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Introduction: Within oncology research, there is a high effort for new approaches to prevent and treat cancer as a life-threatening disease. Specific plant species that adapt to harsh conditions may possess unique properties that may be utilized in the management of cancer. Hypothesis: Chokeberry fruit is rich in secondary metabolites with anti-cancer activities potentially useful in cancer prevention and treatment. Aims of the study and Methods: Based on mentioned hypothesis, the main goal of our study was to evaluate the antitumor effects of dietary administered Aronia melanocarpa L. fruit peels (in two concentrations of 0.3 and 3% [w/w]) in the therapeutic syngeneic 4T1 mouse adenocarcinoma model, the chemopreventive model of chemically induced mammary carcinogenesis in rats, a cell antioxidant assay, and robust in vitro analyses using MCF-7 and MDA-MB-231 cancer cells. Results: The dominant metabolites in the A. melanocarpa fruit peel extract tested were phenolic derivatives classified as anthocyanins and procyanidins. In a therapeutic model, aronia significantly reduced the volume of 4T1 tumors at both higher and lower doses. In the same tumors, we noted a significant dose-dependent decrease in the mitotic activity index compared to the control. In the chemopreventive model, the expression of Bax was significantly increased by aronia at both doses. Additionally, aronia decreased Bcl-2 and VEGF levels, increasing the Bax/Bcl-2 ratio compared to the control group. The cytoplasmic expression of caspase-3 was significantly enhanced when aronia was administered at a higher dosage, in contrast to both the control group and the aronia group treated with a lower dosage. Furthermore, the higher dosage of aronia exhibited a significant reduction in the expression of the tumor stem cell marker CD133 compared to the control group. In addition, the examination of aronia's epigenetic impact on tumor tissue through in vivo analyses revealed significant alterations in histone chemical modifications, specifically H3K4m3 and H3K9m3, miRNAs expression (miR155, miR210, and miR34a) and methylation status of tumor suppressor genes (PTEN and TIMP3). In vitro studies utilizing a methanolic extract of A.melanocarpa demonstrated significant anti-cancer properties in the MCF-7 and MDA-MB-231 cell lines. Various analyses, including Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential, were conducted in this regard. Additionally, the aronia extract enhanced the responsiveness to epirubicin in both cancer cell lines. Conclusion: This study is the first to analyze the antitumor effect of A. melanocarpa in selected models of experimental breast carcinoma in vivo and in vitro. The utilization of the antitumor effects of aronia in clinical practice is still minimal and requires precise and long-term clinical evaluations. Individualized cancer-type profiling and patient stratification are crucial for effectively implementing plant nutraceuticals within targeted anti-cancer strategies in clinical oncology. [ABSTRACT FROM AUTHOR]

Aims Methods Results Conclusion 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. [ABSTRACT FROM AUTHOR]

AbstractSix substituted α-cyano-indolylchalcones have been prepared and their structures were verified by various spectral analysis tools. Compared with the standard drug 5-Fluorouracil) 5-FU(, the anticancer activity against prostate cancer (PC3) and breast cancer cell line (MCF7) was determined using the cytotoxic MTT assay. Also, the cytotoxic effect against normal melanocytes (HFB4) was studied to detect the selectivity of the compounds. Among the series, compound 3e was the most active and selective one toward MCF7 (IC50= 0.18 µmole/mL, SI= 7.6). In silico studies were performed to demonstrate the inhibitory effect of compound 3e on EGFRK, CDK2, and MDM2 domains. Different molecular techniques were performed to know the efficacy of the novel 3e on apoptotic death of breast carcinoma cells. [ABSTRACT FROM AUTHOR]

Regenerative AI is transforming breast cancer diagnosis and treatment through enhanced imaging analysis, personalized medicine, drug discovery, and remote patient monitoring. AI algorithms can detect subtle patterns in mammograms and other imaging modalities with high accuracy, potentially leading to earlier diagnoses. In treatment planning, AI integrates patient-specific data to predict individual responses and optimize therapies. For drug discovery, generative AI models rapidly design and screen novel molecules targeting breast cancer pathways. Remote monitoring tools powered by AI provide real-time insights to guide care. Examples include Google's LYNA for analyzing pathology slides, Kheiron's Mia for mammogram interpretation, and Tempus's platform for integrating clinical and genomic data. While promising, challenges remain, including limited high-quality training data, integration into clinical workflows, interpretability of AI decisions, and regulatory/ethical concerns. Strategies to address these include collaborative data-sharing initiatives, user-centered design, explainable AI techniques, and robust oversight frameworks. In developing countries, AI tools like MammoAssist and Niramai's thermal imaging systemare improving access to screening. Overall, regenerative AI offers significant potential to enhance breast cancer care, but judicious implementation with awareness of limitations is crucial. Coordinated efforts across the healthcare ecosystem are needed to fully realize AI's benefits while addressing challenges. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is a leading cause of cancer-related mortality in women, with a rising incidence globally. Neoadjuvant chemotherapy(NACT) is a standard treatment approach for operable advanced loco-regional breast cancer, aiming to achieve tumor shrinkage, downstaging, and improved surgical outcomes. GATA3 expression has been identified as a significant marker for tumor differentiation, estrogen receptor status, and clinical outcomes in breast cancer. Objectives: To investigate the expression of GATA3 in post-NACT breast carcinoma cases and its utility in confirming histopathological diagnosis of partial and complete response, thereby guiding treatment strategies and predicting patient outcomes. Methods: A cross-sectional study of 60 breast carcinoma cases treated with NACT was conducted at Mysore Medical College and Research Institute. GATA3 expression was evaluated using immunohistochemistry, and its correlation with histopathological response to chemotherapy was assessed. Results: Among 60 cases, GATA3 was expressed in 87% of cases, with 91% of partial responders and 73% of complete responders showing immunopositivity. The study demonstrates GATA3 expression in post-NACT breast carcinoma cases, highlighting its potential as a predictive marker for treatment outcomes. Conclusion: GATA3 is a valuable marker for predicting response to NACT in breast cancer patients, supporting its utility in confirming histopathological diagnosis, guiding treatment strategies, and improving patient outcomes. [ABSTRACT FROM AUTHOR]

Objective: To find out the usefulness of bone scan in all stages of breast cancer. Study Design: Prospective Observation Study. Setting: Surgical Unit I & III Ghulam Muhammad Mahar Medical College Hospital, Sukkur. Period: October 2020 till September 2022. Methods: A total of 300 patients were selected who were newly diagnosed with breast cancer (Biopsy Proven). Data was collected for all these patients which included age, risk factors for breast cancer, findings on local examination, histopathology findings, stage of the cancer and result of the bone scan. Results: In our study, 78% patients were in 4th and 5th decade of life with mean age of 53.46±7.66 years. 'Age above 40' was the commonest risk factor for breast cancer followed by positive family history for breast cancer. Tumor size ranged from 2 to 13.2 cm with mean size of 6.06±1.92 cm. In our study, most common type of carcinoma was invasive ductal carcinoma (71.3%) followed by invasive lobar carcinoma (50%). Only 32 (10.67%) out of 300 patients had positive bone scan. Majority of the bone scan positive cases belonged to the Stage IIIB, IIIC and IV. Conclusion: It is concluded in our study that routine use of bone scan in cases of stage 1 and 2 breast cancer is not recommended; only stage 3A or advances cases should undergo bone scan. [ABSTRACT FROM AUTHOR]

Objective: Breast cancer is one of the most common cancers in women worldwide. This study aims is to investigate the burden of breast cancer in Iran and its relationship with the Human Development Index (HDI) during 2009 to 2019. Study design: The present study is an observational study in Iran during the years 2009 to 2019. Data related to the incidence, mortality, Years of Life with Disability (YLD), Years of Life Lost (YLL) and Disability-Adjusted Life-Years (DALY) of breast cancer in Iran were extracted from the Global Burden of Disease 2019 (GBD-2019) website. Correlation tests are used to check the relationship between these indicators and the human development index. Results: The highest incidence rate of breast cancer in 2019 is related to the provinces of Gilan (29 per 100,000) and Tehran (28.55 per 100,000) and the highest rate of death from breast cancer is related to the provinces of Gilan (10.71 per 100,000). and Semnan (9.97 in 100,000). The results showed that there is a positive and significant correlation between DALY (r = 0.626, P < 0.0001), YLL (r = 0.611, P < 0.0001) and, YLD (r = 0.773, P < 0.0001) breast cancer with HDI index. There is a positive and significant correlation between the incidence (r = 0.794, P < 0.0001) and mortality (r = 0.503, P = 0.003) of breast cancer with the HDI index. Conclusions: Considering that a positive correlation was observed between the incidence and burden of breast cancer and the human development index in the country, it is suggested to implement preventive measures such as public education programs to reduce the incidence and burden of breast cancer and the necessity of screening programs in areas with low human development index. It confirms the diagnosis of disease cases. [ABSTRACT FROM AUTHOR]

Transforming Growth Factor-β (TGF-β) can have both tumour-promoting and tumour-suppressing activity in breast cancer. Elucidating the key downstream mediators of pro-tumorigenic TGF-β signalling in this context could potentially give rise to new therapeutic opportunities and/or identify biomarkers for anti-TGF-β directed therapy. Here, we identify C1orf106 (also known as innate immunity activator INAVA) as a novel TGF-β target gene which is induced in a SMAD3-dependent but SMAD2/SMAD4-independent manner in human and murine cell lines. C1orf106 expression positively correlates with tumourigenic or metastatic potential in human and murine breast cancer cell line models, respectively, and is required for enhanced migration and invasion in response to TGF-β stimulation. C1orf106 promoted self-renewal and colony formation in vitro and may promote tumour-initiating frequency in vivo. High C1orf106 mRNA expression correlates with markers of aggressiveness and poor prognosis in human breast cancer. Taken together, our findings indicate that C1orf106 may act as a tumour promoter in breast cancer. [ABSTRACT FROM AUTHOR]

The phosphatase and tensin homolog (PTEN) gene acts as a tumor suppressor by regulating the PI3K/AKT pathway, crucial for cell growth and survival. Mutations or loss of PTEN are common in breast cancer, leading to uncontrolled cell growth. Understanding PTEN's role is vital for targeted therapies. 276 formalin-fixed paraffin-embedded (FFPE) breast cancer tissue blocks from 2012 to 2016 were analyzed for PTEN expression. Immunohistochemistry was performed to identify and assess tumor related clinicopathological characteristics as well as patient demographics. These were statistically matched with PTEN expression. Only 27.5% of the breast cancer tumors were PTEN-positive. PTEN expression correlated significantly with smaller tumor size, lower tumor grade, positive estrogen and progesterone receptor status, and favorable/unfavorable Ki67 status (p < 0.001). No significant association was found with vascular invasion, histologic type, age, HER2 status, staging, or lymph node involvement (p > 0.05). The study confirms PTEN's association with favorable clinicopathological features in breast cancer, supporting its role as a prognostic marker. These findings underscore the importance of PTEN in breast cancer biology and its potential as a therapeutic target. Furthermore these findings confirm the prevalence of advanced stage and aggressive breast cancer tumors in Ghana. [ABSTRACT FROM AUTHOR]

Background: While Heat Shock Protein 60 (HSP60) has been linked to human tumor, its clinic significance specifically in breast carcinoma is unclear. This investigation aims to retrospectively evaluate how HSP60 protein levels relate to survival outcomes among patients diagnosed with breast carcinoma. Methods: Evaluation of 206 patients diagnosed with breast carcinoma and receiving treatment from January 2012 to April 2018, carried out retrospectively. The protein level of HSP60 in breast carcinoma determined by immunohistochemical. Results: The study provided evidence of a distinct upregulation of HSP60 expression in breast carcinoma tumor samples in contrast to adjacent normal tissue samples. Additionally, heightened HSP60 expression was linked to advanced T stage (P = 0.046), N stage (P = 0.034), tumor metastasis (P = 0.016), pathological grading (P = 0.012), and adjuvant therapy utilization (P = 0.004). Moreover, elevated levels of HSP60 proteins exhibited a significant inverse correlation with overall survival (OS) [hazard ratio (HR) 1.598, P = 0.018] and progression-free survival (PFS) (HR 1.600, P = 0.017) among breast carcinoma patients in univariate analyses. The results of multivariate analyses highlighted HSP60 may serve as an independent predictor for both OS and PFS in breast carcinoma patients (HR 1.525, P = 0.034; HR 1.528, P = 0.033, respectively). Conclusion: The involvement of HSP60 in breast carcinoma progression suggests its potential clinical relevance in treatment target validation and prognostic assessment of the disease. [ABSTRACT FROM AUTHOR]

BACKGROUND Breast carcinoma is a heterogeneous disease characterized by distinct molecular subtypes that influence treatment strategies and patient outcomes. This study explores the significance of immunohistochemical (IHC) profiling in breast carcinoma, focusing on key biomarkers: estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2/Neu). OBJECTIVE To find the correlation of ER, PR and Her2/neu IHC markers with clinical features, tumour size, lymph node involvement and histopathological grade. METHODS A three year prospective observational cross sectional study was conducted in the Department of Pathology, in integration with Department of General Surgery and Radiotherapy at Rangaraya Medical College, Kakinada, Andhra Pradesh, India. A total of 55 cases of breast carcinoma were included in the study. The histopathological grading of the breast carcinoma was done according to the Nottingham modification of the Bloom Richardson grading system. All the cases underwent immunohistochemistry for ER, PR and Her2neu expression. Correlation of ER, PR and Her2neu with various prognostic factors was done. RESULTS The study included a total of 55 cases, out of which 22/55 (40%) were below 40yrs and 33/55 (60%) were above 40yrs. 60% of the tumors were in the size range of 2-5 cm (T2). 34.5% of the tumors belong to N2 category and 58.2% of the tumors were of high grade. 43.6% of the patients fall under Stage IIIA group. 78.2%) were of Invasive Ductal Carcinoma of No Special Type (NST). About 51% of the patients were ER/PR negative. Half of the patients (51%) were Her2/neu negative (Grade I (0/1+)), 25.5% were Her2/neu positive (Grade III) and 23,6 % were unequivocal. CONCLUSION Our study contributes to the body of evidence regarding histological grading and receptor expression in breast cancer within Asian populations. The observed lower rates of ER and PR positivity, alongside the relatively high prevalence of Grade III tumors, highlight the need for ongoing research to understand the factors influencing these trends and to optimize treatment strategies tailored to specific patient demographics. [ABSTRACT FROM AUTHOR]

Aims: Radial sclerosing lesions (RSLs) are benign breast lesions composed of glandular and epithelial proliferations with stellate architecture and fibro‐elastotic stroma, which can mimic invasive carcinoma on imaging. Surgical management following a core biopsy diagnosis of RSLs remains controversial. Methods and results: We retrospectively identified core biopsies with RSLs without atypia who underwent subsequent surgical excision between 2015 and 2021. All core biopsy slides were reviewed to confirm the diagnosis. Imaging was reviewed to determine radiological–pathological concordance. An upgrade was defined as invasive carcinoma or ductal carcinoma in situ (DCIS) in the excision. The final cohort consisted of 130 core biopsies from 124 women (median age = 52 years, range = 27–76). The imaging modality was mammogram in 52 (40%) cases, MRI in 52 (40%) and ultrasound in 26 (20%). One hundred and seven (82%) core biopsies were vacuum‐assisted and 23 (18%) were ultrasound‐guided without vacuum assistance. The median lesion size on imaging was 9 mm (range = 2–41). Overall, two (1%) cases were upgraded at excision, including one microinvasive lobular carcinoma and one 2 mm focus of invasive mammary carcinoma with associated DCIS. In both cases, the upgraded foci of carcinoma were not closely associated with the biopsy site and were considered incidental upgrades. Conclusions: This study adds to the body of literature supporting observation, rather than routine excision of radial sclerosing lesions without atypia. [ABSTRACT FROM AUTHOR]

Abstract The phosphatase and tensin homolog (PTEN) gene acts as a tumor suppressor by regulating the PI3K/AKT pathway, crucial for cell growth and survival. Mutations or loss of PTEN are common in breast cancer, leading to uncontrolled cell growth. Understanding PTEN’s role is vital for targeted therapies. 276 formalin-fixed paraffin-embedded (FFPE) breast cancer tissue blocks from 2012 to 2016 were analyzed for PTEN expression. Immunohistochemistry was performed to identify and assess tumor related clinicopathological characteristics as well as patient demographics. These were statistically matched with PTEN expression. Only 27.5% of the breast cancer tumors were PTEN-positive. PTEN expression correlated significantly with smaller tumor size, lower tumor grade, positive estrogen and progesterone receptor status, and favorable/unfavorable Ki67 status (p 0.05). The study confirms PTEN's association with favorable clinicopathological features in breast cancer, supporting its role as a prognostic marker. These findings underscore the importance of PTEN in breast cancer biology and its potential as a therapeutic target. Furthermore these findings confirm the prevalence of advanced stage and aggressive breast cancer tumors in Ghana.

Abstract Objective Breast cancer is one of the most common cancers in women worldwide. This study aims is to investigate the burden of breast cancer in Iran and its relationship with the Human Development Index (HDI) during 2009 to 2019. Study design The present study is an observational study in Iran during the years 2009 to 2019. Data related to the incidence, mortality, Years of Life with Disability (YLD), Years of Life Lost (YLL) and Disability-Adjusted Life-Years (DALY) of breast cancer in Iran were extracted from the Global Burden of Disease 2019 (GBD-2019) website. Correlation tests are used to check the relationship between these indicators and the human development index. Results The highest incidence rate of breast cancer in 2019 is related to the provinces of Gilan (29 per 100,000) and Tehran (28.55 per 100,000) and the highest rate of death from breast cancer is related to the provinces of Gilan (10.71 per 100,000). and Semnan (9.97 in 100,000). The results showed that there is a positive and significant correlation between DALY (r = 0.626, P

Male breast cancer is an uncommon condition, accounting for less than 1% of all breast carcinomas and under 1.5% of all malignant tumors in men. Skin lesions can often be the initial reason for consultation. At this advanced stage, diagnosis is typically delayed, leading to a poor prognosis. Herein, we report the case of a 66-year-old man who presented with a dermo-epidermal axillary mass, indicative of cutaneous metastasis from an invasive ductal carcinoma.

Objective(s): Breast neoplasm is a malignancy that can have a poor prognosis. The PI3K/AKT signaling pathway is frequently activated in various tumor types, including breast cancer, leading to alterations in the tumor microenvironment and radioresistance. Selective inhibition of PI3Kca (p110a) has been considered an alternative approach to overcome radioresistance, owing to concerns surrounding the excessive side effects of pan-PI3K inhibitors tested in clinical trials. This investigation aimed to evaluate the efficacy of co-administering PI3Kca knocking out with radiation therapy in mitigating radioresistance and suppressing tumor growth in the MDA-MB-231 cell line. Materials and Methods: The present investigation utilized the CRISPR/Cas9 technique to induce a knockout of the PI3Kca gene. Subsequently, after 24 hr of transfection, gene expression, cell proliferation, apoptosis rate, and angiogenesis were assessed. Results: We demonstrated that knocking out PI3Kca, in combination with radiation, increased apoptosis, reduced the expression of PI3Kca and AKT1 genes, and decreased cell proliferation. The CAM assay analysis has demonstrated that knocking out the PI3Kca gene and radiotherapy substantially reduced the total vessel network length and the number of junctions. Conclusion: The findings of our investigation indicate that the integration of radiation therapy with PI3Kca yielded enhanced radiosensitivity, leading to a marked retardation of tumor progression and an increased survival rate. [ABSTRACT FROM AUTHOR]

Posterior reversible encephalopathy syndrome (PRES) in breast carcinoma is a rare disease in clinical practice that is often misdiagnosed and ignored. This study reported a case of a patient admitted to our hospital and discussed the clinical, imaging, and pathogenesis properties of the disease. We retrospectively analyzed the clinical data of this patient and reviewed the relevant literature. Imaging was used to diagnose PRES based on clinical findings, and clinical symptoms improved after discontinuation of the relevant drugs.

Simple Summary: Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a monomeric glycoprotein most commonly associated with myeloid cell differentiation and the stimulation of inflammatory processes. Several studies have shown that cancer cells express GM-CSF; however, the mechanism and effect of this expression has not been fully resolved. Some studies suggest the levels of GM-CSF expression and secretion determine its role in tumor suppression or growth. We believe and begin to outline in the current study, that breast cancer cell expression and secretion of GM-CSF is an operative pro-survival tool utilized to induce fibroblasts, macrophages, and other myeloid-derived cells to produce pro-inflammatory cytokines and growth factors such as interleukins 6 and 8. These pro-survival factors drive tumor progression. Understanding these paracrine signaling networks in the tumor microenvironment will facilitate the development of targeted and efficient therapies to halt tumor progression. This study evaluated the paracrine signaling between breast carcinoma-associated fibroblasts (CAFs) and breast cancer (BCa) cells. Resolving cell–cell communication in the BCa tumor microenvironment (TME) will aid the development of new therapeutics. Here, we utilized our patented TAME (tissue architecture and microenvironment engineering) 3D culture microphysiological system, which is a suitable pathomimetic avatar for the study of the BCa TME. We cultured in 3D BCa cells and CAFs either alone or together in cocultures and found that when cocultured, CAFs enhanced the invasive characteristics of tumor cells, as shown by increased proliferation and spread of tumor cells into the surrounding matrix. Secretome analysis from 3D cultures revealed a relatively high secretion of IL-6 by CAFs. A marked increase in the secretion of granulocyte macrophage-colony stimulating factor (GM-CSF) when carcinoma cells and CAFs were in coculture was also observed. We theorized that the CAF-secreted IL-6 functions in a paracrine manner to induce GM-CSF expression and secretion from carcinoma cells. This was confirmed by evaluating the activation of STAT3 and gene expression of GM-CSF in carcinoma cells exposed to CAF-conditioned media (CAF-CM). In addition, the treatment of CAFs with BCa cell-CM yielded a brief upregulation of GM-CSF followed by a marked decrease, indicating a tightly regulated control of GM-CSF in CAFs. Secretion of IL-6 from CAFs drives the activation of STAT3 in BCa cells, which in turn drives the expression and secretion of GM-CSF. As a result, CAFs exposed to BCa cell-secreted GM-CSF upregulate inflammation-associated genes such as IL-6, IL-6R and IL-8, thereby forming a positive feedback loop. We propose that the tight regulation of GM-CSF in CAFs may be a novel regulatory pathway to target for disrupting the CAF:BCa cell symbiotic relationship. These data provide yet another piece of the cell–cell communication network governing the BCa TME. [ABSTRACT FROM AUTHOR]

Objective To observe the inhibitory effect of intragastric administration of Yishen Qutong granules (YSQTG) on breast cancer bone metastasis in mice, and to explore its possible mechanism of action. Methods Eightyfour female BABL/c mice were randomly divided into seven groups, with 12 mice in each group. Mice in the model group, ML-385 group, and low, medium, and high dose groups were all implanted with the bone-affine breast cancer high meta‑ static cell line 4T1. 2 cell suspension in the left tibia to create the breast cancer bone metastasis models. On the first day af‑ ter implantation, mice in the low, medium, and high dose groups were given YSQTG aqueous solution at 2. 275,4. 55, and 9. 1 g/kg, respectively, by gavage, followed by intraperitoneal injection of normal saline. Mice in the ML-385 group were given distilled water by gavage and intraperitoneal injection of nuclear factor E2-related factor 2(Nrf2) inhibitor ML385(20 mg/kg) dissolved in normal saline. Mice in the blank group, sham operation group, and model group were given equal volume of distilled water by gavage and intraperitoneal injection of normal saline. The dose was administered once a day, for 28 consecutive days. The body weight of mice in each group was recorded from 1 to 4 weeks after treatment, and after 28 days of continuous administration, the mice were sacrificed and the tumor mass was weighed. The left tibia of mice in each group was harvested, and after micro-CT scanning, the bone volume fraction (BV/TV), trabecular thickness (Tb. Th), trabecular number (Tb. N), and trabecular space (Tb. Sp) of cancellous and cortical bone were analyzed. Histopath‑ ological conditions were observed after HE staining, and the number of osteoclasts and the length of contact surface between osteoclasts and bone tissues were analyzed after tartrate acid phosphatase staining. Immunohistochemical method was used to detect the positive expression rates of Kelch-like ECH-associated protein 1(Keap1) and Nrf2 proteins. Results During the 1 to 4 weeks of treatment, the body weight of mice in each group showed a continuous upward trend. At the 4th week of treatment, the body weight of the model group was lower than that of the other groups (all P<0. 05). Compared with the model group, the tumor mass decreased, but only significant difference was found between the ML-385 group and the medi‑ um dose group (P<0. 05). The histopathological examination of the left tibia in the blank group and the sham operation group was normal. In the model group, significant bone metastasis was observed on the left tibia, with the main cellular components of osteogenic bone metastasis. In the ML-385 group and the medium dose group, the formation of bone metas‑ tasis and the degree of bone destruction on the left tibia were less severe in comparison with those of the model group, while the low and high dose groups were similar to the model group. Compared with the blank group and the sham operation group, the BV/TV, Tb. N, Tb. Sp, Tb. Th, osteoclast numbers, osteoclast contact surface length, and the positive ex‑ pression rates of Keap1 and Nrf2 in the left tibia tissues of the model group increased (all P<0. 05)； compared with the model group, the BV/TV, Tb. N, Tb. Sp, Tb. Th, and the positive expression rates of Keap1 and Nrf2 in the left tibia tis‑ sues of the ML-385 group decreased, the Tb. N, Tb. Sp, and Tb. Th in the left tibia tissue of the medium dose group de‑ creased, the Tb. Th decreased in the low and high dose groups, and the numbers of osteoclasts, the length of osteoclast contact surfaces, and the positive expression rate of Nrf2 in the left tibia tissues decreased, while the positive expression rate of Keap1 increased in the low, medium, and high dose groups (all P<0. 05). Conclusions Intragastric administra‑ tion of YSQTG can inhibit the growth of bone metastatic tumors and bone destruction in mice with breast cancer, with the medium dose showing the best effect. The mechanism may be related to the regulation of the Keap1/Nrf2 signaling pathway and the reduction of oxidative stress. [ABSTRACT FROM AUTHOR]

Purpose: The importance of a TP53 mutation has been demonstrated in several tumor types, including breast cancer (BC). However, the accuracy of p53 protein expression as a predictor of gene mutation has not been well studied in BC. Therefore, we evaluated p53 protein expression associated with TP53 mutations in breast cancers from 64 patients. Methods: TP53 mutation was examined using next-generation sequencing (NGS). p53 protein expression was examined using immunohistochemistry (IHC). Results: Among the 64 BCs, 55% demonstrated abnormal expression patterns including 27% overexpression, 22% null, 6% equivocal with 45% having a wild-type pattern. A TP53 mutation was present in 53% (34/64) of tumors including 30% (19/64) demonstrating a missense mutation, 11% (7/64) with a frameshift mutation, 11% (7/64) with a nonsense mutation, and 3% (1/64) with a splice site mutation. Abnormal expression of p53 protein was present in 33 of 34 (97%) tumors carrying a TP53 mutation; conversely, a wild-type pattern was present in 28 of 30 (93%) tumors without a detectable mutation (p < 0.0001). The majority of BCs with a p53 IHC overexpression pattern (15/17, 88%) contained a missense TP53 mutation; while the majority of BCs with a null pattern (12/14, 86%) contained a truncating mutation (p < 0.0001). The BCs with a null pattern are associated with a high Nottingham histological grade and a triple-negative phenotype when compared to those demonstrating overexpression (p < 0.05). Conclusion: These findings suggest that p53 IHC can be a potential surrogate for TP53 mutations in BC. Different p53 expression patterns may correlate with specific TP53 genetic mutations in BC. [ABSTRACT FROM AUTHOR]

Introduction Methods Results Conclusion Male breast cancer is rare and accounts for less than 1% of all breast cancer cases worldwide.This retrospective cohort study included all patients of invasive male breast cancer treated with curative intent by a trimodality approach via a multidisciplinary team at an academic university hospital in India between 2009 and 2023. Records were identified from a prospectively maintained database. Clinicopathological parameters, treatment details and survival were recorded and analysed.Thirty‐four patients were included. The median (IQR) age was 55(44–63) years. Most patients were overall stage III (74%) and node positive (79%) with Scarff‐Bloom‐Richardson grade II (50%). Twenty‐five patients (73%) were oestrogen receptor (ER) positive. Lymphovascular space invasion (LVSI) and perineural invasion (PNI) were present in 62% and 21% of patients, respectively. The most common chemotherapy timing was adjuvant (53%) followed by neoadjuvant (41%), and the most commonly used regimen consisted of a combination of doxorubicin‐cyclophosphamide followed by a taxane (53%). Most (85%) patients underwent a mastectomy, five patients underwent breast conservation. All patients received radiotherapy to a dose of 42.6 Gy in 16 fractions, followed by a tumour bed boost for those undergoing breast conservation. At a median follow‐up of 70 months (range 10–159 months), the five and ten‐year overall survival was 91% and 58%, and the five‐year disease‐free survival (DFS) was 67%. The median DFS was 72 months. On univariate analysis, the tumour sub‐type (Luminal versus TNBC) significantly predicted DFS (P = 0.03 log‐rank).Breast cancer in males has a high incidence of node positivity, ER positivity and LVSI. Even with advanced stages at presentation, trimodality therapy in a multidisciplinary setting offers good long‐term outcomes. [ABSTRACT FROM AUTHOR]

Cutaneous metastasis is rare but may indicate an advanced internal malignancy or a recurrence of a previously treated one and is usually associated with a poor prognosis. They may also pose a diagnostic problem as the clinical manifestations are variable and non‐specific, which could mimic other benign conditions. We report a case of a 48‐year‐old female who presented with a 4‐year history of erythematous papules and vesicles on the trunk mimicking lymphangioma circumscriptum. Skin biopsy and immunohistochemistry were consistent with cutaneous metastasis from breast carcinoma. Cutaneous metastasis presents in a variety of patterns. A high index of suspicion and a low threshold for skin biopsy are paramount to the early diagnosis and treatment. A histopathologic evaluation will help identify the origin of the cutaneous metastasis and can significantly affect the outcome of the treatment. [ABSTRACT FROM AUTHOR]

Despite advances in medical sciences, breast cancer remains a deadly disease globally, primarily affecting women. Fortunately, studies claim that breast cancer is treatable if diagnosed early. Late diagnoses have poor prognoses and can affect the patient's quality of life. Therefore, a significant research body is dedicated to establishing and identifying the disease at an initial stage. Deep learning (DL) techniques are garnering attention for aiding medical professionals in detecting this disease using histopathology (HP) image modality. The heterogeneous nature of this disease subtypes results in the imbalances of benign and malignant subtypes. From a DL point of view, this becomes an imbalanced problem deserving special care. Unfortunately, current DL‐based techniques do not fully address this issue and suffer from poor metrics and robustness. In this work, we present a DL‐based breast cancer automatic detection system (BCADS) using a novel architecture stochastic class‐attention net (SCAN). This technique performed better when combined with label smoothing and test time augmentation. This work outperforms the previously reported results for binary and multiclass on the BreaKHis dataset. Also, we validated our method on separate BACH and BCNB datasets to prove its effectiveness and clinical relevancy. We hope that the designed BCADS will help the treating doctor and pathologist in a meaningful way and thus help to reduce the impact of this deadly disease. [ABSTRACT FROM AUTHOR]

Background: Breast cancer is the commonest malignancy among women globally. The aims of our study were to evaluate the diversity and epidemiology of breast cancer on patients admitted in Burdwan Medical College and Hospital for elective mastectomy for carcinoma breast. Materials and methods: All the patients suspected of breast malignancy were clinically evaluated with age>25 years (as breast cancer is common beyond this age) and were included in the study. All the mastectomy specimens sent to Department of Pathology, Burdwan Medical College & Hospital, for histopathological examination were considered in the study. Results: The range of patients presenting with breast cancer was between 30-65 years, while 29 patients were below the age of 50 years and 17 above it. Maximum nos of case were between 40-49 years. Among the histopathological types of the tumours, IDC NOS constituted 40 cases (86.9%), invasive lobular carcinoma constituted 2 cases (4.3%), medullary carcinoma 2 cases (4.3%), invasive papillary carcinoma and mucinous carcinoma 1 case each (2.2%). T1 (size < 2 cm) was observed in 2 cases (4.3%), T2 (size 2-5 cm) was observed in 10 cases (21.7%). T3 (size > 5cm) was seen in 5 cases (10.9%), T4 (tumour of any size with fixity to the chest wall or skin) was observed in 29 cases (63%). Grading of 42 cases was done and only 1 case (2.4%) of Grade I was seen, whereas 25 cases (59.5%) belonged to Grade II, and 16 cases (38.1%) to Grade III. Out of the 46 cases, Stage IIA constituted 8 cases (17.4%), Stage IIB 3 cases (6.5%), Stage IIIA 6 cases (13%), and Stage IIIB 29 cases (63%). Conclusion: The government needs to urgently strengthen and augment the existing facilities including screening, which is inadequate at present to handle the current breast cancer load in India, especially Eastern India. [ABSTRACT FROM AUTHOR]

Objective To investigate the diagnostic value of serum microRNA-22-3p (miR-22-3p) and cysteinerich protein 61（CYR61) levels in breast cancer and their prediction on recurrence and metastasis. Methods Totally 110 patients with breast cancer (observation group) receiving improved radical surgery were selected and followed up for 1 year； there were 25 patients with recurrence and metastasis and 85 patients without recurrence and metastasis. Mean‑ while, 110 patients with benign breast diseases (control group) were selected during the same period. Peripheral venous blood of all subjects was collected and serum was retained by centrifugation. Serum miR-22-3p was detected by RT-qPCR and serum CYR61 was detected by ELISA. Serum miR-22-3p and CYR61 levels were compared between the observation group and the control group, and between patients with recurrence and metastasis and those without recurrence and metastasis. The value of serum miR-22-3p and CYR61 levels in diagnosis of breast cancer and their predictive value on recur‑ rence and metastasis were analyzed by receiver operating characteristic (ROC) curve. Pearson correlation analysis was used to analyze the relationship between serum miR-22-3p level and serum CYR61 level in breast cancer patients. Results The levels of miR-22-3p in the observation group and control group were 0. 65 ± 0. 14 and 1. 02 ± 0. 23, respec‑ tively, and the levels of CYR61 in the serum were (128. 63 ± 25. 72) and (96. 45 ± 17. 31）µg/L, respectively. The serum miR-22-3p level in the observation group was lower than that in the control group, and the serum CYR61 level was higher than that in the control group (t=14. 802 and 10. 886, respectively, both P<0. 01）. ROC curve analysis showed that the area under the curve (AUC) of serum miR-22-3p and CYR61 levels in the diagnosis of breast cancer alone and combined were 0. 917, 0. 857 and 0. 960, respectively. The AUC of serum miR-22-3p combined with CYR61 levels in the diagnosis of breast cancer was higher than that of either alone (Z=3. 321 and 4. 512, respectively, both P<0. 05）. Serum miR-22-3p levels were 0. 45 ± 0. 12 and 0. 71 ± 0. 24, and serum CYR61 levels were (162. 94 ± 29. 78) and (118. 53 ± 25. 49）µg/L, respectively, in patients with breast cancer recurrence and metastasis and those without metastasis. The serum miR-22-3p level in patients with breast cancer recurrence and metastasis was lower than that in patients without recurrence and metas‑ tasis, and the serum CYR61 level was higher than that in patients without recurrence and metastasis (t=5. 216 and 7. 365, respectively； both P<0. 01）. The AUC of serum miR-22-3p and CYR61 levels alone and combined in the diagnosis of breast cancer recurrence and metastasis were 0. 838, 0. 831 and 0. 932, respectively. The AUC of serum miR-22-3p and CYR61 levels combined in the diagnosis of breast cancer recurrence and metastasis was higher than that of either alone (Z= 2. 493 and 2. 196, respectively； both P<0. 05）. Pearson correlation analysis showed that serum miR-22-3p level was nega‑ tively correlated with serum CYR61 level in breast cancer patients (r=–0. 643, P<0. 05）. Conclusion Both the levels of serum miR-22-3p and CYR61 have certain value for the diagnosis of breast cancer and for the prediction on recurrence and metastasis, and the diagnostic value of them combined is higher [ABSTRACT FROM AUTHOR]

Concerns surrounding breast cancer have been increasing, as it leads to the current global cancer incidence and causes a high mortality rate in women. This study investigated the physiological effects of common dietary polyphenols that might prevent breast cancer progression. Quercetin, kaempferol, and rosmarinic acid were selected to explore their potential bioactivities. Each polyphenol was formulated into a microemulsion to improve its bioactivity and bioavailability. In vitro antioxidant and cytotoxicity activities of the selected polyphenols and their microemulsion forms were further investigated. The optimized microemulsion carrier with 1% oleic acid, 3% ethanol, 10% polysorbate 20, and 86% ultrapure water achieved more than 90% polyphenol encapsulation efficiency. The microemulsion was stable for more than 30 days when encapsulating polyphenol in the fluctuating temperature treatment. In vitro studies suggested that rosmarinic acid-loaded microemulsion had the best antioxidant activity compared with other polyphenol-loaded microemulsions (PL-MEs). Blank microemulsion and all PL-MEs significantly inhibited the proliferation of both hormone-dependent (T47D) and hormone-independent (MDA-MB-231) breast cancer cells. More studies are warranted to confirm the contribution of the microemulsion carrier components to the polyphenols' improved antioxidant activity and high toxicity of PL-MEs on breast cancer cells. [ABSTRACT FROM AUTHOR]

Background: Breast carcinoma (BRCA) is a life-threatening malignancy in women and shows a poor prognosis. Cuproptosis is a novel mode of cell death but its relationship with BRCA is unclear. This study attempted to develop a cuproptosis-relevant prognostic gene signature for BRCA. Methods: Cuproptosis-relevant subtypes of BRCA were obtained by consensus clustering. Differential expression analysis was implemented using the 'limma' package. Univariate Cox and multivariate Cox analyses were performed to determine a cuproptosis-relevant prognostic gene signature. The signature was constructed and validated in distinct datasets. Gene set variation analysis (GSVA) and gene set enrichment analysis (GSEA) were also conducted using the prognostic signature to uncover the underlying molecular mechanisms. ESTIMATE and CIBERSORT algorithms were applied to probe the linkage between the gene signature and tumor microenvironment (TME). Immunotherapy responsiveness was assessed using the Tumor Immune Dysfunction and Exclusion (TIDE) web tool. Real-time quantitative PCR (RT-qPCR) was performed to detect the expressions of cuproptosis-relevant prognostic genes in breast cancer cell lines. Results: Thirty-eight cuproptosis-associated differentially expressed genes (DEGs) in BRCA were mined by consensus clustering and differential expression analysis. Based on univariate Cox and multivariate Cox analyses, six cuproptosis-relevant prognostic genes, namely SAA1, KRT17, VAV3, IGHG1, TFF1, and CLEC3A, were mined to establish a corresponding signature. The signature was validated using external validation sets. GSVA and GSEA showed that multiple cell cycle-linked and immune-related pathways along with biological processes were associated with the signature. The results ESTIMATE and CIBERSORT analyses revealed significantly different TMEs between the two Cusig score subgroups. Finally, RT-qPCR analysis of cell lines further confirmed the expressional trends of SAA1, KRT17, IGHG1, and CLEC3A. Conclusion: Taken together, we constructed a signature for projecting the overall survival of BRCA patients and our findings authenticated the cuproptosis-relevant prognostic genes, which are expected to provide a basis for developing prognostic molecular biomarkers and an in-depth understanding of the relationship between cuproptosis and BRCA. [ABSTRACT FROM AUTHOR]

Background: Mammary carcinoma is the most frequently diagnosed form of carcinoma in women worldwide. The organometallic compounds showed a prospective anticancer activity. This research explored the anticancer efficacy of taxifolin ruthenium-p-cymene counter to breast cancer. Methods: The anticancer efficacy of the novel organometallic compound was investigated via various in vitro and in vivo techniques using breast cancer cell lines and breast cancer model of rat. Results: Target proteins were identified via pharmacophore analysis, which revealed a high binding affinity towards AhR, EGFR, and β-catenin. The compound induced apoptotic events and prevented cancer cell colony formation. Furthermore, decreased expression of AhR, EGFR, and N-cadherin inhibited cancer cell growth, migration, and proliferation. The compound provoked the cell cycle arrest at sub G0/G1 phase, S phase and G2/M phase and inaugurated the caspase-3 dependent apoptotic events. The in-vivo experimentation displayed the fruitful restoration of breast tissue since the complex treatment in DMBA persuaded breast carcinoma in rat. Moreover, the upstream of p53 and caspase-3 expression along with substantially downstream of vimentin, β-catenin, m-TOR and Akt expression. Conclusions: In conclusion, the compound repressed the cancerous cellular viability, migration, and EMT via modulating the AhR/EGFR/ PI3K transduction pathway and the expression of EMT biomarkers such as N-cadherin, E-cadherin, thus eventually revoked the EMT facilitated metastasis of malignant cells.

IntroductionWithin oncology research, there is a high effort for new approaches to prevent and treat cancer as a life-threatening disease. Specific plant species that adapt to harsh conditions may possess unique properties that may be utilized in the management of cancer.HypothesisChokeberry fruit is rich in secondary metabolites with anti-cancer activities potentially useful in cancer prevention and treatment.Aims of the study and MethodsBased on mentioned hypothesis, the main goal of our study was to evaluate the antitumor effects of dietary administered Aronia melanocarpa L. fruit peels (in two concentrations of 0.3 and 3% [w/w]) in the therapeutic syngeneic 4T1 mouse adenocarcinoma model, the chemopreventive model of chemically induced mammary carcinogenesis in rats, a cell antioxidant assay, and robust in vitro analyses using MCF-7 and MDA-MB-231 cancer cells.ResultsThe dominant metabolites in the A. melanocarpa fruit peel extract tested were phenolic derivatives classified as anthocyanins and procyanidins. In a therapeutic model, aronia significantly reduced the volume of 4T1 tumors at both higher and lower doses. In the same tumors, we noted a significant dose-dependent decrease in the mitotic activity index compared to the control. In the chemopreventive model, the expression of Bax was significantly increased by aronia at both doses. Additionally, aronia decreased Bcl-2 and VEGF levels, increasing the Bax/Bcl-2 ratio compared to the control group. The cytoplasmic expression of caspase-3 was significantly enhanced when aronia was administered at a higher dosage, in contrast to both the control group and the aronia group treated with a lower dosage. Furthermore, the higher dosage of aronia exhibited a significant reduction in the expression of the tumor stem cell marker CD133 compared to the control group. In addition, the examination of aronia`s epigenetic impact on tumor tissue through in vivo analyses revealed significant alterations in histone chemical modifications, specifically H3K4m3 and H3K9m3, miRNAs expression (miR155, miR210, and miR34a) and methylation status of tumor suppressor genes (PTEN and TIMP3). In vitro studies utilizing a methanolic extract of A.melanocarpa demonstrated significant anti-cancer properties in the MCF-7 and MDA-MB-231 cell lines. Various analyses, including Resazurin, cell cycle, annexin V/PI, caspase-3/7, Bcl-2, PARP, and mitochondrial membrane potential, were conducted in this regard. Additionally, the aronia extract enhanced the responsiveness to epirubicin in both cancer cell lines.ConclusionThis study is the first to analyze the antitumor effect of A. melanocarpa in selected models of experimental breast carcinoma in vivo and in vitro. The utilization of the antitumor effects of aronia in clinical practice is still minimal and requires precise and long-term clinical evaluations. Individualized cancer-type profiling and patient stratification are crucial for effectively implementing plant nutraceuticals within targeted anti-cancer strategies in clinical oncology.

Regenerative AI is transforming breast cancer diagnosis and treatment through enhanced imaging analysis, personalized medicine, drug discovery, and remote patient monitoring. AI algorithms can detect subtle patterns in mammograms and other imaging modalities with high accuracy, potentially leading to earlier diagnoses. In treatment planning, AI integrates patient-specific data to predict individual responses and optimize therapies. For drug discovery, generative AI models rapidly design and screen novel molecules targeting breast cancer pathways. Remote monitoring tools powered by AI provide real-time insights to guide care. Examples include Google's LYNA for analyzing pathology slides, Kheiron's Mia for mammogram interpretation, and Tempus's platform for integrating clinical and genomic data. While promising, challenges remain, including limited high-quality training data, integration into clinical workflows, interpretability of AI decisions, and regulatory/ethical concerns. Strategies to address these include collaborative data-sharing initiatives, user-centered design, explainable AI techniques, and robust oversight frameworks. In developing countries, AI tools like MammoAssist and Niramai's thermal imaging system are improving access to screening. Overall, regenerative AI offers significant potential to enhance breast cancer care, but judicious implementation with awareness of limitations is crucial. Coordinated efforts across the healthcare ecosystem are needed to fully realize AI's benefits while addressing challenges.

Gallium-68 (68 Ga)-fibroblast activation protein inhibitor (FAPI) positron emission tomography (PET) images the cancer-associated fibroblast that forms a vital component of the tumor microenvironment. It is known that 68 Ga-FAPI PET can aid in differentiating reactive lymph nodes from metastatic lymph nodes. 18 F-fluorodeoxyglucose (FDG) PET/computed tomography (CT) is still the most commonly used PET radiopharmaceutical in the evaluation of a wide range of malignancies including breast carcinoma. Reactive lymph nodes may also show FDG uptake which can hinder optimal assessment for metastatic involvement. We report an interesting case of invasive ductal carcinoma of the right breast with associated World Health Organization clinical stage I acquired immunodeficiency syndrome for which 18 F-FDG PET/CT and 68 Ga-FAPI PET/CT were done. [ABSTRACT FROM AUTHOR]

Introduction: Breast carcinoma is one of the most prevalent types of carcinoma and the leading cause of death among all carcinomas. Recently, vitamin D deficiency has been reported as a risk factor for breast carcinoma. Vitamin D, as an anticarcinoma agent, prevents cellular differentiation, stimulates cell death, reduces angiogenesis, tumour progression, and metastasis. Aim: To investigate the relationship between vitamin D deficiency and the risk of breast carcinoma. Materials and Methods: An observational study was conducted at the Armed Forces Medical College, Pune, Maharashtra, India, between November 2018 and October 2020. A total of 57 cases diagnosed with breast carcinoma and 57 healthy controls were analysed. Physical and reproductive health parameters were compared, along with vitamin D status using student’s t-test and Mann-Whitney U test. Logistic regression was used to assess the risk of breast carcinoma. Results: Out of 114 women, 57 were cases and 57 were controls with a mean age of 52 vs 48 years. The mean value of serum vitamin D levels was significantly lower (19.45 vs 27.91 ng/mL, p

Metastases to the nose and paranasal sinuses are unusual. These tumors are commonly seen in the 4th to 6th decades of life. The clinical presentation may be analogous to that of primary sino-nasal tumors. They usually present with common nasal and ocular symptoms due to which diagnosis may be missed and delayed. Hence, high level of suspicion is necessary for patients with known malignancies presenting with inconsistent or repeated nasal and ocular symptoms. Otorhinolaryngologists should be familiar with these metastases to paranasal sinuses from unusual primary elsewhere in the body, to evaluate and manage these tumors. Retrospective data was collected from the hospital records from 2020-2023. A total 14 cases of sino-nasal malignancies were identified. On further analysis three cases were found to be having distant metastases from primary sites such as kidney, breast and lymph nodes. We are reporting three metastatic malignancies. Each was systematically evaluated, confirming their origin as metastases from other primary sites. They were then managed appropriately.

Abstract Background Some studies have suggested that axillary lymph node dissection (ALND) can be avoided in women with cN0 breast cancer with 1–2 positive sentinel nodes (SLNs). However, these studies included only a few patients with invasive lobular carcinoma (ILC), so the validity of omitting ALDN in these patients remains controversial. This study compared the frequency of non-sentinel lymph nodes (non-SLNs) metastases in ILC and invasive ductal carcinoma (IDC). Materials Methods: Data relating to a total of 2583 patients with infiltrating breast carcinoma operated at our institution between 2012 and 2023 were retrospectively analyzed: 2242 (86.8%) with IDC and 341 (13.2%) with ILC. We compared the incidence of metastasis to SLNs and non-SLNs between the ILC and IDC cohorts and examined factors that influenced non-SLNs metastasis. Results: SLN biopsies were performed in 315 patients with ILC and 2018 patients with IDC. Metastases to the SLNs were found in 78/315 (24.8%) patients with ILC and in 460 (22.8%) patients with IDC (p = 0.31). The incidence of metastases to non-SLNs was significantly higher (p = 0.02) in ILC (52/78–66.7%) compared to IDC (207/460 − 45%). Multivariate analysis showed that ILC was the most influential predictive factor in predicting the presence of metastasis to non-SLNs. Conclusions: ILC cases have more non-SLNs metastases than IDC cases in SLN-positive patients. The ILC is essential for predicting non-SLN positivity in macro-metastases in the SLN. The option of omitting ALND in patients with ILC with 1–2 positive SLNs still requires further investigation.

Objective: Staging workup and detection of distant metastases is important in newly diagnosed breast cancer in order to make treatment decisions and establish the prognosis. There is wide variation in current recommendations for staging investigations in breast cancer. Routine staging is performed for all patients in Bahrain because of lack of consistent guidelines. Optimization of the criteria for staging is important for identification of metastases, while minimizing harm and costs. The aim of this study was to evaluate factors associated with distant metastases in newly diagnosed patients with breast cancer, in order to establish local guidelines for proper selection of patients for systemic staging. Materials and Methods: Patients with newly diagnosed breast cancer at Salmaniya Medical Complex in Bahrain who underwent staging investigations between January 2016 and December 2022 were identified from a pathology database. Patients with previous history of cancer, synchronous tumors, bilateral breast cancer and ductal carcinoma in situ were excluded. Clinical, radiological and pathological data were retrospectively analyzed. Results: A total of 593 patients underwent staging computed tomography and bone scans or a PET scan. Distant metastases were identified in 20.7% of cases. M1 disease was significantly associated with multifocality/multicentricity, high grade tumors, hormone receptor-negative cancers, high Ki67 index, advanced tumor stage, node-positive disease, triple-negative breast cancer, use of PET scans and those who underwent neoadjuvant chemotherapy. Age was not associated with identification of distant metastases. Conclusion: The prevalence of distant metastases in this population of newly diagnosed patients with breast cancer was higher than previously reported. Routine staging of all patients at presentation was not indicated, especially for asymptomatic patients with early breast cancer. This study identified certain groups of patients with a higher risk of distant metastasis, in whom metastatic workup should be performed. These findings may allow for the development of a local guideline that addresses the question of which breast cancer patients need staging investigations for distant metastases.

Breast cancer is the most common cancer and a leading cause of death in women in Saudi Arabia. P16 is a tumour suppressor gene that plays a crucial role in regulating cell cycle. Several studies have investigated the significance of p16 expression in various cancer types. However, the significance of p16 in breast cancer remains controversial and insufficiently studied. The present study aims to examine the association between p16 expression and clinicopathological factors in breast cancer using immunohistochemistry staining. The study utilised 475 prospectively collected tissue samples from 475 women with breast cancer in Saudi Arabia. Nuclear and cytoplasmic immunohistochemical staining of p16 was observed in 338 (71%) of the cases and showed significant direct associations with adverse tumour features, including high tumour grade (p < 0.0001), negative oestrogen receptor/progesterone receptor status (p < 0.001), and lymph node metastasis (p = 0.02). Our study revealed a significant association between p16 protein expression and the established negative prognostic parameters in breast carcinoma including tumour grade, lymph node metastasis, and oestrogen receptor and progesterone receptor status.

Introduction: Breast cancer is the most frequent cause of cancer-related death in women in developing nations. Breast cancer diagnoses have increased as a result of rising awareness among women. The expression of Estrogen receptors (ER) plays a crucial role in determining the responsiveness to specific treatments. Cyclin D1 being a marker for cell proliferation was used in this study. The primary objectives of the current investigation were to investigate the expression of Cyclin-D1 and Estrogen receptor (ER) in breast carcinoma and to establish a relationship between the expression patterns of Cyclin-D1 and ER with the histopathological features of the tumor in breast carcinoma. Materials and methods: The study was conducted in the Department of Pathology, Silchar Medical College and Hospital, Silchar, India, from June 2021 to May 2022. A total of 59 cases of primary breast carcinoma MRM(Modified radical mastectomy) specimens were included in the study. Results: The mean age of the patients was 52.12 ± 12.47 years, and the majority of the patients were in the post-menopausal phase. Lymph node metastasis was observed in 47.5% of the cases, and the majority of the cases were in grade II. The study demonstrated a trend towards increased Cyclin-D1 and ER-positive with aging. Cyclin-D1 positivity decreases and Cyclin-D1 negativity increases as the tumor growth increases. The study showed a statistically significant association (P=0.001) between ER and Cyclin-D1. The majority of post-menopausal patients had ER-positive. Conclusion: The present study provides the incidence of different parameters associated with breast carcinoma and their statistical correlation with CyclinD1 and ER that will provide improved and crucial treatment guidance.

Breast abscess in males is a rare condition, which accounts for 1%-3% of all documented breast diseases. Males with certain risk factors may develop a breast abscess. The ultrasonographic, mammographic, and pathological characteristics of this case will be highlighted in the report. A 51-year-old morbidly obese Saudi male who is a 160-pack-years smoker presented to our surgical clinic complaining of a right breast mass that presented a long time ago and was changing in size. The mass was painless until 5 days prior to presentation. On physical examination, a firm nonmobile 3 × 4 cm mass was felt at 10-12-o'clock, 1 cm away from the nipple. A bilateral X-ray mammogram and ultrasound were performed with fine needle aspiration and culture. The mammogram of the right breast showed a well-circumscribed subareolar mass with equal density, and it was also associated with overlying skin thickening and relative breast parenchymal edema. The fine needle aspiration grossly showed yellowish-green turbid content followed by turbid blood. The anaerobic culture results showed the gram-positive cocci, Finegoldia Magna. The patient was then instructed to take an antibiotic accordingly and return after 1 week. Fine needle aspiration and culture were performed again after antibiotics and grossly showed 2-3 cc of pus without any growth in culture. Male breast disorders are typically benign, with gynecomastia being the most prevalent, and malignancy being the most serious despite its rarity. Breast abscesses are a challenging clinical condition, and radiologists have a pivotal role in evaluation and follow-up of these lesions.

Although diagnostic and therapeutic advances have been made in the treatment of breast cancer, the challenge of effectively controlling tumor progression persists. The objective of this study was to determine the relationship between IDO1 and TDO2 expression in breast cancer by immunohistochemistry and real-time polymerase chain reaction, hormone receptor status, Ki67 proliferation index, molecular classification, metastasis, and to investigate whether IDO1 and TDO2 expression can be used in combination with targeted therapy or as a marker to increase treatment efficacy in selected cases. The study included 74 cases of breast cancer and 14 cases of normal breast tissue as controls. All cases were analyzed for IDO1 and TDO2 by both immunohistochemistry and real-time polymerase chain reaction. The immunohistochemical analysis revealed that IDO1 immunoreactivity was significantly higher in tumor tissue compared to normal breast tissue. A statistically significant correlation was observed between IDO1 immunoreactivity and histologic subtypes. Furthermore, IDO1 gene expression was correlated with IDO1 immunoreactivity. TDO2 immune reactivity did not differ between tumor and non-tumor tissues and no correlation was found between histological subtypes. There was no correlation between TDO2 immunoreactivity and gene expression. The significant increase in IDO1 levels in tumor tissue and high positivity in age, HER2 positive and triple negative cases compared to other cases suggest that IDO1 inhibitors may be suitable for the target patient group in treatment selection.

For the past 2 decades, pathologists have been accustomed to reporting the HER2 status of breast cancer as either positive or negative, based on HER2 IHC. Today, however, there is a clinical imperative to employ a 3-tier approach to interpreting HER2 IHC that can also identify tumours categorised as HER2-low. Meeting this need for a finer degree of discrimination may be challenging, and in this article, we consider the potential for the integration of computational approaches to support pathologists in achieving accurate and reproducible HER2 IHC scoring as well as outlining some of the practicalities involved.

Introduction: Breast carcinoma is one of the most prevalent types of carcinoma and the leading cause of death among all carcinomas. Recently, vitamin D deficiency has been reported as a risk factor for breast carcinoma. Vitamin D, as an anticarcinoma agent, prevents cellular differentiation, stimulates cell death, reduces angiogenesis, tumour progression, and metastasis. Aim: To investigate the relationship between vitamin D deficiency and the risk of breast carcinoma. Materials and Methods: An observational study was conducted at the Armed Forces Medical College, Pune, Maharashtra, India, between November 2018 and October 2020. A total of 57 cases diagnosed with breast carcinoma and 57 healthy controls were analysed. Physical and reproductive health parameters were compared, along with vitamin D status using student's t-test and Mann-Whitney U test. Logistic regression was used to assess the risk of breast carcinoma. Results: Out of 114 women, 57 were cases and 57 were controls with a mean age of 52 vs 48 years. The mean value of serum vitamin D levels was significantly lower (19.45 vs 27.91 ng/mL, p<0.001) than controls. The percentage of serum Vitamin D deficiency was significantly higher in cases (28 (49.1%) vs 12 (21.1%), p<0.001) compared to controls. Vitamin D concentration <20 ng/mL was significantly associated with a higher risk of breast carcinoma (OR 10.8, 95% CI 3.1-37.6). Multiparity =3 was associated with a decreased risk of breast carcinoma (OR 2.250, 95% CI 0.599-8.447) compared to parity =2 (OR 3.241, 95% CI 0.916-11.466). In luminal A and triplenegative subtypes, severe vitamin D deficiency (<20 ng/mL) was observed (p=0.045) compared to other subtypes. Conclusion: The present study findings showed that women diagnosed with breast carcinoma had low vitamin D levels, which were linked to an increased risk and prognosis of breast carcinoma. Furthermore, multiparity lowers the risk of breast carcinoma. [ABSTRACT FROM AUTHOR]

Background: Some studies have suggested that axillary lymph node dissection (ALND) can be avoided in women with cN0 breast cancer with 1–2 positive sentinel nodes (SLNs). However, these studies included only a few patients with invasive lobular carcinoma (ILC), so the validity of omitting ALDN in these patients remains controversial. This study compared the frequency of non-sentinel lymph nodes (non-SLNs) metastases in ILC and invasive ductal carcinoma (IDC). Materials Methods: Data relating to a total of 2583 patients with infiltrating breast carcinoma operated at our institution between 2012 and 2023 were retrospectively analyzed: 2242 (86.8%) with IDC and 341 (13.2%) with ILC. We compared the incidence of metastasis to SLNs and non-SLNs between the ILC and IDC cohorts and examined factors that influenced non-SLNs metastasis. Results: SLN biopsies were performed in 315 patients with ILC and 2018 patients with IDC. Metastases to the SLNs were found in 78/315 (24.8%) patients with ILC and in 460 (22.8%) patients with IDC (p = 0.31). The incidence of metastases to non-SLNs was significantly higher (p = 0.02) in ILC (52/78–66.7%) compared to IDC (207/460 − 45%). Multivariate analysis showed that ILC was the most influential predictive factor in predicting the presence of metastasis to non-SLNs. Conclusions: ILC cases have more non-SLNs metastases than IDC cases in SLN-positive patients. The ILC is essential for predicting non-SLN positivity in macro-metastases in the SLN. The option of omitting ALND in patients with ILC with 1–2 positive SLNs still requires further investigation. [ABSTRACT FROM AUTHOR]

Cancer is a deadly illness with a convoluted pathogenesis. The most prevalent restrictions that frequently result in treatment failure for cancer chemotherapy include lack of selectivity, cytotoxicity, and multidrug resistance. Thus, considerable efforts have been focused in recent years on the establishment of a modernistic sector termed nano-oncology, which offers the option of employing nanoparticles (NPs) with the objective of detecting, targeting, and treating malignant disorders. NPs offer a focused approach compared to conventional anticancer methods, preventing negative side effects. In the present work, a successful synthetic process was used to create magnetic cobalt cores with an AgNPs shell to form bimetallic nanocomposites CoAg, then functionalized with Cis forming novel CoAg@Cis nanohybrid. The morphology and optical properties were determined by TEM, DLS, FTIRs and UV–vis spectroscopy, furthermore, anticancer effect of CoAg and CoAg@Cis nanohybrids were estimated using MTT assay on MCF7 and HCT cell lines. Our results showed that Co@Ag core shell is about 15 nm were formed with dark CoNPs core and AgNPs shell with less darkness than the core, moreover, CoAg@Cis has diameter about 25 nm which are bigger in size than Co@Ag core shell demonstrating the loading of Cis. It was observed that Cis, CoAg and CoAg@Cis induced a decline in cell survival and peaked at around 65%, 73%and 66% on MCF7 and 80%, 76%and 78% on HCT at 100 µg/ml respectively. Compared to Cis alone, CoAg and CoAg@Cis caused a significant decrease in cell viability. These findings suggest that the synthesized CoAg can be used as a powerful anticancer drug carrier. [ABSTRACT FROM AUTHOR]

Background & Objective: p16 has different roles in the nuclear and cytoplasmic locations. The nuclear localization of the p16 protein explains its role in cell cycle regulation. Cytoplasmic expression was considered an artifact in the initial years, but there is evidence to prove that cytoplasmic localization is real and that p16 has different roles in the nuclear and cytoplasmic locations. We aimed to study the immunoexpression of p16 protein in the nuclear and cytoplasmic locations of the epithelial and stromal compartments of fibroadenoma, invasive breast carcinoma, and a select number of phyllodes tumors. Methods: The study included a total of 107 patients, comprising 51 cases of invasive breast carcinoma, 51 cases of fibroadenoma, 4 cases of benign phyllodes tumors, and 1 case of lobular carcinoma in situ (LCIS). The p16 immunohistochemistry was evaluated for nuclear and cytoplasmic localization in the epithelial and stromal compartments of the tumors. Results: Of the 51 fibroadenoma cases, 23 showed strong nuclear p16 epithelial expression, but no case showed cytoplasmic expression. In 19/51 cases, stromal cells also showed strong p16 nuclear expression. Moderate stromal p16 expression was observed in 3 out of 4 cases of benign phyllodes. Out of the 51 cases of invasive carcinoma, 31 showed moderate to strong nuclear p16 immunopositivity, while 27 cases exhibited cytoplasmic p16 expression. We found a statistically significant correlation between moderate to strong nuclear p16 immunoexpression and the molecular subtype of breast carcinoma. Conclusion: The cytoplasmic localization of p16 immunohistochemistry is not seen in epithelial components of fibroadenoma, while it is seen frequently in breast carcinoma. Nuclear p16 expression has a statistically significant correlation with molecular subtypes of breast carcinoma. [ABSTRACT FROM AUTHOR]

OBJECTIVE Breast carcinoma (BC) is the most common cancer in women, and, in particular, some subtypes are established as suitable for immunotherapy strategies targeting immune checkpoints. Programmed cell death-1 (PD-1), as well as cytotoxic T lymphocyte-associated protein-4 (CTLA-4), has an important role in the tumor microenvironment to escape from the immune system. In this study, we examined the relationship of Programmed cell death-1 (PD-L1) expression with survival, recurrence, and other prognostic factors. METHODS This retrospective cohort comprised tissue microarray blocks of 391 cases examined at the same institute between 2000-2012. All cases were completely resected tumors, without neoadjuvant therapy, with more than 5 years of follow-up. Clinical follow-up and all pathologic parameters were recorded. PD-L1 immunohistochemistry (SP263) was applied, then staining details including density, percentage, and patterns were noted for tumor areas and immune cells. PD-L1 expression results were analyzed, and its relationship with prognostic parameters and survival was investigated. RESULTS PD-L1 expression was detected in 90 (24.8%) cases: 55 in only tumor-infiltrating lymphocytes (TILs), 35 in both tumor and TILs. Statistically, there was no significant relationship between PD-L1 expression and survival. However, high histologic grade, high scores in pleomorphism and mitosis, mild stromal reaction, dense immune cell infiltration, perineural invasion, absence of lymph node metastasis, negativity of ER and PR, HER2 expression, and high Ki-67 results had a significant relationship with PD-L1 expression. CONCLUSION Consistent with the literature, our results showed that PD-L1 expression in triple-negative and HER2 overexpressed types and in the presence of TILs is higher than in other breast cancers. [ABSTRACT FROM AUTHOR]

Pigmented mammary Paget disease is a rare variant of mammary Paget disease that is often clinically misdiagnosed as a melanocytic lesion of the skin or nipple–areolar complex. Careful morphological assessment, along with the performance of adequate immunohistochemical stains, will help in achieving the right diagnosis and avoiding misdiagnosis of the entity as malignant melanoma. We report a rare case of pigmented mammary Paget disease with concomitant colonization of the underlying invasive ductal carcinoma by melanocytes mimicking melanoma. [ABSTRACT FROM AUTHOR]

Objective: Staging workup and detection of distant metastases is important in newly diagnosed breast cancer in order to make treatment decisions and establish the prognosis. There is wide variation in current recommendations for staging investigations in breast cancer. Routine staging is performed for all patients in Bahrain because of lack of consistent guidelines. Optimization of the criteria for staging is important for identification of metastases, while minimizing harm and costs. The aim of this study was to evaluate factors associated with distant metastases in newly diagnosed patients with breast cancer, in order to establish local guidelines for proper selection of patients for systemic staging. Materials and Methods: Patients with newly diagnosed breast cancer at Salmaniya Medical Complex in Bahrain who underwent staging investigations between January 2016 and December 2022 were identified from a pathology database. Patients with previous history of cancer, synchronous tumors, bilateral breast cancer and ductal carcinoma in situ were excluded. Clinical, radiological and pathological data were retrospectively analyzed. Results: A total of 593 patients underwent staging computed tomography and bone scans or a PET scan. Distant metastases were identified in 20.7% of cases. M1 disease was significantly associated with multifocality/multicentricity, high grade tumors, hormone receptor-negative cancers, high Ki67 index, advanced tumor stage, node-positive disease, triple-negative breast cancer, use of PET scans and those who underwent neoadjuvant chemotherapy. Age was not associated with identification of distant metastases. Conclusion: The prevalence of distant metastases in this population of newly diagnosed patients with breast cancer was higher than previously reported. Routine staging of all patients at presentation was not indicated, especially for asymptomatic patients with early breast cancer. This study identified certain groups of patients with a higher risk of distant metastasis, in whom metastatic workup should be performed. These findings may allow for the development of a local guideline that addresses the question of which breast cancer patients need staging investigations for distant metastases. [ABSTRACT FROM AUTHOR]

Background: Post-mastectomy adjuvant radiotherapy improves long-term survival by reducing the risk of locoregional recurrence in breast cancer patients with high-risk features. Considering radiation therapy to the left sided chest wall heart is an important organ at risk. Hypo-fractionated radiotherapy is increasingly being used due to involvement of fewer treatment sessions and is almost radio-biologically equivalent to conventionally fractionated radiotherapy. Objective: This study was conducted to evaluate cardiac toxicities between hypo and conventionally fractionated radiotherapy. Methods: This quasi-experimental study was done at the National Institute of Cancer Research and Hospital, Mohakhali, Dhaka from January 2019 to December 2019, 60 patients were purposively assigned into two groups and each group included 30 patients. Arm A: received Conventional fractionated radiotherapy (50Gy/25 fractions over 5 weeks, at 2Gy/fraction). Arm B: received Hypo-fractionated radiotherapy (40.05 Gy in 15 fractions over 3 weeks at 2.67 Gy/fraction). Echocardiography (ECHO), Electrocardiography (ECG) was performed to find the cardiac toxicities. Results: The mean age of the patients in arm A was 50.03 ± 6.82 years and that of arm B was 48.08 ± 5.08 years. No significant statistical difference was found between the two groups regarding socio-demographic variables and clinical presentations. Most of the patients in both arms showed grade 0 cardiac toxicity (arm A: 70% and arm B: 80%) & few showed grade 1 cardiac toxicity (arm A: 20% and arm B: 13.3%) and three patients (10.0%) in arm A and two patients (6.66%) in arm B had shown grade 2 cardiac toxicities six months after treatment. However, this difference was statistically not significant (p >0.05). Before treatment, the ejection fraction (EF) of arm A and arm B were 63.3 ± 5.621 and 64.7± 4.991. Six months after treatment the EF of both arms decreased (arm A 60.2 ± 4.051 & arm B 60.9 ± 5.121) but the difference was statistically not significant (p >0.05). Conclusion: Hypo-fractionated radiotherapy in the adjuvant setting for the treatment of left breast cancer has no additional cardiac toxicity in comparison to conventionally fractionated radiotherapy while maintaining same efficacy. [ABSTRACT FROM AUTHOR]