scholarly journals Prognostic Value of NLRP3 Inflammasome and TLR4 Expression in Breast Cancer Patients

2021 ◽  
Vol 11 ◽  
Author(s):  
Concetta Saponaro ◽  
Emanuela Scarpi ◽  
Margherita Sonnessa ◽  
Antonella Cioffi ◽  
Francesca Buccino ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Nlrp3 Inflammasome ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Receptor Protein ◽  
Breast Cancer Patients ◽  
Tlr4 Expression ◽  
Kaplan Meier ◽  
Invasive Breast Carcinomas ◽  
New Good

Inflammasome complexes play a pivotal role in different cancer types. NOD-like receptor protein 3 (NLRP3) inflammasome is one of the most well-studied inflammasomes. Activation of the NLRP3 inflammasome induces abnormal secretion of soluble cytokines, generating advantageous inflammatory surroundings that support tumor growth. The expression levels of the NLRP3, PYCARD and TLR4 were determined by immunohistochemistry in a cohort of primary invasive breast carcinomas (BCs). We observed different NLRP3 and PYCARD expressions in non-tumor vs tumor areas (p<0.0001). All the proteins were associated to more aggressive clinicopathological characteristics (tumor size, grade, tumor proliferative activity etc.). Univariate analyses were carried out and related Kaplan-Meier curves plotted for NLRP3, PYCARD and TLR4 expression. Patients with higher NLRP3 and TLR4 expression had worse 5-year disease-free survival (DFS) compared to patients with lower NLRP3 and TLR4 expression (p =0.021 and p = 0.009, respectively). In multivariate analysis, TLR4 was confirmed as independent prognostic factors for DFS (HR = 2.03, 95% CI 1.16–3.57, p = 0.014), and high NLRP3 expression showed a slight association with DFS (HR = 1.75, 95% CI 0.98–3.15, p = 0.06). In conclusion, we showed TLR4 expression as independent prognostic factors and we highlighted for the first time that high expression of NLRP3 is linked to a poor prognosis in BC patients. These results suggest that NLRP3 and TLR4 could be two new good prognostic factor for BC patients.

scholarly journals Prevalence, Treatment Patterns, and Prognosis of Low Estrogen Receptor–Positive (1% to 10%) Breast Cancer: A Single Institution’s Experience in Korea

2021 ◽  
Author(s):  
Yeon Hee Park ◽  
Vassiliki Karantza ◽  
Shawna R. Calhoun ◽  
Seri Park ◽  
Sohee Lee ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Prognostic Factors ◽  
Regional Lymph Node ◽  
Menopausal Status ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Rank Test ◽  
Breast Cancer Patients ◽  
Her2 Breast Cancer

Abstract Purpose: To determine prevalence, clinicopathological characteristics, initial treatments, and outcomes associated with low estrogen receptor (ER)–expressing invasive breast cancer.Methods: This retrospective, noninterventional database study included patients undergoing surgery with curative intent for invasive ductal or lobular breast cancer. Patients were treated between January 2003-December 2012. Demographics, clinicopathologic characteristics, initial treatments, and outcomes were abstracted from patient records. Patients were categorized using immunohistochemistry to determine ER, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) levels. ER-positive patients were subclassified as ER-Low (1%–10%) and ER-High (>10%) according to Allred Proportion Score. Disease-free survival (DFS) and overall survival (OS) were estimated by the Kaplan-Meier method and compared among groups by log-rank test.Results: 5930 patients were included (median follow-up, 80.9 months). Of all patients included, 117 (2.0%) had ER-Low tumors, 63 (53.8%) of whom had HER2− tumors and 54 (46.2%) HER2+ tumors. Five-year DFS and OS were highest in the ER-High/HER2− cohort (94.0% and 98.6%, respectively) and lowest in the triple-negative breast cancer (TNBC; 81.3% and 90.1%) and ER-Low/HER2− (85.7% and 92.1%) cohorts. Menopausal status, elevated Ki-67, higher nuclear grade, higher tumor stage, presence of lymphovascular invasion, greater regional lymph node involvement, and larger tumor size were all potential prognostic factors for shorter DFS and OS. Conclusion: Patients with ER-Low/HER2− breast cancer had similar clinicopathological characteristics, treatments, and outcomes as patients with TNBC irrespective of disease setting. Further research is needed to understand predictive and prognostic factors associated with ER-Low/HER2− disease.

scholarly journals NDRG3 overexpression is associated with a poor prognosis in patients with hepatocellular carcinoma

2018 ◽  
Vol 38 (6) ◽  
Author(s):  
Ji-sheng Jing ◽  
Hongbo Li ◽  
Shun-cai Wang ◽  
Jiu-ming Ma ◽  
La-qing Yu ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cox Regression ◽  
Survival Curve ◽  
Disease Free Survival ◽  
Prognostic Indicator ◽  
Clinicopathological Characteristics ◽  
Pcr Analysis ◽  
Kaplan Meier ◽  
Tumor Tissues ◽  
The Relationship

N-myc downstream-regulated gene 3 (NDRG3), an important member of the NDRG family, is involved in cell proliferation, differentiation, and other biological processes. The present study analyzed NDRG3 expression in hepatocellular carcinoma (HCC) and explored the relationship between expression of NDRG3 in HCC patients and their clinicopathological characteristics. We performed quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR) analysis and immunohistochemistry (IHC) analyses on HCC tissues to elucidate NDRG3 expression characteristics in HCC patients. Kaplan–Meier survival curve and Cox regression analyses were used to evaluate the prognoses of 102 patients with HCC. The results revealed that compared with non-tumor tissues, HCC tissues showed significantly higher NDRG3 expression. In addition, our analyses showed that NDRG3 expression was statistically associated with tumor size (P=0.048) and pathological grade (P=0.001). Survival analysis and Kaplan–Meier curves revealed that NDRG3 expression is an independent prognostic indicator for disease-free survival (P=0.002) and overall survival (P=0.005) in HCC patients. The data indicate that NDRG3 expression may be considered as a oncogenic biomarker and a novel predictor for HCC prognosis.

Effect of mast cells on efficacy of anti-angiogenic therapy by secreting matrix-degrading granzyme b.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 11522-11522
Author(s):  
Mark Wroblewski ◽  
Janna-Lisa Velthaus ◽  
Raimund Bauer ◽  
Volkmar Müller ◽  
Christian Schem ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Granzyme B ◽  
Resistance Mechanism ◽  
Disease Free Survival ◽  
Tissue Microarrays ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Angiogenic Therapy ◽  
Kaplan Meier

11522 Background: Resistance towards anti-angiogenic therapy (AAT) still represents a substantial clinical challenge. As mast cell (MC) density is known to correlate with tumor angiogenesis, we analyzed if inhibition of MC holds potential to increase efficacy of AAT in mice and cancer patients. Methods: C57BL/6J (WT), NSG or MC-deficient KitW-sh(Wsh) mice were subcutaneously injected with Panc02, EL4 or BxPC3 cells with or without bone marrow-derived MC. Tumors were treated with 20 mg/kg of anti-VEGFR2 antibodies (DC101) or 25 mg/kg cromoglicic acid. Tissue microarrays from n = 299 breast cancer patients from the GeparQuinto Phase 3 clinical trial were stained for MC and MC numbers were correlated with clinical data. Results: We observed that absence of MC reduced tumor growth and increased the efficacy of AAT in different tumor models. Intriguingly, AAT only initially reduced microvessel proliferation but this was abrogated over time as a result of MC-mediated resistance. We show that MC secrete increased amounts of granzyme b upon therapy, which mobilizes alternative pro-angiogenic factors from the tumor matrix. These factors act beside the targeted VEGFA-VEGFR2-axis and reinduce angiogenesis despite the presence of AAT. Importantly, MC-mediated resistance could be overcome using the FDA-approved MC inhibitor cromoglicic acid. In line with our preclinical data, high intratumoral MC density correlated with disease progression in HR+ breast cancer patients when Bevacizumab was added to standard neodjuvant chemotherapy (HR 8.45, p = 0.006). Accordingly, Kaplan-Meier curves indicated that disease free survival of patients with high tumoral MC density was numerically shorter in the whole cohort and significantly shorter in the HR+ cohort upon addition of AAT to chemotherapy (p = 0.168 and p = 0.004, respectively). Conclusions: Here we unravel a novel resistance mechanism, by which MC hamper efficacy of AAT in mice and cancer patients. In preclinical models this effect could be overcome by combining AAT with an FDA-approved MC inhibitor indicating high clinical relevance. Thus, combination of FDA-approved MC inhibitors with AAT might be a suitable approach to increase efficacy of AAT in the clinic.

scholarly journals Incidence and Survival Trends of Bladder Rhabdomyosarcoma:A SEER-based Analysis of 125 Cases

2020 ◽  
Author(s):  
Pin Li ◽  
Huixia Zhou ◽  
Hualin Cao ◽  
Tao Guo ◽  
Weiwei Zhu ◽  
...  
Keyword(s):  
Prognostic Factors ◽  
Survival Time ◽  
Clinical Outcomes ◽  
Cox Regression ◽  
Survival Curve ◽  
Clinicopathological Characteristics ◽  
Chi Square ◽  
Cox Regression Analysis ◽  
Kaplan Meier ◽  
Significant Factors

Abstract Background To elucidate the bladder rhabdomyosarcoma clinicopathological characteristics and reveal the prognostic factors. Methods We screened data from SEER database (1975-2016) stratified by age group, evaluated the differences between groups with Chi-square and Fisher’s test, conducted the Kaplan-Meier survival analysis and plotted the survival curve. The significant factors were brought into Cox regression analysis and calculated the HR(95%CI). Results About half of the patients who develop bladder RMS will be younger than 2 years of age. Embryonal RMS account for 76% of all histopathology types. Age at diagnosis more than 16-y (HR=6.595,95%CI:3.62-12.01, p=7.04e-10), NOT embryonal rhabdomyosarcoma (HR=3.61, 95%CI:1.99-6.549, p =4.1e-06), without radiotherapy combined or surgery alone (HR=4.382, 95%CI:1.99-6.549, p =2.4e-05) and not performed the surgery (HR=2.982,95%CI:1.263-7.039, p =0.0126) were negatively correlated with 5-year survival time, while race( p =0.341), whether performed the lymphadenectomy( p =0.722) showed no influence on survival time. Cox regression results show that age, histology, SEER stage, treatment combined or alone influence the clinical outcomes. Conclusions We demonstrated the demographic and characteristic of bladder rhabdomyosarcoma, identified and excluded the prognostic factors for the 5-year overall survival and clinical outcomes.

Primary outcome results of NSABP B-32, a randomized phase III clinical trial to compare sentinel node resection (SNR) to conventional axillary dissection (AD) in clinically node-negative breast cancer patients.

2010 ◽  
Vol 28 (18_suppl) ◽  
pp. LBA505-LBA505 ◽  
Author(s):  
D. N. Krag ◽  
S. J. Anderson ◽  
T. B. Julian ◽  
A. Brown ◽  
S. P. Harlow ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Disease Free Survival ◽  
Phase Iii ◽  
Breast Cancer Patients ◽  
Regional Control ◽  
Kaplan Meier ◽  
Regional Node ◽  
Group 2 ◽  
Group 1

LBA505 Background: NSABP B-32 is the largest prospective randomized phase III trial designed to determine in SN negative patients that SNR alone results in the same survival and regional control as SNR + AD while reducing morbidity. It was designed to detect a survival difference of 2% between the 2 groups at 5 years. Methods: 5,611 women with operable, clinically N0, invasive breast cancer were randomized to SNR + AD (Group 1) or to SNR alone with AD only if SNs were positive (Group 2). 3,989 (71.1%) of the 5,611 patients were SN negative and followed for events. 99.9% of these SN negative patients had follow-up information: 1,975 in Group 1 and 2,011 in Group 2. Median time on study was 95.3 months. Patients were well balanced across clinical strata. Log-rank tests for unadjusted analyses and Cox proportional hazard models adjusting for study stratification variables were used to compare overall survival (OS) and disease-free survival (DFS) between the two groups. Two-sided p-values were used. HR values > 1 indicate a more favorable outcome in Group 1 (SNR + AD). Results: Comparisons of OS (Group 1 vs. Group 2) yielded an unadjusted HR of 1.20 (p = 0.12) and an adjusted HR of 1.19 (p=0.13). Five-year Kaplan-Meier estimates for OS are 96.4% in Group 1 and 95.0% in Group 2 and the 8-year estimates are 91.8% and 90.3%, respectively. Comparisons of DFS (Group 1 vs. Group 2) yielded an unadjusted HR of 1.05 (p=0.54) and an adjusted HR of1.07 (p=0.57). No substantial differences could be seen across sites for first treatment failure. Five-year Kaplan-Meier estimates for DFS are 89.0% in Group 1, and 88.6% in Group 2 and the 8-year estimates are 82.4% and 81.5%, respectively. Local and Regional Recurrences: There were 54 local recurrences in Group 1 and 49 in Group 2 (p=0.55). There were 8 regional node recurrences as first events in Group 1 and 14 in Group 2 (p=0.22). Conclusions: No significant differences were observed in OS, DFS, or regional control between the trial groups. Within the limits of this trial, SNR without AD is validated as a safe and effective method for regional node treatment of SN negative breast cancer patients. [Table: see text]

Prognostic significance of MAGE-A10 and NY-ESO-1 cancer-testis antigen in breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e21126-e21126
Author(s):  
Tanja Badovinac Crnjevic ◽  
Jasminka Jakic Razumovic ◽  
Giulio C Spagnoli ◽  
Paula Podolski ◽  
Nera Saric ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Malignant Tumors ◽  
Prognostic Significance ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Curative Surgery ◽  
Kaplan Meier ◽  
Expression Score ◽  
Cancer Testis

e21126 Background: Cancer testis antigens (CTAs) are expressed in a variety of malignant tumors. In normal adult tissues CTA expression is restricted predominantly to germs cells of the adult testis and placenta. Based on their tumor-restricted expression pattern, CTAs are regarded as valuable targets for cancer immunotherapy. The prognostic significance of CTAs in breast cancer has not been analyzed previously. Methods: To evaluate the potential prognostic significance of two member of this family, MAGE-A10 and NY-ESO-1 antigens, we examined their expression in breast cancer patients who underwent curative surgery at our hospital between 2002 and 2003. Paraffin embedded tumor sections were collected retrospectively from 165 breast cancer patients and immunohistochemical staining for MAGE-A10 and NY-ESO-1 was performed. Impact of MAGE-A10 and NY-ESO-1 expression on disease free survival (DFS) and overall survival (OS) was analyzed by the Kaplan-Meier method using 8-year follow up data. Results: MAGE-A10 expression (score ≥2+) was detected in 105/164 (64%) and NY-ESO-1 expression (score ≥2+) was observed in 14/164 (8.5%) patients. 8-year DFS for MAGE-A10 positive patients was 69% and 73% for MAGE-A10 negative (p=0.452). 8-year OS for MAGE-A10 positive patients was 80% and 90% for MAGE-A10 negative (p=0.134). For NY-ESO-1 positive patients 8-year DFS was 67% and 70% for NY-ESO-1 negative patients (p=0.837). 8-year OS for NY-ESO-1 positive patients was 83% and 84% for NY-ESO-1 negative patients. (p=0.991) Conclusions: To our knowledge this is the first study analyzing prognostic significance CTAs in breast cancer. In this retrospective study we did not show statistically significant correlation between MAGE-A10 and NY-ESO-1 expression and clinical outcome. Additional studies are warranted to determine weather this antigens might have prognostic value in breast cancer patients.

scholarly journals Breast Cancer in Chinese Females Aged 25 Years and Younger

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Lixi Li ◽  
Dan Lv ◽  
Jingtong Zhai ◽  
Di Zhang ◽  
Xiuwen Guan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Lymph Node ◽  
Lymph Node Metastasis ◽  
Cancer Patients ◽  
Lymphovascular Invasion ◽  
Clinicopathological Characteristics ◽  
Breast Cancer Patients ◽  
Young Females ◽  
Node Metastasis

Background. Breast cancer has both aggressive clinicopathological characteristics and a poor prognosis in young females. However, limited information is available for breast cancer in Chinese females aged ≤25 years. Therefore, we aimed to explore prognostic factors for invasive disease-free (iDFS) and overall survival (OS) among breast cancer patients aged ≤25 years. Methods. We retrospectively analyzed data from 174 Chinese females aged ≤25 years with invasive breast cancer treated in the Cancer Hospital of the Chinese Academy of Medical Sciences from January 1, 1999, to December 31, 2018. Univariate and multivariate Cox regression analyses were performed to identify independent prognostic factors. Results. The median follow-up time was 75 months (ranging from 1 to 236 months). Breast cancer patients aged ≤25 years exhibited aggressive clinicopathological characteristics, including advanced tumor stage (21.8%), lymph node metastasis (47.1%), lymphovascular invasion (24.1%), estrogen receptor negativity (44.3%), progesterone receptor (PR) negativity (42.5%), and triple-negative breast cancer (25.3%). Among them, 50 cases had locoregional recurrence and metastasis, 20 had bilateral invasiveness, and 33 had breast cancer-specific deaths. Cox multivariate analysis identified that diagnosis delay, PR status, and radiotherapy were significant prognostic factors for both iDFS and OS ( P < 0.05 ). The risk of recurrence and metastasis was five times higher in N3 than in N0 (HR: 6.778, 95% CI: 2.268–17.141, P < 0.001 ). Patients with lymphovascular invasion had a threefold increase in the risk of breast cancer-specific death (HR: 4.217, 95% CI: 1.956–9.090, P < 0.001 ). No differences were observed between mastectomy and breast-conserving surgery (BCS) plus radiotherapy for iDFS or OS (iDFS: χ2 = 0.678, P = 0.410 ; OS: χ2 = 0.165, P = 0.685 ). Conclusions. Breast cancer in females ≤25 years old was associated with aggressive clinical features and a worse prognosis. Young females with breast lumps should receive timely diagnosis and treatment. Young breast cancer patients with lymphovascular invasion, PR-negative status, and lymph node metastasis have an increased risk of experiencing recurrence and metastasis and should hence be closely monitored. Age at diagnosis should not be the sole deciding factor for surgical treatment methods.

The analyses of disease free survival and overall survival in premenopausal and postmenopausal axillary node negative breast cancer patients

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 10757-10757
Author(s):  
N. D. Bajic ◽  
D. D. Scepanovic
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Prognostic Factors ◽  
Disease Free Survival ◽  
Axillary Node ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Node Negative ◽  
Node Negative Breast Cancer ◽  
Significant Difference

10757 Background: The aim of this study was to analyse in which order known traditional prognostic factors predict disease free survival (DFS) and overall survival (OS) in breast cancer patients (pts) who are patohystologicaly axillary node negative. Methods: From 1998 till 2004, 258 patients were treated of axillary node negative breast cancer. We analysed 3 and 5 years (yrs) DFS and 3 and 5 yrs OS for all patients as well as for premenopausal (96 pts, 37%) and postmenopausal (162 pts, 63%). The mean follow-up time for DFS was 60 months (mo) (min 30, max 136 mo) and for OS was 66 mo (min 36, max 140 mo). As prognostic factors for DFS and OS, age, tumour size, HG as well as adjuvant treatment (locoregional and systemic) were analysed accordingly. Fifty two patients (20%) were HG1 while 190 pts (74%), were HG2 & 3; 30 pts (11%) had tumour up to 1cm and 157 pts (61%) had tumours up to 3cm and 71 pts (28%) above 3cm. Radical mastectomy was performed in 92 pts (36%) while conservative surgery were performed in 166 pts (64%). Systemic therapy was applied in 224 pts (87% of which 57% were treated with hormonotherapy). Results: 3 yrs DFS for 258 treated pts were 87% - there was no statistically significant difference among pre- and postmenopausal pts; 5 yrs DFS were 73% with no statistically significant difference among pre- and postmenopausal group of pts (p > 0.05). 3 yrs overall survival were 94% and 5 yrs 80% with no statistically significant difference among pre- and postmenopausal pts (p > 0.05). There were statistically different DFS and OS among those pts treated with adjuvant radiotherapy as well as for those with adjuvant systemic therapy in both group of pts (p < 0.001). Also as independent prognostic factor for DFS and OS were HG (Cox regression model). Conclusions: Although, HG and adjuvant therapy are the most important prognostic factors for DFS and OS in premenopausal and postmenopausal patients, we found that there is no statistically significant difference between the groups respectively. However, life-expectancy for premenopausal patients is longer. Therefore further adjuvant therapy research is needed to achieve better DFS and OS in this group of pts. No significant financial relationships to disclose.

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