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Background: This study aims to deliver more insights on the impact of neoadjuvant treatment on Pd-L1 expression and to evaluate its correlation with clinicopathological factors. Methods: We reviewed 88 TNBC cases for the period 2021–2023. Data on age, tumor size, stage, and treatment were collected. Histological slides were assessed for subtype, grade, and TILs. A total of 48 received neoadjuvant treatment. HER2 and Ki67 were evaluated via immunohistochemistry. PD-L1 expression was tested on primary and residual tumors. Statistical analysis was performed using IBM SPSS (p < 0.05). Results: In this study, PD-L1 positive expression was found in 44.3% of primary tumors, with 52.9% of initially positive cases losing expression post-treatment. TILs were significantly higher in PD-L1-positive tumors (mean 41.79% vs. 27.55%, p = 0.001). A notable correlation was found between PD-L1 expression and Ki-67 proliferation index, with PD-L1-positive tumors having a median Ki-67 of 64.49 compared to 52.86 in negative cases (p = 0.015). Neoadjuvant immunotherapy led to a lower mean residual cancer burden (0.95 vs. 2.55, p = 0.002) compared to chemotherapy alone. Higher Ki-67 levels (≥50%) were associated with better treatment outcomes, showing a mean RCB score of 1.60 versus 3.16 for lower levels (p = 0.022). HER2-negative cases had a higher prevalence of favorable pathological response (54.5%) compared to HER2-low tumors (25%, p = 0.048), because of the strong correlation to high proliferative index. Conclusions: In conclusion, PD-L1 expression in TNBC shows significant discordance post-treatment, highlighting the need for routine testing and further research on predictive biomarkers. [ABSTRACT FROM AUTHOR]

Abstract Background Acinic cell carcinoma (AciCC) of the breast is a rare subtype of breast cancer. It was considered a low-grade triple-negative breast cancer (TNBC) with the potential to progress or transform into a high-grade lesion because of the molecular similarities with conventional aggressive TNBC in several genetic studies. Microscopically, the coexistence of classical low-grade and high-grade triple-negative components in breast AciCC is not uncommon. However, there is a scarcity of research on the comparative histopathological and genetic aspects of both components. Case presentation A 34-year-old woman with a nontender mass in the upper outer quadrant of the left breast was initially diagnosed with a malignant small round cell tumor (undifferentiated or poorly differentiated carcinoma) based on a preoperative biopsy, which was later identified as breast AciCC with a high-grade solid component. Left breast-conserving surgery with sentinel lymph node biopsy was performed. Microscopically, the breast AciCC consisted of a classical acinic component and a high-grade component. The latter demonstrated a solid sheet-like pattern characterized by large, round, pleomorphic or vesicular nuclei, prominent nucleoli, and frequent mitotic activities. Classical acinic architectures focally merged together to form solid nests and transited into high-grade areas. Remarkably, in the high-grade lesion, conventional immunochemical markers for breast AciCC, such as α1-antitrypsin (AAT), Lysozyme (LYS), Epithelial membrane antigen (EMA), S100 protein (S100), and cytokeratin (CK) were negative, whereas cell cycle protein D1 (cyclin D1) and vimentin showed diffuse expression. Next‑generation sequencing (NGS) revealed that 43.5% of variants were identical in both components. Furthermore, PAK5 mutation; copy number (CN) loss of CDH1, CHEK1, and MLH1; and CN gains of CDK6, HGF, and FOXP1 were identified in the high-grade lesion. The patient was treated with eight cycles of adjuvant chemotherapy (epirubicin combined with cyclophosphamide) and radiotherapy after surgery, and she is currently alive for 43 months with no metastases or recurrences. Conclusions This case demonstrates a comparative analysis of the histopathological and genetic characteristics of classical low-grade and high-grade components of AciCC within the same breast. This information may serve as a morphological and molecular basis for further investigation into the molecular mechanisms underlying high-grade lesions in breast AciCC.

Background: Acinic cell carcinoma (AciCC) of the breast is a rare subtype of breast cancer. It was considered a low-grade triple-negative breast cancer (TNBC) with the potential to progress or transform into a high-grade lesion because of the molecular similarities with conventional aggressive TNBC in several genetic studies. Microscopically, the coexistence of classical low-grade and high-grade triple-negative components in breast AciCC is not uncommon. However, there is a scarcity of research on the comparative histopathological and genetic aspects of both components. Case presentation: A 34-year-old woman with a nontender mass in the upper outer quadrant of the left breast was initially diagnosed with a malignant small round cell tumor (undifferentiated or poorly differentiated carcinoma) based on a preoperative biopsy, which was later identified as breast AciCC with a high-grade solid component. Left breast-conserving surgery with sentinel lymph node biopsy was performed. Microscopically, the breast AciCC consisted of a classical acinic component and a high-grade component. The latter demonstrated a solid sheet-like pattern characterized by large, round, pleomorphic or vesicular nuclei, prominent nucleoli, and frequent mitotic activities. Classical acinic architectures focally merged together to form solid nests and transited into high-grade areas. Remarkably, in the high-grade lesion, conventional immunochemical markers for breast AciCC, such as α1-antitrypsin (AAT), Lysozyme (LYS), Epithelial membrane antigen (EMA), S100 protein (S100), and cytokeratin (CK) were negative, whereas cell cycle protein D1 (cyclin D1) and vimentin showed diffuse expression. Next‑generation sequencing (NGS) revealed that 43.5% of variants were identical in both components. Furthermore, PAK5 mutation; copy number (CN) loss of CDH1, CHEK1, and MLH1; and CN gains of CDK6, HGF, and FOXP1 were identified in the high-grade lesion. The patient was treated with eight cycles of adjuvant chemotherapy (epirubicin combined with cyclophosphamide) and radiotherapy after surgery, and she is currently alive for 43 months with no metastases or recurrences. Conclusions: This case demonstrates a comparative analysis of the histopathological and genetic characteristics of classical low-grade and high-grade components of AciCC within the same breast. This information may serve as a morphological and molecular basis for further investigation into the molecular mechanisms underlying high-grade lesions in breast AciCC. [ABSTRACT FROM AUTHOR]

Background: This study aims to deliver more insights on the impact of neoadjuvant treatment on Pd-L1 expression and to evaluate its correlation with clinicopathological factors. Methods: We reviewed 88 TNBC cases for the period 2021–2023. Data on age, tumor size, stage, and treatment were collected. Histological slides were assessed for subtype, grade, and TILs. A total of 48 received neoadjuvant treatment. HER2 and Ki67 were evaluated via immunohistochemistry. PD-L1 expression was tested on primary and residual tumors. Statistical analysis was performed using IBM SPSS (p < 0.05). Results: In this study, PD-L1 positive expression was found in 44.3% of primary tumors, with 52.9% of initially positive cases losing expression post-treatment. TILs were significantly higher in PD-L1-positive tumors (mean 41.79% vs. 27.55%, p = 0.001). A notable correlation was found between PD-L1 expression and Ki-67 proliferation index, with PD-L1-positive tumors having a median Ki-67 of 64.49 compared to 52.86 in negative cases (p = 0.015). Neoadjuvant immunotherapy led to a lower mean residual cancer burden (0.95 vs. 2.55, p = 0.002) compared to chemotherapy alone. Higher Ki-67 levels (≥50%) were associated with better treatment outcomes, showing a mean RCB score of 1.60 versus 3.16 for lower levels (p = 0.022). HER2-negative cases had a higher prevalence of favorable pathological response (54.5%) compared to HER2-low tumors (25%, p = 0.048), because of the strong correlation to high proliferative index. Conclusions: In conclusion, PD-L1 expression in TNBC shows significant discordance post-treatment, highlighting the need for routine testing and further research on predictive biomarkers.

Simple Summary: Breast cancer is the most common cancer among women. Metaplastic breast carcinoma is a rare, heterogeneous group of invasive breast carcinomas that are more aggressive, poorly responsive to neoadjuvant chemotherapy, and have higher rates of chemoresistance than most other breast tumors. This article aims to provide an overview and summary of the current knowledge regarding the translational aspects of metaplastic breast carcinoma that could open the possibility of discovering specific treatment targets and knowing prognostic factors. Breast cancer is the most common cancer among women. Metaplastic breast carcinoma (MpBC) is a rare, heterogeneous group of invasive breast carcinomas, which are classified as predominantly triple-negative breast carcinomas (TNBCs; HR-negative/HER2-negative). Histologically, MpBC is classified into six subtypes. Two of these are considered low-grade and the others are high-grade. MpBCs seem to be more aggressive, less responsive to neoadjuvant chemotherapy, and have higher rates of chemoresistance than other TNBCs. MpBCs have a lower survival rate than expected for TNBCs. MpBC treatment represents a challenge, leading to a thorough exploration of the tumor immune microenvironment, which has recently opened the possibility of new therapeutic strategies. The epithelial–mesenchymal transition in MpBC is characterized by the loss of intercellular adhesion, downregulation of epithelial markers, underexpression of genes with biological epithelial functions, upregulation of mesenchymal markers, overexpression of genes with biological mesenchymal functions, acquisition of fibroblast-like (spindle) morphology, cytoskeleton reorganization, increased motility, invasiveness, and metastatic capabilities. This article reviews and summarizes the current knowledge and translational aspects of MpBC. [ABSTRACT FROM AUTHOR]

Objective: Estrogen receptor (ER) expression is an immunohistochemical marker that is examined in all invasive breast cancers and has prognostic and predictive value. ER-positive breast cancers refer to those that show positivity for ER at 1% cellular expression or higher. The American Society of Clinical Oncology/College of American Pathologists guidelines suggest using the term “low ER-positive breast cancer” for tumors with ER expression between 1% and 10%. Low ER-positive breast cancers exhibit similarities, in terms of disease-free survival and overall survival rates, to triple-negative breast cancers (TNBCs) rather than ER-positive breast cancers. In this study, our aim was to compare the clinicopathological characteristics of low ER-positive breast cancer cases diagnosed and followed in our clinic with TNBCs. Materials and Methods: A total of 26 cases of low ER-positive breast cancer diagnosed at University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital between 2010 and 2016 were retrieved from hospital records. The relevant histopathology slides and blocks were retrieved and re-evaluated retrospectively through microscopic examination. Thirteen cases that met the criteria were included in the study. Additionally, a consecutive series of 13 TNBC cases that did not receive neoadjuvant treatment within the same time period were identified. Results: In the low ER-positive group, the presence of tumor necrosis, as well as histological grade, nuclear grade and Ki-67 proliferation index were significantly lower compared to the TNBC group. Ductal carcinoma in situ (DCIS) was significantly more common in the low ER-positive group compared to the TNBC group. There were no significant differences between the two groups in terms of tumor size, histological tumor type, axillary lymph node involvement, tumor margins, peritumoral and intratumoral inflammation, local recurrence, distant metastasis, survival, and other characteristics. Conclusion: Although our study consisted of a small number of cases, some features showed significant differences between low ER-positive breast cancers and TNBCs. Histological and nuclear grades, as well as the presence of a DCIS component, were associated with low ER-positive breast cancer. In contrast, the presence of tumor necrosis, as well as Grade 3 features and a high Ki-67 proliferation index indicated TNBC.

Abstract Triple‐negative breast cancer (TNBC) is usually an aggressive disease with a poor prognosis and limited treatment options. The neurotrophic tyrosine receptor kinase (NTRK) gene fusions are cancer type‐agnostic emerging biomarkers approved by the Food and Drug Administration (FDA), USA, for the selection of patients for targeted therapy. The main aim of our study was to investigate the frequency of NTRK aberrations, i.e. fusions, gene copy number gain, and amplification, in a series of TNBC using different methods. A total of 83 TNBCs were analyzed using pan‐TRK immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), real‐time polymerase chain reaction (RT‐PCR), and RNA‐based next‐generation sequencing (NGS). Of 83 cases, 16 showed pan‐TRK positivity although no cases had NTRK‐fusions. Indeed, FISH showed four cases carrying an atypical NTRK1 pattern consisting of one fusion signal and one/more single green signals, but all cases were negative for fusion by NGS and RT‐PCR testing. In addition, FISH analysis showed six cases with NTRK1 amplification, one case with NTRK2 copy number gain, and five cases with NTRK3 copy number gain, all negative for pan‐TRK IHC. Our data demonstrate that IHC has a high false‐positive rate for the detection of fusions and molecular testing is mandatory; there is no need to perform additional molecular tests in cases negativity for NTRK by IHC. In conclusion, the NTRK genes are not involved in fusions in TNBC, but both copy number gain and amplification are frequent events, suggesting a possible predictive role for other NTRK aberrations.

Objective: Estrogen receptor (ER) expression is an immunohistochemical marker that is examined in all invasive breast cancers and has prognostic and predictive value. ER-positive breast cancers refer to those that show positivity for ER at 1% cellular expression or higher. The American Society of Clinical Oncology/College of American Pathologists guidelines suggest using the term "low ER-positive breast cancer" for tumors with ER expression between 1% and 10%. Low ER-positive breast cancers exhibit similarities, in terms of disease-free survival and overall survival rates, to triple-negative breast cancers (TNBCs) rather than ER-positive breast cancers. In this study, our aim was to compare the clinicopathological characteristics of low ER-positive breast cancer cases diagnosed and followed in our clinic with TNBCs. Materials and Methods: A total of 26 cases of low ER-positive breast cancer diagnosed at University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital between 2010 and 2016 were retrieved from hospital records. The relevant histopathology slides and blocks were retrieved and reevaluated retrospectively through microscopic examination. Thirteen cases that met the criteria were included in the study. Additionally, a consecutive series of 13 TNBC cases that did not receive neoadjuvant treatment within the same time period were identified. Results: In the low ER-positive group, the presence of tumor necrosis, as well as histological grade, nuclear grade and Ki-67 proliferation index were significantly lower compared to the TNBC group. Ductal carcinoma in situ (DCIS) was significantly more common in the low ER-positive group compared to the TNBC group. There were no significant differences between the two groups in terms of tumor size, histological tumor type, axillary lymph node involvement, tumor margins, peritumoral and intratumoral inflammation, local recurrence, distant metastasis, survival, and other characteristics. Conclusion: Although our study consisted of a small number of cases, some features showed significant differences between low ER-positive breast cancers and TNBCs. Histological and nuclear grades, as well as the presence of a DCIS component, were associated with low ER-positive breast cancer. In contrast, the presence of tumor necrosis, as well as Grade 3 features and a high Ki-67 proliferation index indicated TNBC. [ABSTRACT FROM AUTHOR]

Triple‐negative breast cancer (TNBC) is usually an aggressive disease with a poor prognosis and limited treatment options. The neurotrophic tyrosine receptor kinase (NTRK) gene fusions are cancer type‐agnostic emerging biomarkers approved by the Food and Drug Administration (FDA), USA, for the selection of patients for targeted therapy. The main aim of our study was to investigate the frequency of NTRK aberrations, i.e. fusions, gene copy number gain, and amplification, in a series of TNBC using different methods. A total of 83 TNBCs were analyzed using pan‐TRK immunohistochemistry (IHC), fluorescence in situ hybridization (FISH), real‐time polymerase chain reaction (RT‐PCR), and RNA‐based next‐generation sequencing (NGS). Of 83 cases, 16 showed pan‐TRK positivity although no cases had NTRK‐fusions. Indeed, FISH showed four cases carrying an atypical NTRK1 pattern consisting of one fusion signal and one/more single green signals, but all cases were negative for fusion by NGS and RT‐PCR testing. In addition, FISH analysis showed six cases with NTRK1 amplification, one case with NTRK2 copy number gain, and five cases with NTRK3 copy number gain, all negative for pan‐TRK IHC. Our data demonstrate that IHC has a high false‐positive rate for the detection of fusions and molecular testing is mandatory; there is no need to perform additional molecular tests in cases negativity for NTRK by IHC. In conclusion, the NTRK genes are not involved in fusions in TNBC, but both copy number gain and amplification are frequent events, suggesting a possible predictive role for other NTRK aberrations. [ABSTRACT FROM AUTHOR]

Objective To screen out the immune-related LncRNA genes in triple-negative breast cancer (TNBC) and to construct a prognostic prediction model of TNBC. Methods ① We downloaded the transcriptome RNA expression profiling raw data of TNBC tissues and para-cancer tissues from the Cancer Genome Atlas (TCGA) project, and combined with the Immport database to screen TNBC immune-related lncRNAs. Furthermore, univariate and multivariate Cox analyses were used to screen immune-related lncRNAs closely related to TNBC and prognosis, and then immune-related ln cRNAs closely related to prognosis were determined according to the optimal AIC value. ② Based on the immune-related lncRNAs, the prognostic prediction model of TNBC was constructed. ③ The TNBC patient samples were divided into highrisk and low-risk groups based on the median of the risk score values calculated from the TNBC prognostic risk model, and survival was compared between the high- and low-risk groups. ④ ROC and principal component analysis (PCA） were used to evaluate the predictive efficacy of the TNBC prognostic prediction model. ⑤ Multivariate Cox analysis was used to analyze the independence of TNBC prognostic prediction model in predicting efficacy. Results A total of 369 immune-related lncRNAs were obtained from 65 TNBC tissue samples. Three immune-related lncRNAs (AC090181. 2, LINC01235, and LINC01943） were obtained by univariate and multivariate Cox analyses, and the prognostic prediction model of TNBC was constructed. The formula of the model was as follows： risk score (RS） = (– 6. 24904×AC090181. 2） + (0. 240562×LINC01235） + (–2. 18153×LINC01943). There was significant difference between the high-risk group and the low-risk group (P<0. 001). The predictive model of TNBC had a good predictive effect on the prognosis of patients (AUC = 0. 910； the distribution of projection points was different between the high- and low-risk groups, and the discrimination degree was high). TNBC prognostic prediction model could predict TNBC prognosis independently (HR=1. 028，P< 0. 05). Conclusion We have successfully constructed a prognostic prediction model consisting of three immune-related LncRNAs (AC090181. 2, LINC01235, and LINC01943） closely related to prognosis, which can better predict the prognosis of TNBC patients. [ABSTRACT FROM AUTHOR]

Background: Metastatic breast carcinoma (mBC) is frequently encountered and may be challenging to diagnose as the tumor cells can morphologically resemble carcinomas of other primary origins. An additional challenge is that direct smears are often the only sample type available for immunostaining studies in cytology. Trichorhinophalangeal syndrome GATA‐binding type 1 1 (TRPS1) is a highly sensitive marker for BC compared to the commonly used marker GATA3, especially in triple‐negative BC (TNBC), in histologic samples. However, its sensitivity and specificity in mBC and other GATA3‐positive tumors have not been studied. Methods: The authors identified the following cytology cases: 37 GATA3‐positive mBC cases and 19 available cases that were deemed mBC but were GATA3‐negative during the original case workup and five cases of each of eight epithelioid entities known to have high rates of GATA3 positivity and commonly seen in cytology practice. Immunostainings of TRPS1 and GATA3 were performed on the chosen smears following standard protocols. Results: TRPS1 was positive in all 37 GATA3‐positive mBC cases and in 18 of the 19 GATA3‐negative mBC cases. TRPS1 was negative in all five of the seven frequently GATA3‐positive epithelioid entities, with the exception of salivary duct carcinomas where GATA3 was positive in a rate ranging 60%–100% among them. Conclusions: TRPS1 is as sensitive as GATA3 in GATA3‐positive mBC and is more sensitive than GATA3 in TNBC. TRPS1 is negative in most GATA3‐positive nonbreast tumors. Thus, the combination of TRPS1 and GATA3 could be used to differentiate breast primary from others in most situations. TRPS1 is more sensitive than GATA3 in triple‐negative breast carcinoma and is more specific than GATA3 in entities reportedly positive for GATA3 on cytology smears. [ABSTRACT FROM AUTHOR]

A 48-year-old female presented to the ED with worsening headache and neck pain for the past week. Her medical history is significant for recurrent left-sided triple-negative breast cancer (TNBC) with metastasis to the chest wall, liver, and lungs, initially diagnosed two years ago. She underwent a left-sided mastectomy and received radiation therapy and chemotherapy. Physical examination was remarkable for nuchal rigidity and photophobia. MRI of the brain with contrast was performed, and the results were consistent with the new calvarium, skull, and upper cervical spine osseous metastases without any intracranial metastatic disease. This case report presents a rare cause of nuchal rigidity and photophobia due to an uncommon metastatic pattern in a patient with TNBC., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Katkov et al.)

Neoadjuvant chemotherapy (NAC) is increasingly used for high-risk breast cancer to achieve pathologic complete response (pCR), an indicator of event-free survival and favorable survival outcomes. Integrating MRI and Ki-67 biomarker analysis into predictive models offers a promising approach to optimize NAC response assessment and guide personalized treatment strategies. This study evaluates the validity of combined MRI and Ki-67 metrics for predicting pCR. We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, including studies on NAC-treated breast cancer patients assessed by MRI and Ki-67. The predictive models were evaluated based on key parameters, including MRI-based tumor size reduction and Ki-67 levels, with outcomes measured by area under the receiver operating characteristic curve (AUC) and calibration metrics. Findings across ten studies consistently show that high Ki-67 levels and significant tumor size reduction on MRI are predictive of pCR, achieving AUCs near 0.90. The analysis highlighted that models integrating MRI with Ki-67 metrics outperformed single-modality approaches, showing enhanced predictive accuracy and calibration. However, high heterogeneity (I² = 77%) was noted, suggesting variability in imaging and Ki-67 assessment protocols across studies. This study underscores the combined utility of MRI and Ki-67 for the non-invasive prediction of pCR, offering both structural and biological insights into tumor responsiveness. The results align with prior research, affirming the role of Radiomic-clinicopathological models in providing a more comprehensive assessment compared to individual markers. Further refinement of imaging and biomarker protocols could improve model reproducibility and applicability. Our findings highlight the robust predictive accuracy of MRI-Ki-67 integrated models for assessing pCR, marking a significant step toward personalized cancer care. Future studies should focus on refining these models with additional biomarkers and standardized protocols, facilitating their integration into routine clinical oncology to enhance treatment decision-making and patient outcomes., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Kolli et al.)

Triple-negative breast carcinoma (TNBC) remains a formidable clinical hurdle owing to its high aggressiveness and scant therapeutic options. Nonetheless, the evolving landscape of immunotherapeutic strategies opens up promising avenues for tackling this hurdle. This review discusses the advancing immunotherapy for TNBC, accentuating personalized interventions due to tumor microenvironment (TME) diversity. Immune checkpoint inhibitors (ICIs) hold pivotal significance, both as single-agent therapies and when administered alongside cytotoxic agents. Moreover, the concurrent inhibition of multiple immune checkpoints represents a potent approach to augment the efficacy of cancer immunotherapy. Synergistic effects have been observed when ICIs are combined with targeted treatments like PARP inhibitors, anti-angiogenics, and ADCs (antibody-drug conjugates). Emerging tactics include tumor vaccines, cellular immunotherapy, and oncolytic viruses, leveraging the immune system's ability for selective malignant cell destruction. This review offers an in-depth examination of the diverse landscape of immunotherapy development for TNBC, furnishing meticulous insights into various advancements within this field. In addition, immunotherapeutic interventions offer hope for TNBC, needing further research for optimization., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Triple negative breast carcinoma (TNBC) has the highest mortality among all the breast carcinoma subtypes, but paradoxically, it shows the best response to neoadjuvant chemotherapy (NACT). Tumor infiltrating lymphocytes (TIL) density has been shown to have prognostic significance in TNBC. However, there are limited data on TIL subpopulation and their association with response to NACT in TNBC.Materials and Methods: The study included 80 consecutive patients with TNBC prospectively diagnosed for two and half years, who underwent tru-cut biopsy before NACT, followed by subsequent definite surgical procedures. Global TIL profile and immunohistochemistry (IHC) analysis of CD3, CD4, CD8, CD20, and CD56 were done on all baseline tru-cut biopsies and post-NACT surgical specimens.Results: Almost half the patients were postmenopausal with a mean age of 45.89 ± 4.62 years. The majority had low CD3, low CD4, low CD56, low CD20, and high CD8 positivity in both pre- and post-NACT specimens. On multivariate analysis, low CD3, CD4, CD56 and CD 20 were established as independent predictor of poor pathologic response (PR). Low CD4 (adjusted odds ratio [OR]: 228.46) was associated with the highest OR for poor PR. Low CD8 was associated with significantly decreased odds of poor PR on univariate analysis (OR: 0.26), but it was not been established as an independent predictor of PR on multivariate logistic regression. NACT did not significantly alter the profile of TILs.Conclusions: TIL profile with low CD3, CD4, CD20, and CD56 expression predicts PR to NACT in TNBC and may thus help in prognostication of these patients. [ABSTRACT FROM AUTHOR]

Objective To observe the effects of cyperenone combined with carboplatin on the proliferation and apoptosis of triple-negative breast cancer cell line MDA-MB-231, and to explore their mechanism. Methods MDA-MB-231 cells were divided into four groups: simple cell group, carboplatin-treated group, cyperenone-treated group, and cyperenone combined with carboplatin group. DMSO was added to the simple cell group, carboplatin (20 μmol/L) was added to the carboplatin group, cyperenone (0. 4 mmol/L) was added to the carboplatin-treated group, and carboplatin (20 μmol/L) and cyperenone (0. 4 mmol/L) were added to the carboplatin combined with carboplatin group. The cell survival rate of each group was measured by CCK-8 assay. The cell cloning ability of each group was observed by cell cloning experiment, which was expressed by cell colony number. The distribution of cell cycle and the rate of apoptosis were observed by flow cytometry. The endoplasmic reticulum stress-related proteins PERK, CHOP and apoptosis-related proteins BAX and Bcl-2 were detected by Western blotting. Results The cell survival rates of the carboplatin group and cyperenone group were lower than that of the simple cell group, while the cell survival rate of the cyperenone combined with carboplatin group was lower than those of the other three groups (all P<0. 05). The number of cell colonies in the simple cell group, carboplatin-treated group, cyperenone-treated group, and cyperenone combined with carboplatin group were 328 ± 18, 204 ± 10, 138 ± 13 and 47 ± 5, respectively, and there was significant difference between groups (all P<0. 05). The cell cycle of MDA-MB-231 was blocked in the G2/M phase in the carboplatin group, MDA-MB-231 cell cycle was blocked in the G0/G1 phase in the cyperenone group, and cell cycle of MDA-MB-231 was both blocked in the G2/M phase and G0/ G1 phase in the cyperenone combined with carboplatin group. The apoptosis rates of the carboplatin group and cyperenone group were higher than that of simple cell group, while the apoptosis rate of the cyperenone combined with carboplatin group was higher than those of the other three groups (all P<0. 05). Compared with the simple cell group, the relative expression levels of PERK, CHOP and Bax proteins significantly increased and the relative expression of Bcl-2 protein significantly decreased in the carboplatin group and cyperenone group (all P<0. 05). Compared with the other three groups, the relative expression levels of PERK, CHOP and Bax proteins significantly increased, and the relative expression of Bcl-2 protein significantly decreased in the cyperenone combined with carboplatin group (all P<0. 05). Conclusion The combination of cyperenone and carboplatin can inhibit the proliferation and promote the apoptosis of triple-negative breast cancer cells, and their mechanism may be related to the regulation of endoplasmic reticulum stress-mediated apoptosis pathway. [ABSTRACT FROM AUTHOR]

Abstract Background High grade basal-like breast carcinomas are triple negative, express basal cytokeratins, and are known for the overall poor prognosis and aggressive behavior. HPV related multiphenotypic sino-nasal carcinoma has overlapping histology with basal-like breast carcinomas, but carry the defining feature of association with high risk HPV. Case presentation We present a case of a perimenopausal woman with a non-healing ulcerated lesion involving the nipple and breast following a trauma. Biopsy performed showed an HPV-positive basal-like carcinoma with squamous differentiation involving the breast, analogous to multiphenotypic carcinoma previously described in the sinonasal tract. Conclusion This is the first report of a case of a high- risk HPV related basal-like carcinoma with squamous differentiation, described in the literature. We highlight the morphology and immunophenotype of this lesion and its recognition when compared to other multiphenotypic lesions of the breast, and suggest that pathologists should consider HPV evaluation when encountering similar basal-like tumors involving the breast.

Background Breast cancer (BC) is the leading cause of cancer-related deaths in women worldwide. There has been a significant increase in the incidence of BC in Pakistan. Family history, older age, obesity, tobacco use, oral contraceptive use, early menarche, and hormonal replacement therapy are among the major risk factors. The most common histological subtype of BC is invasive ductal carcinoma (IDC). Molecular subtypes of BC include mainly Luminal A, Luminal B, human epidermal growth factor receptor 2 (HER-2) enriched, and triple-negative BC subtypes, with the triple-negative subtype having the worst prognosis. CK5/6 serves as a basal keratin biomarker. This aimed to assess the expression of CK5/6 in IDC of the breast belonging to different molecular classes and to compare its expression with traditionally defined prognostic factors for different molecular subtypes. Methodology A cross-sectional, observational study was conducted at the Chughtai Institute of Pathology after approval from the Institutional Review Board (approval number: 1198/IRB/CIP). All cases during a period of six months (April 2023 to September 2023) were sampled using non-probability convenient sampling. All mastectomy samples diagnosed as IDC were included in the study. After standard tissue processing, paraffin tissue blocks and slides were prepared followed by hematoxylin & eosin staining. Hormonal receptors (estrogen receptor, progesterone receptor, HER-2) were assessed for cases to segregate them into molecular subtypes. CK5/6 antibody was then applied and the data were collected on a pre-designed proforma. SPSS version 25.0 (IBM Corp., Armonk, NY, USA) was used for data analysis. Results Of a total of 85 cases, 19 (22.3%) were positive for CK5/6. Of these 19 cases, the majority (68%, p = 0.001) belonged to the triple-negative class of tumors, comprising 13 cases. No case from the Luminal A class showed expression for CK5/6 stain (p = 0.028). Overall, four cases of the Luminal B subtype showed CK5/6 positivity (10.8%, p = 0.022) while two cases of the HER-2-enriched subtype were positive for the stain (33.3%, p > 0.05). These results were analyzed in relation to different prognostic factors. The majority of CK5/6-positive cases showed lymphovascular invasion (42%) and belonged to grade 3 tumors (57.8%). Conclusions The expression of CK5/6 in IDC of the breast is associated with poor prognostic factors such as triple-negative molecular subtypes, high histological grade, lymphovascular invasion, positive nodal status, and high pathological stage., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Institutional Review Board, Chughtai Institute of Pathology issued approval 1198/IRB/CIP. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Yasin et al.)

Triple-negative breast carcinomas constitute a wide spectrum of lesions, mostly being highly aggressive. Nevertheless, some special histologic subtypes can have low malignant potential. The purpose of the present paper is to review diagnostic criteria and prognostic parameters of breast neoplasms of special histotypes. Specifically, adenoid cystic carcinoma, adenomyoepithelioma, acinic cell carcinoma, mucoepidermoid carcinoma, tall cell carcinoma with reverse polarity, and secretory carcinoma will be discussed. For each tumour, definition and morphological and molecular features, together with prognostic parameters, will be presented. Paradigmatic cases will be illustrated. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to measure the expression of PD-L1, CD1a (a marker for immature dendritic cells), and CD83 (a marker for mature dendritic cells) and further examine the associations of PD-L1, CD83, and CD1a with overall survival (OS) in triple-negative breast carcinoma patients. Methods: PD-L1, CD1a, and CD83 expression in breast carcinoma tissues and CD83 expression in lymph node tissues were examined by immunohistochemistry and tissue microarray in 159 patients. Patients were classified into the low, medium, and high PD-L1, CD1a, and CD83 levels. Pearson χ2 test was used to analyze the correlations between PD-L1, CD1a, and CD83. The Kaplan-Meier method was used to calculate the OS. Multivariate analysis was used to identify determinants of 3- and 5-year OS. Results: 25.1, 25.8, and 49.1% of the patients had low, medium, and high PD-L1 levels, respectively. PD-L1 levels significantly correlated with CD1a (r = 0.30409, p < 0.001) and CD83 levels (r = 0.6146, p < 0.001) in breast carcinoma tissue, as well as CD83 levels (r = 0.17508, p = 0.027) in lymph node. The median OS was 83 months (range 12–106), and the 3- and 5-year OS rates were 94.97% (95% CI 91.57–98.37) and 86.79% (95% CI 81.53–92.06), respectively. Moreover, patients with high median CD1a levels had a significantly lower 5-year OS rate (75.6%) than those with low median CD1a levels (93.5%, p = 0.038). Conclusion: PD-L1, CD1a, and CD83 are variably expressed in triple-negative breast carcinoma tissues, and PD-L1 expression correlates with CD1a and CD83. Higher CD1a levels correlate with PD-L1 expression and predict worse OS in triple-negative breast carcinoma. [ABSTRACT FROM AUTHOR]

Acinic cell carcinoma of the breast is a rare subtype of triple-negative breast cancer that recapitulates the appearance of tumors seen in salivary glands. We present the case of a 42-year-old woman with an irregular, nontender mass above the left nipple during routine obstetric appointment at 24 weeks gestation. She was subsequently diagnosed with triple-negative invasive ductal carcinoma of the left breast, Nottingham grade 3, via core needle biopsy. She was treated with neoadjuvant therapy (doxorubucin and cyclophosphamide) antenatally and paclitaxel in the postpartum period followed by left mastectomy with sentinel node biopsy. The carcinoma in the mastectomy specimen showed a spectrum of morphologic patterns with immunohistochemistry revealing strong positivity for alpha-1-antichymotrypsin, epithelial membrane antigen (EMA), lysozyme, and S100. The histomorphology paired with the immunoprofile led us to the diagnosis of acinic cell carcinoma. We retrospectively performed immunostains in the core biopsy specimen, which demonstrated GATA-3 and DOG-1 positivity. Next-generation sequencing of the postneoadjuvant specimen using a 70-gene panel revealed 2 single-nucleotide variant (SNV) mutations: tumor protein 53 (TP53) (c.747G>T) SNV mutation and rearranged during transfection (RET) (c.2899G>A) SNV mutation. [ABSTRACT FROM AUTHOR]

Triple-negative breast carcinoma (TNBC) is an aggressive disease that has a poor prognosis since it lacks effective treatment methods. Neurotrophic tyrosine receptor kinase (NTRK) fusion genes are excellent candidates for targeted RTK inhibitor therapies and there are available targeted therapy drugs for the treatment of TRK fusion-positive tumors in a tumor agnostic pattern. Our study was designed to investigate the NTRK gene fusion status in TNBC patients and to determine whether RTK-targeted therapies are suitable for TNBC patients. A total of 305 TNBC patients were enrolled in our study. IHC was employed as a prescreening method, and IHC positive cases were further submitted for evaluation by FISH, RT-PCR, and NGS methods. NTRK IHC was evaluated successfully in 287 of the 305 cases, and there were 32 (11.15%) positive cases. FISH was carried out in the 32 IHC positive cases. There were 13 FISH-positive cases if the threshold was set as >15% of the 100 counted tumor cells having a split orange and green signal with more than one signal diameter. There were only 2 FISH-positive cases if the cutoff value was defined as >15% of the counted tumor cells having a split signal with more than two signal diameter widths. One of the FISH-positive cases had a separate NTRK3 FISH signal in 88% of the tumor cells, and its IHC result was strong nuclear staining in all the tumor cells. After evaluation of the morphology, it was re-diagnosed as secretory breast carcinoma, and the NGS result confirmed that it had a NTRK3-ETV6 fusion gene. The other FISH-positive cases were all negative for NTRK gene fusion in the NGS or RT-PCR examination. The NTRK gene fusion rate was low in our TNBC cohort. NTRK gene fusion may be a rare event in TNBC. The high false-positive rate of NTRK gene fusion detected by IHC questions its role as a prescreening method in TNBC. More data may be needed to determine a suitable threshold for NTRK FISH in TNBC in the future. More studies are needed to confirm whether RTK-targeted therapies are appropriate treatments for TNBC patients.

Purpose: Two types of macrophages are present in tumor microenvironment. M1 macrophages exhibit potent anti-tumor properties, while M2 macrophages play the pro-tumoral roles. The presence of M2 macrophages is associated with worsened overall survival in triple-negative breast carcinoma (TNBC) patients. However, the relationship between M2 macrophages and response to neoadjuvant chemotherapy (NAC) is unknown. Methods: M2 macrophages were investigated on biopsy whole sections from 66 TNBCs treated with NAC by CD163 together with other immune checkpoint markers (PD1, PD-L1 and CD8) using a multi-color immunohistochemical multiplex assay. Results: Incomplete response was significantly associated with older age, lower PD-L1 expression (tumor and stroma), lower levels of CD8-positive TILs in stroma, but higher level of CD163-positive macrophages, with the level of CD163-positive M2 macrophages in peritumoral area as the strongest factor. Conclusions: Our data have demonstrated that the level of CD163-positive M2 macrophages was significantly higher in TNBC patients with incomplete response than patients with complete response, suggesting M2 macrophages' important role in predicting TNBC patients' response to NAC. [ABSTRACT FROM AUTHOR]

Background: Triple-negative breast cancer constitutes approximately 12%-17% of all breast cancer cases, and >33% of patients develop distant metastases. Systemic cytotoxic chemotherapy is the primary treatment for patients with metastatic triple-negative breast cancer; however, the role of first-line platinum-based chemotherapy in these patients remains controversial. This meta-analysis evaluated the efficacy and safety of platinum-based first-line chemotherapy for patients with metastatic triple-negative breast cancer. Methods: We systematically searched the PubMed, Embase, Cochrane, and Clinical Trials registry databases up to June 1, 2020 to identify randomized controlled trials that investigated platinum-based vs. first-line platinum-free chemotherapy in patients with metastatic triple-negative breast cancer. We used fixed and random effects models to calculate pooled hazard ratios and odds ratios with 95% confidence intervals for progression-free and overall survival, objective response rates, and grade 3 and 4 adverse events. Results: Four randomized controlled trials (N = 590 patients) were included. Platinum-based chemotherapy significantly increased the objective response rates from 43.1% to 62.7% (odds ratio 2.34, 95% confidence interval 1.66-3.28, P < 0.001). Three randomized controlled trials (N = 414 patients) reported survival outcomes. Patients administered platinum-based regimens showed significantly longer progression-free survival (hazard ratio 0.55, 95% confidence interval 0.37-0.82, P = 0.004) and a nonsignificant trend toward improved overall survival (hazard ratio 0.76, 95% confidence interval 0.57-1.00, P = 0.05). Only 2 studies reported the rates of grade 3 and 4 adverse events; grade 3-4 thrombocytopenia was more commonly associated with platinum-based chemotherapy (odds ratio 7.54, 95% confidence interval 1.37-41.60, P = 0.02) and grade 3-4 fatigue with platinum-free chemotherapy (odds ratio 0.23, 95% confidence interval 0.08-0.68, P = 0.008). Conclusions: First-line platinum-based chemotherapy was associated with significantly increased objective response rates, longer progression-free survival, and a nonsignificant trend toward improved overall survival in patients with metastatic triple-negative breast cancer at the high risk of grade 3-4 thrombocytopenia. [ABSTRACT FROM AUTHOR]

Neoadjuvant chemoimmunotherapy with pembrolizumab now defines the standard of care for early high-risk triple-negative breast cancer (TNBC). However, the role of pembrolizumab in neoadjuvant therapy (NAT) for estrogen receptor-positive (ER+) breast cancer remains uncertain. A 39-year-old G2P2 female discovered a palpable mass in the right breast while breastfeeding her 7-month-old child, leading to the diagnosis of a high-grade ER+ (80% moderate staining), human epidermal growth factor receptor 2-negative (ErbB2-) invasive ductal carcinoma with axillary nodal involvement. Gene expression profiling with the MammaPrint 70-gene signature and BluePrint 80-gene signature revealed a tumor with high-risk, basal-type biology. The multidisciplinary breast cancer team recommended NAT with pembrolizumab, carboplatin, paclitaxel, doxorubicin, and cyclophosphamide. Within six weeks, the patient exhibited a remarkable response, with no palpable mass or lymph node, and post-treatment examinations confirmed a complete clinical and radiologic response. The patient underwent lumpectomy and sentinel lymph node biopsy, revealing a pathological complete response with minimal ductal carcinoma in situ and negative axillary nodes. Adjuvant radiation therapy was administered, and the patient completed adjuvant pembrolizumab, currently showing no evidence of recurrence. This case underscores the potential benefits of neoadjuvant chemoimmunotherapy for patients with ER+ErbB2- high-risk, basal-type breast cancer. The use of immunotherapy in patients with pregnancy-associated breast cancer remains to be further investigated., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. University of Nebraska Medical Center issued approval 0430-23-EP. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: Jairam Krishnamurthy, MD declare(s) personal fees from Agendia/Gilead Sciences/AstraZeneca Pharmaceuticals/TerSera Therapeutics/Genzyme Corporation. Dr. J. Krishnamurthy reports consulting and speaker fees from Agendia, consulting fees from Gilead Sciences, consulting fees with AstraZeneca Pharmaceuticals, consulting fees with TerSera Therapeutics, and consulting fees with Genzyme Corporation. Juan A. Santamaria-Barria, MD declare(s) food and beverage payments from Agendia/Axogen/Sientra. Dr. J. Santamaria reports food and beverage payments from Agendia, Axogen, and Sientra. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Jiang et al.)

Extremophilic organisms have the potential to tolerate extremely challenging environments of nature. This property can be accredited to its production of novel secondary metabolites that possess anticancer and other pharmaceutical values. The present study was aimed to investigate the anticancer activity of crude secondary metabolite extract (CSME) obtained from the radiation-tolerant bacterium Deinococcus radiodurans in triple-negative human breast carcinoma (MDA-MB-231) cells. The 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay showed the antiproliferative potential of CSME in MDA-MB-231 cells (IC50 = 25 μg/ml) and MCF-7 cells (IC50 = 10 μg/ml). Further, the CSME treatment led to the production of intracellular reactive oxygen species (ROS) and nuclear membrane alterations with the formation of apoptotic bodies in MDA-MB-231 cells. Considerable DNA damage and low antioxidant status were observed in CSME-treated MDA-MB-231 cells. The results also showed that the CSME treatment induced apoptotic markers expression in MDA-MB-231 cells. Western blot results illustrated significant upregulation of p53, caspase-3, and caspase-9 proteins expression. Then, we analyzed the presence of secondary metabolites which may be linked with antiproliferative potential of CSME by gas chromatography-mass spectrometry (GC-MS). The results illustrated the presence of 23 bioactive compounds some of which are already reported to possess anticancer properties. The study indicates that the CSME of D. radiodurans possess anticancer properties and exhibit the potential to be used as an anticancer agent.

INTRODUCTION: The present histologic and immunohistochemical prognostic markers of breast carcinoma do not effectively identify the subset of patients with poor prognosis. Y-Box binding protein 1 (YB1) is a novel biomarker which may identify and aid in targeted personalized therapy for such patients. MATERIALS AND METHODS: The study was conducted on histopathology specimens of 74 patients of breast carcinoma who had undergone modified radical mastectomy. YB1 immunohistochemistry (IHC) was performed on manual tissue microarray blocks (each having 15 cores). The YB1 expression was quantified in terms of “immunoreactive score” which was correlated with clinical parameters, hormone receptor status, and Her2neu overexpression by IHC. The Her2neu status of the equivocal cases was further evaluated by fluorescent in situ hybridization (FISH). RESULTS: YB1 was positive in 36/74 (48.6%) cases. On IHC and analysis by FISH, 25/74 (34%) cases had Her2neu overexpression. Estrogen receptor (ER) and progesterone receptor (PR) positivity was found in 42% and 36.5% cases, respectively. YB1 immunopositivity was negatively correlated with ER and PR expression, but showed a significant positive correlation with Her2neu expression. No correlation was found with other clinical parameters, tumor stage, and grade, except lymph node involvement, which showed a positive association with YB1 expression. Triple-negative breast carcinoma constituted 25.6% of the total cases, out of which 73.6% were YB1 positive. CONCLUSION: This study found that YB1 has an association with Her2neu expression. It may in future provide a therapeutic target in Her2neu overexpressing tumors.

GATA3 is the most used marker to determine tumors' breast origin, but its diagnostic value in triple-negative breast cancer (TNBC) is limited. The newly identified TRPS1 is highly sensitive and specific for breast carcinoma, especially TNBC. Here, we compared the utility of TRPS1 and GATA3 expression in a subset of salivary gland-type breast tumors (including adenoid cystic, acinic cell, and secretory carcinomas [AdCC, ACC, and SC, respectively]), and we compared TRPS1 and GATA3 expression of such tumors with head and neck (H&N) and AdCC of upper respiratory tumors. TRPS1 was strongly expressed in basaloid TNBC and AdCCs with solid components, including 100 % of mixed and solid breast AdCCs. However, TRPS1 was positive in only 50 % cribriform AdCCs. Expression patterns of TRPS1 in H&N and upper respiratory AdCC were similar. TRPS1 was positive in 30 % of H&N cribriform AdCCs but was strongly expressed in mixed AdCC (67 %) and solid AdCC (100 %). In the upper respiratory AdCCs, TRPS1 was positive in 58.4 % of cribriform AdCCs and positive in 100 % of AdCCs with solid components. On the contrary, GATA3 was negative in predominant AdCCs of the breast, H&N, and upper respiratory tract. These data show that GATA3 and TRPS1 expression varies AdCCs. In addition, TRPS1 and GATA3 expression patterns were similar SC and ACC of breast and H&N. Both markers were positive in SC and negative in ACC. Therefore, TRPS1 and GATA3 cannot be used to differentiate salivary gland-type carcinomas of breast origin from those of upper respiratory or H&N origin., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The study aim is to model local data for costs and health benefits of atozolizumab (АТЕ) + nanoparticle albumin-bound paclitaxel (NABPAC) in comparison with monotherapy NAB-PAC for treatment of patients with metastatic triple-negative breast carcinoma (mTNBC) in Bulgaria. The input data in the model are the assessed therapeutic efficacy and safety in the IM passion randomized multicenter clinical trial. Modeling was performed using the TreeAge Pro Healthcare Software product. A cost-effectiveness analysis was made and incremental cost-effectiveness ratio (ICER) of АТЕ + NAB-PAC in comparison with NAB-PAC for treatment of patients with mTNBC was calculated. The results showed that the combination of immunotherapy (atezolizumab) and chemotherapy (NAB-paclitaxel) prolongs statistically significantly the disease progression-free survival and the overall survival. Modeling of data for further health benefits and costs based on the clinical endpoints identified and measured in the IM passion 130 clinical trial concluded that the combination of immunotherapy and chemotherapy demonstrates therapeutic superiority in comparison with the separate administration of chemotherapy but it is not a cost-effective therapy due to its high price. [ABSTRACT FROM AUTHOR]

Purpose: Ultrasound-targeted microbubble destruction (UTMD) has been reported to be a meritorious technique for drug targeting delivery. In this study, we aimed to evaluate the synergistic antiangiogenic effect of UTMD combined with Endostar on triple-negative breast carcinoma tumors. Materials and methods: The lipid-shelled microbubbles (MBs) conjugated with Endostar were constructed using a biotin–avidin bridging chemistry method, and the morphological characteristics and drug-conjugating content were determined. MBs were administered intravenously to nude mice bearing MDA-MB-231 breast carcinoma xenografts and ultrasound exposure followed. The tumor microcirculation was observed by contrast-enhanced ultrasonography (CEUS) and the Endostar biodistribution was detected by enzyme-linked immunosorbent assay. Twenty-four breast carcinoma-bearing nude mice were divided into four groups. After treatment, every 3 days for 15 days the in vivo antitumor effects were assessed by calculating the tumor growth inhibition rate (TGIR). The tumor microcirculation was observed by CEUS, the tumor microvessel density (MVD) was calculated by immunohistochemistry under a microscope, and the vascular endothelial growth factor (VEGF) gene expression was detected by real-time quantitative polymerase chain reaction. Results: The prepared Endostar-conjugated MBs were round and well-dispersed with a mean size of 2.8 ± 0.7 µm and a drug conjugating content of 800.72 ± 70.53 µg/108 MBs. UTMD blocked the tumor microcirculation, and improved Endostar release in the targeted tumor tissue with a drug content of 1.12 ± 0.43 µg/gram protein, which was about three times higher than that in Endostar group or Endostar conjugated MBs group. Endostar-conjugated MBs combined with UTMD treatment achieved the optimal antitumor effects in vivo with a TGIR of 46.29%, and apparent antiangiogenic effects with minimal tumor blood perfusion, MVD and VEGF gene expression level. Conclusion: UTMD can improve Endostar delivery in the targeting tumor tissue and mediate synergistic antiangiogenetic and antitumor effects, which may be a potential therapeutic strategy for refractory breast cancer. [ABSTRACT FROM AUTHOR]

Trichorhinophalangeal syndrome type 1 (TRPS1) has been reported to be a sensitive and specific immunohistochemical (IHC) marker for breast carcinomas, especially when determining primary site of origin. However, there is limited data on TRPS1 expression in prostate and bladder cancers. A two-phase study was performed with 1) an exploratory cohort analyzing TRPS1 gene alterations in prostate, bladder, and breast carcinoma and TPRS1 mRNA expression data in prostate and bladder carcinoma; and 2) TRPS1 and GATA3 IHC in a confirmatory cohort in prostate, bladder, and breast carcinoma samples. Gene alterations were identified in a subset of breast, bladder, and prostate carcinomas and mRNA was consistently detected. In the IHC cohort, 183/210 (87.1 %) of breast, 22/69 (31.9 %) of prostate, and 20/73 (27.4 %) of urothelial carcinomas showed staining with TRPS1. Intermediate to high expression of TRPS1 was observed in 173/210 (82.8 %) of breast, 17/69 (24.6 %) of prostate, and 15/73 (20.5 %) of urothelial carcinomas. Furthermore, in prostate cancer, 26.9 % of pelvic lymph node metastases and 50 % in sites of distant metastases showed expression. Increased TRPS1 mRNA expression (p = 0.032) and IHC expression (p = 0.040) correlated with worse overall survival in bladder cancer. By comparison, GATA3 IHC stained 136/210 (64.8 %) of breast, 0/69 (0 %) of prostate, and 63/73 (93 %) of bladder carcinomas. Intermediate to high expression of GATA3 was seen in 131/210 (62.4 %) of breast and 63/73 (93 %) of bladder carcinomas. This study shows there is significant staining of TRPS1 in bladder and prostate cancers. As a result, comprehensive studies are needed to establish the true specificity of TRPS1 IHC stain across various tumor types before its widespread clinical adoption., Competing Interests: Declaration of competing interest The authors have no relevant conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Second primary malignancies (SPMs) are known to be associated with neuroendocrine tumors (NETs). The association necessitates a careful assessment of the dual-tracer positron emission tomography–computed tomography (PET-CT) imaging findings to identify these malignancies earlier. Such early diagnosis can provide incremental benefit for screening these SPMs apart from their known applications in the management of NETs. A case of incidentally detected metachronous triple-negative breast carcinoma on dual-tracer PET-CT imaging is presented using 18fluoro-2-deoxy-D-glucose (FDG) and 68Ga-DOTATATE that showed a high uptake on FDG but no uptake on somatostatin receptor-based imaging. [ABSTRACT FROM AUTHOR]

Objective: Estrogen receptor (ER) expression is an immunohistochemical marker that is examined in all invasive breast cancers and has prognostic and predictive value. ER-positive breast cancers refer to those that show positivity for ER at 1% cellular expression or higher. The American Society of Clinical Oncology/College of American Pathologists guidelines suggest using the term "low ER-positive breast cancer" for tumors with ER expression between 1% and 10%. Low ER-positive breast cancers exhibit similarities, in terms of disease-free survival and overall survival rates, to triple-negative breast cancers (TNBCs) rather than ER-positive breast cancers. In this study, our aim was to compare the clinicopathological characteristics of low ER-positive breast cancer cases diagnosed and followed in our clinic with TNBCs., Materials and Methods: A total of 26 cases of low ER-positive breast cancer diagnosed at University of Health Sciences Turkey, İzmir Tepecik Training and Research Hospital between 2010 and 2016 were retrieved from hospital records. The relevant histopathology slides and blocks were retrieved and re-evaluated retrospectively through microscopic examination. Thirteen cases that met the criteria were included in the study. Additionally, a consecutive series of 13 TNBC cases that did not receive neoadjuvant treatment within the same time period were identified., Results: In the low ER-positive group, the presence of tumor necrosis, as well as histological grade, nuclear grade and Ki-67 proliferation index were significantly lower compared to the TNBC group. Ductal carcinoma in situ (DCIS) was significantly more common in the low ER-positive group compared to the TNBC group. There were no significant differences between the two groups in terms of tumor size, histological tumor type, axillary lymph node involvement, tumor margins, peritumoral and intratumoral inflammation, local recurrence, distant metastasis, survival, and other characteristics., Conclusion: Although our study consisted of a small number of cases, some features showed significant differences between low ER-positive breast cancers and TNBCs. Histological and nuclear grades, as well as the presence of a DCIS component, were associated with low ER-positive breast cancer. In contrast, the presence of tumor necrosis, as well as Grade 3 features and a high Ki-67 proliferation index indicated TNBC., Competing Interests: Conflict of Interest: The authors have no conflicts of interest to declare., (©Copyright 2024 by the Turkish Federation of Breast Diseases Societies / European Journal of Breast Health published by Galenos Publishing House.)

INTRODUCTION: The present histologic and immunohistochemical prognostic markers of breast carcinoma do not effectively identify the subset of patients with poor prognosis. Y-Box binding protein 1 (YB1) is a novel biomarker which may identify and aid in targeted personalized therapy for such patients. MATERIALS AND METHODS: The study was conducted on histopathology specimens of 74 patients of breast carcinoma who had undergone modified radical mastectomy. YB1 immunohistochemistry (IHC) was performed on manual tissue microarray blocks (each having 15 cores). The YB1 expression was quantified in terms of “immunoreactive score” which was correlated with clinical parameters, hormone receptor status, and Her2neu overexpression by IHC. The Her2neu status of the equivocal cases was further evaluated by fluorescent in situ hybridization (FISH). RESULTS: YB1 was positive in 36/74 (48.6%) cases. On IHC and analysis by FISH, 25/74 (34%) cases had Her2neu overexpression. Estrogen receptor (ER) and progesterone receptor (PR) positivity was found in 42% and 36.5% cases, respectively. YB1 immunopositivity was negatively correlated with ER and PR expression, but showed a significant positive correlation with Her2neu expression. No correlation was found with other clinical parameters, tumor stage, and grade, except lymph node involvement, which showed a positive association with YB1 expression. Triple-negative breast carcinoma constituted 25.6% of the total cases, out of which 73.6% were YB1 positive. CONCLUSION: This study found that YB1 has an association with Her2neu expression. It may in future provide a therapeutic target in Her2neu overexpressing tumors. [ABSTRACT FROM AUTHOR]

Highlights • Adenoid cystic carcinoma (ACC) of the breast is a rare type of primary breast cancer accounting for less than 0.1% of all primary breast cancers. • Unlike other triple negative breast cancers that are associated with poor prognosis, ACC has an overall excellent prognosis. • Mammographically, these tumors may appear as asymmetric densities or irregular masses. Sonographically, they appear as well-defined, irregular, heterogeneous, or hypoechoic masses. Nonetheless, the radiographic findings are non-specific and can be misdiagnosed as benign lesions. Subsequently, it could be challenging for a radiologist to make the correct diagnosis of carcinoma without histologic confirmation. • Due to the rarity of the tumor and large variations in the patterns of practice, guidelines for treatment have not been established. Because of these distinct clinicopathologic features that set it apart from the other triple negative breast cancers, an understanding of ACC of the breast is essential for surgical pathologists, breast surgeons, and oncologists. Abstract Introduction Adenoid cystic carcinoma of the breast (breast-ACC) is a rare tumor with a favorable prognosis, despite its triple-negative status and special type of basal-like tumor for which scant population-based descriptive data exist. We sought to provide new population-based information on breast-ACC in India. Due to the paucity of the number of cases, the natural history of the disease is not fully understood. This study was undertaken to examine the clinico-pathological characteristics of the disease and to evaluate the outcome of surgical intervention in a tertiary referral care centre. Materials and methods A retrospective analysis of all patients diagnosed and treated for ACC Breast in our hospital over the past 10 years was carried out (2005–2015). A database of the characteristics of these patients was developed. In all, 14 patients were identified. The investigations performed included routine blood investigations, chest X-ray, bone scan and either an ultrasound or a CT scan. Results During the time period of 10 years, of 2347 with breast malignancy admitted to our department, only 14 were diagnosed as having ACC (3.15%). All patients were women (100%). The patients had a median age of 60.7 years (range 37–81). The most common symptom was lump in the breast. Two patients (14.2%) presented with nipple and skin retraction and two patients (14.2%) were asymptomatic with the diagnosis made by an incidental finding on routine examination. The CT and/or magnetic resonance imaging (MRI) showed the typical features of carcinoma breast. All the 14 patients were taken up for surgery. Nine patients underwent Modified radical mastectomy and five patients underwent Breast conservation surgery. Axillary lymph node dissection was carried out in seven patients and sentinel lymph node biopsy in the remaining. Tumor cells had a characteristic histologic pattern of ACC of the breast. Perineural invasion was present in six cases. Discussion ACC of the breast is a very rare malignancy, accounting for less than 0.1% of all breast neoplasms. It affects the left and right breasts equally and tumors arise irrespective of the breast quadrants. However, in about 50 percent of patients, lesions are found in subareolar region. Pain or tenderness described in the minority of cases has not been correlated with histologically-confirmed perineural invasion. ACC is categorized as a basal-like subtype of breast carcinoma. Most cases are macroscopically well-circumscribed. Occasionally, pink, tan, or gray microcysts are evident. A tumor typically consists of a dual-cell population of luminal and myoepithelial-basal cells which may be arranged in one or more of three architectural patterns: tubular-trabecular, cribriform, and solid-basaloid. There is no consensus on the optimal management for patients with ACC of the breast. Based on its indolent clinical course and favorable outcome, ACC of the breast is generally cured by breast-conserving surgery, such as wide excision or quadrantectomy with or without radiotherapy. Conclusion Breast-ACC among women is characterized by ER-negative/PR-negative expression, rare regional lymph node involvement, a favorable prognosis with excellent survival, and absence of associated cancers. These findings reinforce the importance of tailored treatments for breast-ACC and the apparent heterogeneity of basal-like breast cancers. [ABSTRACT FROM AUTHOR]

Purpose: Dysregulation of miRNA profile has been associated with a broad spectrum of cellular processes underlying progression of various human malignancies. Increasing evidence suggests that specific microRNA clusters might be of clinical utility, especially in triple-negative breast carcinoma (TNBC), devoid of both predictive markers and potential therapeutic targets. Here we provide a comprehensive review of the existing data on microRNAs in TNBC, their molecular targets, a putative role in invasive progression with a particular emphasis on the epithelial-to-mesenchymal transition (EMT) and acquisition of stem-cell properties (CSC), regarded both as prerequisites for metastasis, and significance for therapy.Methods: PubMed and Medline databases were systematically searched for the relevant literature. 121 articles have been selected and thoroughly analysed.Results: Several miRNAs associated with EMT/CSC and invasion were identified as significantly (1) upregulated: miR-10b, miR-21, miR-29, miR-9, miR-221/222, miR-373 or (2) downregulated: miR-145, miR-199a-5p, miR-200 family, miR-203, miR-205 in TNBC. Dysregulation of miR-10b, miR-21, miR-29, miR-145, miR-200 family, miR-203, miR-221/222 was reported of prognostic value in TNBC patients.Conclusion: Available data suggest that specific microRNA clusters might play an important role in biology of TNBC, understanding of which should assist disease prognostication and therapy. [ABSTRACT FROM AUTHOR]

Purpose: Secretory breast cancer (SBC) is one of the rarest breast cancer (BC), representing the majority of BC in childhood. Nevertheless, it elicits a lot of interest both for the peculiar morphology and the characteristic genetic features. Currently, there is no consensus on optimal treatment strategy. Therefore, it is useful to report every case in order to establish treatment algorithms.Methods: We describe the case of a 6-year-old boy diagnosed with a SBC, with peculiar genomic and immunohistochemical features. Moreover, we carried out a review of the literature in order to analyze the present state of knowledge about this rare entity.Results: To the best of our knowledge, there are only 120 cases published in literature, only 32 in males and only 2 younger than 6 years. Furthermore, this one had peculiar genomic and immunohistochemical features. Indeed, even if SBC expresses basal-cell markers, our patient had a triple-negative tumor expressing both basal and luminal cell markers. Furthermore, the boy’s genomic profile revealed not only positivity for the typical SBC’s translocation t(12;15), but also for a 3q28 duplication, found in his father (healthy) and paternal grandfather (with a previous BC). None were positive for BRCA mutation. This locus includes only one gene encoding for a growth factor recently linked to Early Infantile Epileptic Encephalopathy-47 and Idiopathic ventricular tachycardia. Even if the literature does not provide evidence of a pathogenic role it is not possible to exclude a cancer-predisposing activity.Conclusions: SBC is a rare type of BC, characterized by triple-negative features with an unexpectedly good prognosis. More data are needed to fully understand the behavior of this cancer and genomic profiling could be helpful in improving its diagnosis and management. [ABSTRACT FROM AUTHOR]

Background: This study investigated the effect of postmastectomy radiotherapy (PMRT) in patients with stage II-III triple-negative breast cancer (TNBC) after neoadjuvant chemotherapy (NAC) and modified radical mastectomy (MRM). Patients and methods: A total of 104 women with stage II-III TNBC who received NAC and MRM at our institution between January 2000 and July 2007 were identified. Patients were divided into 2 groups (PMRT and non-PMRT) for statistical analysis. Results: The median follow-up time was 64 months (range 12-123 months). The 5 year cumulative locoregional recurrence (LRR) and disease recurrence (DR) rates were 26.5% and 49.6%, respectively. Despite their more adverse prognostic features, patients with PMRT had lower 5 year cumulative LRR and DR rates than those without PMRT (LRR: 18.3% vs 52.2%, respectively, p=0.0005; DR: 45% vs 69.1%, p=0.0334, respectively). On multivariate analysis of the entire study cohort, forgoing PMRT was significantly associated with developing LRR and DR. Subset analysis revealed that PMRT significantly reduced the 5 year LRR rate in patients with pre-chemotherapy clinical stages IIA (8.3% vs 46.2%, p=0.019) and IIIA (16% vs 66.7%, p=0.003). PMRT also significantly reduced the 5 year DR rate in patients with pre-chemotherapy clinical stage IIA (24.5% vs 69.3%, p=0.0151) and ⋝IIIB (70.8% vs 100%, p=0.0481). Conclusion: In our cohort of patients with TNBC treated with NAC and MRM, PMRT significantly improved locoregional control and disease-free survival in the entire cohort as well as in patients with stage IIA disease. Our results may help in tailoring adjuvant treatment decisions for these particular patient populations. [ABSTRACT FROM AUTHOR]

BACKGROUND: The characterization of poorly differentiated neoplasms in fine-needle aspiration (FNA) and small biopsy specimens usually requires immunohistochemistry (IHC) with a panel of markers. Because of an increasing need to preserve limited diagnostic material for tumor genotyping and a mounting demand for cost containment, the authors investigated the usefulness of dual-color IHC with antibodies directed against broad-spectrum keratins and SOX10, a neuroectodermal transcription factor consistently expressed in melanoma, in the workup of epithelioid malignant neoplasms. METHODS: A total of 107 cases of FNA cell blocks (49 cases) and small biopsies (58 cases) were selected, including 34 melanomas, 31 epithelioid/pleomorphic sarcomas, and 42 carcinomas. IHC was performed on all specimens using a peroxidase-based brown chromogen for SOX10 and an alkaline phosphatase-based red chromogen for keratins AE1/AE3. The presence or absence of staining in lesional cells was scored. RESULTS: The majority of tumors demonstrated 1 of 3 distinct patterns: 1) malignant melanomas with nuclear SOX10 (sensitivity of 94% and specificity of 95%); 2) epithelioid/ pleomorphic sarcomas negative for both SOX10 and AE1/AE3 (sensitivity of 84% and specificity of 88%); and 3) carcinomas with cytoplasmic AE1/AE3 (sensitivity of 76% and specificity of 98%). In addition, a fourth pattern with cytoplasmic AE1/AE3 and nuclear SOX10 was observed in a subset of carcinomas, most notably triple-negative breast cancers. CONCLUSIONS: SOX10/keratin dual-color IHC appears to be an effective, sensitive, and specific test to distinguish between melanoma, sarcoma, and carcinoma. This approach can identify melanoma, prioritize additional studies, and limit the number of markers needed to workup an epithelioid malignant neoplasm, thereby potentially reducing costs and preserving valuable tissue for ancillary studies with which to guide therapy. [ABSTRACT FROM AUTHOR]

Objective The aim of this study was to investigate the clinicopathological characteristic of adenoid cystic carcinoma (ACC). Materials and methods The clininopathological features, along with relapse free survival(RFS) and overall survival(OS) of 36 patients with ACC were retrospectively investigated and compared with those of 108 grade 1 invasive ductal carcinoma not-otherwise-specified (G1-IDC-NOS) patients. Results Most cases of ACC were ER, PR and HER-2 negative which was classified as triple-negative subtype. Five cases were concomitant with other pathological types of cancer. Axillary lymph node dissection(ALND) was performed in 31 patients and 2 of them with lymph nodes metastasis. Two patients died of lung metastases at 46 and 116 months after the surgery respectively. Compared with G1-IDC-NOS, ACC showed lower Ki-67 index, less lymph nodes metastasis, lower P53 expression, and higher proportion in location of upper outer quadrant of breast. There was no difference of OS and RFS between ACC and G1-IDC-NOS. Conclusions ACC of the breast was a rare disease with a good prognosis although most of them were classified as triple-negative subtype. And the value of axillary node dissection and adjuvant therapy needs to be further investigated. [ABSTRACT FROM AUTHOR]

Background The present study aims to evaluate the response of locally advanced breast carcinoma (LABC) to neoadjuvant chemotherapy (NACT) using image-guided clip placement based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria. Methods Thirty-four patients with LABC were included in the study. Consent for three-dimensional titanium clip placement (400/300/200 mm Liga clips) under local anesthesia with USG guidance was obtained. Serial sonographic/X-ray evaluations of tumor bed size were conducted before every cycle of NACT. All data were recorded in millimeters of concentric tumor regression/non-regression. Tumor regression in a concentric or Swiss cheese pattern and non-responders were evaluated. Assessment of the response to NACT was performed using RECIST criteria, dividing it into four categories. Tumor response was confirmed with computerized tomography (CT) conducted before and after the completion of NACT. Patients underwent surgical management, mostly modified radical mastectomy (MRM), as they had locally advanced breast carcinoma. Following MRM, the clips in the specimen guided the original site of the tumor for histopathological evaluation and response to chemotherapy. Results Tumor response was classified into four types: complete response (CR), partial response (PR), progressive disease (PD), and stable disease. RECIST 1.1 criteria were elaborated and defined. Data for all patients were entered into an Excel sheet (Microsoft Corporation, Redmond, Washington) to prepare a master chart, and the following observations were made and analyzed using SPSS software. The duration of chemotherapy for the study population ranged from 32 to 206 days, with a mean (±SD) of 111.82 (± 52.64) days and a median (IQR) of 81 (63, 158) days. The mean period between clip insertion and completion of NACT was 111.82 days. The baseline sum diameters and post-NACT diameters of the tumors were 70.50 (±13.60) mm before NACT and 17.75 (±17.20) mm after NACT. Hence, the mean size of the lump was statistically significantly lower after NACT, with a mean difference of 52.75 (p<0.05). The mean rate of reduction in tumor diameter was found to be 74.32% (±23.44%) based on RECIST 1.1 criteria. Pathological response was observed in all patients except for 8.8% of the patients. Clinical complete response was seen in 35.29% of patients, and partial response was observed in 52.92% of the patients based on RECIST 1.1 criteria. The study thus demonstrates the effectiveness of NACT in LABC, with a mean reduction in tumor diameter of 74.32%, assessed with the help of RECIST 1.1 criteria. Conclusion NACT for patients with LABC has shown a significant reduction in tumor size. NACT should be the initial mode of management for patients with LABC. RECIST 1.1 criteria are effective and can be used to assess tumor response to NACT. This has aided in the stratification of the response of NACT for further management through systemic therapy (adjuvant chemotherapy) after the surgical excision of the tumor., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Pandurangappa et al.)