Aggressive Breast Carcinoma Research Articles

The Utility of [18]F-Fluorocholine Positron Emission Computed Tomography and [18]F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in Evaluating Breast Cancer Phenotypes: A Pilot Study.

The utility of the [18]F fluorodeoxyglucose positron emission tomography-computed tomography ([18]F FDG PET-CT) marker for breast cancer is well established. Given its limitations in localizing FDG-negative malignant tumors, the expression of [18]F-fluorocholine ([18]-FCH) may potentially be helpful to improve the overall accuracy in evaluating breast cancer. This study determined the potential of [18]- FCH PET CT as a potential marker in assessing breast cancer phenotypes. We recruited consecutive patients with biopsy-proven breast carcinoma who underwent [18] F-FCH PET-CT following the [18]F-FDG PET-CT imaging. The subjects were dichotomized into human epidermal growth factor receptor 2 (HER2)-negative and HER2-positive genotypes. The maximum standardized uptake value (SUVmax; g/dL) was used to predict the two groups of variables. Global health status (GHS) score based on the EORTC quality of life questionnaire (QLQ) was used to evaluate the outcome of the cohort subjects at 6, 12, and 24 months. There were 21 females with a mean age of 54.48 ± 12.17 years. Eighteen patients had invasive ductal carcinoma (18/21;85.8%) on histology, with 11 (52.4%) were HER2-negative genotype. There was higher sensitivity and specificity of [18]-FCH-PET/CT in breast lesions at 40% and 68.8% compared to [18]FDGPET/CT with 33.3% and 66.7%, respectively. There were significant differences between [18]F-FCH SUVmax (g/dL) of the HER-negative as compared to the HER2- positive group (1.99 g/dL vs. 0.2 g/dL; P < .05). High SUVmax (g/dL) of [18]F-FCH had predicted the HER-negative genotype at the cutoff value of 0.75 (P < .05). High [18]F-FCH showed significantly poor scoring of GHS parameters compared to low FCH at 6 months (mean SUVmax 8.06 vs. 5.40 respectively; P < .05). [18]F-FCH PET-CT is a potential marker in localizing and predicting aggressive breast carcinoma phenotypes.

Latissimus Dorsi Flap Revisited: Coverage of Large Chest Wall Defects Following Mastectomy for Locally Advanced Breast Carcinoma and Angiosarcoma.

The latissimus dorsi myocutaneous flap (LDMF) remains a significant tool in the armamentarium of the oncoplastic breast surgeon. Despite declining popularity for reconstruction, owing to the increasing use of implants and free flaps, it still has an important role in certain salvage situations and as a flap to cover large defects. We report our experience with the use of LDMF for immediate coverage of large mastectomy defects when options are limited. Retrospective series of prospectively collected patient records. Patient and tumour characteristics, length of stay, and post-operative and oncologic outcomes are reported. Patients with angiosarcoma were discussed at tertiary sarcoma centres as per national guidelines. Operations were carried out by oncoplastic breast surgeons. The case series was approved by the institutional information governance department in line with institutional requirements for patient data sharing. All patients provided written consent for photography. Descriptive statistics were used to report findings.Median (IQR) was used for continuous variables. Six women were included, with a median age of 62.5 years, from December 2019 to October 2022. Follow-up ranged from 15 to 49 months. Median tumour size was 72.5 (16.25) mm. Four patients had locally advanced breast carcinoma (LABC), and two had breast angiosarcoma. The donor site and chest wall defects were closed primarily in all cases. Median length of stay was three nights. All mastectomy wounds healed without issues and any delay to their adjuvant treatment. One patient had a minor latissimus dorsi (LD) donor site wound breakdown managed conservatively. Three patients had adjuvant radiotherapy after surgery. Four patients, one after high-grade angiosarcoma and three after aggressive breast carcinoma, had a locoregional recurrence or distant metastases and succumbed within 20 months of surgery. The LDMF can be a reliable option for the primary closure of large post-mastectomy wounds. Its use can lead to timely wound healing, allowing patients to undergo adjuvant treatment without delay. However, the overall oncologic outcomes in patients with LABC and angiosarcoma are poor due to the underlying aggressive tumour biology. Long-term outcomes are to be interpreted with caution due to the small number of patients with diverse pathologic features.

Targeting Receptor Tyrosine Kinases as a Novel Strategy for the Treatment of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) comprises a group of aggressive and heterogeneous breast carcinoma. Chemotherapy is the mainstay for the treatment of triple-negative tumors. Nevertheless, the success of chemotherapeutic treatments is limited by their toxicity and development of acquired resistance leading to therapeutic failure and tumor relapse. Hence, there is an urgent need to explore novel targeted therapies for TNBC. Receptor tyrosine kinases (RTKs) are a family of transmembrane receptors that are key regulators of intracellular signaling pathways controlling cell proliferation, differentiation, survival, and motility. Aberrant activity and/or expression of several types of RTKs have been strongly connected to tumorigenesis. RTKs are frequently overexpressed and/or deregulated in triple-negative breast tumors and are further associated with tumor progression and reduced survival in patients. Therefore, targeting RTKs could be an appealing therapeutic strategy for the treatment of TNBC. This review summarizes the current evidence regarding the antitumor activity of RTK inhibitors in preclinical models of TNBC. The review also provides insights into the clinical trials evaluating the use of RTK inhibitors for the treatment of patients with TNBC.

Nitrogen isotopic composition as a gauge of tumor cell anabolism-to-catabolism ratio.

Studies have suggested that cancerous tissue has a lower 15N/14N ratio than benign tissue. However, human data have been inconclusive, possibly due to constraints on experimental design. Here, we used high-sensitivity nitrogen isotope methods to assess the 15N/14N ratio of human breast, lung, and kidney cancer tissue at unprecedented spatial resolution. In lung, breast, and urothelial carcinoma, 15N/14N was negatively correlated with tumor cell density. The magnitude of 15N depletion for a given tumor cell density was consistent across different types of lung cancer, ductal in situ and invasive breast carcinoma, and urothelial carcinoma, suggesting similar elevations inthe anabolism-to-catabolism ratio. However, tumor 15N depletion was higher in a more aggressive metaplastic breast carcinoma. These findings may indicate the ability of certain cancers to more effectively channel N towards growth. Our results support 15N/14N analysis as a potential tool for screening biopsies and assessing N metabolism in tumor cells.

Correlation of Expression of Androgen Receptors and P16 in Triple Negative Breast Carcinoma - A Five Years Retrospective and Prospective Study

AIM AND OBJECTIVE Triple negative breast carcinoma (TNBC) is an aggressive breast carcinoma, lacking estrogen receptor (ER),progesterone receptor (PR) and human epidermal growth factor receptor 2 (Her2neu receptor) amplification, thereby, unresponsive to conventional hormonal therapy. The aim of present study is to examine androgen receptor (AR) and p16 expression in TNBC cases and explore its clinical significance in view of potential AR and p16 targeted TNBC therapy. MATERIAL AND METHOD A total 94 TNBC patients were included in this 5 years (3 years retrospective and 2 years prospective) study, conducted at Department of Pathology, JNMCH, Aligarh. Immunohistochemical stains for AR and p16 were performed and their relationship with TNBC clinicopathological data were analyzed. Positive AR expression was defined as ≥1% nuclear staining wheras positive p16 expression was defined as score of ≥1which in turn calculated as product of intensity score and extent of positivity score of cytoplasmic and nuclear stained cells. RESULT Out of 94 TNBC patients, 92 cases were of invasive carcinoma (NST) and 2 cases were invasive lobular carcinoma.AR was expressed in 38/94 (40.4%) cases, all of which were of invasive carcinoma (NST) type. We observed higher expression rate in postmenopausal women i.e.43.2% (16/37) cases and in patients with age ≥60 years i.e. 66.7% (8/12) cases. Statistical analysis showed significant association of AR + TNBC cases with larger tumor size (p= 0.017412) and lymph node metastases (p= 0.033119). Higher expression rate was found in lower grade and stage III, however statistically insignificant.p16 protein was positively expressed in 72.3% (68/94) of the total TNBC cases. We observed higher expression rate in premenopausal women i.e.78.9%(48/57) cases and in patients with age 40-49 years i.e. 84.4% (27/32) . Significantly higher p16 expression rate was found in grade II (90%) followed by grade I (66.7%) and grade III (65%) (p= 0.04). CONCLUSION TNBC was more common in older age group and had a higher propensity for lymph node metastases. AR positive and p16 positive TNBC cases may represent a breast cancer subtype with unique features that may be amenable to treatment with alternative targeted therapy.

Gambogic acid inhibits tumor metastasis through blocking matrix metalloproteinases mediated TGF-β1 activation

ContextTumor metastasis is the major death factor in cancer patients. Transforming growth factor-β (TGF-β) is an important cytokine promoting tumor metastasis and blocking TGF-β shows crucial antitumor application prospects. In the tumor microenvironment (TME), TGF-β is always highly activated and matrix metalloproteinases (MMPs) are an important TGF-β promoting factor. It gives us a crucial inspiration that TGF-β in TME can be selectively inhibited by specifically correcting TGF-β promoters in TME. Gambogic acid (GA) is an anti-tumor natural product with the activity to inhibit tumor metastasis by preventing the expression of MMP-2, 9. In this study, we explored whether GA could inhibit tumor metastasis by blocking MMPs mediated TGF-β activation. MethodsTwo extremely aggressive tumor cell lines, B16F10 melanoma and 4T1 breast carcinoma were chosen for this study. The in vitro protein expression level and mRNA level of MMPs were determined by ELISA and RT-PCR respectively. The cell mobility, invasion rate, and morphological changes with various treatments were depicted via scratches, transwell assay and immunofluorescence respectively. For further in vivo confirmation, animal models of melanoma, as well as breast cancer, were respectively established using the two cell lines, and metastasis together with related protein expression levels were estimated after treatment with GA. ResultsGA could suppress the expression of MMP-2, 3, 9, which further blocked TGF-β activation. Meanwhile, GM6001 presented a consistent effect. Via inhibiting MMPs-mediated TGF-β upregulation, both GA and GM6001 could suppress the migration and invasion ability of tumor cells in vitro and inhibits tumor metastasis in vivo. Also, GA and GM6001 could downregulate TGF-β downstream signaling pathway. Therefore, the present study provide an important enlightenment for tumor control by specifically blocking TGF-β in TME without affecting normal function of TGF-β. ConclusionsGA can inhibit tumor metastasis by blocking MMPs mediated TGF-β activation. Specifically correcting complicated pro-TGF-β factors in TME may be a more appropriate strategy to suppress metastasis without affecting TGF-β normal function.

Spontaneous regression of biologically aggressive breast carcinoma: A case report

The spontaneous regression of cancer is the partial or complete remission of a tumor without treatment, and this has been linked to trauma and infection. The present case details the rare spontaneous regression of a triple negative Grade III ductal carcinoma in the breast. The findings suggest that in our case, this may have been triggered by biopsy and marker clip deployment, and it highlights the importance of being aware of this unusual occurrence so timely diagnosis can be made without causing undue anxiety in patients.

Expression of fascin in Invasive mammary cancer - A study at a Tertiary care centre in Southern India

Introduction and Aim: Breast cancer is the commonest malignancy in women. Most women do not die of the primary tumor but from metastasis and local invasion. Augmented motility of cancer cells corroborates with greater metastatic potential, that is brought about by actin cytoskeleton. Fascin, a cytoplasmic F-actin-bundling protein that cross-links actin filaments and its overexpression is strongly associated with metastatic progression and poor prognosis. The present study aims to determine the fascin protein expression by immunohistochemistry in invasive breast carcinoma and to correlate the same with the existing prognostic factors. Methods: Immunohistochemical expression of fascin in 100 cases of invasive mammary carcinoma was studied. Data collected was scored based on intensity and statistically analyzed using GNU-PSPP version 0.10 software. To determine significant clinico-pathological differences between fascin expression in positive and negative tumors, Pearson Chi-square test was used. Results: It was noted that 22 of the 100 cases were positive with a score of 3 or more. A significant association of nodal status with fascin (p value &lt;0.05) was noted. Higher proportion of fascin positive tumors were node negative. There was an inverse correlation between ER/PR/HER2 status and fascin positivity. The corresponding p values for ER, PR and HER2 with fascin were &lt;0.05. On the contrary 12(57.15%) of the 21 triple negative cases were fascin positive. The p value was &lt;0.001 indicating a significant correlation between molecular subtypes and fascin expression. A more of the fascin positive tumors fell in the triple negative category. Conclusion: Higher proportion of fascin positive cases in the node negative category, an inverse correlation between fascin expression and individual ER/PR, HER2 expression and larger number of fascin positive cases in the triple negative category. These findings point an association of fascin with aggressive breast carcinomas.

Metaplastic Carcinoma of the Breast: MRI Features with Clinical and Histopathologic Correlation

Metaplastic carcinoma of the breast (MCB) is a rare type of breast carcinoma, and there are only limited data about the MRI findings of MCB. This article aimed to review the MRI features of MCB and correlate the MRI findings with clinical and histopathologic characteristics. A total of 23 patients were enrolled from a signal institution. The clinical data, histological diagnosis and MRI findings were retrospectively reviewed. The average age of the 23 patients was 51.6 years. Twenty-one (91.3%) patients presented with a palpable mass. Squamous cell carcinoma was the most common subtype (10/23, 43.5%). Axillary lymph node metastasis was detected in 4 (17.4%) patients. The immunohistochemical profile showed the estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor-2 (Her-2) expression were negative in 87.0%, 95.7%, and 91.3% of the patients respectively. On MRI, most cases exhibited an irregular mass (18/23, 78.3%) with high signal intensity on T2-weighted images (22/23,95.7%), non-circumscribed margin (19/23, 82.6%), heterogeneous enhancement (13/23, 56.5%), Type III (12/23, 52.2%) time intensity curve, and diffusion restriction (20/23, 87.0%) on diffusion weighted images (DWI). MCB most commonly demonstrated definitely malignant MRI features, which may reflect the histopathologic characteristic of this rare and aggressive breast carcinoma.

Quantitative glycoproteomics analysis identifies novel FUT8 targets and signaling networks critical for breast cancer cell invasiveness

BackgroundWe recently showed that fucosyltransferase 8 (FUT8)-mediated core fucosylation of transforming growth factor-β receptor enhances its signaling and promotes breast cancer invasion and metastasis. However, the complete FUT8 target glycoproteins and their downstream signaling networks critical for breast cancer progression remain largely unknown.MethodWe performed quantitative glycoproteomics with two highly invasive breast cancer cell lines to unravel a comprehensive list of core-fucosylated glycoproteins by comparison to parental wild-type and FUT8-knockout counterpart cells. In addition, ingenuity pathway analysis (IPA) was performed to highlight the most enriched biological functions and signaling pathways mediated by FUT8 targets. Novel FUT8 target glycoproteins with biological interest were functionally studied and validated by using LCA (Lens culinaris agglutinin) blotting and LC–MS/MS (liquid chromatography–tandem mass spectrometry) analysis.ResultsLoss-of-function studies demonstrated that FUT8 knockout suppressed the invasiveness of highly aggressive breast carcinoma cells. Quantitative glycoproteomics identified 140 common target glycoproteins. Ingenuity pathway analysis (IPA) of these target proteins gave a global and novel perspective on signaling networks essential for breast cancer cell migration and invasion. In addition, we showed that core fucosylation of integrin αvβ5 or IL6ST might be crucial for breast cancer cell adhesion to vitronectin or enhanced cellular signaling to interleukin 6 and oncostatin M, two cytokines implicated in the breast cancer epithelial–mesenchymal transition and metastasis.ConclusionsOur report reveals a comprehensive list of core-fucosylated target proteins and provides novel insights into signaling networks crucial for breast cancer progression. These findings will assist in deciphering the complex molecular mechanisms and developing diagnostic or therapeutic approaches targeting these signaling pathways in breast cancer metastasis.

Role of ADCC, CDC, and CDCC in Vaccine-Mediated Protection against Her2 Mammary Carcinogenesis.

Amplification or mutation of the Her2 oncoantigen in human mammary glands leads to the development of an aggressive breast carcinoma. Several features of this breast carcinoma are reproduced in mammary carcinomas that spontaneously arise in female transgenic mice bearing the activated rat Her2 oncogene under transcriptional control of the mouse mammary tumor virus promoter-BALB-neuT (neuT) mice. We previously demonstrated that carcinoma progression in neuT mice can be prevented by DNA vaccination with RHuT, a plasmid coding for a chimeric rat/human Her2 protein. RHuT vaccination exerts an antitumor effect, mostly mediated by the induction of a strong anti-rat Her2 antibody response. IgG induced by RHuT vaccine mainly acts by blocking Her2 signaling, thus impairing cell cycle progression and inducing apoptosis of cancer cells, but other indirect effector mechanisms could be involved in the antibody-mediated protection. The recruitment of cells with perforin-dependent cytotoxic activity, able to perform antibody-dependent cellular cytotoxicity, has already been investigated. Less is known about the role of the complement system in sustaining antitumor response through complement-dependent cytotoxicity and cellular cytotoxicity in vaccinated mice. This work highlights that the weight of such mechanisms in RHuT-induced cancer protection is different in transplantable versus autochthonous Her2+ tumor models. These results may shed new light on the effector mechanisms involved in antibody-dependent anti-cancer responses, which might be exploited to ameliorate the therapy of Her2+ breast cancer.

High Pregnane X Receptor (PXR) Expression Is Correlated with Poor Prognosis in Invasive Breast Carcinoma.

Pregnane X Receptor (PXR) is involved in human cancer, either by directly affecting carcinogenesis or by inducing drug-drug interactions and chemotherapy resistance. The clinical significance of PXR expression in invasive breast carcinoma was evaluated in the present study. PXR protein expression was assessed immunohistochemically on formalin fixed paraffin-embedded breast invasive carcinoma tissue sections, obtained from 148 patients, and was correlated with clinicopathological parameters, molecular phenotypes, tumor cells’ proliferative capacity, and overall disease-free patients’ survival. Additionally, the expression of PXR was examined on human breast carcinoma cell lines of different histological grade, hormonal status, and metastatic potential. PXR positivity was noted in 79 (53.4%) and high PXR expression in 48 (32.4%), out of 148 breast carcinoma cases. High PXR expression was positively associated with nuclear grade (p = 0.0112) and histological grade of differentiation (p = 0.0305), as well as with tumor cells’ proliferative capacity (p = 0.0051), and negatively with luminal A subtype (p = 0.0295). Associations between high PXR expression, estrogen, and progesterone receptor negative status were also recorded (p = 0.0314 and p = 0.0208, respectively). High PXR expression was associated with shorter overall patients’ survival times (log-rank test, p = 0.0009). In multivariate analysis, high PXR expression was identified as an independent prognostic factor of overall patients’ survival (Cox-regression analysis, p = 0.0082). PXR expression alterations were also noted in breast cancer cell lines of different hormonal status. The present data supported evidence that PXR was related to a more aggressive invasive breast carcinoma phenotype, being a strong and independent poor prognosticator.

Regulation of Tumor Metabolism and Extracellular Acidosis by the TIMP-10-CD63 Axis in Breast Carcinoma.

A hallmark of malignant solid tumor is extracellular acidification coupled with metabolic switch to aerobic glycolysis. Using the human MCF10A progression model of breast cancer, we show that glycolytic switch and extracellular acidosis in aggressive cancer cells correlate with increased expression of tissue inhibitor of metalloproteinase-1 (TIMP-1), known to induce intracellular signal transduction through the interaction with its cell surface receptor CD63, independent of its metalloproteinase inhibitory function. We found that, in aggressive breast carcinoma, the TIMP-1–CD63 signaling axis induced a metabolic switch by upregulating the rate of aerobic glycolysis, lowering mitochondrial respiration, preventing intracellular acidification, and inducing extracellular acidosis. Carbonic anhydrase IX (CAIX), a regulator of cellular pH through the hydration of metabolically released pericellular CO2, was identified as a downstream mediator of the TIMP-1–CD63 signaling axis responsible for extracellular acidosis. Consistently with our previous study, the TIMP-1–CD63 signaling promoted survival of breast cancer cells. Interestingly, breast carcinoma cell survival was drastically reduced upon shRNA-mediated knockdown of CAIX expression, demonstrating the significance of CAIX-regulated pH in the TIMP-1–CD63-mediated cancer cell survival. Taken together, the present study demonstrates the functional significance of TIMP-1–CD63–CAXI signaling axis in the regulation of tumor metabolism, extracellular acidosis, and survival of breast carcinoma. We propose that this axis may serve as a novel therapeutic target.

Plasma-synthesized mussel-inspired gold nanoparticles promote autophagy-dependent damage-associated molecular pattern release to potentiate immunogenic cancer cell death

The development of an efficient tumor-specific therapeutic approach, which functions against the primary tumor and also repairs the host immune system to eradicate distant tumors, remains a clinical issue. Herein, this study focuses on the use of polydopamine-coated gold nanoparticles ([email protected] NPs) that showed excellent selectivity towards cancer cells. The [email protected] NPs were prepared by a plasma synthesis method with a short reaction time and minimize the use of chemicals. Prominently, [email protected] NPs not only exhibited high cellular internalization but also stimulated immunogenic cell death (ICD) in aggressive breast carcinoma cells. Moreover, it was observed that damage-associated molecular patterns (DAMPs) were released by damaged cells together with the autophagy process after [email protected] NPs exposure, which acted as endogenous danger signals to regulate the consequent immune response. This study highlights the novel mechanism of [email protected] NPs-triggered anti-tumor immunity against immunosuppressive cancers, demonstrated the potential of the [email protected] NPs for cancer immunotherapy.

E2A Modulates Stemness, Metastasis, and Therapeutic Resistance of Breast Cancer.

Cancer stem cells (CSC) are considered responsible for tumor initiation, therapeutic resistance, and metastasis. A comprehensive knowledge of the mechanisms governing the acquisition and maintenance of cancer stemness is crucial for the development of new therapeutic approaches in oncology. E2A basic helix-loop-helix (bHLH) transcription factors are associated with epithelial-mesenchymal transition (EMT) and tumor progression, but knowledge of their functional contributions to cancer biology is still limited. Using a combination of in vivo and in vitro analyses in a novel PyMT-E2A conditional knockout mouse model and derived primary tumor cell lines, we report here an essential role of E2A in stemness, metastasis, and therapeutic resistance in breast cancer. Targeted deletion of E2A in the mammary gland impaired tumor-initiating ability and dedifferentiation potential and severely compromised metastatic competence of PyMT-driven mammary tumors. Mechanistic studies in PyMT-derived cell lines indicated that E2A actions are mediated by the upregulation of Snai1 transcription. Importantly, high E2A and SNAIL1 expression occurred in aggressive human basal-like breast carcinomas, highlighting the relevance of the E2A-Snail1 axis in metastatic breast cancer. In addition, E2A factors contributed to the maintenance of genomic integrity and resistance to PARP inhibitors in PyMT and human triple-negative breast cancer cells. Collectively, these results support the potential for E2A transcription factors as novel targets worthy of translational consideration in breast cancer. SIGNIFICANCE: These findings identify key functions of E2A factors in breast cancer cell stemness, metastasis, and drug resistance, supporting a therapeutic vulnerability to targeting E2A proteins in breast cancer.

GATA3 as an Adjunct Prognostic Factor in Breast Cancer Patients with Less Aggressive Disease: A Study with a Review of the Literature.

Background: GATA binding protein 3 (GATA3) expression is positively correlated with estrogen receptor (ER) expression, but its prognostic value as an independent factor remains unclear. Thus, we undertook the current study to evaluate the expression of GATA3 and its prognostic value in a large series of breast carcinomas (BCs) with long-term follow-up. Methods: A total of 702 consecutive primary invasive BCs resected between 1989 and 1993 in our institution were arranged in tissue microarrays, immunostained for ER, progesterone receptor (PR), ki-67, HER2, p53, and GATA3, and scored. Clinico-pathological data were retrospectively collected. Results: GATA3 was evaluable in 608 (87%) of the 702 cases; it was positive in 413 (68%) cases and negative in 195 (32%) cases. GATA3 positivity was significantly associated with lower grade (p < 0.0001), size (p = 0.0463), stage (p = 0.0049), ER+ (p < 0.0001), PR+ (p < 0.0001), HER2− (p = 0.0175), and p53 wild-type pattern (p < 0.0001). The median follow-up was 183 months, GATA3 positivity was associated with better overall survival (HR 0.70, p = 0.001), and its prognostic value was retained in a multivariate analysis. The association with better overall survival was stronger in patients with grade 1–2, pT1–2, pN0, stage I–II, ER+, PR+, ki-67 < 20%, HER2−, a wild-type p53 immunohistochemical pattern, and in luminal B BC. Conclusions: Our findings indicate that GATA3 is a positive prognostic marker in BC patients, especially in patients with biologically less aggressive BC. Incorporating GATA3 immunohistochemistry into routine practice could help further stratify BC patients for their risk.

Comparison of ER, PR and HER-2/NEU reactivity pattern with histological grade, type, tumour size, Lymphovascular invasion, mitotic index and lymph node status in breast cancer

Context: Breast cancer prognosis is related to a variety of clinical, pathologic and molecular features which include classical prognostic factors viz. Histological grade, morphological type, tumour size, mitotic index, Lymphovascular invasion and lymph node metastases. Estrogen and progesterone receptors (ER, PR) and more recently, HER-2/neu have with increasing importance influenced the management of the malignancy. The presence of hormone receptors (ER and PR) in the tumour tissue correlates well with the response to hormone therapy and chemotherapy. Aims: To assess ER, PR and Her2neu status in breast cancer and to compare ER, PR and Her2neu status with other prognostic factors like tumour size, pathological type, histological grade, lymph node status, mitotic index and Lymphovascular invasion in breast cancer. Methods and materials: A total of 100 cases of breast cancer reported at pathology department during a period from January 2019 to August 2020 are enrolled in the study. Representative sections with tumour and the adjacent normal breast tissue (internal control) are processed for ER, PR and HER-2/neu immuno-histochemical staining. Tumour size, morphological type, Histological grading, Mitotic index, Lymphovascular invasion, Lymph Node status were studied. Results: Occurrence of breast carcinoma is higher in older women (> 50 years of age). The prevalence of ER, PR, HER-2/neu expression are high (ER-73.0%, PR - 65.0% and HER-2/neu - 28.0%). About 14.0% tumour are triple negative. Increased HER2/neu positivity is noticed in ER and PR negative tumours. Two third (66.0%) tumour’s size is from 2 to 5 cm. Proportion of Grade II (39.0%) and Grade III tumour (37.0%) are high. Most common pathologic type of carcinoma is Infiltrating duct carcinoma, not otherwise specified (85.0%) followed by Mucinous carcinoma (5.0%), Invasive papillary carcinoma (4.0%) and Invasive lobular carcinoma (2.0%). PR positivity is increased with increasing tumour size. (p value = 0.01). PR positivity decreases with the increase in grade. (p value = 0.03). HER/ 2neu expression decreased with rising age. (p value = 0.03). Conclusion: The findings suggest that women in our population more often have histologically less aggressive breast carcinoma with a smaller number of triple negative tumours (14%), so they are likely to be more susceptible to conventional hormonal and targeted antibody treatment.

MCM2 Expression in Different Molecular Subtypes of Epithelial Breast Cancers and its Association with Clinicopathological Parameters and Ki-67 Expression

Introduction: Breast cancer is one of the most common malignancies, with few subtypes having a more aggressive outcome and resistance to conventional therapies, Triple Negative Breast Cancers (TNBCs) being one such variant. The Ki-67 lacks reproducibility and a standardised cut-off. MCM2 (Minichromosome Maintenance 2) has role in DNA repair and replication and its role as alternate marker for prognosis has been studied in this case. Aim: To study MCM2 expression with respect to histologic grade, stage, nodal status and molecular subtypes of breast carcinoma. Also, to look for any correlation between Ki-67 and MCM2 expressions. Materials and Methods: A cross-sectional, observational study conducted on a group of 20 patients who underwent mastectomy in a Tertiary Care Centre, R.G. Kar Medical College and Hospital, Kolkata, West Bengal, India, for a total duration of six months. Histologic grading, staging, nodal status was evaluated from Haematoxylin and Eosin (H&amp;E) stained sections. Formalin-Fixed Paraffin-Embedded (FFPE) blocks suitable for Immunohistochemistry (IHC) were selected and MCM2, Estrogen Receptor (ER), Human Epidermal Growth Factor Receptor 2 (HER2), Progesterone Receptor (PR)/neu and Ki-67 were performed. Scores given based on visual examination under light microscope. Analysis was done using IBM Statistical Package for the Social Sciences (SPSS) version 25.0 software. Results: Most of the subjects belonged to 41-55 years age group. Statistical significance was seen between high MCM2 and Ki- 67 expressions (p-value=0.0171) and high histologic grade and TNBCs (p-value=0.009). High MCM2 and Ki-67 expressions also come with increased risk for advanced disease. High Ki-67 is also a risk predictor for lymph node positive cases. Positive correlation was seen between MCM2 and (R)= 0.4318. Conclusion: The MCM2 is a predictor for adverse outcomes in breast carcinoma cases. It may serve as an alternative to Ki-67 as a proliferation marker, to guide clinicians in treatment strategies. Its role as a therapeutic target in aggressive breast carcinomas may be evaluated with larger study population in the future.

Cardiac radiation-induced sarcomas: A SEER population-based study and a literature review

PurposeThe aim of this study was to better understand the incidence and the clinical characteristics of cardiac radiation-induced sarcomas (RIS). Material and methodsWe used the surveillance, epidemiology, and end results (SEER) program cancer registry data, the largest cancer database in the United States in order to identify all cardiac RIS between 1973 and 2015. We relied on the Memorial Sloan–Kettering Cancer Center (MSKCC)-modified 1948 Cahan criterions for RIS identification. ResultsOut of 8,136,951 cancer patients from the SEER database, we identified 448 patients diagnosed with cardiac sarcomas. Of these 448 cardiac sarcoma patients, two were considered to have developed a cardiac RIS: a metastatic rhabdomyosarcoma occurring after one to two years following lung carcinoma irradiation, and a soft tissue sarcoma (of unspecified type) developed six years after radiation therapy for an aggressive left-sided breast carcinoma. Based on this observation, we estimated that cardiac RIS represented about 0.4% (95% CI 0.1%–1.6%) of all cardiac sarcomas. A literature review has been conducted and yielded three additional cases of cardiac RIS. ConclusionCardiac RIS are extremely rare malignancies, associated with a very pejorative prognosis. The two reported histologies are angiosarcomas and rhabdomyosarcomas, which might be over-represented among cardiac RIS. A metastatic evolution is possible for cardiac radiation-induced rhabdomyosarcomas. Surgical excision, when feasible, is a therapeutic option and is the only specific treatment reported to this date.

Potential Diagnostic and Prognostic Utility of miR-141, miR-181b1, and miR-23b in Breast Cancer.

miRNAs, a group of short noncoding RNAs, are key regulators of fundamental cellular processes and signaling pathways. Dysregulation of miRNA expression with known oncogenic or tumor suppressor functions has been associated with neoplastic transformation. Numerous studies have reported dysregulation of miRNA-141, miR-181b1, and miR-23b in a wide range of malignancies, including breast cancer. To the best of our knowledge, no previous study had demonstrated the expression of miR-141-3p, miR-181b1-5p, and miR-23b-3p in different histological grades and molecular subtypes of breast cancer. Here, we identified differential expression of these three miRNAs in breast cancer tissues compared with benign breast fibroadenomas. In addition, high expression levels of miR-141-3p and miR-181b1-5p are strongly associated with aggressive breast carcinomas. We also confirmed the clinical potential of using the three miRNAs individually or combined as diagnostic and prognostic markers in breast cancer. Using bioinformatics analyses, we identified 23 hub genes of these three miRNAs which are involved in key signaling pathways in breast cancer. Furthermore, the KM plotter online database analysis demonstrates the association between elevated expression of miR-141 and miR-181b and shorter overall survival of breast cancer patients. Together, our data suggest an oncogenic role of the studied miRNAs and highlight their molecular roles and potential clinical applications in breast cancer.