Invasive Ductal Carcinoma Research Articles

Anthropometric equation has sufficient diagnostic capacity to identify sarcopenia in women with breast cancer

BackgroundSarcopenia is a common condition in women with breast cancer, however still presents limitations for an effective diagnosis. This study aimed to evaluate the agreement and diagnostic accuracy of an anthropometric equation in diagnosing sarcopenia in women with breast cancer based on different constructs.MethodsCross-sectional study carried out with women with breast cancer aged ≥ 20 years. Sarcopenia was identified according to the European Working Group on Sarcopenia in Older People 2 (EWGSOP2) criteria. Muscle strength was obtained by the handgrip strength test (HGS) and muscle mass (MM) by dual-energy x-ray absorptiometry (DXA) and by the anthropometric predictive equation. For the diagnosis of sarcopenia, eight constructs were proposed based on the MM assessment method (equation or DXA) and different cutoff points. Agreement analyses using Cohen’s Kappa test and diagnostic performance measures were performed. The significance level for all tests was 5%.ResultsA total of 122 women, with a mean age of 55.3 ± 11.4 years, were evaluated. There was a predominance of brown participants (50.8%), insufficiently active (57.4%), with diagnosis time ≤ 3 months (54.1%), and with invasive breast carcinoma (69.7%). The prevalence of sarcopenia ranged from 3.3 to 8.2%, depending on the construct used. The constructs determined from the cutoff points < 16.0 kg/< 7.58 m² and < 23.0 kg/< 7.58 m² were the ones that showed the best ability to detect sarcopenia.ConclusionThe anthropometric equation showed sufficient diagnostic capacity to be used as an alternative in identifying sarcopenia in women with breast cancer.

OmicsFootPrint: a framework to integrate and interpret multi-omics data using circular images and deep neural networks.

The OmicsFootPrint framework addresses the need for advanced multi-omics data analysis methodologies by transforming data into intuitive two-dimensional circular images and facilitating the interpretation of complex diseases. Utilizing deep neural networks and incorporating the SHapley Additive exPlanations algorithm, the framework enhances model interpretability. Tested with The Cancer Genome Atlas data, OmicsFootPrint effectively classified lung and breast cancer subtypes, achieving high area under the curve (AUC) scores-0.98±0.02 for lung cancer subtype differentiation and 0.83±0.07 for breast cancer PAM50 subtypes, and successfully distinguished between invasive lobular and ductal carcinomas in breast cancer, showcasing its robustness. It also demonstrated notable performance in predicting drug responses in cancer cell lines, with a median AUC of 0.74, surpassing nine existing methods. Furthermore, its effectiveness persists even with reduced training sample sizes. OmicsFootPrint marks an enhancement in multi-omics research, offering a novel, efficient and interpretable approach that contributes to a deeper understanding of disease mechanisms.

Long-term Survival Outcomes in Locally Advanced Breast Cancer after Mastectomy with or without Breast Reconstruction.

There is ongoing debate about the safety of breast reconstruction for patients with locally advanced breast cancer (LABC) who have undergone total mastectomy (TM). More and more LABC patients are undergoing breast reconstruction after TM, but its long-term survival outcomes remain unclear. This study aims to compare the survival outcomes of LABC patients who underwent breast reconstruction after TM with those who did not, based on a large sample. We collected data for all LABC patients who underwent TM with or without breast reconstruction in the Surveillance, Epidemiology, and End Results (SEER) database. We divided patients into two groups: TM group and total mastectomy with reconstruction (TM+R) group. The primary outcomes were overall survival (OS) and breast cancer-specific survival (BCSS). Propensity score matching (PSM) analysis was used to eliminate imbalances of baseline data between the in tow groups. Data were analyzed using chi-square tests, Kaplan-Meier methods, and univariate and multivariate cox regression analyses. We identified 39,112 eligible patients (33,169 patients received TM and 5,943 received TM+R), and 8,680 patients were matched after PSM (4,340 patients received TM and 4,340 received TM+R). Patients with middle age, white, married, lived in urban, IIB-IIIA stage, invasive ductal carcinoma (IDC), pathological grade II-III, hormone receptor positive, and undergone chemotherapy were more likely to receive breast reconstruction. After PSM, Kaplan-Meier survival analysis showed better OS and BCSS in the TM+R group versus the TM group (OS:P&lt;0.001; BCSS: P=0.008). Multivariate cox regression analysis showed that TM+R significantly improved OS and BCSS (OS: hazard ratio (HR) 0.73, 95% CI [0.68,0.79], P&lt;0.001; BCSS: 95% CI [0.79,0.94], P=0.001). Subgroup analysis showed that patients with old age, white, and hormone receptor positive had better OS and BCSS by TM+R compared to TM. Breast reconstruction after total mastectomy is associated with better OS and BCSS in patients with LABC.

Combining metabolomics and machine learning to discover biomarkers for early-stage breast cancer diagnosis.

There is an urgent need for better biomarkers for the detection of early-stage breast cancer. Utilizing untargeted metabolomics and lipidomics in conjunction with advanced data mining approaches for metabolism-centric biomarker discovery and validation may enhance the identification and validation of novel biomarkers for breast cancer screening. In this study, we employed a multimodal omics approach to identify and validate potential biomarkers capable of differentiating between patients with breast cancer and those with benign tumors. Our findings indicated that ether-linked phosphatidylcholine exhibited a significant difference between invasive ductal carcinoma and benign tumors, including cases with inconsistent mammography results. We observed alterations in numerous lipid species, including sphingomyelin, triacylglycerol, and free fatty acids, in the breast cancer group. Furthermore, we identified several dysregulated hydrophilic metabolites in breast cancer, such as glutamate, glycochenodeoxycholate, and dimethyluric acid. Through robust multivariate receiver operating characteristic analysis utilizing machine learning models, either linear support vector machines or random forest models, we successfully distinguished between cancerous and benign cases with promising outcomes. These results emphasize the potential of metabolic biomarkers to complement other criteria in breast cancer screening. Future studies are essential to further validate the metabolic biomarkers identified in our study and to develop assays for clinical applications.

Nuclear staining for pan-Trk by immunohistochemistry is highly specific for secretory carcinoma of breast: pan-Trk in various subtypes of breast carcinoma

AimsSecretory carcinoma of breast (SCB) typically harbours ETV6-NTRK3 gene fusion. Pan-Trk immunohistochemistry analysis (IHC) has been shown to be sensitive for SCB diagnosis. However, weak focal pan-Trk nuclear staining was...

Abstract A028: Cycling T regulatory cells architect an immune escape hub during in situ to invasive breast carcinoma transition

Abstract A028: Cycling T regulatory cells architect an immune escape hub during <i>in situ</i> to invasive breast carcinoma transition

Discordance of human epidermal growth factor receptor 2-low status between breast primary and distant metastases with clinical-pathological correlation.

Breast cancer with human epidermal growth factor receptor 2 (HER2) immunohistochemistry (IHC) 1+ or 2+ with negative in-situ hybridisation (ISH) (HER2-low) can now be targeted by HER2 antibody drug conjugates. We set out to compare HER2 status between matched primary invasive breast carcinoma (IBC) and distant metastases (DM) with clinical-pathological correlation, with specific interest in HER2-low. Biomarker studies and clinical-pathological features of primary IBC with matched DM diagnosed between 2021 and 2022 were retrospectively analysed. HER2 status was assessed per 2023 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines for IHC (4B5) and ISH (IQFISH pharmDX). Bilateral breast primaries were excluded. HER2 IHC 0 to 1+ were reassessed. One hundred and forty-seven cases of primary IBC with matched DM were identified. Biomarkers were performed on core biopsy (n = 74) and resection (n = 73). One hundred and twenty-six (86%) were initially classified as 'HER2-negative'; of these, 67 (46%) were reclassified as HER2-low. Patients with HER2-positive primaries were younger (P = 0.01) and had an increased incidence of micropapillary carcinoma (P = 0.02). HER2-low primaries also had an increased incidence of micropapillary carcinoma (P = 0.02) and oestrogen receptor (ER) positivity (P = 0.02) compared to HER2 0. One hundred and sixty-nine matched DM cases excluding bone metastasis were identified (range = one to seven metastases per IBC). The most common sites of metastases were liver (50 of 169, 30%), lung (36 of 169; 21%), distant lymph node (26 of 169, 15%); 138 DM cases (82%) were previously classified as 'HER2-negative', and 62 (37%) were reclassified as HER2-low. Like HER2-low primaries, HER2-low metastases were frequently ER-positive (52 of 62; 84%) (P = 0.02). Brain metastases were more frequently HER2-positive (five of 32; 16%) (P = 0.04). Comparing HER2 status in matched primaries and DM, HER2 status was discordant in 62 cases (37%). Most changes occurred from HER2-low to HER2 0 (33 of 169, 20%), HER2 0 to HER2-low (17 of 169, 10%) and HER2-low to positive (10 of 169, 6%). All HER2-low to HER2 0 changes were HER2 1+ to 0. In 30 patients with multiple DM sites (47 cases), HER2 status among different DM samples was discordant in 16 patients (53%), mainly from HER2-low to HER2 0 (16 of 47, 34%). A significant proportion of previous 'HER2-negative' primaries and DM cases were reclassified as HER2-low. Discordant HER2 status between IBC primary and metastasis and between different DM sites demonstrated tumour heterogeneity and highlights the need for HER2 retesting in distant metastasis.

Correlation of tumor budding with a novel and other established prognostic parameters in patients with invasive breast carcinoma.

Breast cancer is the most common malignancy among women. Established prognostic markers in breast carcinomas include tumor size, histologic grade, nodal status, lymphovascular invasion, perineural invasion, hormone receptor status, HER-2 status, and age. To correlate peripheral tumor budding (pTB) with stromal tumor-infiltrating lymphocytes (sTILs) and established prognostic factors in invasive breast carcinoma. It is a retrospective study conducted at multiple centers including a tertiary care center. 100 cases were included over a period of 2.5 years. All cases of invasive breast carcinoma (IBC) in which excision specimens with lymph node dissection were available were studied. Slides were reviewed for pTB and sTILs. Tumor budding of ≤20/10 hpf was considered low tumor budding, and >20 buds/10 hpf was considered high tumor budding. Tumor budding was correlated with age, tumor size, lymphovascular invasion, perineural invasion, tumor stage (pT, pN), stromal tumor-infiltrating lymphocytes, tumor grade, ductal carcinoma in situ, hormonal receptors, and HER2neu. Fisher exact test and Chi-square test were used. We found that high tumor budding was seen in 34 cases and low tumor budding in 66 cases. There was a statistically significant association between high tumor budding and tumor size (P = 0.007), lymphovascular invasion (P < 0.001), perineural invasion (P = 0.004), tumor staging/pT (P = 0.006), nodal staging/pN (P = 0.001), and low sTILs (P < 0.001). However, the association of high tumor budding with parameters like age (P = 0.979), histological type (P = 0.243), tumor grade (P = 0.052), DCIS (P = 0.478), and ER (P = 0.633), and PR (P = 0.544), HER2Neu status (P = 0.171) was not significant. This study suggests tumor budding score can be used as a prognostic indicator for breast cancer.

Differential Expression of Circulating miR-195 in a Sample of Iraqi Breast Cancer Patients Associations with Molecular Subtypes and Disease Stages

Breast cancer (BC) is a multifaceted disease characterized by different molecular subtypes and stages. MicroRNAs (miRNAs)are increasingly becoming recognized as valuable tools for predicting and identifying persons with BC, particularly miR-195. This study aimed to evaluate the expression of miR-195 in BC patients and its correlation with demographic and clinical parameters. The study involved 60 female BC patients and 60 healthy controls. Demographic analysis showed that 65% of BC patients have a family history of BC. Invasive ductal carcinoma (IDC) was the most prevalent type (85%), and luminal A was the most common molecular subtype (57%). The majority of cases were in stage II (40%) and stage III (36%), with patients primarily in the 40-59 age range (70%). RT-qPCR analysis revealed significant upregulation of miR-195 (6.752 ± 4.06-fold change) in BC patients compared to healthy controls. However, expression levels varied among molecular subtypes and stages. Triple-negative BC patients showed significant downregulation of miR-195 (0.45±0.3-fold change) compared to other subtypes. Similarly, stage IV patients exhibited significant downregulation (0.63±0.24-fold decrease) compared to earlier stages. Interestingly, no significant differences in miR-195 expression were observed among different BC types (IDC, ILC, and others). These findings suggest that miR-195 could potentially serve as a biomarker for BC, particularly in distinguishing molecular subtypes and advanced stages. However, further research is needed to validate its clinical utility and understand its role in BC progression and prognosis.

Quality of Life of Breast Cancer Women under Treatment at a Tertiary Care Center of Western Maharashtra

Background: ‘Breast cancer’ the most common cancer amongst females in India. Having good Quality of life (QoL) among the patients undergoing treatment is one of the vital and significant factors for ensuring holistic approach to treatment and well-being of cancer patients. The present study was conducted to assess the QoL and its determinants among breast cancer patients undergoing treatment at a tertiary care institute in western Maharashtra. Material and Methodology: 300 histopathologically confirmed breast cancer patients undergoing treatment at a tertiary care centre were divided into three groups to include 100 patients in each group. Group 1 (patients with duration of treatment 1 to 2 years) Group 2 (patients with duration of treatment 2 to 5 years) and Group 3 (more than 5 years). Validated tool Function Assessment of Cancer Therapy Breast specific (FACT-B) questionnaire was used to collect information on QoL and analysed using appropriate statistical tests. Results: Mean age of patients was 53.2 + 10.08 years, 136 (45.33%) were from age group 51 to 65 years. Majority of the patients 106 (35.33%) were educated till secondary schooling and 172 (57.33 %) were belonging to the middle-upper class. Lump in breast was most common presenting symptom in 235 (78.33%) cases followed by nipple retraction. 275 (91.67 %) cases had infiltrating ductal Carcinoma and 144 (48%) patents were in Stage II cancer. Over all mean FACT-B score for QoL was 104.02 + 18.65 out of 141. Mean FACT-B score for Group 1, Group 2 and Group 3 was 88.18 +17.20, 105.89 + 11.78 and 118.28 + 12.45 respectively with (p&lt; 0.05), suggests significant improvement in QoL with increase in time elapsed since treatment. Conclusion: Socio-demographic factors, type of surgery and duration of treatment had significant effect on QoL among breast cancer patients. Apropos physicians, paramedic staff and domestic care givers need to be sensitised on importance of QoL for collective and deliberate efforts to achieve holistic care. QoL can be made integral part of breast cancer treatment and management policy or programme.

Sneaky DCIS-looking Invasive Ductal Carcinoma of the Breast in the Extensive DCIS Background

Abstract Introduction/Objective In the most cases, invasive ductal carcinoma (IDC) of the breast is identifiable when they present with classic infiltrative growth pattern. However, subset of IDC can occur in a very sneaky way, significantly mimicking the appearance of ductal carcinoma in situ (DCIS). In this condition, it’s much more easier to miss the invasive component without pulling ancillary staining when morphologic findings are extremely compatible with DCIS, especially the diagnosis of DCIS was made on the previous biopsy. Methods/Case Report Retrospective analysis of the histologic and immunohistochemical findings of pure DCIS and DCIS-looking invasive ductal carcinoma. Results (if a Case Study enter NA) Here, we reported a 55 year-old female who was noted to have microcalcification at the 11:00 o’clock of the right posterior breast on routine mammographic examination in 09/2023. Biopsy of the calcification area in 10/2023 reported high grade DCIS (ER+ PR-). Histologic examination of subsequent mastectomy specimen showed two separate DCIS-looking areas. Immunohistochemical (IHC) staining showed that myoepithelial markers, p63 and smooth muscle myosin heavy chain (SMMHC), were retained at the periphery of all the expanded acini in one area. Unexpectedly and surprisingly, p63 and SMMHC were completely lost at the periphery of part of the DCIS-looking acini in another area, immunohistochemically compatible with the diagnosis of invasive ductal carcinoma admixed with DCIS. Conclusion Knowing that invasive ductal carcinoma of the breast can present as DCIS-looking morphology, especially given the condition that the diagnosis of DCIS was rendered on the previous biopsy, will enhance awareness of pathologists to recognize sneaky DCIS-looking invasive ductal carcinoma in the extensive DCIS background. In turn, this will prevent misdiagnosis and under-treatment of patients with invasive ductal carcinoma of the breast.

Association of p53 expression in various molecular subtypes of invasive breast carcinoma NOS

Breast cancer is the second most common cause of mortality for women after heart disease. Consequently, stopping it is difficult at all times. Metastasis frequently occurs to distant organs such the liver, lung, and brain.All specimens from lumpectomies, simple and modified radical mastectomies, and trucut biopsies identified as Invasive Ductal Carcinoma Not Otherwise Specified at the Central Diagnostic Laboratory of the Pathology Department at tertiary care centre, were included in the study. Immunohistochemical markers were utilised and haematoxylin and eosin sections were examined.Association of p53 expression in various molecular subtypes of invasive breast carcinoma NOS. All lumpectomy specimens simple and modified radical mastectomy, trucut biopsies specimens diagnosed as invasive carcinoma breast not otherwise specified, submitted to the Department of Pathology, AJIMS, Mangalore for histopathological study are included in this study.Statistical analysis of the data was performed using SPSS 20.0.The continuous variables were presented as mean±SD. Categorical variables were presented in frequency and percentage. Categorical variables were analysed using Chi square test. A p value&amp;#60;0.05 was considered statistically significant.This study is on the expression of p53 in invasive ductal carcinoma of the breast type NOS and correlating it with different histological grades, tumour sizes, and molecular subtypes. This study showed expression of p53 is independent of molecular subtype.

Not All Therapy-Related Neoplasms are Myeloid: A Case Report of Rare B-ALL With t(5;14) Following Alkylating Agent Treatment

Abstract Introduction/Objective Most therapy-related hematologic neoplasms are myeloid (t-MN). Although not recognized as a distinct entity in the WHO classification of hematologic neoplasms, therapy-related acute lymphoblastic leukemia (t- ALL) cases have been previously reported. ALL incidence increases with any previous malignancy and is higher in those with previous treatment, supporting the concept of therapy-related ALL. B lymphoblastic leukemia/lymphoma (B- ALL) with t(5:14) is a rare subtype of the ALL (&amp;lt;1%) harboring a IL-3/IGH gene translocation. We present the first case of B-ALL with t(5;14) following treatment with alkylating agents for breast carcinoma. Methods/Case Report A 79-year-old female received docetaxel, carboplatin, trastuzumab, pertuzumab, Herceptin and radiotherapy for an invasive ductal breast carcinoma. Two years later, she developed progressive pancytopenia requiring a bone marrow biopsy. Results (if a Case Study enter NA) The bone marrow aspirate smears demonstrated B-ALL with 25% blasts, limited neutrophilic maturation, moderate erythroid dysplasia, and decreased megakaryocytes with occasional atypical forms. On the biopsy, atypical megakaryocytes and lymphoblasts were positive for TP53 immunohistochemical stain. On flow cytometry, blasts were positive for CD19, cCD79a, CD22, CD10, TdT, and HLA-DR and only 6% were positive for CD34. Next generation sequencing showed TP53 and NRAS mutation. Karyotyping revealed 46, XX, t (5;14) (q33; q13) and trisomy 21. Conclusion B-ALL with t (5;14); IGH/IL3 fusion has not been previously reported following treatment with alkylating agents. The presence of morphologic myeloid dysplasia developing after chemotherapy with alkylating agents support causality being therapy related rather than an independent process. The case expands the breadth of known therapy- related hematologic neoplasms and raises questions regarding the mechanisms of leukemogenesis.

Mammary Schistosomiasis: Malignancy Mimicker or More?

Abstract Introduction/Objective Schistosomiasis is a neglected tropical disease (NTD) which affects more than 200 million people worldwide, with approximately 85% of cases occurring in sub-Saharan Africa. It serves both as an important etiologic agent in the development of carcinomas of many organ systems, as well as a common incidental histological finding in various organs, including the prostate, lung, spine, and liver. Detection of Schistosoma ova in the breast is rare. Here, we present a case of schistosomiasis of the breast in a patient concurrently diagnosed with breast carcinoma of the contralateral breast. Methods/Case Report A 48-year-old Mozambican female presented with a right breast mass, with suspicious microcalcifications detected in the contralateral breast on mammography. Biopsy confirmed invasive ductal carcinoma of no special type (NST) in the right breast and identified Schistosoma ova in the left, notably lacking an associated inflammatory response. A Ziehl-Neelsen special histochemical stain was negative, favoring schistosoma Hematobium species. Results (if a Case Study enter NA) NA Conclusion Our case marks the first in English literature where schistosomiasis was identified in the context of contralateral breast carcinoma, posing the question as to whether there is an association between schistosomiasis and breast carcinoma in our patient. One possible theory suggests hyperestrogenism secondary to Schistosoma infection in the liver. Breast schistosomiasis presenting as microcalcifications poses a diagnostic challenge, as it may clinically and radiologically resemble malignant breast disease. Histopathological diagnosis is crucial to confirm the diagnosis and prevent unnecessary procedures. Contrary to other organ systems, our case highlighted that schistosomiasis in the breast may not be accompanied by any inflammatory response. Definitive conclusions regarding the exact species of schistosomiasis cannot be drawn histologically based solely on H&amp;E findings due to the plane of sectioning; therefore, performing a Ziehl-Neelsen stain is beneficial. As screening mammography increases in endemic areas, a high index of suspicion and further research is warranted.

Method for co-registration of high-resolution specimen PET-CT with histopathology to improve insight into radiotracer distributions

BackgroundAs the spatial resolution of positron emission tomography (PET) scanners improves, understanding of radiotracer distributions in tissues at high resolutions is important. Hence, we propose a method for co-registration of high-resolution ex vivo specimen PET images, combined with computed tomography (CT) images, and the corresponding specimen histopathology.MethodsWe applied our co-registration method to breast cancer (BCa) specimens of patients who were preoperatively injected with 0.8 MBq/kg [18\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$$^{18}$$\\end{document}F]fluorodeoxyglucose ([18F]FDG). The method has two components. First, we used an image acquisition scheme that minimises and tracks tissue deformation: (1) We acquired sub-millimetre (micro)-PET-CT images of ±2 mm-thick lamellas of the fresh specimens, enclosed in tissue cassettes. (2) We acquired micro-CT images of the same lamellas after formalin fixation to visualise tissue deformation. (3) We obtained 1 hematoxylin and eosin (H&E) stained histopathology section per lamella of which we captured a digital whole slide image (WSI). Second, we developed an automatic co-registration algorithm to improve the alignment between the micro-PET-CT images and WSIs, guided by the micro-CT of the fixated lamellas. To estimate the spatial co-registration error, we calculated the distance between corresponding microcalcifications in the micro-CTs and WSIs. The co-registered images allowed to study standardised uptake values (SUVs) of different breast tissues, as identified on the WSIs by a pathologist.ResultsWe imaged 22 BCa specimens, 13 cases of invasive carcinoma of no special type (NST), 6 of invasive lobular carcinoma (ILC), and 3 of ductal carcinoma in situ (DCIS). While the cassette framework minimised tissue deformation, the best alignment between the micro-PET-CT images and WSIs was achieved after deformable co-registration. We found an overall average co-registration error of 0.74 ± 0.17 mm between the micro-PET images and WSIs. (Pre)malignant tissue (including NST, ILC, and DCIS) generally showed higher SUVs than healthy tissue (including healthy glandular, connective, and adipose tissue). As expected, inflamed tissue and skin also showed high uptake.ConclusionsWe developed a method to co-register micro-PET-CT images of surgical specimens and WSIs with an accuracy comparable to the spatial resolution of the micro-PET images. While currently, we only applied this method to BCa specimens, we believe this method is applicable to a wide range of specimens and radiotracers, providing insight into distributions of (new) radiotracers in human malignancies at a sub-millimetre resolution.

PER3 promoter hypermethylation correlates to the progression of pan-cancer

BackgroundMalignant cells exhibit reduced period circadian regulator 3 (PER3) expression. However, the underlying mechanisms of variations in PER3 expression in cancers and the specific function of PER3 in tumor progression remain poorly understood.ResultsWe explored multiple public databases, conducted bioinformatics analyses, and performed in vitro and in vivo experiments for validation. We found PER3 expression was decreased in most types of cancers, and PER3 downregulation was associated with a poor prognosis in 8 types of cancer. PER3 promoter methylation levels were increased in 11 types of cancer. Promoter hypermethylation (CpG islands [CGIs] cg12258811 and cg14204433) correlated with decreased PER3 expression in six cancers (breast invasive carcinoma, colon adenocarcinoma, head and neck squamous cell carcinoma, kidney renal papillary cell carcinoma [KIRP], lung adenocarcinoma [LUAD], and uterine corpus endometrial carcinoma). CGI cg12258811 hypermethylation was associated with reduced survival time and advanced cancer stages. Moreover, the bisulfite pyrosequencing assay confirmed CGI cg12258811 hypermethylation and its negative correlation with PER3 expression. In vitro and in vivo experiments demonstrated that PER3 inhibited KIRP and LUAD progression. Decitabine enhanced PER3 expression and inhibited KIRP cell functions by reducing promoter (cg12258811) methylation level.ConclusionsOur findings advanced the mechanistic understanding of variations in PER3 expression in cancers and confirmed the tumor-associated function of PER3 hypermethylation and downregulation.

SPECC1 as a pan-cancer biomarker: unraveling its role in drug sensitivity and resistance mechanisms

Previous studies have shown a relationship between SPECC1 and the prognosis of breast cancer, indicating a potential function for SPECC1 in the initiation and progression of cancer. However, the role played by SPECC1 in other tumors is not yet known. Therefore, we used bioinformatics techniques to conduct a thorough investigation into the possible mechanism of SPECC1 in pan-cancer, analyzing data reported in the literature as well as databases such as GTEx and CCLE, cBioportal, TCGA, and UCSC XENA. Comparing the results with matching normal tissues, the majority of cancers, including pancreatic adenocarcinoma (PAAD) and breast invasive carcinoma (BRCA), exhibited higher levels of SPECC1, while hepatocellular carcinoma (HCC) showed lower expression levels. SPECC1 was also found to be genetically mutated in endometrial cancer, sarcoma, and esophageal cancer. The prognosis of lung adenocarcinoma, kidney papillary cell carcinoma, and breast cancer is highly correlated with dysregulation of SPECC1 expression. This work helps guide clinical therapy by highlighting the sensitivity of tumor-treating medicines and the prognostic importance of SPECC1 in various malignancies. KEGG pathway enrichment analysis revealed focused adhesion, collagen-containing extracellular matrix (collagen), and the primary enrichment domains for SPECC1-related genes. These findings were obtained through gene annotation (GO) examination of SPECC1 expression. Primary mediators of the cytokine-cytokine receptor interaction include PICOC1-associated genes, cell-substrate junction genes, and extracellular matrix containing collagen. PICOC1-associated genes primarily mediate the PI3K-AKT signaling pathway. Drug sensitivity assay showed that SPECC1 high-expressing cell lines were more sensitive to docetaxel, doxorubicin, etc. In conclusion, the current study shows how SPECC1 is expressed in different cancers and how this expression relates to the prognosis of the tumor. It also revealed the mutations and copy number variations of SPECC1 in various tumors and its potential involvement in cellular pathway regulatory networks and cytological processes. This study examines the relationship between immune genes, cellular infiltration, and immunological scores in the tumor microenvironment, which explain the severity of the disease. This study looks at the response of SPEC1 expression to anticancer therapy. Explains the prognostic significance and drug response of SPECC-1.

Pilomatrix-like breast carcinoma: A mammary analog of pilomatrix-like high-grade endometrioid carcinoma (PiMHEC).

To describe what is, to our knowledge, the first recognized case of a triple-negative breast carcinoma (TNBC) with a PiMHEC-like phenotype.Pilomatrix-like high-grade endometrioid carcinoma (PiMHEC) is a high-grade carcinoma with divergent differentiation resembling cutaneous pilomatrix carcinoma that was recently described in the endometrium and ovary. For reference, pertinent features of PiMHEC include (1)high-grade basaloid to squamoidmorphology withthe presence of ghost cells; (2) only focal p63 and/or p40 expression despite a squamoid appearance; (3) CTNNB1 mutation, accompanied by diffusely aberrant β-catenin expression and LEF1 and/or CDX2 expression; and (4) loss of site-specific markers (ie, PAX8, ER). Here we report the histologic, immunophenotypic and molecular genetic features ofa case of a triple-negative breast carcinoma (TNBC) with a PiMHEC-like phenotype. The tumor developed immediately adjacent to a HER2+, androgen receptor (AR)+, GATA3+ conventional grade 3 invasive ductal carcinoma (IDC) with only membranous β-catenin expression. The PiMHEC-like component had all of the above-noted morphologic and immunophenotypic features of endometrial PiMHEC but with loss of GATA3 and AR rather than PAX8 and ER.Molecular analysis performed on both tumor components demonstrated a shared TP53 point mutation and an exon 3 CTNNB1 mutation restricted to the PiMHEC-like component, implying a clonal relationship with secondary acquisition of CTNNB1. Following neoadjuvant chemotherapy, the HER2+ conventional component had completely resolved, but the PiMHEC-like component had very little response. This case demonstrates that a PiMHEC-like phenotype may be seen as a form of TNBC that can develop from conventional IDC, with loss of site-specific biomarkers, acquisition of CTNNB1 mutation, and resistance to conventional chemotherapy.

Statin Therapy Reduces Radiation-Induced Cardiotoxicity in Patients With Breast Cancer Receiving Adjuvant Radiotherapy.

To evaluate the efficacy of statin therapy in reducing major adverse cardiovascular event (MACE) risk among patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. A retrospective cohort study was conducted using data from the Taiwan Cancer Registry Database linked to the National Health Insurance Research Database. Patients diagnosed with left-sided early breast invasive ductal carcinoma between 2016 and 2019 were included. Propensity score matching was employed to compare MACE risk between statin users and nonusers. Cox regression models were used to estimate adjusted hazard ratios (aHRs) for MACE, considering cumulative defined daily doses and daily defined doses of statins. Among 1481 patients undergoing breast-conserving surgery and adjuvant whole breast radiotherapy, statin use significantly reduced MACE risk (aHR, 0.34 [95% CI, 0.25-0.44]). Hydrophilic statins, particularly rosuvastatin and pravastatin, demonstrated the greatest risk reduction. Higher cumulative defined daily doses and daily intensity doses of statins were associated with lower MACE risk, indicating a dose-response relationship. The 5-year cumulative incidence of MACE was significantly lower in statin users compared with nonusers (12.24% versus 31.70%). Statin therapy is associated with a reduced risk of MACE in patients with breast cancer undergoing breast-conserving surgery and adjuvant whole breast radiotherapy. Hydrophilic statins rosuvastatin and pravastatin exhibit the most pronounced cardioprotective effects. These findings suggest a potential role for statins in mitigating cardiovascular complications in this population and highlight the need for further research to optimize statin therapy in survivors of breast cancer undergoing radiotherapy.

Associations between BCL-2 expression and different histopathological prognostic factors in different molecular subtypes of invasive breast carcinoma of no special type.

Breast cancer is heterogeneous and the existing prognostic classifiers are limited in accuracy, leading to the unnecessary treatment of numerous women. B-cell lymphoma 2 (BCL-2), an anti-apoptotic protein, has been proposed as a marker of poor prognosis, associated with resistance to therapy in most tumor types expressing BCL-2. In breast cancer, however, BCL-2 expression has been reported to be a favorable prognostic factor. This study aimed to describe the association between BCL-2 and other well-known pathological prognostic markers among different molecular sub-types of invasive breast carcinoma of no special type (IBC; NST). BCL-2 expression, as well as that of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2), were immunohistochemically (IHC) evaluated and compared with other pathological factors, including tumor size, grade, tumor-infiltrating lymphocytes (TILs), lymph-vascular invasion (LVI), and lymph node (LNd) metastasis, in 128 breast cancer cases diagnosed with IBC; NST. Moreover, we analyzed the correlation between BCL-2 expression and relapse-free survival (RFS) in all patients over a two-year period. We found that BCL-2 expression had different pathological prognostic factor associations with different molecular subtypes of breast carcinoma. In the luminal A (i.e., hormonal receptor-positive and HER2-negative) and triple-negative subtypes, the expression of BCL-2 in tumor cells was significantly associated with tumor size, tumor grade, and TILs. BCL2-positive expression in luminal IBC; NST patients resulted in a significantly favorable two-year survival. BCL-2 expression in IBC; NST has different prognostic effects depending on the molecular subtype of the cancer. In cancers with a HER2-enriched phenotype, BCL-2 expression was a marker of poor prognosis, while in cancers with a hormone receptor-positive phenotype, BCL-2 expression had a better prognostic impact.