scholarly journals Soluble Neuropilin-1 is an independent marker of poor prognosis in early breast cancer

2021 ◽  
Author(s):  
Tilman D. Rachner ◽  
Sabine Kasimir-Bauer ◽  
Andy Goebel ◽  
Kati Erdmann ◽  
Oliver Hoffmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Poor Prognosis ◽  
Therapeutic Potential ◽  
Transmembrane Protein ◽  
Tumor Biology ◽  
Tumor Stage ◽  
Her2 Status ◽  
Tyrosine Kinase Receptor ◽  
Neuropilin 1

Abstract Background Neuropilin-1 (NRP-1) is a transmembrane protein that acts as a multifunctional non-tyrosine kinase receptor with an established role in development and immunity. NRP-1 also regulates tumor biology, and high expression levels of tissue NRP-1 have been associated with a poor prognosis. Recently, ELISA-based quantification of soluble NRP-1 (sNRP-1) has become available, but little is known about the prognostic value of sNRP-1 in malignancies. Materials and methods We measured sNRP-1 in the serum of 509 patients with primary early breast cancer (BC) at the time of diagnosis using ELISA. Results Mean serum values of sNRP-1 were 1.88 ± 0.52 nmol/l (= 130.83 ± 36.24 ng/ml). SNRP-1 levels weakly correlated with age, and were higher in peri- and postmenopausal patients compared to premenopausal patients, respectively (p < 0.0001). Low levels of sNRP-1 were associated with a significant survival benefit compared to high sNRP-1 levels at baseline (p = 0.005; HR 1.94; 95%CI 1.23–3.06). These findings remained significant after adjustment for tumor stage including lymph node involvement, grading, hormone receptor, HER2 status, and age (p = 0.022; HR 1.78; 95%CI 1.09–2.91). Conclusion Our findings warrant further investigations into the prognostic and therapeutic potential of sNRP-1 in BC.

Ki67 as Proliferative Marker in Patients with Early Breast Cancer and Its Association with Clinicopathological Factors

Oncology ◽  
2021 ◽  
pp. 1-10
Author(s):  
Amelie de Gregorio ◽  
Thomas Wolfram Paul Friedl ◽  
Eva Hering ◽  
Peter Widschwendter ◽  
Nikolaus de Gregorio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Tumor Biology ◽  
Growth Factor Receptor ◽  
University Hospital ◽  
Proliferation Index ◽  
Her2 Status ◽  
Clinicopathological Factors ◽  
Her2 Positive ◽  
Proliferative Marker

<b><i>Introduction:</i></b> Ki67 as a proliferative marker has prognostic and therapeutic relevance in early breast cancer (EBC). However, standard cutoffs for distinguishing low and high Ki67 do not exist. <b><i>Material and Methods:</i></b> Data from all patients treated at the University Hospital Ulm for EBC between January 2013 and December 2015 with documented results for internal Ki67 assessment of the primary (<i>n</i> = 917) tumor were retrospectively analyzed evaluating the associations between Ki67 and other clinicopathological factors. <b><i>Results:</i></b> 595 (64.9%) patients had a Ki67 &#x3c;20% and 322 (35.1%) a Ki67 ≥20%. The median Ki67 was 10% (range 1–90%). Median Ki67 values according to the hormone receptor (HR)/ human epidermal growth factor receptor 2 (HER2) subtypes were 10% for HR-positive/HER2 negative (HR+/HER2−) disease (<i>n</i> = 717), 20% for HR+/HER2+ (<i>n</i> = 76), 30% for HR−/HER2+ (<i>n</i> = 45), and 60% for HR−/HER2− (<i>n</i> = 75). 75.2% or 89.3% of all patients with HER2-positive or triple-negative disease had a Ki67 ≥20%, respectively. Using a multivariable logistic regression with Ki67 (&#x3c;20% vs. ≥20%) as binary dependent variable, younger age, positive nodal status, higher grading, histological nonspecific type carcinoma, negative HR status, and positive HER2 status were shown to be significantly associated with a higher proliferative index (Ki67 ≥20%). <b><i>Conclusion:</i></b> This analysis described Ki67 in different subtypes in EBC and its association with clinicopathological factors. According to more aggressive tumor biology, the respective subgroups also showed higher median Ki67 levels. However, definition of low and high proliferation index itself is difficult. It is essential to interpret Ki67 indices carefully with regard to the own institutional values and other clinicopathological factors.

HER2 status in early breast cancer: Relevance of cell staining patterns, gene amplification and polysomy 17

2007 ◽  
Vol 43 (16) ◽  
pp. 2339-2344 ◽  
Author(s):  
Rosalba Torrisi ◽  
Nicole Rotmensz ◽  
Vincenzo Bagnardi ◽  
Giuseppe Viale ◽  
Barbara Del Curto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Amplification ◽  
Early Breast Cancer ◽  
Her2 Status ◽  
Polysomy 17 ◽  
Cell Staining

scholarly journals Interleukin-19 in Breast Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Ying-Yin Chen ◽  
Chien-Feng Li ◽  
Ching-Hua Yeh ◽  
Ming-Shi Chang ◽  
Chung-Hsi Hsing
Keyword(s):  
Breast Cancer ◽  
Therapeutic Potential ◽  
Endotoxic Shock ◽  
Tumor Stage ◽  
Advanced Tumor Stage ◽  
Duct Carcinoma ◽  
Advanced Tumor ◽  
And Migration

Inflammatory cytokines within the tumor microenvironment are linked to progression in breast cancer. Interleukin- (IL-) 19, part of the IL-10 family, contributes to a range of diseases and disorders, such as asthma, endotoxic shock, uremia, psoriasis, and rheumatoid arthritis. IL-19 is expressed in several types of tumor cells, especially in squamous cell carcinoma of the skin, tongue, esophagus, and lung and invasive duct carcinoma of the breast. In breast cancer, IL-19 expression is correlated with increased mitotic figures, advanced tumor stage, higher metastasis, and poor survival. The mechanisms of IL-19 in breast cancer have recently been explored bothin vitroandin vivo. IL-19 has an autocrine effect in breast cancer cells. It directly promotes proliferation and migration and indirectly provides a microenvironment for tumor progression, which suggests that IL-19 is a prognostic marker in breast cancer and that antagonizing IL-19 may have therapeutic potential.

Adjuvant Chemotherapy: Which Patient? What Regimen?

2013 ◽  
pp. 3-8 ◽  
Author(s):  
Natalie Turner ◽  
Laura Biganzoli ◽  
Luca Malorni ◽  
Ilenia Migliaccio ◽  
Erica Moretti ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adjuvant Chemotherapy ◽  
Breast Cancer Subtype ◽  
Tumor Biology ◽  
Patient Characteristics ◽  
Tumor Stage ◽  
Luminal A ◽  
Genomic Analyses ◽  
Cancer Subtype ◽  
Clinicopathologic Factors

In the past, treatment decisions regarding adjuvant chemotherapy in early breast cancer (EBC) were made solely based on clinicopathologic factors. However, with increased awareness of the importance of underlying tumor biology, we are now able to use genomic analyses to determine molecular breast cancer subtype and thus identify patients with tumors that are chemotherapy resistant and unlikely to benefit from the addition of chemotherapy. Although genomics has allowed some patients to avoid chemotherapy—specifically those with luminal A–like breast cancer—these assays do not indicate which regimen is most appropriate. For this, consideration must be given to the combination of underlying tumor biology, tumor stage, and patient characteristics, such as age and tolerability of side effects.

DOES ONE SIZE FIT ALL? COST UTILITY ANALYSES OF ALTERNATIVE MAMMOGRAPHIC FOLLOW-UP SCHEDULES, BY RISK OF RECURRENCE

2015 ◽  
Vol 31 (5) ◽  
pp. 281-288 ◽  
Author(s):  
Taryn Bessen ◽  
Dorothy M.K. Keefe ◽  
Jonathan Karnon
Keyword(s):  
Breast Cancer ◽  
Postmenopausal Women ◽  
Early Breast Cancer ◽  
Poor Prognosis ◽  
Controlled Trial ◽  
Discrete Event ◽  
Prognostic Index ◽  
Cost Effective ◽  
Risk Of Recurrence

Objectives: International guidelines recommend annual mammography after early breast cancer, but there is no randomized controlled trial evidence to support this schedule over any other. Given that not all women have the same risk of recurrence, it is possible that, by defining different risk profiles, we could tailor mammographic schedules that are more effective and efficient.Methods: A discrete event simulation model was developed to describe the progression of early breast cancer after completion of primary treatment. Retrospective data for 1,100 postmenopausal women diagnosed with early breast cancer in South Australia from 2000 to 2008 were used to calibrate the model. Women were divided into four prognostic subgroups based on the Nottingham Prognostic Index of their primary tumor. For each subgroup, we compared the cost-effectiveness of three different mammographic schedules for two different age groups.Results: Annual mammographic follow-up was not cost-effective for most postmenopausal women. Two yearly mammography was cost-effective for all women with excellent prognosis tumors; and for women with good prognosis tumors if high compliance rates can be achieved. Annual mammography for 5 years and 2 yearly surveillance thereafter (a mixed schedule) may be cost-effective for 50- to 69-year-old women with moderate prognosis tumors, and for women aged 70–79 years with poor prognosis tumors. For younger women with poor prognosis tumors, annual mammography is potentially cost-effective.Conclusions: Our results suggest that mammographic follow-up could be tailored according to risk of recurrence. If validated with larger datasets, this could potentially set the stage for personalized mammographic follow-up after breast cancer.

Correlation of BMI with tumor stage in early breast cancer patients (pts): Pooled analysis of the German SUCCESS A, B, and C trials.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1602-1602
Author(s):  
Carola Anna Melcher ◽  
Uta Ortmann ◽  
Christoph Scholz ◽  
Thomas Zwingers ◽  
Andreas Schneeweiss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lymph Node ◽  
Early Breast Cancer ◽  
Primary Breast Cancer ◽  
Tumor Stage ◽  
Lymph Node Involvement ◽  
Phase Iii ◽  
Tumor Characteristics ◽  
Node Involvement ◽  
Disease Free

1602 Background: Independent from known prognostic factors, e.g., tumor size and nodal status, obesity is a risk factor for poor disease free, distant disease free, and overall survival in breast cancer. The aim of this analysis was to examine the correlation of the body mass index (BMI) with tumor characteristics in early breast cancer. Methods: We analyzed the data of 7,997 pts with early, node positive or high risk node negative primary breast cancer treated with adjuvant taxan-based chemotherapy within the German multicenter phase III SUCCESS A, B, or C trials. The pts’ tumor stage at primary diagnosis was classified according to the UICC tumor-node-metastasis (TNM) classification. Additionally, the tumor’s hormone-receptor status and HER2/neu status were determined. Before enrollment into the study each patient was grouped according to the WHO global database on BMI. Contingency table methods were used to analyze the correlation of BMI and tumor characteristics. Results: Among the 7,997 pts 100 (1.3%) pts were underweight, 3,556 (44.5%) pts were normal weight, 2,569 (32.1%) pts were overweight and 1,772 (22.2%) were obese. Of all pts 4,508 pts (56.4%) suffered from a pT2-4 tumor, 4830 (60.4%) showed lymph node involvement (pN1-3) and 7509 (93.9%) had G2-3 tumors. 5839 pts (73.0%) showed positivity for ER or PR and 935 (11.7%) for HER2/neu. Overweight and obese pts had significantly larger tumors compared to pts with normal BMI (p<0.0001; p<0.0001). Furthermore, overweight and obesity were associated with a significantly higher rate of lymph node involvement (p=0.0001; p=0.0003) respectively. In contrast neither grading, tumor histology, ER/PR-status nor HER2/neu-overexpression were correlated with BMI. Conclusions: These data are the first to show in a large number of pts that both obese and overweight women suffering from primary breast cancer have significantly larger tumors and more often positive axillary lymph nodes. As there are no differences in tumor biology, the advanced tumor stage might be due to more difficult and delayed detection of breast cancer and lymph node lesions in these women.

Hormone receptor-dependent regulation of ABAT and beta-alanine metabolism in breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 11112-11112 ◽  
Author(s):  
Jan Budczies ◽  
Scarlet F. Brockmoeller ◽  
Berit Mueller ◽  
Manfred Dietel ◽  
Oliver Fiehn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Grade ◽  
Staining Intensity ◽  
Tumor Stage ◽  
Her2 Status ◽  
Rna Expression ◽  
Breast Cancers ◽  
Strong Negative Correlation ◽  
Data Set ◽  
Beta Alanine

11112 Background: Recently, we identified beta-alanine as biomarker for breast cancer using GC-MS based metabolomics. Beta-alanine is increased in breast cancer compared to normal tissues and in the more aggressive ER- subtype compared to ER+ breast cancer. Beta-alanine is a substrate of 4-aminobutyrate aminotransferase (ABAT), can be catabolised to malonate semialdehyde and used for reduction of NAD and acetylation of coenzyme A. The aim of the current study is to analyze ABAT protein and RNA expression in a large cohort of breast cancers. Methods: The specificity of a polyclonal antibody against ABAT was validated using siRNA in MFC7 cells. A cohort of 164 paraffin-embedded breast cancer tissues from the METAcancer biobank was investgated by immunohistochemistry. Tumor cells were evaluated separately for staining intensity (low, moderate or high) and percentage of stained cells. A cohort of 156 METAcancer samples was investigated for gene expression using whole genome DASL. Results: ABAT protein intensity correlated strongly with estrogen receptor (ER) status (p < 0.001), but not with HER2 status. In particular, the ABAT protein was highly expressed in 41% of the ER+ tissues, but only in 2% of the ER- tissues. Further, ABAT intensity correlated strongly with tumor grade (p < 0.001). ABAT intensity did not correlate with tumor stage or nodal status. Explorative evaluation of ABAT protein in normal cells revealed weak expression in some of the ducts and negative expression in adipose cells. ABAT protein and RNA expression strongly correlated in the subcohort investigated by DASL. Analysis of a large external data set (publicly available at www.kmplot.com) showed that low ABAT expression is associated with an unfavorable prognosis of breast cancer. Both, ABAT protein and RNA expression, showed a strong negative correlation with beta-alanine abundance. Conclusions: We reported on changes in beta-alanine metabolism that occur between the molecular subtypes of breast cancer and normal breast tissue. High expression of ABAT in ER+ breast cancer is compatible with catabolic use of beta-alanine. Differently, beta-alanine might be preferable used anabolic in ER- breast cancer, possibly for the synthesis of carnosine.

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