abstract: Purpose: To assess the performance of computer extracted feature analysis of dynamic contrast enhanced (DCE) magnetic resonance images (MRI) of axillary lymph nodes. To determine which quantitative features best predict nodal metastasis. Methods: This institutional board-approved HIPAA compliant study, in which informed patient consent was waived, collected enhanced T1 images of the axilla from patients with breast cancer. Lesion segmentation and feature analysis were performed on 192 nodes using a laboratory-developed quantitative image analysis (QIA) workstation. The importance of 28 features were assessed. Classification used the features as input to a neural net classifier in a leave-one-case-out cross-validation and evaluated with receiver operating characteristic (ROC) analysis. Results: The area under the ROC curve (AUC) values for features in the task of distinguishing between positive and negative nodes ranged from just over 0.50 to 0.70. Five features yielded AUCs greater than 0.65: two morphological and three textural features. In cross-validation, the neural net classifier obtained an AUC of 0.88 (SE 0.03) for the task of distinguishing between positive and negative nodes. Conclusion: QIA of DCE MRI demonstrated promising performance in discriminating between positive and negative axillary nodes.

A longitudinal mediation analysis of the effect of negative-self-schemas on positive symptoms via negative affect.

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Jaya, E S; Ascone, L; Lincoln, T M

2018-06-01

Cognitive models postulate that negative-self-schemas (NSS) cause and maintain positive symptoms and that negative affect mediates this link. However, only few studies have tested the temporal mediation claim systematically using an appropriate design. A longitudinal cohort design in an online community sample (N = 962) from Germany, Indonesia, and the USA was used. NSS, negative affect and positive symptoms were measured at four time-points (T0-T3) over a 1-year period. Cross-lagged panel and longitudinal mediation analyses with structural equation modeling were used to test the temporal mediation. Independent cross-lagged panel models showed a significant unidirectional longitudinal path from NSS to positive symptoms (T2-T3, β = 0.18, p negative affect (T0-T1, γ = 0.14, p negative affect at T1 and T2 to positive symptoms at T3 (unstandardized indirect effect coefficient = 0.020, p affective pathway from NSS to positive symptoms via negative affect. Specifically, our data indicate that NSS and negative affect influence each other and build up over the course of several months before leading on to positive symptoms. We conclude that interrupting this process by targeting NSS and negative affect early in the process could be a promising strategy to prevent the exacerbation of positive symptoms.

5-FU and ixabepilone modify the microRNA expression profiles in MDA-MB-453 triple-negative breast cancer cells

OpenAIRE

YAO, YONGSHAN; CHEN, SHENGHAN; ZHOU, XIN; XIE, LI; CHEN, AIJUN

2013-01-01

This study aimed to discover new potential mechanisms of chemotherapy with drugs used in the treatment of luminal androgen receptor (LAR)-type triple-negative breast cancer (TNBC). We examined the microRNA (miRNA) expression profiles of LAR-type TNBC in vitro, and explored the variation in miRNA expression profiles in cells when treated with the chemotherapy drugs capecitabine and ixabepilone. The present study revealed that the expression levels of the three antitumor miRNAs, miR-122a, miR-1...

Presenting symptoms and clinical findings in HPV-positive and HPV-negative oropharyngeal cancer patients.

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Carpén, Timo; Sjöblom, Anni; Lundberg, Marie; Haglund, Caj; Markkola, Antti; Syrjänen, Stina; Tarkkanen, Jussi; Mäkitie, Antti; Hagström, Jaana; Mattila, Petri

2018-05-01

Oropharyngeal squamous cell carcinoma (OPSCC) is divided in two different disease entities depending on HPV involvement. We investigated differences in presenting symptoms and clinical findings in patients with HPV-positive and -negative OPSCC tumors. Altogether 118 consecutive patients diagnosed with primary OPSCC between 2012 and 2014 at the Helsinki University Hospital were included. HPV-status of the tumors was assessed by PCR detection of HPV DNA and immunostaining with p16-INK4a antibody. Fifty-one (47.7%) of the patients had HPV-positive and 56 (52.3%) HPV-negative tumors. Forty-nine (49/51, 96.1%) of the HPV+ tumors were also p16+ showing high concordance. The most common presenting symptom among HPV+/p16+ patients was a neck mass (53.1%), whereas any sort of pain in the head and neck area was more frequently related to the HPV-/p16- (60.0%) group. HPV+/p16+ tumors had a tendency to locate in the tonsillar complex and more likely had already spread into regional lymph nodes compared with HPV-/p16- tumors. Smoking and heavy alcohol consumption were significantly more common among HPV-/p16- patients but also rather common among HPV+/p16+ patients. This analysis of symptoms and signs confirm that OPSCC can be dichotomized in two distinct disease entities as defined by HPV status.

Efficacy of the Positive Parenting Program (Triple-P for a Group of Parents of Children with Attention Deficit Hyperactivity Disorder (ADHD

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Mehdi Tehranidoost

2008-07-01

Full Text Available "nObjective: To evaluate the efficacy of the Positive Parenting Program (Triple-P for parents of children with attention deficit hyperactivity disorder (ADHD. "nMethod:  Sixty families who had at least one child with clinically diagnosed ADHD aged between 6 to12 were recruited from the consecutive referrals to a child and adolescent psychiatric clinic. Families were randomly assigned to the intervention group (who participated in an 8- week- group Triple-P, N=30 and a control group (N=30. Parents completed the battery of self-report questionnaires of triple-P at the beginning and after the 8th session. "nResults: There were no significant differences in pre intervention measures between the two groups. Comparing the pre and post intervention data, the Triple- P group was associated with significantly lower levels of parent reported child behavior problems (P=0.001, lower levels of dysfunctional parenting (P=0.001 and greater parental competence (P=0.001 than the control group. The parents the in triple-P group had significant improvement on measures of depression, anxiety and stress, in comparison with the control group (P=0.001. This study did not follow the long term effect which marks its limitation. "nConclusion: The Triple-P program can be recommended for parents of children with ADHD to reduce the problem behavior of their children and to improve their abilities.

Obesity and the relationship with positive and negative affect.

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Pasco, Julie A; Williams, Lana J; Jacka, Felice N; Brennan, Sharon L; Berk, Michael

2013-05-01

To examine the cross-sectional association between overweight and obesity and positive and negative affect. Participants included 273 women, aged 29-84 years, who were enrolled in the Geelong Osteoporosis Study (GOS). Weight and height were measured and overweight and obesity determined from body mass index (BMI; kg/m(2)) according to WHO criteria. Medical history and lifestyle exposures were assessed by questionnaire. Positive and negative affect scores were derived using the validated 20-item Positive and Negative Affect Schedule (PANAS) and categorised into tertiles. A pattern of greater negative affect scores was observed for increasing levels of BMI. Setting normal weight as the referent category, the odds for having a negative affect score in the highest tertile were sequentially increased for women who were overweight (OR = 1.31, 95% CI: 0.72-2.40) and obese (OR = 1.95, 95% CI: 1.02-3.73). The association between obesity and increased negative affect was diminished by adjusting for physical illness (adjusted OR = 1.76, 95% CI: 0.91-3.42). These associations were not substantially influenced by positive affect score or other exposures. No association was detected between BMI categories and positive affect scores. We report data suggesting that obesity is associated with greater negative affect scores, reflecting emotions such as distress, anger, disgust, fear and shame, and that this association is attenuated by physical illness. Further investigations are now warranted to explore possible mechanistic interplay between pathological, neurobiological and psychosocial factors.

Triple correlation in temporomandibular joint dysfunction: MR imaging with arthrography, arthroscopy, and open surgery

International Nuclear Information System (INIS)

Rao, V.M.; Farole, A.; Karasick, D.

1988-01-01

Triple correlation of MR imaging with arthrography, arthroscopy, and open surgery was performed in 24 patients (34 temporomandibular joints) with ages ranging from 17 to 66 years. MR imaging showed disk position and morphologic features accurately in 30 joints (88%). It was false negative in one joint and false positive in three joints (9%). Degenerative changes were accurately detected with MR imaging, arthrography, and arthroscopy. Adhesions were diagnosed with arthrography in eight joints, arthroscopy in 14, and MR imaging in none. Disk perforations seen at open surgery were not detected with MR imaging. In conclusion, there is an overlap of information presented by various modalities. MR imaging is better than arthrography detecting disk morphologic features and displacement. Arthrography may add information by showing meniscal dynamics. Arthroscopy entails direct observation of superior joint space only and can detect adhesions and perforations better, but it may alter disk position and dynamics. In the more difficult cases, triple correlation may be needed, as modalities can be complementary

Lymph node retrieval during esophagectomy with and without neoadjuvant chemoradiotherapy: prognostic and therapeutic impact on survival.

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Koen Talsma, A; Shapiro, Joel; Looman, Caspar W N; van Hagen, Pieter; Steyerberg, Ewout W; van der Gaast, Ate; van Berge Henegouwen, Mark I; Wijnhoven, Bas P L; van Lanschot, J Jan B; Hulshof, Maarten C C M; van Laarhoven, Hanneke W M; Nieuwenhuijzen, Grard A P; Hospers, Geke A P; Bonenkamp, Johannes J; Cuesta, Miguel A; Blaisse, Reinoud J B; Busch, Olivier R C; ten Kate, Fiebo J W; Creemers, Geert-Jan; Punt, Cornelis J A; Plukker, John T M; Verheul, Henk M W; van Dekken, Herman; van der Sangen, Maurice J C; Rozema, Tom; Biermann, Katharina; Beukema, Jannet C; Piet, Anna H M; van Rij, Caroline M; Reinders, Janny G; Tilanus, Hugo W

2014-11-01

We aimed to examine the association between total number of resected nodes and survival in patients after esophagectomy with and without nCRT. Most studies concerning the potentially positive effect of extended lymphadenectomy on survival have been performed in patients who underwent surgery alone. As nCRT is known to frequently "sterilize" regional nodes, it is unclear whether extended lymphadenectomy after nCRT is still useful. Patients from the randomized CROSS-trial who completed the entire protocol (ie, surgery alone or chemoradiotherapy + surgery) were included. With Cox regression models, we compared the impact of number of resected nodes as well as resected positive nodes on survival in both groups. One hundred sixty-one patients underwent surgery alone, and 159 patients received multimodality treatment. The median (interquartile range) number of resected nodes was 18 (12-27) and 14 (9-21), with 2 (1-6) and 0 (0-1) resected positive nodes, respectively. Persistent lymph node positivity after nCRT had a greater negative prognostic impact on survival as compared with lymph node positivity after surgery alone. The total number of resected nodes was significantly associated with survival for patients in the surgery-alone arm (hazard ratio per 10 additionally resected nodes, 0.76; P=0.007), but not in the multimodality arm (hazard ratio 1.00; P=0.98). The number of resected nodes had a prognostic impact on survival in patients after surgery alone, but its therapeutic value is still controversial. After nCRT, the number of resected nodes was not associated with survival. These data question the indication for maximization of lymphadenectomy after nCRT.

Prejudice Masquerading as Praise: The Negative Echo of Positive Stereotypes.

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Siy, John Oliver; Cheryan, Sapna

2016-07-01

Five studies demonstrate the powerful connection between being the target of a positive stereotype and expecting that one is also being ascribed negative stereotypes. In Study 1, women who heard a man state a positive stereotype were more likely to believe that he held negative stereotypes of them than women who heard no stereotype. Beliefs about being negatively stereotyped mediated the relationship between hearing a positive stereotype and believing that the stereotyper was prejudiced. Studies 2 to 4 extended these results to Asian Americans and accounted for alternative explanations (e.g., categorization threat). In Study 5, the same positive stereotype (e.g., good at math) was directed to Asian American men's racial or gender identity. Their perceptions about whether negative racial or gender stereotypes were being applied to them depended on the identity referenced by the positive stereotype. Positive stereotypes signal a latent negativity about one's group, thereby explaining why they can feel like prejudice. © 2016 by the Society for Personality and Social Psychology, Inc.

Microglandular adenosis: a prime suspect in triple-negative breast cancer development.

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Tsang, Julia Ys; Tse, Gary Mk

2016-06-01

Microglandular adenosis (MGA) and atypical MGA (AMGA) are unusual lesions of the breast. They were once regarded as benign proliferative lesions and innocent bystanders. Several lines of evidence suggested that they could be neoplastic, clonal lesions and a non-obligate precursor for triple-negative breast cancers (TNBC). Recent work published in The Journal of Pathology by Guerini-Rocco and colleagues provided further evidence regarding the precursor-product relationship between MGA/AMGA and TNBC. Using a massively parallel sequencing approach, they demonstrated that MGA/AMGA, particularly those associated with TNBC, could be clonal neoplastic lesions showing clonal non-synonymous mutations, but none in pure MGA. Importantly, those alterations were observed in the associated TNBC. They were also able to identify recurrent alterations in TP53 in those MGA/AMGA cases as well as their associated TNBC. The findings, in conjunction with others, underscore the significance for MGA in clinical diagnosis. The potential of a benign lesion to progress into an aggressive malignant tumour implies that modification of the current management approach may be necessary. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2016 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Integration of Genomic, Biologic, and Chemical Approaches to Target p53 Loss and Gain-of-Function in Triple Negative Breast Cancer

Science.gov (United States)

2016-09-01

in this progress report: p53 triple-negative breast cancer subtypes gene expression somatic cell genetics CRISPR / Cas 3. ACCOMPLISHMENTS Major...report, we described the creation of an isogenic p53 mutant TNBC cell line panel using CRISPR / Cas -mediated genome editing8 and the resultant...LOF null state. To validate that mutant p53 is directly responsible for this altered transcription, we will use the same CRISPR -mediated genome

Autobiographical memories for negative and positive events in war contexts

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Antonio L. Manzanero

2015-01-01

Full Text Available The aim of the present study was to examine the phenomenological qualities of self-reported negative and positive memories. The study was conducted in the Gaza Strip, Palestine, and a total of 134 autobiographical memories about negative and positive events were analyzed using a version of the Phenomenological Questionnaire for Autobiographical Memory (Manzanero & López, 2007. Participants were university students, 80 percent were women and 20 percent were men. Results showed that negative memories are more confused, more complex, and decay more over time than positive ones. In contrast, no differences were found between positive and negative memories on sensory information, spatial location, vividness, definition, accessibility, fragmentation, recall perspective, doubts about the accuracy of the memory, and how much participants recovered and talked about the event. High Dimensional Visualization (HDV graph revealed that there were individual differences between negative and positive memories but no consistent differences across participants.

Effectiveness of the triple P positive parenting program on parenting: A meta-analysis

NARCIS (Netherlands)

Graaf, I. de; Speetjens, P.; Smit, F.; Wolff, M. de; Tavecchio, L.

2008-01-01

Triple P is a parenting program intended to prevent and to provide treatment for severe behavioral, emotional, and developmental problems in children. The aim of this meta-analysis was to assess the effectiveness of Triple P Level 4 interventions on parenting styles and parental competency. Level 4

Triple Positive Solutions of a Nonlocal Boundary Value Problem for Singular Differential Equations with p-Laplacian

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Jufang Wang

2013-01-01

Full Text Available We establish the existence of triple positive solutions of an m-point boundary value problem for the nonlinear singular second-order differential equations of mixed type with a p-Laplacian operator by Leggett-William fixed point theorem. At last, we give an example to demonstrate the use of the main result of this paper. The conclusions in this paper essentially extend and improve the known results.

Accuracy of 18F-FDG PET/CT for lymph node staging in non-small-cell lung cancers

Institute of Scientific and Technical Information of China (English)

LIU Bao-jun; DONG Jing-cheng; XU Chang-qing; ZUO Chuan-tao; LE Jing-jing; GUAN Yi-hui; ZHAO Jun; WU Jin-feng; DUAN Xiao-hong; CAO Yu-xue

2009-01-01

Background This retrospective study evaluated the diagnostic accuracy of 2-(F18)-fluoro-2-deoxy-D-glucose-positron emission tomography(18F-FDG-PET)/COmputed tomography(PET/CT)in the preoperative diagnosis of metastatic mediastinal and hilar lymph node in patients with non-small-cell lung cancer(NSCLC).Methods A total of 39 patients received preoperative 18F-FDG PET/CT and the postoperative biopsy.We compared preoperative PET/CT scan results with corresponding intraoperative histopathalogic findings in 39 NSCLC patients.The sensitivity,specificity,accuracy,positive and negative predictive value of 18F-FDG PET/CT were assessed.Results Histopathologic examination confirmed metastasis in 57 out of the 208 excised lymph nodes;23 of the 57 nodes were mediastinal and hilar lymph nodes.The sensitivity,specificity,accuracy,positive predictive value and negative predictive value of PET/CT in the preoperative diagnosis of mediastinal lymph node metastasis in NSCLC patients were 65%,96.8%,92%,78.5%and 90%,respectively.Conclusions PET/CT scan showed good accuracy in the preoperative diagnosis of mediastinal and hilar lymph node metastasis in the patients with NSCLC.We recommend that PET/CT scanning be used as a first-line evaluation tool for tumor diagnosis,therapy evaluation and follow-up.

Conditional internalization of PEGylated nanomedicines by PEG engagers for triple negative breast cancer therapy

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Su, Yu-Cheng; Burnouf, Pierre-Alain; Chuang, Kuo-Hsiang; Chen, Bing-Mae; Cheng, Tian-Lu; Roffler, Steve R.

2017-06-01

Triple-negative breast cancer (TNBC) lacks effective treatment options due to the absence of traditional therapeutic targets. The epidermal growth factor receptor (EGFR) has emerged as a promising target for TNBC therapy because it is overexpressed in about 50% of TNBC patients. Here we describe a PEG engager that simultaneously binds polyethylene glycol and EGFR to deliver PEGylated nanomedicines to EGFR+ TNBC. The PEG engager displays conditional internalization by remaining on the surface of TNBC cells until contact with PEGylated nanocarriers triggers rapid engulfment of nanocargos. PEG engager enhances the anti-proliferative activity of PEG-liposomal doxorubicin to EGFR+ TNBC cells by up to 100-fold with potency dependent on EGFR expression levels. The PEG engager significantly increases retention of fluorescent PEG probes and enhances the antitumour activity of PEGylated liposomal doxorubicin in human TNBC xenografts. PEG engagers with specificity for EGFR are promising for improved treatment of EGFR+ TNBC patients.

A biomimetic collagen derived peptide exhibits anti-angiogenic activity in triple negative breast cancer.

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Elena V Rosca

Full Text Available We investigated the application of a mimetic 20 amino acid peptide derived from type IV collagen for treatment of breast cancer. We showed that the peptide induced a decrease of proliferation, adhesion, and migration of endothelial and tumor cells in vitro. We also observed an inhibition of triple negative MDA-MB-231 xenograft growth by 75% relative to control when administered intraperitoneally for 27 days at 10 mg/kg. We monitored in vivo the changes in vascular properties throughout the treatment using MRI and found that the vascular volume and permeability surface area product decreased significantly. The treatment also resulted in an increase of caspase-3 activity and in a reduction of microvascular density. The multiple mode of action of this peptide, i.e., anti-angiogenic, and anti-tumorigenic, makes it a viable candidate as a therapeutic agent as a monotherapy or in combination with other compounds.

HER-2, ER, PR status concordance in primary breast cancer and corresponding metastatic lesion in lymph node in Chinese women.

Science.gov (United States)

Li, Min Hua; Hou, Chuan Ling; Wang, Cheng; Sun, Ai Jing

2016-04-01

To compare the expression of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER-2) in the primary site and the metastatic lesion of lymph nodes in invasive breast cancer for investigating whether the expression of these biomarkers in the primary site could act as a surrogate to the lymphatic metastatic lesion in the same patient. In lymphatic metastatic lesion and corresponding primary lesion of 107 cases of invasive breast cancer, ER and PR statuses were assessed by immunohistochemistry (IHC). HER-2 expression level was evaluated by IHC and/or fluorescence in situ hybridization (FISH). In the primary lesions, 43.9% were ER positive; 46.7% were PR positive; 34.6% were HER-2 positive. In corresponding lymphatic metastatic lesions, the HER-2 status was concordant in 90 patients; 9 patients were diagnosed positive in metastatic lesion while negative in primary lesion; 8 patients were negative in metastatic lesion while positive in primary site (agreement, 84.1%; κ=0.647). A change in ER status was observed in 24 cases: 17 cases positive in metastatic site while negative in primary site; 7 cases negative in metastatic site while positive in primary site (agreement, 77.6%; κ=0.534). PR status discordance between the primary lesion and the metastatic regional lymph nodes was reported in 19 cases (agreement, 82.2%; κ=0.640). This study revealed that there was only a moderate concordance of ER, PR and HER-2 status between primary tumors and metastatic lymph nodes. These results indicate that it was inappropriate to predict the status of ER, PR and HER-2 in metastatic lymph nodes based on the results of evaluation of that in primary lesions. Copyright © 2015 Elsevier GmbH. All rights reserved.

[How children show positive and negative relationships on their drawings].

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Gramel, Sabine

2005-01-01

This study analyses, whether pictures of children showing a positive relationship are significantly different from those showing a negative one with respect to several criteria. The study involved a random selection of 45 children aged 4;6 to 11;6 years. The children painted a picture with themselves and a person they liked and a picture of themselves with someone they disliked. For the most part, the children drew pictures of themselves with peers both with respect to positive as well as negative images. In an interview afterwards, the children specified the criteria in their drawings by which the quality of the particular relationship can be identified. Positive and negative relationship paintings differ in the character of activity described. The sun as an element in children's paintings is painted not more frequent on positive compared to negative pictures. The colour black is used more often in the drawings signifying negative relationships. While girls used more colour in negative relationship drawings, boys used more colour in the positive ones. There was no significant difference in the use of favourite colours and decorative elements between the two groups. Only in negative relationship drawings people were looking away from each other. Smiling individuals were more common in the positive relationship pictures and in pictures painted by the 6 to 8 year olds. A greater distance between the individuals emerged on negative relationship drawings of the girls.

ONC201 Demonstrates Antitumor Effects in Both Triple-Negative and Non-Triple-Negative Breast Cancers through TRAIL-Dependent and TRAIL-Independent Mechanisms.

Science.gov (United States)

Ralff, Marie D; Kline, Christina L B; Küçükkase, Ozan C; Wagner, Jessica; Lim, Bora; Dicker, David T; Prabhu, Varun V; Oster, Wolfgang; El-Deiry, Wafik S

2017-07-01

Breast cancer is a major cause of cancer-related death. TNF-related apoptosis-inducing ligand (TRAIL) has been of interest as a cancer therapeutic, but only a subset of triple-negative breast cancers (TNBC) is sensitive to TRAIL. The small-molecule ONC201 induces expression of TRAIL and its receptor DR5. ONC201 has entered clinical trials in advanced cancers. Here, we show that ONC201 is efficacious against both TNBC and non-TNBC cells ( n = 13). A subset of TNBC and non-TNBC cells succumbs to ONC201-induced cell death. In 2 of 8 TNBC cell lines, ONC201 treatment induces caspase-8 cleavage and cell death that is blocked by TRAIL-neutralizing antibody RIK2. The proapoptotic effect of ONC201 translates to in vivo efficacy in the MDA-MB-468 xenograft model. In most TNBC lines tested (6/8), ONC201 has an antiproliferative effect but does not induce apoptosis. ONC201 decreases cyclin D1 expression and causes an accumulation of cells in the G 1 phase of the cell cycle. pRb expression is associated with sensitivity to the antiproliferative effects of ONC201, and the compound synergizes with taxanes in less sensitive cells. All non-TNBC cells ( n = 5) are growth inhibited following ONC201 treatment, and unlike what has been observed with TRAIL, a subset ( n = 2) shows PARP cleavage. In these cells, cell death induced by ONC201 is TRAIL independent. Our data demonstrate that ONC201 has potent antiproliferative and proapoptotic effects in a broad range of breast cancer subtypes, through TRAIL-dependent and TRAIL-independent mechanisms. These findings develop a preclinical rationale for developing ONC201 as a single agent and/or in combination with approved therapies in breast cancer. Mol Cancer Ther; 16(7); 1290-8. ©2017 AACR . ©2017 American Association for Cancer Research.

Overweight as a Prognostic Factor for Triple-Negative Breast Cancers in Chinese Women.

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Shuang Hao

Full Text Available Obesity is associated with poorer outcomes in patients with hormone receptor-positive breast cancers, but this association is not well established for women with triple-negative breast cancers (TNBC. Here, we investigated the prognostic effects of body mass index (BMI on clinical outcomes in patients with TNBC.We identified 1106 patients with TNBC who met the inclusion criteria and were treated between January 2002 and June 2012. Clinical and biological features were collected to evaluate the relation between BMI and breast cancer-specific survival (BCSS and overall survival (OS after controlling for other clinically significant variables.Of 1106 patients, 656 (59.3% were normal weight (BMI ≤24 and 450 patients (40.7% were overweight(BMI>24. Median follow-up time was 44.8 months. Breast cancer specific death was observed in 140 patients. After adjusting for clinicopathologic risk factors, overweight was associated with OS (hazard ratio [HR]: 1.46, 95% confidence interval [CI]: 1.04-2.06, P =0.028 but not BCSS (HR: 1.34, 95% CI: 0.90-2.01, P =0.15in all the patients with TNBC. When stratified with menopausal status, overweight was associated with BCSS and OS (HR: 2.27, 95% CI: 1.11-4.63, P = 0.024 and HR: 2.16, 95% CI: 1.21-3.87, P = 0.010, respectively in premenopausal women. BMI was not associated with BCSS or OS in postmenopausal women.Overweight is an independent prognostic factor of OS in all women with TNBC, and menopause status may be a mitigating factor. Among premenopausal women, overweight women are at a greater risk of poor prognosis than normal weight women. If validated, these findings should be considered in developing preventive programs.

An evaluation of the efficacy of a triple P-positive parenting program podcast series.