scholarly journals Expression of Pentose Phosphate Pathway-Related Proteins in Breast Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Junjeong Choi ◽  
Eun-Sol Kim ◽  
Ja Seung Koo
Keyword(s):  
Breast Cancer ◽  
Pentose Phosphate Pathway ◽  
Molecular Subtype ◽  
Pentose Phosphate ◽  
The Cancer Genome Atlas ◽  
Related Factor ◽  
Mrna Levels ◽  
Luminal A ◽  
Her 2 ◽  
Related Proteins

Purpose. The purpose of this study was to assess the expression of pentose phosphate pathway- (PPP-) related proteins and their significance in clinicopathologic factors of breast cancer. Methods. Immunohistochemical staining for PPP-related proteins (glucose-6-phosphate dehydrogenase [G6PDH], 6-phosphogluconolactonase [6PGL], 6-phosphogluconate dehydrogenase [6PGDH], and nuclear factor-erythroid 2-related factor 2 [NRF2]) was performed using tissue microarray (TMA) of 348 breast cancers. mRNA levels of these markers in publicly available data from the Cancer Genome Atlas project and Kaplan-Meier plotters were analyzed. Results. Expression of G6PDH and 6PGL was higher in HER-2 type (p<0.001 and p=0.009, resp.) and lower in luminal A type. 6PGDH expression was detected only in TNBC subtype (p<0.001). G6PDH positivity was associated with ER negativity (p=0.001), PR negativity (p=0.001), and HER-2 positivity (p<0.001), whereas 6PGL positivity was associated with higher T stage (p=0.004). The 562 expression profile from the TCGA database revealed increased expression of G6PDH and 6PG in the tumor compared with normal adjacent breast tissue. The expression of G6PDH was highest in HER-2 type. HER-2 and basal-like subtypes showed higher expression of 6PGDH than luminal types. Conclusion. PPP-related proteins are differentially expressed in breast cancer according to molecular subtype, and higher expression of G6PDH and 6PGL was noted in HER-2 subtype.

scholarly journals Differential Site-Based Expression of Pentose Phosphate Pathway-Related Proteins among Breast Cancer Metastases

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Yoon Jin Cha ◽  
Woo Hee Jung ◽  
Ja Seung Koo
Keyword(s):  
Breast Cancer ◽  
Brain Metastases ◽  
Pentose Phosphate Pathway ◽  
Metastatic Breast ◽  
Pentose Phosphate ◽  
Related Factor ◽  
Breast Cancers ◽  
Ki 67 ◽  
Her 2 ◽  
Related Proteins

Purpose. We aimed to investigate the expression of pentose phosphate pathway- (PPP-) related proteins in metastatic breast cancer and its relationship with clinicopathologic factors.Methods. Tissue samples from 126 metastatic breast cancers were included in a tissue microarray. Expression of PPP-related proteins [glucose-6-phosphate dehydrogenase (G6PDH), 6-phosphogluconolactonase (6PGL), 6-phosphogluconate dehydrogenase (6PGDH), and nuclear factor erythroid 2-related factor (NRF2)] was determined by immunohistochemistry.Results. G6PDH (p=0.011) and cytoplasmic NRF2 (p=0.001) showed the highest expression in brain metastases. Human epidermal growth factor receptor (HER-2) positivity was associated with G6PDH (p<0.001) and cytoplasmic NRF2 (p=0.015) positivity. A high Ki-67 labeling index (LI) was correlated with nuclear NRF2 positivity (p=0.037), and HER-2-positive luminal B type was associated with G6PDH positivity (p=0.001). On multivariate Cox analysis, independent risk factors of short overall survival were 6PGL positivity in bone metastasis (HR 4.180, 95% CI 1.160–15.06,p=0.029) and low Ki-67 LI in lung metastasis (HR 11.853, 95% CI 1.841–76.30,p=0.009).Conclusion. Differential expression of PPP-related proteins correlated with different prognoses and metastatic sites, with the highest expression in brain metastases, and could be a potential therapeutic target.

scholarly journals Apparent diffusion coefficient cannot predict molecular subtype and lymph node metastases in invasive breast cancer: a multicenter analysis

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Alexey Surov ◽  
Yun-Woo Chang ◽  
Lihua Li ◽  
Laura Martincich ◽  
Savannah C. Partridge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Diffusion Coefficient ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Luminal A ◽  
Ki 67 ◽  
Luminal B ◽  
Apparent Diffusion ◽  
Adc Values ◽  
Her 2

Abstract Background Radiological imaging plays a central role in the diagnosis of breast cancer (BC). Some studies suggest MRI techniques like diffusion weighted imaging (DWI) may provide further prognostic value by discriminating between tumors with different biologic characteristics including receptor status and molecular subtype. However, there is much contradictory reported data regarding such associations in the literature. The purpose of the present study was to provide evident data regarding relationships between quantitative apparent diffusion coefficient (ADC) values on DWI and pathologic prognostic factors in BC. Methods Data from 5 centers (661 female patients, mean age, 51.4 ± 10.5 years) were acquired. Invasive ductal carcinoma (IDC) was diagnosed in 625 patients (94.6%) and invasive lobular carcinoma in 36 cases (5.4%). Luminal A carcinomas were diagnosed in 177 patients (28.0%), luminal B carcinomas in 279 patients (44.1%), HER 2+ carcinomas in 66 cases (10.4%), and triple negative carcinomas in 111 patients (17.5%). The identified lesions were staged as T1 in 51.3%, T2 in 43.0%, T3 in 4.2%, and as T4 in 1.5% of the cases. N0 was found in 61.3%, N1 in 33.1%, N2 in 2.9%, and N3 in 2.7%. ADC values between different groups were compared using the Mann–Whitney U test and by the Kruskal-Wallis H test. The association between ADC and Ki 67 values was calculated by Spearman’s rank correlation coefficient. Results ADC values of different tumor subtypes overlapped significantly. Luminal B carcinomas had statistically significant lower ADC values compared with luminal A (p = 0.003) and HER 2+ (p = 0.007) lesions. No significant differences of ADC values were observed between luminal A, HER 2+ and triple negative tumors. There were no statistically significant differences of ADC values between different T or N stages of the tumors. Weak statistically significant correlation between ADC and Ki 67 was observed in luminal B carcinoma (r = − 0.130, p = 0.03). In luminal A, HER 2+ and triple negative tumors there were no significant correlations between ADC and Ki 67. Conclusion ADC was not able to discriminate molecular subtypes of BC, and cannot be used as a surrogate marker for disease stage or proliferation activity.

scholarly journals MiR-100 is a predictor of endocrine responsiveness and prognosis in patients with operable luminal breast cancer

ESMO Open ◽  
2020 ◽  
Vol 5 (5) ◽  
pp. e000937
Author(s):  
Annalisa Petrelli ◽  
Sara Erika Bellomo ◽  
Ivana Sarotto ◽  
Franziska Kubatzki ◽  
Paola Sgandurra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prospective Study ◽  
Endocrine Therapy ◽  
Molecular Subtype ◽  
Molecular Taxonomy ◽  
Endocrine Resistance ◽  
The Cancer Genome Atlas ◽  
Response To Treatment ◽  
Luminal Breast Cancer ◽  
Luminal A

PurposeOverexpression of miR-100 in stem cells derived from basal-like breast cancers causes loss of stemness, induction of luminal breast cancer markers and response to endocrine therapy. We, therefore, explored miR-100 as a novel biomarker in patients with luminal breast cancer.MethodsmiR-100 expression was studied in 90 patients with oestrogen-receptor-positive/human-epidermal growth factor receptor 2-negative breast cancer enrolled in a prospective study of endocrine therapy given either preoperatively, or for the treatment of de novo metastatic disease. Response was defined as a Ki67 ≤2.7% after 21±3 days of treatment. The prognostic role of miR-100 expression was evaluated in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) and The Cancer Genome Atlas (TCGA) breast cancer datasets. Additionally, we explored the correlation between miR-100 and the expression its targets reported as being associated with endocrine resistance. Finally, we evaluated whether a signature based on miR-100 and its target genes could predict the luminal A molecular subtype.ResultsBaseline miR-100 was significantly anticorrelated with baseline and post-treatment Ki67 (p<0.001 and 0.004, respectively), and independently associated with response to treatment (OR 3.329, p=0.047). In the METABRIC dataset, high expression of miR-100 identified women with luminal A tumours treated with adjuvant endocrine therapy with improved overall survival (HR 0.55, p<0.001). miR-100 was negatively correlated with PLK1, FOXA1, mTOR and IGF1R expression, potentially explaining its prognostic effect. Finally, a miR-100-based signature developed in patients enrolled in the prospective study outperformed Ki67 alone in predicting the luminal A phenotype.ConclusionsOur findings suggest that miR-100 should be further explored as a biomarker in patients with luminal breast cancer.

scholarly journals Expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer

2013 ◽  
Vol 20 (3) ◽  
pp. 339-348 ◽  
Author(s):  
Sewha Kim ◽  
Do Hee Kim ◽  
Woo-Hee Jung ◽  
Ja Seung Koo
Keyword(s):  
Breast Cancer ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Glutamine Metabolism ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Luminal A ◽  
Luminal B ◽  
Related Proteins ◽  
Glutaminase 1

The aim of this study was to investigate the expression of glutamine metabolism-related proteins to determine whether glutamine is metabolized differently according to breast cancer molecular subtype. We generated a tissue microarray of 702 breast cancer patients and performed immunohistochemical staining for glutamine metabolism-related proteins, including glutaminase 1 (GLS1 (GLS)), glutamate dehydrogenase (GDH (H6PD)), and amino acid transporter-2 (ASCT2 (SLC1A5)), which were separately evaluated in tumor and stroma compartments and then analyzed by breast cancer molecular subtypes. Breast cancers were classified as follows: 293 luminal A (41.7%), 166 luminal B (23.6%), 67 HER2 type (9.6%), and 176 TNBC (25.1%). HER2 type showed the highest stromal GLS1 (P=0.001), tumoral GDH (P=0.001), stromal GDH (P<0.001), and tumoral ASCT (P<0.001) expression. We identified differential expression of glutamine metabolism-related proteins according to molecular subtype of breast cancer. The highest glutamine metabolic activity was seen in HER2-type breast cancer.

scholarly journals Immunohistochemical tests for diagnostics of infiltrative forms of breast cancer and identification of molecular subtype in women of different ages in Dnipro city

2017 ◽  
Vol 8 (2) ◽  
pp. 204-209
Author(s):  
T. M. Shevchenko ◽  
P. V. Gazdyuk ◽  
A. M. Bondar ◽  
O. Y. Govoruha
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Molecular Subtype ◽  
Luminal A ◽  
Luminal B ◽  
Different Ages ◽  
Her 2 ◽  
Duct Cancer ◽  
High Level ◽  
Immunohistochemical Testing

The article presents the results of histological and immunohistochemical testing of women of different ages who are suffering from infiltrative forms of breast cancer in Dnipro. The study presents the distribution of receptors of estrogens and progesterone (ER, PR), HER-2/neu (necessary for prescribing treatment) and Кi-67 (reveals additional features of a tumour). Considering that luminal types of breast cancer include tumours whose receptors express to ER and PR, depending on the kind of expression HER2/neu, they are classified into A (do not express HER2/neu) and B (express HER2/neu). Tumours with hyperexpression of HER2/neu and lack of ER and PR are called HER2+. The research conducted has shown that duct cancer is by far the commonest form, at 81%. In duct cancer, undifferentiated stage and moderately-differentiated stage cancer prevails, whereas with nodule cancer the majority (80%) have moderately-differentiated stage cancer. We discovered a correlative link between the stage of differentiation and the percentage of metastasis both in duct and nodule breast cancer. But nodule breast cancer is more aggressive: with metastasis occurring in 31.2% of women even in cases of moderately-differentiated stage cancer. Only duct cancer is able to produce slime, which distinguishes it from other forms. Combined forms of cancer are rare, but they lead to metastases in all cases. Most women with infiltrative cancer in Dnipro are aged between 51 and 60. There has been observed the increase in cases of breast cancer among young women; the most widespread among infiltrated forms of breast cancer is subtype Luminal A, which has the best prognosis. As the research shows, women under 60 tend to have less aggressive subtypes, which are easy to treat, whereas in older patients their aggressiveness increases substantially, which means an unfavourable prognosis and lower effectiveness of treatment. Кі-67 marker increases substantially in the absence of ER and PR, which means a high level of tumour aggressiveness. Luminal A subtype in not aggressive in most cases, which means the most favourable prognosis. Luminal B is partly aggressive which leads to a high percentage of metastasis, but thanks to ER+ or PR+, it is successfully treated by hormone therapy, which can lead to a positive prognosis. Overall, HER2+ and triple negative are the most aggressive. 

Gata-3 and KI-67 expression in correlation with molecular subtypes of breast cancer

2021 ◽  
pp. 1-5
Author(s):  
M. Husni Cangara ◽  
Upik A. Miskad ◽  
Rina Masadah ◽  
Berti J. Nelwan ◽  
Syarifuddin Wahid
Keyword(s):  
Breast Cancer ◽  
Hormone Receptor ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Receptor Expression ◽  
Luminal A ◽  
Ki 67 ◽  
Her 2 ◽  
Hormone Receptor Expression

OBJECTIVES: This study aims to evaluate and compare four breast cancer subtypes defined by immunohistochemistry expression of ER, PR, and HER-2 in correlation with Ki-67 and GATA-3 expression. METHODS: Slides from 89 paraffin blocks of invasive breast cancer patients with four molecular subtypes based on HER-2, ER, and PR expression were then stained with Ki-67 and GATA-3 antibodies to evaluate their expression in correlation with molecular subtype and metastases to lymph nodes. RESULTS: This study was a retrospective study of 89 invasive breast cancers. Luminal A; Luminal B; HER2+; and triple-negative types were 35 (39.3%), 10 (11.2%), 27 (30.3%), and 17 (19.1%) samples. Expression of Ki-67 was increased in triple-negative (TN) tumor compared to non-triple-negative (non-TN) tumor subtypes (p < 0.05). This Ki-67 expression was inversely correlated with the positivity of hormone receptor expression related to lymph-node metastases in TN-type tumors. Sixty-two (57%) samples were immunohistochemically positive for GATA-3. GATA-3 positive samples were significantly more likely to be ER and PR-positive, Ki-67 negative, and luminal A tumors. CONCLUSIONS: Subtype triple-negative breast cancer correlates with high expression of Ki-67 that contributes to poor prognosis of this subtype. The higher Ki-67 expression was correlated with the absence of hormone receptor expression compared with the negativity of Her-2 expression, downplay a role in nodal metastases in a triple-negative tumor. GATA-3 positive breast cancer showed luminal differentiation characterized by high ER expression and mainly was classified as luminal A type tumor with a better prognosis.

scholarly journals Prevalence of Molecular Subtypes of Breast Carcinoma and Its Comparison between Two Different Age Groups: A Retrospective Study from a Tertiary Care Center of Northeast India

2021 ◽  
Vol 10 (04) ◽  
pp. 220-224
Author(s):  
Jagannath Dev Sharma ◽  
Sachin Khanna ◽  
Shubhra Ramchandani ◽  
Lopa Mudra Kakoti ◽  
Argha Baruah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Retrospective Study ◽  
Triple Negative ◽  
Molecular Subtypes ◽  
Molecular Subtype ◽  
Age Groups ◽  
Age Group ◽  
Luminal A ◽  
Luminal B ◽  
Her 2

Abstract Objective The aim of the study is to see the prevalence of different molecular subtypes in breast cancer patients among two different age groups: ≤40 years and >40 years. Materials and Methods Retrospective study was conducted from January 2019 to December 2019. We studied 568 cases of breast carcinoma and classified them into four molecular subtypes—luminal A, luminal B, human epidermal growth factor-2 (HER 2), and triple negative. Cases were divided into two different groups: (1) ≤40 years and (2) >40 years. Statistical Analysis was done by using SPSS software version 20.0. Results Out of 568 cases, 151 (26.6%) were ≤40 years of age and 417 (73.4%) were >40 years of age. The most common histological subtype of breast cancer was ductal carcinoma in 548 cases and the most common grade was grade III. Immunohistochemistry was done in 432 patients. In younger age group, the most common molecular subtype was luminal B (31%) followed by triple negative (20%), luminal A (14%), and then HER 2 (5.3%), while in the older age group most common molecular subtype was luminal B (27.8%) followed by triple negative (14%), HER 2 (12.2%), and then luminal A (12%). Conclusion Luminal B is found to be the most common subtype in Northeast Indian women with breast cancer, as compared with other studies in which luminal A was the most common subtype. This could be due to the reason that Ki-67 was not done in most of the other studies.

Locoregional recurrence risk for women with various molecular subtypes of breast cancer treated with multicatheter interstitial accelerated partial-breast irradiation: Results from Pooled Registry of Multicatheter Interstitial Sites (PROMIS).

2014 ◽  
Vol 32 (26_suppl) ◽  
pp. 73-73
Author(s):  
Bethany Marie Anderson ◽  
Mitchell Kamrava ◽  
Jason Wang ◽  
D. Jeffrey Demanes ◽  
Margaret B. Snyder ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Molecular Subtype ◽  
Accelerated Partial Breast Irradiation ◽  
Partial Breast Irradiation ◽  
Breast Irradiation ◽  
Luminal A ◽  
Luminal B ◽  
Patient Cohort ◽  
Her 2

73 Background: This study was performed to determine in breast tumor recurrence (IBTR) and regional nodal recurrence (RNR) rates for women with different subtypes of invasive ductal breast cancer treated with multicatheter interstitial accelerated partial breast irradiation (mAPBI). Methods: Data from 5 institutions was collected for patients treated from 1992-2013. We report the outcomes of 821 women with 830 breast cancers, all with ≥ 1 year of follow-up after completion of mAPBI. Molecular subtype analysis was performed for 582 women in whom ER, PR, Her-2, and grade were known. The Kaplan-Meier method was used to calculate overall survival (OS), IBTR and RNR. A univariate proportional hazard model was performed to estimate the risk of IBTR based upon molecular subtype, age, grade, N-stage, T-stage, margin status, tumor size, dose rate, endocrine therapy, and chemotherapy. Results: The median age of our patient cohort was 60 years. 50.0% (n = 415) of women had luminal A, 6.9% (n = 57) luminal B, 5.7% (n = 47) luminal Her-2, 1.8% (n = 15) Her-2, and 5.8% (n = 48) triple negative breast cancer (TNBC); an additional 29.8% (n = 248) could not be subtyped. With a median follow-up time of 6.5 years, the 5-year OS of our patient cohort was 94.8%. The 5-year IBTR was 3.5% for luminal A, 4.1% for luminal B, 5.1% for luminal Her-2, 13.3% for Her-2, 11.3% for TNBC, and 1.7% for non-subtyped women. Positive surgical margins and high grade correlated with risk for IBTR; molecular subtype and other variables did not. The 5-year RNR rates were 0.3% for luminal A, 4.6% for luminal B, 2.6% for luminal Her-2, 34.5% for Her-2, and 2.3% for TNBC. RNR risk was significantly higher for women with Her-2 compared to the other 4 subtypes. In addition, risk of RNR was significantly higher for women with luminal B compared to those of luminal A. Conclusions: Women with Her-2 and luminal B breast cancer may have higher RNR but not IBTR risk after mAPBI, as compared with women with luminal A subtype. Further follow-up, correlation with use of trastuzumab, and comparison of outcomes with whole breast irradiation will be valuable.

Molecular classification of breast cancer. Treatment and prognosis implications.

2021 ◽  
Vol 32 (2) ◽  
pp. 155-159
Author(s):  
M Alcaide Lucena ◽  
CJ Rodríguez González ◽  
S de Reyes Lartategui ◽  
R Gallart Aragón ◽  
MT Sánchez Barrón ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Treatment ◽  
Molecular Classification ◽  
Breast Cancer Treatment ◽  
Cáncer De Mama ◽  
Luminal A ◽  
Luminal B ◽  
Her 2

Resumen Los avances recientes en el campo de la biología molecular y la secuenciación del genoma se han traducido en una nueva clasificación del cáncer de mama, que busca mayor precisión y se correlaciona mejor con el riesgo de recaída de la enfermedad y la respuesta al tratamiento. Establece cuatro subtipos de cáncer de mama: luminal A, luminal B, HER 2 positivo y triple negativo, siendo el subtipo luminal A el de mejor pronóstico, y el triple negativo, el de peor pronóstico. Si combinamos la clasificación clásica histológica con la nueva molecular, nos permite encuadrar a estas pacientes de una forma más precisa en función del riesgo, definiendo así un manejo terapéutico adaptado.

scholarly journals Palbociclib and fulvestrant act in synergy to modulate central carbon metabolism in breast cancer cells

2018 ◽  
Author(s):  
Benedikt Warth ◽  
Amelia Palermo ◽  
Nicholas J.W. Rattray ◽  
Nathan V Lee ◽  
Zhou Zhu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Estrogen Receptor ◽  
Cancer Cells ◽  
Pentose Phosphate Pathway ◽  
Metabolic Pathways ◽  
Breast Cancer Cells ◽  
Pentose Phosphate ◽  
List Type ◽  
Estrogen Receptor Positive ◽  
Positive Breast Cancer

SummaryPalbociclib, is a selective inhibitor of cyclin-dependent kinases 4 and 6 and used as a first-line treatment for patients with estrogen receptor positive breast cancer. It has been shown that patients have improved progression-free survival when treated in combination with fulvestrant, an estrogen receptor antagonist. However, the mechanisms for this survival advantage are not known. We sought to analyze metabolic and transcriptomic changes in MCF-7 adenocarcinoma breast cancer cells following single and combined treatments to determine if selective metabolic pathways are targeted during combination therapy. Our results showed that individually, the drugs caused metabolic disruption to the same metabolic pathways, however fulvestrant additionally attenuated the pentose phosphate pathway and the production of important coenzymes. A comprehensive effect was observed when the drugs were applied together, confirming the combinatory therapy′s synergism in the cell model. This study highlights the power of merging high-dimensional datasets to unravel mechanisms involved in cancer metabolism and therapy.Highlights○First study employing multi-omics to investigate combined therapy on breast cancer cells○Fulvestrant attenuates the pentose phosphate pathway and coenzyme production○Synergism of palbociclib and fulvestrant was confirmed in vitro○Altered key pathways have been identifiedeTOC BlurbJohnson et al. applied an innovative multi-omics approach to decipher metabolic pathways affected by single versus combination dosing of palbociclib and fulvestrant in estrogen receptor positive breast cancer. Key metabolites and genes were correlated within metabolic pathways and shown to be involved in the drugs′ synergism.

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