scholarly journals miRNA Expression Analysis: Cell Lines HCC1500 and HCC1937 as Models for Breast Cancer in Young Women and the miR-23a as a Poor Prognostic Biomarker

2020 ◽  
Vol 14 ◽  
pp. 117822342097784
Author(s):  
Sara S Oltra ◽  
Maria Peña-Chilet ◽  
Maria T Martinez ◽  
Eduardo Tormo ◽  
Juan Miguel Cejalvo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Young Women ◽  
Mirna Expression ◽  
Young Patients ◽  
Breast Cancer Patients ◽  
Old Patients ◽  
Cellular Models ◽  
Hcc1937 Cell ◽  
Mirna Expression Data

Purpose: The study of breast cancer nearly always involves patients close to menopause or older. Therefore, young patients are mostly underrepresented. Our aim in this study was to demonstrate biological differences in breast cancer of young people using as a model available cell lines derived from people with breast cancer younger than 35 years. Methods: Global miRNA expression was analyzed in breast cancer cells from young (HCC1500, HCC1937) and old patients (MCF-7, MDA-MB-231, HCC1806, and MDA-MB-468). In addition, it was compared with same type of results from patients. Results: We observed a differential profile for 155 miRNAs between young and older cell lines. We identified a set of 24 miRNA associated with aggressiveness that were regulating pluripotency of stem cell-related pathways. Combining the miRNA expression data from cell lines and breast cancer patients, 132 miRNAs were differently expressed between young and old samples, most of them previously found in cell lines. MiR-23a-downregulation was also associated with poor survival in young patients. Conclusions: Our results suggest that HCC1500 and HCC1937 cell lines could be suitable cellular models for breast cancer affecting young women. The miR-23a-downregulation could have a potential role as a poor prognosis biomarker in this age group.

scholarly journals Impact of Different Modules of 21-Gene Assay in Early Breast Cancer Patients

2021 ◽  
Author(s):  
Mengdi Chen ◽  
Deyue Liu ◽  
Weilin Chen ◽  
Weiguo Chen ◽  
Kunwei Shen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Young Patients ◽  
Breast Cancer Patients ◽  
Old Patients ◽  
Gene Assay ◽  
Risk Patients ◽  
Group A ◽  
Group B ◽  
The Impact

Abstract Background: Young patients were under-evaluated in the construction and validation of the 21-gene Assay Recurrence Score (RS). Previous evidence suggested that RS performed differently according the ages of patients. Our study aimed to explore the molecular driving patterns in patients of different ages.Methods: A total of 1,078 estrogen receptor (ER)-positive breast cancer patients between Jan 2009 and Mar 2017 from Shanghai Jiao Tong University Breast Cancer Data Base were divided into three subgroups: Group A, ≤40y and premenopausal (n=97); Group B, >40y and premenopausal (n=284); Group C, postmenopausal (n=697). The correlation of RS and its modules and the variance of RS modules was explored.Results: Estrogen module had a stronger correlation with RS in patients >40y (ρ = -0.76 in Group B and -0.79 in Group C) compared with patients ≤40y (ρ = -0.64). Contrarily, the correlation between RS and invasion group was weaker in patients >40y (ρ = 0.29 in Group B and 0.25 in Group C) than in patients ≤40y (ρ = 0.44). The proliferation module contributed most to the variance in young patients (37.3%) while ER module contributed most in old patients (54.1% in Group B and 53.4% in Group C). For RS >25, proliferation module was the leading driver in all three subgroups (ρ = 0.38, 0.53 and 0.52 in Group A, B and C) while estrogen module had a weaker association with RS. The negative impact of ER related features on RS was stronger in clinical low-risk patients while the positive effect of proliferation module was stronger in clinical high-risk patients.Conclusions: RS was primarily driven by estrogen module in patients regardless of age, but the proliferation module had a stronger impact on RS in patients ≤40y than in those >40y. The impact of modules varied in patients with different genetic and clinical risk.

scholarly journals Clinical utility of genomic signatures in young breast cancer patients: a systematic review

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Cynthia Villarreal-Garza ◽  
Ana S. Ferrigno ◽  
Cynthia De la Garza-Ramos ◽  
Regina Barragan-Carrillo ◽  
Matteo Lambertini ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Young Women ◽  
Young Patients ◽  
Distant Recurrence ◽  
Similar Rate ◽  
Breast Cancer Patients ◽  
Genomic Signatures ◽  
Hormone Sensitive ◽  
Young Breast Cancer

Abstract Risk stratification by genomic signatures has been shown to improve prognostication and guide treatment decisions among patients with hormone-sensitive breast cancer. However, their role in young women has not been fully elucidated. In this review, a systematic search was conducted for published articles and abstracts from major congresses that evaluated the use of genomic signatures in young breast cancer patients. A total of 71 studies were analyzed, including 561,188 patients of whom 27,748 (4.9%) were young. Women aged ≤40 years were subjected to genomic testing at a similar rate to older women but had a higher proportion of intermediate- to high-risk tumors when classified by EndoPredict (p = 0.04), MammaPrint (p < 0.01), and Oncotype DX (p < 0.01). In young women with low genomic risk, 6-year distant recurrence-free survival was 94%, while 5-year overall survival was nearly 100%. Nonetheless, young patients classified as low-risk had a higher tendency to receive chemotherapy compared to their older counterparts. In conclusion, genomic tests are useful tools for identifying young patients in whom chemotherapy omission is appropriate.

scholarly journals HDAC5 Inhibitors as a Potential Treatment in Breast Cancer Affecting Very Young Women

Cancers ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 412 ◽  
Author(s):  
Sara S. Oltra ◽  
Juan Miguel Cejalvo ◽  
Eduardo Tormo ◽  
Marta Albanell ◽  
Ana Ferrer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Young Women ◽  
Older Patients ◽  
Survival Rates ◽  
Young Patients ◽  
Dose Dependence ◽  
Potential Treatment ◽  
Proliferation And Apoptosis ◽  
Worse Prognosis

Background: Breast cancer in very young women (BCVY) defined as <35 years old, presents with different molecular biology than in older patients. High HDAC5 expression has been associated with poor prognosis in breast cancer (BC) tissue. We aimed to analyze HDAC5 expression in BCVY and older patients and their correlation with clinical features, also studying the potential of HDAC5 inhibition in BC cell lines. Methods: HDAC5 expression in 60 BCVY and 47 older cases were analyzed by qRT-PCR and correlated with clinical data. The effect of the HDAC5 inhibitor, LMK-235, was analyzed in BC cell lines from older and young patients. We performed time and dose dependence viability, migration, proliferation, and apoptosis assays. Results: Our results correlate higher HDAC5 expression with worse prognosis in BCVY. However, we observed no differences between HDAC5 expression and pathological features. Our results showed greatly reduced progression in BCVY cell lines and also in all triple negative subtypes when cell lines were treated with LMK-235. Conclusions: In BCVY, we found higher expression of HDAC5. Overexpression of HDAC5 in BCVY correlates with lower survival rates. LMK-235 could be a potential treatment in BCVY.

scholarly journals MAT2A Localization and Its Independently Prognostic Relevance in Breast Cancer Patients

2021 ◽  
Vol 22 (10) ◽  
pp. 5382
Author(s):  
Pei-Yi Chu ◽  
Hsing-Ju Wu ◽  
Shin-Mae Wang ◽  
Po-Ming Chen ◽  
Feng-Yao Tang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Survival Rate ◽  
Protein Expression ◽  
Cancer Patients ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Breast Cancer Patients ◽  
Expression Ratio

(1) Background: methionine cycle is not only essential for cancer cell proliferation but is also critical for metabolic reprogramming, a cancer hallmark. Hepatic and extrahepatic tissues methionine adenosyltransferases (MATs) are products of two genes, MAT1A and MAT2A that catalyze the formation of S-adenosylmethionine (SAM), the principal biological methyl donor. Glycine N-methyltransferase (GNMT) further utilizes SAM for sarcosine formation, thus it regulates the ratio of SAM:S-adenosylhomocysteine (SAH). (2) Methods: by analyzing the TCGA/GTEx datasets available within GEPIA2, we discovered that breast cancer patients with higher MAT2A had worse survival rate (p = 0.0057). Protein expression pattern of MAT1AA, MAT2A and GNMT were investigated in the tissue microarray in our own cohort (n = 252) by immunohistochemistry. MAT2A C/N expression ratio and cell invasion activity were further investigated in a panel of breast cancer cell lines. (3) Results: GNMT and MAT1A were detected in the cytoplasm, whereas MAT2A showed both cytoplasmic and nuclear immunoreactivity. Neither GNMT nor MAT1A protein expression was associated with patient survival rate in our cohort. Kaplan–Meier survival curves showed that a higher cytoplasmic/nuclear (C/N) MAT2A protein expression ratio correlated with poor overall survival (5 year survival rate: 93.7% vs. 83.3%, C/N ratio ≥ 1.0 vs. C/N ratio < 1.0, log-rank p = 0.004). Accordingly, a MAT2A C/N expression ratio ≥ 1.0 was determined as an independent risk factor by Cox regression analysis (hazard ratio = 2.771, p = 0.018, n = 252). In vitro studies found that breast cancer cell lines with a higher MAT2A C/N ratio were more invasive. (4) Conclusions: the subcellular localization of MAT2A may affect its functions, and elevated MAT2A C/N ratio in breast cancer cells is associated with increased invasiveness. MAT2A C/N expression ratio determined by IHC staining could serve as a novel independent prognostic marker for breast cancer.

scholarly journals Clinical Significance of Annexin A2 Expression in Breast Cancer Patients

Cancers ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 2
Author(s):  
Lee D. Gibbs ◽  
Kelsey Mansheim ◽  
Sayantan Maji ◽  
Rajesh Nandy ◽  
Cheryl M. Lewis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Significance ◽  
Cell Lines ◽  
Breast Cancer Subtypes ◽  
Enzyme Linked Immunosorbent Assay ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Cancer Subtypes ◽  
Tumor Tissues

Increasing evidence suggests that AnxA2 contributes to invasion and metastasis of breast cancer. However, the clinical significance of AnxA2 expression in breast cancer has not been reported. The expression of AnxA2 in cell lines, tumor tissues, and serum samples of breast cancer patients were analyzed by immunoblotting, immunohistochemistry, and enzyme-linked immunosorbent assay, respectively. We found that AnxA2 was significantly upregulated in tumor tissues and serum samples of breast cancer patients compared with normal controls. The high expression of serum AnxA2 was significantly associated with tumor grades and poor survival of the breast cancer patients. Based on molecular subtypes, AnxA2 expression was significantly elevated in tumor tissues and serum samples of triple-negative breast cancer (TNBC) patients compared with other breast cancer subtypes. Our analyses on breast cancer cell lines demonstrated that secretion of AnxA2 is associated with its tyrosine 23 (Tyr23) phosphorylation in cells. The expression of non-phosphomimetic mutant of AnxA2 in HCC1395 cells inhibits its secretion from cells compared to wild-type AnxA2, which further suggest that Tyr23 phosphorylation is a critical step for AnxA2 secretion from TNBC cells. Our analysis of AnxA2 phosphorylation in clinical samples further confirmed that the phosphorylation of AnxA2 at Tyr23 was high in tumor tissues of TNBC patients compared to matched adjacent non-tumorigenic breast tissues. Furthermore, we observed that the diagnostic value of serum AnxA2 was significantly high in TNBC compared with other breast cancer subtypes. These findings suggest that serum AnxA2 concentration could be a potential diagnostic biomarker for TNBC patients.

scholarly journals Polyphenol-Enriched Blueberry Preparation Controls Breast Cancer Stem Cells by Targeting FOXO1 and miR-145

Molecules ◽  
2021 ◽  
Vol 26 (14) ◽  
pp. 4330
Author(s):  
Jean-François Mallet ◽  
Roghayeh Shahbazi ◽  
Nawal Alsadi ◽  
Chantal Matar
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Mirna Expression ◽  
Epigenetic Mechanism ◽  
Breast Cancer Cell Lines ◽  
Relative Expression ◽  
Target Proteins ◽  
Pathological Characteristics

Scientific evidence supports the early deregulation of epigenetic profiles during breast carcinogenesis. Research shows that cellular transformation, carcinogenesis, and stemness maintenance are regulated by epigenetic-specific changes that involve microRNAs (miRNAs). Dietary bioactive compounds such as blueberry polyphenols may modulate susceptibility to breast cancer by the modulation of CSC survival and self-renewal pathways through the epigenetic mechanism, including the regulation of miRNA expression. Therefore, the current study aimed to assay the effect of polyphenol enriched blueberry preparation (PEBP) or non-fermented blueberry juice (NBJ) on the modulation of miRNA signature and the target proteins associated with different clinical-pathological characteristics of breast cancer such as stemness, invasion, and chemoresistance using breast cancer cell lines. To this end, 4T1 and MB-MDM-231 cell lines were exposed to NBJ or PEBP for 24 h. miRNA profiling was performed in breast cancer cell cultures, and RT-qPCR was undertaken to assay the expression of target miRNA. The expression of target proteins was examined by Western blotting. Profiling of miRNA revealed that several miRNAs associated with different clinical-pathological characteristics were differentially expressed in cells treated with PEBP. The validation study showed significant downregulation of oncogenic miR-210 expression in both 4T1 and MDA-MB-231 cells exposed to PEBP. In addition, expression of tumor suppressor miR-145 was significantly increased in both cell lines treated with PEBP. Western blot analysis showed a significant increase in the relative expression of FOXO1 in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Furthermore, a significant decrease was observed in the relative expression of N-RAS in 4T1 and MDA-MB-231 cells exposed to PEBP and in MDA-MB-231 cells exposed to NBJ. Our data indicate a potential chemoprevention role of PEBP through the modulation of miRNA expression, particularly miR-210 and miR-145, and protection against breast cancer development and progression. Thus, PEBP may represent a source for novel chemopreventative agents against breast cancer.

scholarly journals Antiestrogen-resistant human breast cancer cells require activated Protein Kinase B/Akt for growth

2005 ◽  
Vol 12 (3) ◽  
pp. 599-614 ◽  
Author(s):  
T Frogne ◽  
J S Jepsen ◽  
S S Larsen ◽  
C K Fog ◽  
B L Brockdorff ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cell Lines ◽  
Human Breast Cancer ◽  
Neutralizing Antibodies ◽  
Breast Cancer Cells ◽  
Resistant Cell ◽  
Breast Cancer Patients ◽  
Human Breast ◽  
Mcf 7

Development of acquired resistance to antiestrogens is a major clinical problem in endocrine treatment of breast cancer patients. The IGF system plays a profound role in many cancer types, including breast cancer. Thus, overexpression and/or constitutive activation of the IGF-I receptor (IGF-IR) or different components of the IGF-IR signaling pathway have been reported to render breast cancer cells less estrogen dependent and capable of sustaining cell proliferation in the presence of antiestrogens. In this study, growth of the antiestrogen-sensitive human breast cancer cell line MCF-7 was inhibited by treatment with IGF-IR-neutralizing antibodies. In contrast, IGF-IR-neutralizing antibodies had no effect on growth of two different antiestrogen-resistant MCF-7 sublines. A panel of antiestrogen-resistant cell lines was investigated for expression of IGF-IR and either undetectable or severely reduced IGF-IR levels were observed. No increase in insulin receptor substrate 1 (IRS-1) or total PKB/Akt (Akt) was detected in the resistant cell lines. However, a significant increase in phosphorylated Akt (pAkt) was found in four of six antiestrogen-resistant cell lines. Overexpression of pAkt was associated with increased Akt kinase activity in both a tamoxifen- and an ICI 182,780-resistant cell line. Inhibition of Akt phosphorylation by the phosphatidylinositol 3-kinase (PI3-K) inhibitor wortmannin or the Akt inhibitor SH-6 (structurally modified phosphatidyl inositol ether liquid analog PIA 6) resulted in a more pronounced growth inhibitory effect on the antiestrogen-resistant cells compared with the parental cells, suggesting that signaling via Akt is required for antiestrogen-resistant cell growth in at least a subset of our antiestrogen-resistant cell lines. PTEN expression and activity was not decreased in cell lines overexpressing pAkt. Our data demonstrate that Akt is a target for treatment of antiestrogen-resistant breast cancer cell lines and we suggest that antiestrogen-resistant breast cancer patients may benefit from treatment targeted to inhibit Akt signaling.

scholarly journals Real-World Data Related to Non-Metastatic Breast Cancer in Young Women: Experience of a Single Institution

2018 ◽  
Vol 64 (1) ◽  
pp. 45-53
Author(s):  
Juliana Cunha e Silva Ominelli De Souza ◽  
Andrew Sá Nunes ◽  
Jesse Lopes Da Silva ◽  
Aline Coelho Gonçalves ◽  
Suzanne Crocamo Ventilari Da Costa
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lymph Node ◽  
Young Women ◽  
Advanced Disease ◽  
Young Patients ◽  
Metastatic Breast ◽  
Lymph Node Involvement ◽  
Axillary Lymph ◽  
Node Involvement

Introduction: Breast cancer is the leading cause of cancer-related deaths in women aged 20-59 years. Younger women usually have more aggressive tumors and more advanced disease with larger size and axillary lymph node involvement. There have been few studies assessing the characteristics of breast cancer in very young women. Objective: Evaluate the epidemiological and clinical profile of non-metastatic very young patients with breast cancer. Method: We performed a retrospective analysis to evaluate the epidemiological and clinical profile of non-metastatic breast cancer in patients ≤ 30 years of age treated between 1993 and 2011 at the Brazilian National Cancer Institute José Alencar Gomes da Silva. We evaluated relapse-free survival (RFS) and overall survival (OS). Results: Of the 196 patients evaluated, 181 (90%) had ductal carcinoma, 79 (40%) had high-grade tumors, and 102 (52%) had hormone receptor-positive tumors. 117 patients(60%) had stage III disease at diagnosis. The median age was 29 years (range, 17-30 years). Of 185 patients who underwent surgery, 156 (84.3%) underwent total mastectomy and 171 (92%) underwent axillary lymph node dissection. 119 patients received neoadjuvant chemotherapy, and 14 patients (9.3%) underwent neoadjuvant radiotherapy. After a median follow-up of 81.5 months, 109 patients (55%) had relapsed and 81 (41%) had died. The median RFS and OS were 49.5 months and 134 months, respectively. Lymph node involvement and neoadjuvant chemotherapy were associated with shorter RFS and OS. Conclusion: Breast cancer is uncommon in young patients, especially in those ≤ 30 years of age. We found a predominance of locally advanced disease and worse prognostic pathological characteristics. Despite the aggressive treatment, our patients had worse outcomes than those reported by other authors.

O-180 Oocyte vitrification for fertility preservation does not delay the initiation of neoadjuvant chemotherapy for breast cancer

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
I Sellami ◽  
M Grynberg ◽  
A Benoit ◽  
C Sifer ◽  
A Mayeur ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Cancer Patients ◽  
Fertility Preservation ◽  
Cancer Diagnosis ◽  
Ovarian Tissue ◽  
Young Patients ◽  
Oocyte Retrieval ◽  
Breast Cancer Patients ◽  
Oocyte Vitrification

Abstract Study question Does oocyte vitrification for fertility preservation (FP) delay the initiation of neoadjuvant chemotherapy for breast cancer? Summary answer The indication of neoadjuvant chemotherapy for breast cancer should not be considered as an impediment to urgent oocyte vitrification for FP. What is known already FP is considered as one of the most important issues to address for young breast cancer patients. Cryopreservation of oocytes or embryos may be considered after controlled ovarian hyperstimulation (COH) or in vitro maturation (IVM). Pregnancies have been reported after reutilization of oocytes frozen following both procedures. Although oocyte competence is better after COH, this strategy requires on average 13 days to be achieved. In addition, the safety of ovarian stimulation before tumor removal is currently not formally established. In case of neoadjuvant chemotherapy, the risk-benefit balance of COH is not well known. Study design, size, duration Retrospective cohort study including all breast cancer patients eligible for oocyte vitrification following COH or IVM before initiation of neoadjuvant chemotherapy between January 2016 and December 2020. Participants/materials, setting, methods Inclusion criteria were: female patients with confirmed non metastatic breast cancer, 18 to 40 years of age, with indication of neoadjuvant chemotherapy, who have had oocyte retrieval for FP after COH or IVM +/- cryopreservation of ovarian tissue. Various time-points related to cancer diagnosis, FP or chemotherapy were obtained from medical record review. Main results and the role of chance A total of 198 patients with confirmed breast cancer who had oocyte retrieval following COH (n = 57) or IVM +/- cryopreservation of ovarian tissue (n = 141) for FP prior to neoadjuvant chemotherapy were included. Although women in IVM group were significantly younger as compared to patients who underwent COH (31.7 ± 4.2 vs. 33.3 ± 4.0 years, p = 0.019), ovarian reserve parameters, BMI and cancer stage did not differ between the two groups. Overall, the average time from cancer diagnosis to chemotherapy start was similar between patients having undergone COH or IVM before oocyte vitrification (37.3 ± 13.8 vs. 36.9 ±13.5 days in COH and IVM groups respectively, p=0.857). Limitations, reasons for caution The time from referral to FP consultation may have influenced the type of FP. In addition, the retrospective nature of the present analysis may constitute a limitation. Moreover, the efficiency and security of the different FP strategies used has not been analysed. Wider implications of the findings Oocyte vitrification following COH or IVM was not associated with delayed breast cancer treatment in the neoadjuvant setting, so long as there was a prompt FP referral. Young patients undergoing neoadjuvant chemotherapy should be informed of these findings to avoid unnecessary anxiety due to concern for delays. Trial registration number Not applicable

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