Stages Of Breast Cancer Development Research Articles

Prognostic Role of Prolactin-Induced Protein (PIP) in Breast Cancer.

Prolactin-inducible protein (PIP), also referred to as gross cystic disease fluid protein 15 (GCDFP-15), has been a trending topic in recent years due to its potential role as a specific marker in breast cancer. PIP binds to aquaporin-5 (AQP5), CD4, actin, fibrinogen, β-tubulin, serum albumin, hydroxyapatite, zinc α2-glycoprotein, and the Fc fragment of IgGs, and the expression of PIP has been demonstrated to be modulated by various cytokines, including IL4/13, IL1, and IL6. PIP gene expression has been extensively studied due to its captivating nature. It is influenced by various factors, with androgens, progesterone, glucocorticosteroids, prolactin, and growth hormone enhancing its expression while estrogens suppress it. The regulatory mechanisms involve important proteins such as STAT5A, STAT5B, Runx2, and androgen receptor, which collaborate to enhance PIP gene transcription and protein production. The expression level of PIP in breast cancer is dependent on the tumor stage and subtype. Higher expression is observed in early-stage tumors of the luminal A subtype, while lower expression is associated with luminal B, basal-like, and triple-negative subtypes, which have a poorer prognosis. PIP expression is also correlated with apocrine differentiation, hormone receptor positivity, and longer metastasis-free survival. PIP plays a role in supporting the immune system's antitumor response during the early stages of breast cancer development. However, as cancer progresses, the protective role of PIP may become less effective or diminished. In this work, we summarized the clinical significance of the PIP molecule in breast cancer and its potential role as a new candidate for cell-based therapies.

Interrelation of HLA-I and class II major histocompatibility complex molecules with clinical and morphological signs of breast cancer: A retrospective cohort study

Background. For a long time, interest in the HLA peptide complex is unabated, the clinical significance of which in cancer is still the subject of intense debate. Through the presentation of HLA antigens, tumor cells become available for recognition and destruction by effector cells of the immune system. A detailed analysis of the expression status of HLA molecules by breast cancer cells is of both scientific and important practical value. It can provide additional information about the immune system to determine a further strategy for treating breast cancer.
 Aim. To evaluate the frequency of expression of HLA-I and class II molecules by breast cancer cells and to determine its relationship with the morphological and clinical characteristics of the tumor.
 Materials and methods. This study included 82 patients with breast cancer who received treatment at the Blokhin National Medical Research Center of Oncology. Immunophenotyping of the primary tumor was performed by the immunohistochemical method (immunofluorescent staining) on cryostat sections. The reaction was evaluated using a ZEISS luminescent microscope (AXIOSKOP, Germany). The frequency of expression of HLA-I and class II molecules was studied depending on the clinical and morphological characteristics of breast cancer.
 Results. It was found that the frequency of expression of HLA I and II class molecules by breast cancer cells differed. HLA class I antigens are preserved in almost half of the cases 54.5%, while HLA class II antigens are preserved in 22.0%. Associations of molecules of the major histocompatibility complex with clinical and morphological signs of breast cancer were revealed. The frequency of HLA-DR negative cases increases in the stage advanсed (p=0.029). The frequency of monomorphic expression of HLA class II with T1 tumor was 50% versus 0% at T4 tumor (p=0.032). Estrogen receptor-negative tumors in most cases did not express HLA-II class (85.2% vs 64%; p=0.034). No connection with other clinical and morphological features of the tumor has been established.
 Conclusion. In most cases of breast cancer, the expression of HLA class II molecules is lost, while the expression of HLA class I is preserved in half of the cases. Monomorphic expression of HLA class II is characteristic of the early stage of breast cancer development and predominantly of receptor-positive tumors.

Abstract SY25-02: Double-edged “soil”: Stromal microenvironment in breast cancer development

Abstract SY25-02: Double-edged “soil”: Stromal microenvironment in breast cancer development

Mulberry leaf polysaccharide extracted by response surface methodolog suppresses the proliferation, invasion and migration of MCF-7 breast cancer cells

Breast cancer with highly heterogeneous characteristics is the main cause of cancer deaths in women all over the world. Chemotherapy-assisted diet therapy has become an effective way to improve the quality of life of cancer patients. Currently numerous dietary components have been found to inhibit the molecular events and signalling pathways associated with various stages of breast cancer development, but the dietary components extraction and its regulation mechanism were long-term and complex. In this study, low-temperature ultrasonic-assisted method was used to extract MLP, and through employing the Design-Expert software, the optimal conditions for MLP extraction were ultrasonic power 179.34 W, ultrasonic time 13.92 min, and ratio (v/w, mL/g) of water to raw material 23.55. Subsequent experiments evaluated the antioxidant activity of mulberry leaf polysaccharide and found that it has obvious ability to scavenge DPPH free radicals. Interestingly, the extracted MLP could inhibit the cell viability, migration and invasion of breast cancer cells in vitro. Therefore, we suggested MLP could been used as an antioxidant supplement that contains these micronutrients for cancer patients or used to develop anti-oxidant functional health food for breast cancer patients.

ResNet-SCDA-50 for Breast Abnormality Classification.

(Aim) Breast cancer is the most common cancer in women and the second most common cancer worldwide. With the rapid advancement of deep learning, the early stages of breast cancer development can be accurately detected by radiologists with the help of artificial intelligence systems. (Method) Based on mammographic imaging, a mainstream clinical breast screening technique, we present a diagnostic system for accurate classification of breast abnormalities based on ResNet-50. To improve the proposed model, we created a new data augmentation framework called SCDA (Scaling and Contrast limited adaptive histogram equalization Data Augmentation). In its procedure, we first conduct the scaling operation to the original training set, followed by applying contrast limited adaptive histogram equalisation (CLAHE) to the scaled training set. By stacking the training set after SCDA with the original training set, we formed a new training set. The network trained by the augmented training set, was coined as ResNet-SCDA-50. Our system, which aims at a binary classification on mammographic images acquired from INbreast and MINI-MIAS, classifies masses, microcalcification as "abnormal", while normal regions are classified as "normal". (Results) We present the first attempt to use the image contrast enhancement method as the data augmentation method, resulting in an averaged 98.55 percent specificity and 92.83 percent sensitivity, which gives our best model an overall accuracy of 95.74 percent. (Conclusion) Our proposed method is effective in classifying breast abnormality.

The Tumor Microenvironment of Primitive and Metastatic Breast Cancer: Implications for Novel Therapeutic Strategies.

Breast cancer evolves thanks to a dense and close interaction with the surrounding tumor microenvironment (TME). Fibroblasts, leukocytes, blood and lymphatic endothelial cells and extracellular matrix are the constituents of this entity, and they synergistically play a pivotal role in all of the stages of breast cancer development, from its onset to its metastatic spread. Moreover, it has been widely demonstrated that variations to the TME can correspond to prognosis variations. Breast cancer not only modulates the transformation of the environment within the mammary gland, but the same process is observed in metastases as well. In this minireview, we describe the features of TME within the primitive breast cancer, throughout its evolution and spread into the main metastatic sites.

Abstract B102: Epithelium-derived cytokines in breast carcinogenesis

Abstract Novel approaches in cancer immunotherapy have led to effective therapeutics against late-stage cancers. However, the role of the immune system in protection against early-stage cancers remains uncertain. We have previously discovered that thymic stromal lymphopoietin (TSLP) blocks early stages of breast cancer development through activation of CD4+ T cells. TSLP is an epithelium-derived danger signal that plays a key role in initiating an immune response upon cell damage and stress. The aim of this study is to investigate the potential involvement of other epithelial-derived cytokines in the activation of an immune response against premalignant breast lesions. To identify these signals, we analyzed the expression of a wide range of epithelium-derived cytokines in normal mammary glands, premalignant lesions, and late-stage tumors of MMTV-PyMT (PyMTtg) and K14-Cre, Brca1f/f, p53f/f mouse models. These mice spontaneously develop breast tumors that resemble human luminal and basal-like breast cancers, respectively. Of the cytokines examined, IL-1a was highly expressed in premalignant lesions compared to mammary glands and tumors. Additionally, IL-12p40 was upregulated in both early and late stages of breast cancer compared to normal mammary gland. Other cytokines, like IL-7, IL-11, and IL-24, were highly expressed in the mammary gland, but their expression was lost during breast tumorigenesis. In conclusion, we identified upregulation of IL-1a and IL-12p40 in early-stage breast cancer, suggesting a role for these cytokines in inducing antitumor immunity in the breast. Furthermore, we demonstrate selection against expression of IL-7, IL-11, and IL-24 during the process of cancer initiation and promotion, suggesting a role in normal mammary gland homeostasis and possibly immunity against breast carcinogenesis. Taken together, we have identified potential novel therapeutic targets that can be leveraged for breast cancer immunoprevention. Citation Format: Sanne Kroon, Kaitlin Dempsey, Margherita Boieri, Shawn Demehri. Epithelium-derived cytokines in breast carcinogenesis [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2019 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(3 Suppl):Abstract nr B102.

Multidisciplinary cooperation strengthens individualized management of breast cancer in pregnancy

As the pregnant patient with breast cancer is in a special physiological period, both the efficacy of mother and the safety of developing fetus should be considered during the whole process of diagnosis and treatment. It is particularly important for multidisciplinary teams including breast, obstetrics and nursing departments to make a secure and effective individualized plan for those in different gestational week and different stages of breast cancer development. Pregnancy risk assessment and whole-process multidisciplinary case management mode for breast cancer during pregnancy are helpful for the early detection of abnormal health status of pregnant women and fetuses, enabling rapid and efficient treatment, reducing the occurrence of adverse medical events, and maximizing the safety of pregnant women and fetuses. Obstetricians should pay attention to the chief complaints of pregnant women and conduct regular breast ultrasound examinations. Once anything suspicious is found, breast surgeons need to take charge of a multidisciplinary discussion. Not only should the multidisciplinary collaborative outpatient clinic determine the treatment plan for breast cancer during pregnancy, but also the concept of multidisciplinary collaboration should be incorporated into the follow-up treatment process, including active surgical treatment, selection of neoadjuvant chemotherapy and adjuvant chemotherapy, avoidance of endocrine therapy, targeted therapy and radiotherapy, and adherence to multidisciplinary follow-up, etc. Multidisciplinary case management of breast cancer during pregnancy is necessary and feasible, and more prospective clinical studies need to be carried out to help improve clinical diagnosis and treatment strategies.

Cytotoxic T cell depletion with increasing epithelial abnormality in women with benign breast disease

PurposeWe quantified cytotoxic T cells in nonmalignant breast tissues from women with and without subsequent breast cancer to assess evidence of whether immunosurveillance may be suppressed prior to tumor development.MethodsWe used an age-matched set of breast tissues from women with benign breast disease (BBD) who subsequently developed breast cancer (BBD with later BC), women with BBD who remained cancer free (BBD cancer-free), and normal Komen Tissue Bank (KTB) tissue donors (KTB controls). We evaluated terminal duct lobular units (lobules) for degree of epithelial abnormality and density of dual-positive CD8/CD103 T cells, as CD103+ cells are thought to be a subset of CD8+ cytotoxic T cells located primarily in the intraepithelial compartment.ResultsIn 10 sets of age-matched women, 256 breast lobules were studied: 85 in BBD women with later BC, 85 in BBD cancer-free women, and 86 in KTB donors. The majority of all lobules were histologically normal (N = 143, 56%), with 65 (25%) nonproliferative fibrocystic change, and 48 (19%) proliferative epithelial change (with or without atypia). In BBD women with later BC, median CD8+/CD103+ cell density was 39.6, 31.7, and 10.5 cells/mm2 (p = 0.002) for normal, nonproliferative, and proliferative lobules. In BBD cancer-free women, median CD8+/CD103+ cell density values were 46.7, 14.3, and 0 cells/mm2 (p = 0.004) respectively. In KTB donors, CD8+/CD103+ cell density was not significantly different across the lobule types (medians 0, 5.8, 10.7, p = 0.43).ConclusionIn women with BBD, breast lobules with increasing epithelial abnormality show significant decreases in cytotoxic T cells as measured by CD8/CD103 staining, suggesting that impaired immunosurveillance may be a component of the earliest stages of breast cancer development.

The dual role of tumor necrosis factor-alpha (TNF-α) in breast cancer: molecular insights and therapeutic approaches.

Breast cancer is the most prevalent cancer among women worldwide and the fifth cause of death among all cancer patients. Breast cancer development is driven by genetic and epigenetic alterations, with the tumor microenvironment (TME) playing an essential role in disease progression and evolution through mechanisms like inflammation promotion. TNF-α is one of the essential pro-inflammatory cytokines found in the TME of breast cancer patients, being secreted both by stromal cells, mainly by tumor-associated macrophages, and by the cancer cells themselves. In this review, we explore the biological and clinical impact of TNF-α in all stages of breast cancer development. First of all, we explore the correlation between TNF-α expression levels at the tumor site or in plasma/serum of breast cancer patients and their respective clinical status and outcome. Secondly, we emphasize the role of TNF-α signaling in both estrogen-positive and -negative breast cancer cells. Thirdly, we underline TNF-α involvement in epithelial-to-mesenchymal transition (EMT) and metastasis of breast cancer cells, and we point out the contribution of TNF-α to the development of acquired drug resistance. Collectively, these data reveal a pro-tumorigenic role of TNF-α during breast cancer progression and metastasis. We systemize the knowledge regarding TNF-α-related therapies in breast cancer, and we explain how TNF-α may act as both a target and a drug in different breast cancer therapeutic approaches. By corroborating the known molecular effects of TNF-α signaling in breast cancer cells with the results from several preclinical and clinical trials, including TNF-α-related clinical observations, we conclude that the potential of TNF-α in breast cancer therapy promises to be of great interest.

MicroRNA in Early-Stage Breast Cancer in Lebanese Women

PURPOSE Breast cancer is the most prevalent female cancer and has a higher incidence in young Lebanese patients as compared with the West. Interestingly, this particularity of breast cancer in the Lebanese population was not found to be associated with higher BRCA1/2 gene mutations. Hence, our research focuses on investigating molecular mechanisms and associated epigenetic signatures that underlie breast cancer in young patients. We are specifically interested in microRNA (miRNA), small noncoding RNAs that act as master players at all stages of breast cancer development and that are increasingly recognized as potential diagnostic and prognostic biomarkers. We have previously shown that differential expression of certain miRNAs in Lebanese breast cancer tissues could be different than what is reported in the West. METHODS We recently assessed the miRNA microarray profile expression in Lebanese breast cancer tissues, performed a comparative miRNA profile analysis with matched American samples, and predicted the role of dysregulated miRNA in early breast cancer through mRNA-miRNA integration analysis. RESULTS Although most of the dysregulated miRNA in Lebanese patients with breast cancer is similar to that in American population, differences in miRNA expression exist and can be attributed either to the patient’s age at diagnosis or to an ethnic variation. We are currently studying circulating miRNA in the blood of Lebanese patients with breast cancer, and a dysregulated signature will be presented. CONCLUSION Our data provide a basis for additional investigation that should be performed to comprehend dysregulated miRNA implication in breast cancer, especially in young patients, and the role of circulating miRNAs as potential biomarkers for breast cancer early detection.

Abstract 4948: T helper 2 cells block breast cancer promotion

Abstract New immune-based strategies for cancer treatment including the activation of tumor-infiltrating CD8+ cytotoxic T lymphocytes (CTLs) have led to effective therapeutics against late-stage disease. However, the function of the immune system in combating the early-stage cancers remains uncertain. To establish a mechanism that activates immune cells against early carcinogenesis, we have studied the role of an epithelial-derived cytokine, thymic stromal lymphopoietin (TSLP), in early stages of breast cancer development. We have previously discovered that TSLP blocks breast carcinogenesis through the activation of CD4+ T cells that heavily infiltrate the sites of developing cancer in the breast gland without affecting the normal tissue.To investigate the mechanism by which TSLP-stimulated CD4+ T cells suppress spontaneous breast cancer development, we used MMTV-PyMT transgenic mouse models (PyMTtg) that spontaneously develop breast tumors and resemble the human luminal breast cancer. These mice were crossed into TSLP transgenic mice that produce TSLP under the promoter of a skin-specific keratin 14 promoter (K14-TSLPtg), plus additional knockouts including TSLPR-/- and IL4rα;-/-. Tumor development was arrested in K14-TSLPtg;PyMTtg mice compared to PyMTtg counterparts as their tumors failed to progress to high grade. The tumor suppressive mechanism of CD4+ T cells was mediated by a block in cancer cell proliferation, but not by cytotoxicity. Polarization of CD4+ T cells into T helper 2 (Th2) subtype was essential for blocking breast tumor development, and the tumor suppression was achieved by CD4+ T cells in the absence of CD8+ T and B cells. Finally, we found the basal levels of TSLP released by premalignant breast epithelial cells to be protective against the early phases of breast cancer development.In conclusion, we demonstrate that CD4+ Th2 cells block early stages of breast carcinogenesis. TSLP stimulated CD4+ Th2 cells induce an arrest in cancer cell proliferation, which represents a novel mode of immunity with great potential for the prevention and treatment of breast cancer. Citation Format: Margherita Boieri, Anna Malishkevich, Lauren Steidl, Kenneth Ngo, Sowmya Iyer, Mary Awad, Johannes Kreuzer, Wilhelm Haas, Miguel Rivera, Shadmehr Demehri. T helper 2 cells block breast cancer promotion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4948.

Milk fermented by Lactobacillus casei CRL431 modifies cytokine profiles associated to different stages of breast cancer development in mice.

Breast cancer is one of the leading causes of death worldwide. It is recognised that immune system influences its promotion, progression, and metastasis, as well as their responsiveness to therapies. Previously, it was reported that milk fermented by Lactobacillus casei CRL431 decreased tumour growth and metastasis in a mouse breast cancer model, through the modulation of the host immune response. The aim of the present work was to analyse the systemic immune response induced by the administration of probiotic fermented milk (PFM) at different stages of cancer development, evaluating cytokines produced by splenocytes stimulated in vitro with 4T1 tumour cells, or its conditioned medium (CM). Groups of healthy mice and mice bearing 4T1 tumour or suffering metastasis after tumour surgery were studied. Results showed that at the early stages, PFM maintained pro-inflammatory response associated to the delay or the inhibition of tumour growth. PFM administration to mice bearing tumour maintained an important inflammatory response; however, in contrast to the milk group, this response was regulated to avoid exacerbation of inflammation. In the metastasis model, the benefits of PFM were associated to avoid the immunosuppression associated to high interleukin-10 levels. In conclusion, as cancer cells induce modifications of the immune response to favour their own growth at each stage of cancer development, PFM administration stimulated different profile of cytokines to respond to these modifications and fight against cancer cells.

Response of breast cancer cells to IFNα-2b in 2D and 3D cell cultures.

The effect of IFNα-2b on the migration, proliferation, and expression of epithelial and mesenchymal markers of MCF-7 tumor adenocarcinoma cells in 2D and 3D cell cultures was examined. A significant cytostatic effect of IFNα-2b on the tumor population was detected. It was found that changes in the expression of epithelial (CKs and EpCAM) and mesenchymal markers were caused by changing the growth type of the tumor population. IFNα-2b inhibited migration of tumor cells to the suspension fraction and promoted an increase in expression of CK and EpCAM in 2D and 3D cell cultures, but only in the 3D culture was expression of vimentin increased. IFNα-2b caused an increase in CK and EpCAM expression by 50.5% and 47.8%, respectively, compared with the control in the 2D cell culture. In the 3D cell culture this increase was 33% and 34%, respectively, compared with the control. IFNα-2b stimulated the differentiation and inhibited the migrational ability of tumor cells in the early stages of breast cancer development.

Chemoprevention of Breast Cancer With Vitamins and Micronutrients: A Concise Review.

Numerous dietary components and vitamins have been found to inhibit the molecular events and signalling pathways associated with various stages of breast cancer development. To identify the vitamins and dietary micronutrients that exert protective effects against breast cancer and define their mechanism of action, we performed a literature review of in vitro, animal and epidemiological studies and selected the in vitro and animal studies with robust molecular evidence and the epidemiological studies reporting statistically significant inverse associations for a breast cancer-specific protective effect. There is sufficient evidence from in vitro, animal and epidemiological human studies that certain vitamins, such as vitamin D3, folate, vitamin B6, and beta carotene as well as dietary micronutrients, such as curcumin, piperine, sulforaphane, indole-3-carbinol, quercetin, epigallocatechin gallate (EGCG) and omega-3 polyunsaturated fatty acids (PUFAs), display an antitumoral activity against breast cancer and have the potential to offer a natural strategy for breast cancer chemoprevention and reduce the risk of breast cancer recurrence. Therefore, a supplement that contains these micronutrients, using the safest form and dosage should be investigated in future breast cancer chemoprevention studies and as part of standard breast cancer therapy.

Identification of a gene signature for different stages of breast cancer development that could be used for early diagnosis and specific therapy.

Breast cancer (BC) is a heterogeneous disease where the survival rate of patients decreases with progression of the disease. BC usually has a linear progression, classified into normal/benign, atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC). This study aimed to identify gene signature for each of these subgroups.We performed human transcriptome array analysis on 5 patient samples from each Normal, ADH, IDC and DCIS and 2 replicates of MCF10A cell line representative of each subgroup.We identified SFRP1 and snoRNAs (especially SNORD115 and SNORD114) as the initial regulators of cancer progression, accompanied by significant changes in extracellular matrix organization. Tumor progression to the IDC stage showed upregulation of tumor promoting genes responsible for increased invasion, inflammation, survival in stress environment and metastasis.The gene signatures identified in this study could represent potential biomarkers for each subgroup of breast cancer progression, which could assist in early diagnosis of breast cancer progression as well as treatment interventions. Moreover, these gene signatures could serve in discovery of specific targeted therapies for each subgroup.

DOT device as absolutely safe and ergonomic tool for diagnosing breast cancer and monitoring the dynamics of development or rehabilitation of this disease

The paper discusses topical results on early and absolutely safe diagnosis of breast cancer with the help of the domestic DOT apparatus It is shown that in the prevention of breast cancer at the preclinical stage of the development of this disease with the help of DOT it becomes possible to apply artificial intelligence for its timely detection Using an array of thermal examination data the patient s MF allows for an effective choice of treatment strategy by selecting optimal therapy at this stage of breast cancer development

Integrin expression and glycosylation patterns regulate cell-matrix adhesion and alter with breast cancer progression

Integrins are the major cell adhesion glycoproteins involved in cell-extracellular matrix (ECM) interaction and metastasis. Further, glycosylation on integrin is necessary for its proper folding and functionality. Herein, differential expression of integrins viz., αvβ3 and αvβ6 was examined in MDA-MB-231, MDA-MB-468 and MCF-10A cells, which signify three different stages of breast cancer development from highly metastatic to non-tumorigenic stage. The expression of αvβ3 and αvβ6 integrins at mRNA and protein levels was observed in all three cell lines and the results displayed a distinct pattern of expression. Highly metastatic cells showed enhanced expression of αvβ3 than moderate metastatic and non-tumorigenic cells. The scenario was reversed in case of αvβ6 integrin, which was strongly expressed in moderate metastatic and non-tumorigenic cells. N-glycosylation of αvβ3 and αvβ6 integrins is required for the attachment of cells to ECM proteins like fibronectin. The cell adhesion properties were found to be different in these cancer cells with respect to the type of integrins expressed. The results testify that αvβ3 integrin in highly metastatic cells, αvβ6 integrin in both moderate metastatic and non-tumorigenic cells play an important role in cell adhesion. The investigation typify that N-glycosylation on integrins is also necessary for cell-ECM interaction. Further, glycosylation inhibition by Swainsonine is found to be more detrimental to invasive property of moderate metastatic cells. Conclusively, types of integrins expressed as well as their N-glycosylation pattern alter during the course of breast cancer progression.

111P - Effect of IFNα-2b on migrational ability of tumor cells on early stages of breast cancer development

111P - Effect of IFNα-2b on migrational ability of tumor cells on early stages of breast cancer development

Expression Study and Clinical Correlations of MYC and CCAT2 in Breast Cancer Patients

Background:Colon cancer-associated transcript 2 (CCAT2) is a newly recognized lncRNA transcribed from the 8q24 genomic region. It functions as an oncogene in various types of cancers including breast cancer, in which it affects Wnt/β-catenin pathway. Previous studies have shown a putative interaction between this lncRNA and MYC proto-oncogene.Methods:In the current study, we evaluated the expression of CCAT2 in breast cancer tissues with regards to the expression of its target MYC. In addition, we assessed the relationship between CCAT2 and MYC expression levels in tumor tissues and the clinical prognostic characteristics of breast cancer patients.Results:MYC expression levels were significantly up-regulated in tumor tissues compared with adjacent non-cancerous tissues (ANCTs), while such analysis showed no statistically significant difference between these two tissue types in CCAT2 expression. Starkly increased CCAT2 gene expression levels were found in 12/48 (25%) of cancer tissue samples compared with their corresponding ANCTs. Furthermore, significant inverse correlations were found between CCAT2 expression and stage, as well as lymph node involvement. Besides, a significant inverse correlation was found between the relative MYC expression in tumor tissues compared with their corresponding ANCTs and disease stage.Conclusions:These results highlight the significance of MYC and CCAT2 expressions in the early stages of breast cancer development and suggest a potentially significant role for CCAT2 in a subset of breast cancer patients, which could be applied as a potential therapeutic target in these patients.