scholarly journals Unbiased Lipidomic Profiling of Triple-Negative Breast Cancer Tissues Reveals the Association of Sphingomyelin Levels with Patient Disease-Free Survival

Metabolites ◽  
2018 ◽  
Vol 8 (3) ◽  
pp. 41 ◽  
Author(s):  
Preeti Purwaha ◽  
Franklin Gu ◽  
Danthasinghe Piyarathna ◽  
Theckelnaycke Rajendiran ◽  
Anindita Ravindran ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Triple Negative ◽  
Therapeutic Targets ◽  
Disease Free Survival ◽  
Sphingolipid Metabolism ◽  
Free Survival ◽  
Cancer Aggressiveness ◽  
Novel Biomarkers ◽  
Disease Free

The reprogramming of lipid metabolism is a hallmark of many cancers that has been shown to promote breast cancer progression. While several lipid signatures associated with breast cancer aggressiveness have been identified, a comprehensive lipidomic analysis specifically targeting the triple-negative subtype of breast cancer (TNBC) may be required to identify novel biomarkers and therapeutic targets for this most aggressive subtype of breast cancer that still lacks effective therapies. In this current study, our global LC-MS-based lipidomics platform was able to measure 684 named lipids across 15 lipid classes in 70 TNBC tumors. Multivariate survival analysis found that higher levels of sphingomyelins were significantly associated with better disease-free survival in TNBC patients. Furthermore, analysis of publicly available gene expression datasets identified that decreased production of ceramides and increased accumulation of sphingoid base intermediates by metabolic enzymes were associated with better survival outcomes in TNBC patients. Our LC-MS lipidomics profiling of TNBC tumors has, for the first time, identified sphingomyelins as a potential prognostic marker and implicated enzymes involved in sphingolipid metabolism as candidate therapeutic targets that warrant further investigation.

Development of prognostic nomograms using institutional data for patients with triple-negative breast cancer

2021 ◽  
Author(s):  
Jie-Yu Zhou ◽  
Kang-Kang Lu ◽  
Wei-Da Fu ◽  
Hao Shi ◽  
Jun-Wei Gu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Predictive Accuracy ◽  
Area Under The Curve ◽  
Disease Free Survival ◽  
Discriminative Ability ◽  
Free Survival ◽  
Disease Free

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.

scholarly journals AKAP3 correlates with triple negative status and disease free survival in breast cancer

BMC Cancer ◽  
2015 ◽  
Vol 15 (1) ◽  
Author(s):  
Rezvan Esmaeili ◽  
Keivan Majidzadeh-A ◽  
Leila Farahmand ◽  
Maryam Ghasemi ◽  
Malihe Salehi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Free Survival ◽  
Disease Free

scholarly journals Role of GATA3 exon 6 germline mutations in breast cancer progression in Egyptian female patients

2020 ◽  
pp. 153537022095861
Author(s):  
Iman H Ibrahim ◽  
Heba G Abdel-Aziz ◽  
Fatema EM Hassan ◽  
Hesham SA El-Sameea
Keyword(s):  
Breast Cancer ◽  
Cancer Progression ◽  
Disease Free Survival ◽  
Germline Mutations ◽  
Breast Cancer Progression ◽  
Protein Coding ◽  
Free Survival ◽  
Disease Free ◽  
Gata3 Protein

Several mutations act as driver mutations in breast cancer, including GATA3 mutations. Reports of the relation between GATA3 mutations and breast cancer prognosis remain conflicting. Also, the role of GATA3 germline mutations is not well studied. We hypothesize that different mutation types could have different effects. Also, this study aims to assess effect of GATA3 mutations on GATA3 protein function as a transcription factor, and target pathways affected. DNA from de novo breast cancer female patients was sequenced to detect exon 6 GATA3 mutation. Sequence analysis was performed along with clinical and prognostic parameters and disease-free survival. Public datasets were analyzed for differentially expressed genes and pathways with mutant GATA3 patients. Mutations in GATA3 exon 6 were detected in 56.1% of patients (including 2 novel, Lys368fs, Pro354Lys). Intronic mutations were significantly higher in long disease-free survival group, while frameshift mutations were significantly higher in short DFS group. Patients with tumor size ≥20 had significantly higher protein coding and lower intronic mutations compared to patients with tumor size <20 mm. Differential expression and pathway analysis showed that mutant GATA3 had lost its negative regulatory effect on several pathways such as: signaling by interleukins, regulation of TP53 expression, and RUNX3 regulated CDKN1A transcription pathway. PIK3CA, SKP1, FBP1, SMAD3, ANXA9 and CLSTN2 were positively correlated to wild-type GATA3 expression, but not mutant GATA3. Intronic germline mutations of GATA3 could be related to better prognosis, while protein coding GATA3 germline mutations could be related to unfavorable prognosis. GATA3 mutations lead to dysregulation of pathways related to immunity, breast cancer development, and metabolism. Impact statement GATA3 mutations are known to play an important role in breast cancer progression. The exact role and mechanisms of these mutations remain controversial as some studies suggest a relation to breast tumor growth, while others suggest a relation to longer survival. GATA3 germline mutations are not well studied in breast cancer. In this study, it was hypothesized that different types of GATA3 mutations could contribute to the breast cancer progression in different ways. GATA3 exon 6, which is important for GATA3 protein functions, was reported to have hotspots, and hence it was selected for study. Intronic GATA3 germline mutations were found to be related to favorable prognosis, while protein coding mutations were found to be related to unfavorable prognosis. Bioinformatics study of large publically available datasets showed that GATA3 mutations lead to dysregulation of pathways related to T-cells activation, inflammation, and breast cancer development.

Different effects of insulin-like growth factor-1 receptor expression on prognosis of estrogen receptor positive versus triple-negative invasive ductal breast carcinoma

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 3546-3546
Author(s):  
J. Wesseling ◽  
H. Hartog ◽  
H. Horlings ◽  
B. van der Vegt ◽  
A. Ajouaou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Growth Factor ◽  
Triple Negative ◽  
Systemic Treatment ◽  
Disease Free Survival ◽  
P Value ◽  
Invasive Ductal Breast Carcinoma ◽  
Free Survival ◽  
Disease Free

3546 Background: The insulin-like growth factor type 1 receptor (IGF-1R) is involved in progression and sensitivity to systemic treatment of breast cancer. Moreover, targeted inhibition of IGF-1R is likely to be beneficial in systemic treatment. However, it is unknown how to select patients for IGF-1R targeted therapy. Therefore, we studied the relation between IGF-1R expression and prognosis in invasive ductal breast carcinomas. Methods: Immunohistochemistry was performed on tumor tissue of a consecutive cohort of 429 female patients treated for operable primary invasive ductal breast carcinoma. TMA sections were stained with antibodies against IGF1-R, insulin receptor (IR), ER, PR, HER-2, epidermal growth factor receptor (EGFR) and phosphorylated-Akt (p-Akt). Cytoplasmic and membranous IGF-1R staining were scored separately, as the relevance of IGF-1R cellular localization is yet unknown. Associations between IGF-1R expression with clinical and tumor characteristics were evaluated in a multivariate Cox regression model. To study in more detail the prognostic role of IGF-1R expression in triple negative invasive ductal carcinomas (TN IDCs), 51 TN IDCs from the series described above were combined with 64 TN IDCs from an independent dataset with similar patient and clinico-pathological characteristics. Results: Patients with tumors expressing both ER and cytoplasmic IGF-1R have a longer disease free survival (HR = 0.20; 95% CI 0.07 - 0.63; p-value = 0.006) and breast cancer specific survival (HR = 0.20, 95% CI 0.07 - 0.63, p-value = 0.002), independent of other known prognostic factors. Conversely, in the combined series of 105 TN IDCs, cytoplasmic IGF-1R expression was associated with a shorter disease free survival (HR = 2.29; 95% CI 1.08 - 4.48, p-value = 0.03). In a multivariate model including known prognostic factors, cytoplasmic IGF-1R expression was nearly significantly related to a shorter disease free survival (HR 2.06; 95% CI 0.95 - 4.47; p = 0.07). Conclusions: The favorable versus unfavorable association with prognosis of IGF-1R expression in ER positive versus TN IDCs may provide new opportunities to select patients for IGF-1R targeted therapy. No significant financial relationships to disclose.

The prognostic importance of triple negative breast cancer: A population based study in India

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22219-e22219
Author(s):  
B. S. Ajaikumar ◽  
R. Rao ◽  
J. Prabhu ◽  
J. D. Kulkarni ◽  
P. K ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Regression Analysis ◽  
Cancer Patients ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Breast Cancer Patients ◽  
Free Survival ◽  
Node Status ◽  
Disease Free

e22219 Background: Triple-negative (ER-negative, PR-negative, HER2/neu negative) breast cancer has distinct clinical and pathologic features, and is a clinical problem because of its typically high grade, relatively poor prognosis, aggressive behavior and lack of targeted therapies leaving chemotherapy as the mainstay of treatment. This study envisaged to analyse the influence of triple negativity status on survival and disease free survival in prospective cohort of breast cancer patients. Methods: Breast tumors of 215 women aged 30–75, diagnosed from 2004 were tested for ER, PR and HER2 positivity by immunohistochemistry and correlated with clinical outcomes such as recurrence, disease free survival and overall survival using Kaplan Meiers Survival analysis and Coxs regression analysis. The study cohort was followed up for 60 months or until death whichever was earlier. Results: Triple negativity significantly influenced disease free survival (46 ± 3, 41, 52) vs. non triple negative cohort (mean ± SE; 95%CI, 37 ± 2; 32, 40) and log rank = 2.1, p = 0.04. However triple negativity did not influence overall survival in months (56 ± 0; 55, 56) vs. non triple negative cohort (43 ± 1; 42, 45), (log rank = 1.78, p = 0.16). However, the mean disease free survival was (45 ± 7; 32, 58) months for patients >40 years age vs (37 ± 4; 33, 39) for patients < 40 years of age (log rank = 2.87, p =0.02). Stage of disease, node status, grade and menopausal status did not influence disease free survival significantly. However, Cox regression analysis did not predict significant effects of triple negativity on overall survival or disease free survival when controlled for confounding factors such as age, node status, stage etc Conclusions: Our observations suggest that triple negativity can significantly affect progression of breast cancer in Indian breast cancer patients and longer follow up is necessary (10 years) to determine its effects on survival. No significant financial relationships to disclose.

Clinical impact of 18F-FDG–PET in breast cancer: Survival analysis and comparison of intrinsic subtypes with standardized uptake value.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12005-e12005
Author(s):  
Sung Gwe Ahn ◽  
Hak Min Lee ◽  
Seung Ah Lee ◽  
Tae Joo Jeon ◽  
Young Hoon Yoo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Analysis ◽  
Fdg Pet ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Clinical Impact ◽  
Free Survival ◽  
18F Fdg ◽  
Validation Set ◽  
Disease Free

e12005 Background: [18F] fluorodeoxyglucose positron emission tomography (18F-FDG–PET) scans are known as an important imaging study with their reflection biological activity in various malignancies. To investigate clinical impact of 18F-FDG–PET in breast cancer, we performed survival analysis with maximum standardized uptake values (SUVmax), and compared SUVmax according to breast cancer subtypes. Methods: We reviewed the medical records of 462 patients with breast cancer who underwent primary surgery between April 2004 and December 2008 at single institute. Patients were classified as 4 subtypes: luminal A, luminal B, HER2 and triple negative. The entire patients were randomly assigned as training set (n=220) and validation set (n=242). Results: High SUVmax vs. low SUVmax group was defined with cut-off points of 4 in a training set.At a median follow-up of 6.03 years, the patients with high SUVmax had a shorter disease-free survival in a validation set (p = 0.018, log-rank test). Using multivariate analysis for disease-free survival in the entire patients, high SUVmax was demonstrated as a poor prognostic factor (hazard ratio 2.34, 95% confidence interval 1.18-4.67). In the comparison among subtypes, mean of SUVmax was higher in triple negative type and HER2 type. Also, high SUVmax was significantly associated with larger tumor size, positive node, high Ki67 (≥14%), ER negative, and high histologic grade, and HER2 positive. Conclusions: In breast cancer, the patients with higher SUVmax showed a shorter disease-free survival. Higher SUVmax found in HER-2 and triple negative type suggests that 18F-FDG PET could reflect molecular signature.

Vitamin D status and survival in patients with triple negative breast cancer.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e18210-e18210
Author(s):  
John Khoury ◽  
Sruthi Jinna ◽  
Ali Sahlieh ◽  
Rebecca Chacko ◽  
David Macari ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Vitamin D ◽  
Postmenopausal Women ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Disease Free Survival ◽  
Premenopausal Women ◽  
Stage I ◽  
Free Survival ◽  
Disease Free

e18210 Background: Although many studies have investigated the association of blood 25OH-vitamin D (vit-D) levels with breast cancer prognosis, the results have been mixed. It has been suggested that low vit-D concentrations were associated with advanced tumor stage and triple-negative (TNBC) subtype. We retrospectively investigated associations of serum vit-D levels with triple negative breast cancer outcome. Methods: Out of 797 cases of TNBC diagnosed at William Beaumont Hospital between 2006-2017, 163 patients had vit-D level available within 1 year prior to diagnosis. Analyses of vit-D levels was classified by 3 cut points (deficient, < 20.0 ng/mL; insufficient, 20.0-29.9 ng/mL; sufficient, ≥30.0 ng/mL). Primary outcomes are disease free survival (DFS) and overall survival (OS). SPSS statistics 25 software was used to analyze the data. Results: Median age of diagnosis of TNBC was 60. Of these patients 43.6% were diagnosed with stage I, 37.4% at stage II, 4.9% at stage III and 4.9% at stage IV. 47.2% of the patients had sufficient vit-D level prior to diagnosis, 28.2% with insufficient vit-D level and 24.5% with deficient vit-D. Vit-D deficiency was more prevalent in premenopausal than in postmenopausal women (33.3%, 41% and 25.6% in premenopausal women for deficient, insufficient and sufficient levels respectively vs 21.8%, 24.2% and 54% in postmenopausal women). Rates of Vit-D deficiency were not different between early disease and advanced disease (24.3% of patient with stage I-II vs 25% in patients with stage III-IV). Median OS and disease-free survival were not statistically different among the 3 different categories. 5-year OS was 91%, 91% and 85% for deficient, insufficient and sufficient levels respectively. 5-year DFS was 93%, 95% and 95% for deficient, insufficient and sufficient levels respectively. Multivariate COX regression analysis demonstrated that age and stage were associated with mortality, whereas vit-D level was not. Conclusions: The results from this study show that adequate vit-D level do not have an impact on OS and DFS in patients with triple negative breast cancer. Premenopausal women are more likely to have inadequate vit-D level. Identification and treatment of vitamin D deficiency is still important for musculoskeletal health and possibly extraskeletal health in general population and breast cancer survivors specifically.

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