Chromatin accessibility landscape and active transcription factors in primary human invasive lobular and ductal breast carcinomas.

BACKGROUND: Invasive lobular breast carcinoma (ILC), the second most prevalent histological subtype of breast cancer, exhibits unique molecular features compared with the more common invasive ductal carcinoma (IDC). While genomic and transcriptomic features of ILC and IDC have been characterized, genome-wide chromatin accessibility pattern differences between ILC and IDC remain largely unexplored. METHODS: Here, we characterized tumor-intrinsic chromatin accessibility differences between ILC and IDC using primary tumors from The Cancer Genome Atlas (TCGA) breast cancer assay for transposase-accessible chromatin with sequencing (ATAC-seq) dataset. RESULTS: We identified distinct patterns of genome-wide chromatin accessibility in ILC and IDC. Inferred patient-specific transcription factor (TF) motif activities revealed regulatory differences between and within ILC and IDC tumors. EGR1, RUNX3, TP63, STAT6, SOX family, and TEAD family TFs were higher in ILC, while ATF4, PBX3, SPDEF, PITX family, and FOX family TFs were higher in IDC. CONCLUSIONS: This study reveals the distinct epigenomic features of ILC and IDC and the active TFs driving cancer progression that may provide valuable information on patient prognosis.

Establishment and characterization of three stable Basal/HER2-positive breast cancer cell lines derived from Chinese breast carcinoma with identical missense mutations in the DNA-binding domain of TP53.

BACKGROUND: Basal/human epidermal growth factor receptor (HER)2-positive (HER2+) breast cancer is resistant to monoclonal antibody (herceptin) treatment. There are currently only three basal/HER2+ breast cancer cell lines available, but they are not from Chinese populations. METHODS: Three immortalized cell lines (ZJU-0327, ZJU-0725, and ZJU-1127) were established from invasive ductal breast carcinoma tissue of two patients treated by surgical resection at our center. The cell lines were characterized in terms of histology, therapeutic response, and biomarker expression. Their tumorigenic potential was evaluated in an athymic nude (BALB/C nu) mouse xenograft model. Cell authentication testing by the techniques of short tandem repeat. RESULTS: ZJU-0327, ZJU-0725, and ZJU-1127 cell lines were maintained for more than 110 passages in vitro. The cells grew as monolayers; showed typical epithelial morphology and ultrastructure; were polyploid; had doubling times of 18, 57.5, and 18 h, respectively; had a near-tetraploid (ZJU-0327 and ZJU-1127) or aneuploid (ZJU-0725) karyotype with structural aberrations and tumor protein 53 mutation; insensitive to chemotherapeutic drugs and/or radiation; show high invasiveness and tumorigenicity in mice; and had no mycoplasma contamination. The cell lines were basal/HER2+, expressed cluster of differentiation, and were associated with poor prognosis. Cell authentication testing by the American Type Culture Collection confirmed the human origin of the cell lines, which did not match those in existing databases. CONCLUSIONS: The three novel basal/HER2+ breast cancer cell lines recapitulating the malignant characteristics of the parent tumor's, and can be useful for clarifying the molecular pathogenesis of basal/HER2+ breast cancer.

IQ-domain GTPase-activating protein 1 promotes the malignant phenotype of invasive ductal breast carcinoma via canonical Wnt pathway.

IQ-domain GTPase-activating protein 1 is a scaffolding protein with multidomain which plays a role in modulating dishevelled (Dvl) nuclear translocation in canonical Wnt pathway. However, the biological function and mechanism of IQ-domain GTPase-activating protein 1 in invasive ductal carcinoma (IDC) remain unknown. In this study, we found that IQ-domain GTPase-activating protein 1 expression was elevated in invasive ductal carcinoma, which was positively correlated with tumor grade, lymphatic metastasis, and poor prognosis. Coexpression of IQ-domain GTPase-activating protein 1 and Dvl in the nucleus and cytoplasm of invasive ductal carcinoma was significantly correlated but not in the membrane. Postoperative survival in the patients with their coexpression in the nucleus and cytoplasm was obviously lower than that without coexpression. The positive expression rates of c-myc and cyclin D1 were significantly higher in the patients with nuclear coexpression of Dvl and IQ-domain GTPase-activating protein 1 than that with cytoplasmic coexpression, correlating with poor prognosis. IQ-domain GTPase-activating protein 1 significantly enhanced cell proliferation and invasion in invasive ductal carcinoma cell lines by interacting with Dvl in cytoplasm to promote Dvl nuclear translocation so as to upregulate the expression of c-myc and cyclin D1. Collectively, our data suggest that IQ-domain GTPase-activating protein 1 may promote the malignant phenotype of invasive ductal carcinoma via canonical Wnt signaling, and it could be used as a potential prognostic biomarker for breast cancer patients.

MRI-based machine learning radiomics for prediction of HER2 expression status in breast invasive ductal carcinoma.

Background: Human epidermal growth factor receptor 2 (HER2) is a tumor biomarker with significant prognostic and therapeutic implications for invasive ductal breast carcinoma (IDC). Objective: This study aimed to explore the effectiveness of a multisequence magnetic resonance imaging (MRI)-based machine learning radiomics model in classifying the expression status of HER2, including HER2-positive, HER2-low, and HER2 completely negative (HER2-zero), among patients with IDC. Methods: A total of 402 female patients with IDC confirmed through surgical pathology were enrolled and subsequently divided into a training group (n = 250, center I) and a validation group (n = 152, center II). Radiomics features were extracted from the preoperative MRI. A simulated annealing algorithm was used for key feature selection. Two classification tasks were performed: task 1, the classification of HER2-positive vs. HER2-negative (HER2-low and HER2-zero), and task 2, the classification of HER2-low vs. HER2-zero. Logistic regression, random forest (RF), and support vector machine were conducted to establish radiomics models. The performance of the models was evaluated using the area under the curve (AUC) of the operating characteristics (ROC). Results: In total, 4506 radiomics features were extracted from multisequence MRI. A radiomics model for prediction of expression state of HER2 was successfully developed. Among the three classification algorithms, RF achieved the highest performance in classifying HER2-positive from HER2-negative and HER2-low from HER2-zero, with AUC values of 0.777 and 0.731, respectively. Conclusions: Machine learning-based MRI radiomics may aid in the non-invasive prediction of the different expression status of HER2 in IDC.

Metaplastic Breast Carcinoma: A Rare Presentation in a Young Female With Double Hormone Receptor-Positive Tumor.

Metaplastic breast carcinoma (MBC) represents a rare subtype of breast cancer, characterized by poor prognostic indicators that have been recently identified. Clinical and radiological presentations often mimic other breast cancer types, necessitating immunohistochemistry (IHC) for accurate diagnosis. In this study, we report a case involving a 31-year-old female presenting with a painless, fixed, non-inflammatory mass in the left breast, which was confirmed as MBC. Treatment encompassed lumpectomy, chemotherapy, radiotherapy, and subsequent hormonal therapy. Understanding this rarely reported yet aggressive form of breast cancer holds significant importance for clinicians, enabling them to promptly establish a diagnosis and implement effective management strategies.

Development and validation of survival nomograms in elder triple-negative invasive ductal breast carcinoma patients.

BACKGROUND: We aimed to develop a nomogram to predict the overall survival of elderly patients with Triple-negative invasive ductal breast carcinoma (TNIDC). RESEARCH DESIGN AND METHODS: 12165 elderly patients with nonmetastatic TNIDC were retrieved from the SEER database from 2010 to 2019 and were randomly assigned to training and validation cohorts. Stepwise Cox regression analysis was used to select variables for the nomogram based on the training cohort. Univariate and multivariate Cox analyses were used to calculate the correlation between variables and prognosis of the patients. Survival analysis was performed for high- and low-risk subgroups based on risk score. RESULTS: Eleven predictive factors were identified to construct our nomograms. Compared with the TNM stage, the discrimination of the nomogram revealed good prognostic accuracy and clinical applicability as indicated by C-index values of 0.741 (95% CI 0.728-0.754) against 0.708 (95% CI 0.694-0.721) and 0.765 (95% CI 0.747-0.783) against 0.725 (95% CI 0.705-0.744) for the training and validation cohorts, respectively. Differences in OS were also observed between the high- and low-risk groups (p < 0.001). CONCLUSION: The proposed nomogram provides a convenient and reliable tool for individual evaluations for elderly patients with M0_stage TNIDC. However, the model may only for Americans.

Adenoma of the Nipple: A Case Report.

Nipple adenomas are rare, benign breast lesions that present similarly to breast malignancies, often manifesting with unilateral bloody discharge, a palpable mass, and/or nipple distortion. Imaging techniques have limited specificity in distinguishing nipple adenomas from malignancy; therefore, clinicians must rely on histologic and immunohistochemistry evaluation. Here, we highlight the case of a 69-year-old woman with bilateral nipple adenomas presenting as an enlarging nipple mass with chronic nipple discharge. Complete lesion resection with clear margins stands as the primary route of management and complete avoidance of re-occurrence. However, partial excision with nipple preservation has been reported to be successful in selected cases.

Breast Cancer Metastasis to Colon.

Breast cancer metastasis to the colon is exceedingly rare, with only 17 reported cases in the literature thus far. This report describes a 67-year-old female who presented to the Emergency Department for large volume melena in the setting of bilateral metastatic ductal breast carcinoma, left triple negative and right HER2+, and T4N0M0 non-small cell lung cancer. On routine CT abdomen/pelvis imaging, the patient had a 7 cm mass arising from the transverse colon. Colonoscopy revealed a non-obstructing necrotic mass in the proximal descending colon. The patient underwent a partial colectomy, small bowel resection, and gastric wedge resection. The patient recovered from surgery and was discharged home with palliative services. The patient passed away four months after discharge due to numerous metastases.

Expression analysis of novel long non-coding RNAs for invasive ductal and invasive lobular breast carcinoma cases.

AIM: Long non-coding RNAs (LncRNAs) serve as important regulatory molecules of gene expression and protein functionality at multiple biological levels, and their deregulation plays a key role in tumorigenesis including in breast cancer metastasis. Therefore, in this study, we aim to compare the expression of novel lncRNAs in the landscape of invasive ductal carcinoma (IDC) and invasive lobular (ILC) carcinoma of breast. MAIN METHODS: We have designed an in-silico approach to find the lncRNAs that regulate the breast cancer. Then, we used the clinical samples to carry out the verification of our in silico finding. In the present study, the tissues of breast cancer were deparaffinized. RNA was extracted by the TRIzole method. After synthesizing cDNA from the extracted RNA, expression levels of lncRNAs were analyzed by qPCR using primers specifically designed and validated for the targeted lncRNAs. In this study, breast biopsy materials from 41 female patients with IDC and 10 female patients with ILC were examined histopathological and expression changes of candidate lncRNAs were investigated in line with the findings. The results were analyzed using IBM SPSS Statistics 25 version. RESULTS: The mean age of the cases was 53.78 ± 14.96. The minimum age was 29, while the maximum age was 87. While 27 of the cases were pre-menopausal, 24 cases were post-menopausal. The number of hormone receptor-positive cases was found to be 40, 35, and 27 for ER, PR, and cerb2/neu, respectively. While the expressions of LINC00501, LINC00578, LINC01209, LINC02015, LINC02584, ABCC5-AS1, PEX5L-AS2, SHANK2-AS3 and SOX2-OT showed significant differences (p < 0.05), the expressions of LINC01206, LINC01994, SHANK2-AS1, and TPRG1-AS2 showed no significant differences (p > 0.05). In addition, it was determined that the regulation of all lncRNAs could be able to involve in the development of cancer such as the NOTCH1, NFKB, and estrogen receptor signalings. CONCLUSION: As a result, it was thought that the discovery of novel lncRNAs might be an important player in the diagnosis, prognosis and therapeutic development of breast cancer.

Mind the Gap: Recurrence of Oligometastatic Breast Invasive Ductal Carcinoma in the Sternal Gap of Two Tangential Photon Fields of Bilateral Whole Breast Irradiation a Decade Later.

Despite bilateral breast cancer being a rare clinical entity compared to unilateral breast cancer, both share a treatment paradigm of breast-conserving therapy for limited disease and metastasis direct therapy for oligometastatic disease. We present a case of left breast invasive ductal carcinoma in the setting of original bilateral breast cancer, now with oligometastatic recurrence to the soft tissue of the sternum, notably in an area not previously irradiated, over a decade later.

Upgrade Rate of Ductal Carcinoma In Situ to Invasive Carcinoma and the Clinicopathological Factors Predicting the Upgrade Following a Mastectomy: A Retrospective Study.

Background The rate of upgrading ductal carcinoma in situ (DCIS) to invasive cancer varies widely in the literature with no consensus regarding sentinel lymph node biopsy (SLNB) for DCIS; however, some guidelines do recommend it in the event of a mastectomy. The primary aim of this study was to determine the upgrade rate of DCIS to invasive carcinoma (IC) in patients undergoing mastectomy for DCIS and identify the clinicopathological predicting factors for the upgrade. The secondary aim was to determine the SLNB positivity rate. Methodology We retrospectively analysed consecutive patients with DCIS diagnosed through a biopsy who then underwent mastectomy over a 10-year period (2010 to 2020). Clinical, radiological, and histological variables were collected from medical records. Results We studied 143 women (mean age = 57.4 years, range = 26-85 years) who underwent mastectomy for DCIS identified on biopsy. Almost two-thirds (62.9%, 90/143) of the patients were detected on screening mammography, while 35.6% (51/143) were diagnosed following presentation with either an area of palpable concern or nipple discharge. The most common mammographic presentation of DCIS was calcification (83.9%, 120/143), and, in 85.9% of the patients, the mammographic lesion was more than 20 mm. High-grade DCIS was noted in 76.9% of preoperative biopsy results, while the rest was either low or intermediate-grade DCIS. Overall, 24.5% (35/143) were upgraded to IC (upgraded group) on postoperative histology, whereas 108/143 remained DCIS postoperatively (pure DCIS group). The positivity rate of SLNB was 4.8%. Multifocality was the only significant predictor of IC on multivariate analyses of clinicopathological predictors (odds ratio = 3.0, 95% confidence interval = 1.0-8.7). The presence of comedonecrosis was higher in the upgraded group compared to the pure DCIS group (42.9% vs. 27.8%), but this was not statistically significant. Conclusions In our study cohort, nearly one in four (24.5%) patients were upgraded from DCIS to IC on postoperative histology, with an SLNB positivity rate of 4.8%. This is important when counselling patients regarding the risk of coincident occult IC and the importance of SLNB at the time of mastectomy. Multifocality on preoperative imaging was the only significant predictive factor. Based on this result, we recommend that SLNB should also be considered if patients have multifocal DCIS and planned for oncoplastic breast-conserving surgery. However, further studies are required to investigate the association between multifocal DCIS and the risk of upgrading to IC.

Metabolomic study of serum in patients with invasive ductal breast carcinoma with LC-MS/MS approach.

BACKGROUND: Invasive ductal carcinoma (IDC) is the most common type of breast cancer so its early detection can lead to a significant decrease in mortality rate. However, prognostic factors for IDC are not adequate and we need novel markers for the treatment of different individuals. Although positron emission tomography and magnetic resonance imaging techniques are available, they are based on morphological features that do not provide any clue for molecular events accompanying cancer progression. In recent years, "omics" approaches have been extensively developed to propose novel molecular signatures of cancers as putative biomarkers, especially in biofluids. Therefore, a mass spectrometry-based metabolomics investigation was performed to find some putative metabolite markers of IDC and potential metabolites with prognostic value related to the estrogen receptor, progesterone receptor, lymphovascular invasion, and human epidermal growth factor receptor 2. METHODS: An untargeted metabolomics study of IDC patients was performed by liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). The multivariate principal component analysis by XCMS online built a model that could separate the study groups and define the significantly altered m/z parameters. The most important biological pathways were also identified by pathway enrichment analysis. RESULTS: The results showed that the significantly altered metabolites in IDC serum samples mostly belonged to amino acids and lipids. The most important involved pathways included arginine and proline metabolism, glycerophospholipid metabolism, and phenylalanine, tyrosine, and tryptophan biosynthesis. CONCLUSIONS: Significantly altered metabolites in IDC serum samples compared to healthy controls could lead to the development of metabolite-based potential biomarkers after confirmation with other methods and in large cohorts.

Isolated Leptomeningeal Metastasis of Breast Cancer During Neo-Adjuvant Chemotherapy: A Case Report.

The incidence of symptomatic brain metastasis from breast cancer ranges from ~10% to 15%. Brain parenchymal metastasis comprises most of this and has been studied more extensively, whereas isolated leptomeningeal carcinomatosis (LC) is exceedingly rare. The diagnosis is most commonly made by lumbar puncture and cerebrospinal fluid (CSF) cytology, although it is persistently negative in about 10% of patients, and hence its pre-mortem diagnosis remains difficult and controversial. There are limited therapeutic options available making the prognosis abysmal. It has been reported that locally responsive breast cancers on chemotherapy can develop CNS metastasis; the blood-brain barrier and the unique brain microenvironment are hypothesized to promote distinct molecular features in such CNS metastases. We present a 37-year-old female with a large triple-negative, node-positive grade three invasive ductal carcinomas with Ki-67 70%. Despite the local response to neoadjuvant chemotherapy, she developed rapidly worsening multiple neurological symptoms. MRI brain showed leptomeningeal enhancement and CSF cytology results were negative with inconclusive other CSF studies. The patient deteriorated very rapidly and a post-mortem diagnosis of isolated LC was made. The notable aspects of this case include the development of a rapidly progressive isolated LC despite the good local response to the chemotherapy, which requires further studying. As the currently available diagnostic and therapeutic tools have limitations, research can be critical in providing better outcomes for this fatal disease.

A Collision Tumor in the Breast Consisting of Invasive Ductal Carcinoma and Malignant Melanoma.

Collision tumors are rare neoplasms that consist of at least two different cell lineages at the same site. Given the many possible combinations that can occur, collision tumors, while rare, have been reported in multiple locations such as the stomach, bladder, and thyroid. Collision tumors are rarely found in breast tissue, with only a few cases reported in the literature. We herein report a unique case of a 79-year-old woman with a history of melanoma who presented with a left breast mass that was subsequently found to have invasive ductal carcinoma (IDC) and metastatic melanoma in the breast tissue. This is one of the first reported combinations of these two malignancies.

An Unusual Occurrence of Uterine Metastases in a Case of Invasive Ductal Breast Carcinoma.

Breast cancer is the most frequent cancer in women and has a high proclivity for metastasizing, yet it seldom affects gynaecological organs. We present a case of invasive ductal carcinoma of the breast that metastasized to the uterus following initial curative treatment. Our patient was taking tamoxifen, which can induce endometrial hyperplasia and make diagnosis more complicated.

An analysis of Ki-67 expression in stage 1 invasive ductal breast carcinoma using apparent diffusion coefficient histograms.

BACKGROUND: To investigate the value of apparent diffusion coefficient (ADC) histograms in differentiating Ki-67 expression in T1 stage invasive ductal breast carcinoma (IDC). METHODS: The records of 111 patients with pathologically confirmed T1 stage IDC who underwent magnetic resonance imaging prior to surgery were retrospectively reviewed. The expression of Ki-67 in tumor tissue samples from the patients was assessed using immunohistochemical (IHC) staining, with a cut-off value of 25% for high Ki-67 labeling index (LI). ADC images of the maximum lay of tumors were selected, and the region of interest (ROI) of each lay was delineated using the MaZda software and analyzed by histogram. The correlations between the histogram characteristic parameters and the Ki-67 LI were investigated. Additionally, the histogram characteristic parameters of the high Ki-67 group (n=54) and the low Ki-67 group (n=57) were statistically analyzed to determine the characteristic parameters with significant difference. Receiver operator characteristic (ROC) analyses were further performed for the significant parameters. RESULTS: The mean value, and the 1st, 10th, 50th, 90th, and 99th percentiles were found to be negatively correlated with the expression of Ki-67 (all P values <0.001), with a correlation coefficient of -0.624, -0.749, -0.717, -0.621, -0.500, and -0.410, respectively. In the high Ki-67 group, the mean value, and the 1st, 10th, 50th, 90th, and 99th percentiles extracted by the histogram were significantly lower (all P values <0.05) than that of the low Ki-67 group, with areas under the ROC curves ranging from 0.717-0.856. However, the variance, skewness, and kurtosis did not differ between the two groups (all P values >0.05). CONCLUSIONS: Histogram-derived parameters for ADC images can serve as a reliable tool in the prediction of Ki-67 proliferation status in patients with T1 stage IDC. Among the significant ADC histogram values, the 1st and 10th percentiles showed the best predictive values.

Establishment and Characterization of a HER2-Positive Cell Line Derived From the Pleural Effusion of a Drug-Resistant Breast Cancer Patient.

Drug resistance is a daunting challenge in the treatment of breast cancer, making it an urgent problem to solve in studies. Cell lines are important tools in basic and preclinical studies; however, few breast cell lines from drug-resistant patients are available. Herein, we established a novel HER2-positive breast cancer cell line from the pleural effusion of a drug-resistant metastatic breast cancer patient. This cell line has potent proliferative capability and tumorigenicity in nude mice but weak invasive and colony-forming capability. The molecular subtype of the cell line and its sensitivity to chemotherapeutics and HER2-targeting agents are different from those of its origin, suggesting that the phenotype changes between the primary and metastatic forms of breast cancer.

Clinical values of two estrogen receptor signaling targeted lncRNAs in invasive ductal breast carcinoma.

BACKGROUND: Invasive ductal carcinoma (IDC) is the most frequent type of breast cancer (BC) in women, with a high clinical burden due to its high invasive properties. Despite of quickly emerging new data regarding the molecular heterogeneity of invasive cancers, far less is known about the molecular patterns among cases of IDC. An expanding body of evidence has demonstrated that dysregulation of long noncoding RNAs (lncRNAs) is involved in the heterogeneity feature of BC. METHODS: In this study, we analyzed the expression levels of two novel lncRNAs LOC100288637 and RP11-48B3 in 51 IDC tissues in comparison with adjacent non-cancerous tissues. And finally, bio-informatic evaluation has been done. RESULTS: The results of quantitative polymerase chain reaction showed that LOC100288637 and RP11-48B3 were significantly overexpressed in tumor tissues compared to normal samples (P = 0.0085 and P = 0.0002, respectively). Also, the two lncRNAs were overexpressed in both MDA-MB-231 and MCF-7 BC cell lines, nevertheless, with a higher expression pattern in MDA-MB-231 than MCF7 cell line. Furthermore, LOC100288637 had an elevated expression level in HER-2 positive tumors compared to HER-2 negative tumors (P = 0.031). Interestingly, the lncRNA RP11-48B3.4 was upregulated in IDC subjects with the age at menarche < 14 years compared to patients with the age at menarche 14 (P = 0.041). It was observed in another result that lncRNA RP11-48B3.4 is significantly upregulated in tumors with a lower histological grade compared to tumor samples with higher grades (P = 0.047). And finally, using bio-informatic evaluation, we found a predicted interaction between RP11-48B3.4 and mRNA zinc finger and BTB domain containing 10 (ZBTB10). CONCLUSION: Altogether, our findings suggest that these lncRNAs with potential oncogenic roles are involved in the pathogenesis of IDC with clinical significance and they may therefore serve as novel markers for the dia-gnosis and treatment of IDC.

The influence of size, depth and histologic characteristics of invasive ductal breast carcinoma on thermographic properties of the breast.

Invasive breast carcinoma is the most common oncologic disease worldwide. The existing diagnostic methods use morphologic changes in the breast to diagnose a carcinoma when it has reached a certain size. Therefore, it is important to augment the morphologic diagnostic examinations with a new method that focuses on characteristics other than morphology such as electromagnetic changes produced by cancer. 50 adult female patients with confirmed ductal carcinoma following a core biopsy due to a suspicious breast mass were included in the study. They underwent breast thermography using a specially designed infrared camera. The data collected was statistically analyzed to determine how the presence of a tumor and its histologic characteristics influence breast thermographic properties. Twenty eight [56 %] patients in the study had an abnormal thermogram. Following statistical analysis, it was found that temperature of the diseased breast was directly correlated to tumor volume [p=0.009] and negatively correlated to depth of tumor [p=0.042]. Tumors that were ER+ and PR+ tumors produced warmer temperatures [p=0.017 and p=0.038 respectively] than tumors without these receptors. HER2 status and Ki-67 index had no statistical correlation with breast temperature. Tumor size, distance from the skin surface and receptor status cause changes in breast thermographic properties. Despite technical advances in the field of thermography, there are still contradictory results associated with thermography. Its diagnostic abilities are generally poorer than conventional methods and its use in breast cancer screening or as an adjunctive tool for diagnostic purposes is not recommended.

Molecular docking based screening analysis of GSK3B.

GSK3B has been an interesting drug target in the pharmaceutical industry. Its dysfunctional expression has prognostic significance in the top 3 cause of death associated with non-communicable diseases (cancer, Alzheimer's disease and type 2 diabetes). Previous studies have shown clearly that inhibiting GSK3B has proven therapeutic significance in Alzheimer's disease, but its contribution to various cancers has not been clearly resolved. In this study we report the contribution and prognostic significance of GSK3B to two breast cancer subtypes; ductal carcinoma in-situ (DCIS) and invasive ductal carcinoma (IDC) using the Oncomine platform. We performed high throughput screening using molecular docking. We identified BT-000775, a compound that was subjected to further computational hit optimization protocols. Through computational predictions, BT-000775 is a highly selective GSK3B inhibitor, with superior binding affinity and robust ADME profiles suitable for the patho-physiological presentations.