Types Of Breast Tumors Research Articles

The impact of 9-azaglycophymine and phenylguanidine derivatives on the proliferation of various breast cancer cell lines in vitro and in vivo

Quinazolinones, particularly 9-azaglycophymines, and closely related derivatives and precursors were tested in vitro against various breast cancer cell lines representing the major types of breast tumors. Among the 49 compounds tested, azaglycophymine derivative 19 with an electron-withdrawing substituent demonstrated the most significant anti-proliferative effects, with IC50 values of around 4 µM. Extensive cell-based investigations revealed that compound 19 induced caspase-dependent apoptosis in HCC1937 (human TNBC), BT-474 (human HER2+/HR+), and 4T1 (mouse TNBC) cells. In contrast, in MDA-MB-468 (human TNBC) and MCF-7 (human HR+) cells, the cell death was induced via a non-apoptotic pathway. The in vivo efficacy of compound 19 was validated using a syngeneic orthotopic 4T1 model in BALB/c mice, resulting in significant reduction of 4T1 breast tumor growth upon intraperitoneal (i.p.) application of doses of 5 or 20 mg/kg. These findings highlight the potential of compound 19 as a promising scaffold for the development of new therapeutic agents for various types of breast cancer and a first structure-activity insight.

Primary Large-Cell Neuroendocrine Carcinoma of the Breast.

Breast neuroendocrine carcinoma (NECB) is a rare type of breast tumor. Large-cell neuroendocrine carcinomas of the breast (LCNECB) are a special and rare histological subtype of NECB. Here, we present a case of a 59-year-old woman who was diagnosed with an LCNECB. A mass in the upper outer quadrant of the right breast was revealed via imaging. A histological examination showed the tumor cells were composed of clusters of large cells with obvious atypia that were polygonal or irregularly shaped. The patient underwent a right-breast-conserving radical surgery and sentinel lymph node biopsy (SLB). A histopathological examination revealed that the tumor of the right breast was 2.5 × 2 cm in size with vascular invasion, and the sentinel lymph node was negative. The immunohistochemical results showed that the tumor cells were diffuse and positive for chromogranin A (CgA), synaptophysin (Syn), and INSM1. The patient successfully completed chemotherapy and radiotherapy and is currently undergoing endocrine therapy.

Deep learning-assisted distinguishing breast phyllodes tumours from fibroadenomas based on ultrasound images: a diagnostic study.

To evaluate the performance of ultrasound-based deep learning (DL) models in distinguishing breast phyllodes tumours (PTs) from fibroadenomas (FAs) and their clinical utility in assisting radiologists with varying diagnostic experiences. We retrospectively collected 1180 ultrasound images from 539 patients (247 PTs and 292 FAs). Five DL network models with different structures were trained and validated using nodule regions annotated by radiologists on breast ultrasound images. DL models were trained using the methods of transfer learning and 3-fold cross-validation. The model demonstrated the best evaluation index in the 3-fold cross-validation was selected for comparison with radiologists' diagnostic decisions. Two-round reader studies were conducted to investigate the value of DL model in assisting 6 radiologists with different levels of experience. Upon testing, Xception model demonstrated the best diagnostic performance (area under the receiver-operating characteristic curve: 0.87; 95% CI, 0.81-0.92), outperforming all radiologists (all P < .05). Additionally, the DL model enhanced the diagnostic performance of radiologists. Accuracy demonstrated improvements of 4%, 4%, and 3% for senior, intermediate, and junior radiologists, respectively. The DL models showed superior predictive abilities compared to experienced radiologists in distinguishing breast PTs from FAs. Utilizing the model led to improved efficiency and diagnostic performance for radiologists with different levels of experience (6-25 years of work). We developed and validated a DL model based on the largest available dataset to assist in diagnosing PTs. This model has the potential to allow radiologists to discriminate 2 types of breast tumours which are challenging to identify with precision and accuracy, and subsequently to make more informed decisions about surgical plans.

Synchronous Breast and Colorectal Malignant Tumors-A Systematic Review.

Our aim is to describe the main diagnostic and therapeutic challenges for synchronous breast and colorectal tumors. We performed a systematic review of the literature for cases or case series, using established keywords (synchronous breast and colon tumor and synonyms) for the period of 1970-2023. Five reviewers independently screened the literature, extracted data, and assessed the quality of the included studies. The results were processed according to the PRISMA 2020 guidelines. A total of 15 cases were included in the study, including 2 males (age 50 and 57) and 13 females (median age 60, with range from 40 to 79). In a vast majority of the cases, the diagnosis of synchronous tumor was prompted by the first tumor's workup. The first diagnosed tumor was colorectal in nine cases and a breast tumor in six cases. The most common histopathological type of breast tumor was invasive ductal carcinoma, and the colon tumors were exclusively adenocarcinomas. All cases had a surgical indication for both breast and colorectal tumor, except one case, in which the breast tumor had multiple metastasis. In four cases, the surgery was performed concomitantly (colectomy and mastectomy). In three cases, surgery was initially carried out for the breast tumor, followed by colon surgery. Oncological treatment was indicated depending on the tumor stage. For the treatment of synchronous tumors, the Tumor Board (T.B) decision is mandatory and must be personalized for each patient. Developing new methods of treatment and investigation may play an important role in the future for understanding synchronous tumor development, incidence, and outcome.

A prospective comparative study of preoperative and postoperative clinicopathological correlation of fibroadenoma of breast: A study protocol

Fibroadenoma of the breast most often arises during the late teens and early reproductive years. It is the most prevalent tumor in women &lt; 30 years. After the age of 40 to 45, fibroadenomas are rarely observed as new masses in women. Fibroadenomas are made up of both epithelial and stromal components. Fibroadenoma is the most frequent type of breast tumor. It is crucial to diagnose preoperatively, both clinically and pathologically, by using F.N.A.C. Postoperatively, Fibroadenoma is confirmed histopathology. However, malignant transformation is very rare in Fibroadenoma of the breast. Early identification, accurate analysis, and appropriate management are advantageous. The current study's goal is to examine preoperative and postoperative clinicopathological aspects of Fibroadenoma and to assess any differences between preoperative and postoperative diagnosis in patients admitted to Jawaharlal Nehru Medical College, Sawangi (M), Wardha, Maharashtra, India.

Abstract IA009: Single strand DNA GAP accumulation as a functional biomarker for DNA Repair Inhibitors

Abstract Deficiency of homologous recombination (HR)-mediated DNA repair occurs through genetic or epigenetic inactivation of the BRCA1 and BRCA2 (BRCA1/2) genes. HR-deficiency also provides unique opportunities for targeted therapy, through the mechanism of synthetic lethality, as exemplified by the hypersensitivity of BRCA1/2-mutated tumors to PARP inhibitors (PARPi). To date, several PARP inhibitors have been approved for clinical use. The promising clinical response of patients with germline BRCA1/2-mutations prompted the use of PARPi for patients with somatic BRCA1/2 mutations as well. In addition, these results extended the use of PARPi for various types of ovarian, breast, pancreatic, and prostate tumors with HR defects. PARPi resistance is emerging as the major obstacle to clinical effectiveness in patients with HR-deficient tumors. PARPi resistance results from several independent mechanisms, leading to the restoration of Homologous Recombination and/or Replication Fork stabilization. The absence of alternative options for patients with tumors with innate or acquired resistance underlines the urgency to develop additional therapeutics. More recent studies have identified new synthetic lethal opportunities for BRCA1/2 deficient tumors. Knockout of the genes for POLQ (DNA polymerase theta) or for USP1 (Ubiquitin Specific Protease 1) results in killing of these tumors, and inhibitors of these enzymes are emerging as promising agents for HR-deficient tumors. POLQ and USP1 expression is particularly high in subtypes of breast and ovarian tumors with defects in HR. As a result, POLQi or USP1i in HR-deficient tumors induces cell death. POLQi or USP1i can synergize with PARPi in killing HR-deficient tumors or PARPi-resistant tumors. BRCA1/2 deficient tumors have an increase in single strand DNA gaps (ssGAPs) near replication forks. Treatment with PARPi results in an increase in the size and number for these ssGAPs, ultimately leading to DSBs and cell death. Interestingly, PARPi resistance results, at least in part, from the ability of resistant cells to close the ssGAPs through enhanced POLQ and USP1 activity, thereby providing a rationale for the combination of PARP1, POLQi, and USP1 in HR-deficient cancers. USP1 inhibition was synergistic with PARP and POLQ inhibition in BRCA1-mutant cells, with enhanced ssDNA gap accumulation. Moreover, this synergy was observed in a set of patient-derived ovarian cancer organoids (PDOs), thus confirming the sensitivity of BRCA1-deficient cells to inhibition by these agents. The accumulation of ssDNA gaps after treatment with a USP1i, PARP, or POLQi correlated with the sensitivity to these drugs in all models tested. Ovarian cancer PDOs provide a powerful tool for detecting drug synergy and for rapid in vitro sensitivity testing. The detection of ssDNA gap accumulation may be a useful predictive biomarker for response to DNA Repair inhibitors as monotherapy or in combination in ongoing clinical trials. Citation Format: Alan D. D'Andrea. Single strand DNA GAP accumulation as a functional biomarker for DNA Repair Inhibitors [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Expanding and Translating Cancer Synthetic Vulnerabilities; 2024 Jun 10-13; Montreal, Quebec, Canada. Philadelphia (PA): AACR; Mol Cancer Ther 2024;23(6 Suppl):Abstract nr IA009.

Abstract LB333: Improved spatially resolved single-cell transcriptomic imaging in archival tissues with MERSCOPE

Abstract The advent of spatial transcriptomics has enabled a revolution in how complex tissues are studied. However, samples with lower quality RNA due to degradation, protein crosslinking, or high RNase content remain challenging for spatial transcriptomic measurement. In particular, formalin fixed, paraffin embedded (FFPE) tissues are the most widely used sample types in clinical and molecular diagnosis, yet they are notoriously difficult for single-cell transcriptomic analysis. To accurately profile the gene expression in FFPE samples in situ, a spatial transcriptomics technique with high detection efficiency and single molecule resolution is required. The Vizgen® MERSCOPE® Platform for spatial genomics is built on Multiplexed Error Robust in situ Hybridization (MERFISH) technology and directly profiles the transcriptome of intact tissues with high sensitivity in high-quality samples. Here we present an updated workflow to perform MERFISH in low and high-quality samples. We demonstrated its application in more than 5 FFPE sample types from mouse and human, including archival samples. For each tissue type, hundreds of thousands of cells were captured using the updated MERSCOPE Platform workflow, generating 100s million counts and their spatial information for profiled genes in each sample. The updated workflow involves streamlined sample preparation and chemistry optimization to improve sensitivity. MERSCOPE accurately profiled gene expression in situ and mapped cell types in archival human samples across a range of low and high RNA qualities. We compared the performance of MERSCOPE imaging using the updated protocol to the previous version and observed a significant increase in gene counts per 100 micron2 of tissue. We also demonstrated increased reproducibility between replicates with the streamlined workflow and chemistry. Furthermore, we demonstrated the updated workflow is compatible with simultaneous protein-based cell boundary staining. Finally, we constructed a spatially resolved single-cell atlas across low-quality archival breast and lung tumor types, mapped and cataloged different cell types within the tumor microenvironment, and systematically characterized the gene expression among cells. Spatially resolved transcriptomic profiling of low-quality samples at single-cell level provides enormous opportunities in cancer research. These improvements will enable new genomic inquiries into previously intractable tissues like FFPE, leading to new biological insights into cancer progression. Citation Format: Jiang He, Bin Wang, Justin He, Renchao Chen, Benjamin Patterson, Sudhir Tattikota, Timothy Wiggin, Lizi Maziashvili, Peter Reinhold, Manisha Ray, George Emanuel. Improved spatially resolved single-cell transcriptomic imaging in archival tissues with MERSCOPE [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr LB333.

Breast Tumor Tissue Image Classification Using Single-Task Meta Learning with Auxiliary Network.

Breast cancer has a high mortality rate among cancers. If the type of breast tumor can be correctly diagnosed at an early stage, the survival rate of the patients will be greatly improved. Considering the actual clinical needs, the classification model of breast pathology images needs to have the ability to make a correct classification, even in facing image data with different characteristics. The existing convolutional neural network (CNN)-based models for the classification of breast tumor pathology images lack the requisite generalization capability to maintain high accuracy when confronted with pathology images of varied characteristics. Consequently, this study introduces a new classification model, STMLAN (Single-Task Meta Learning with Auxiliary Network), which integrates Meta Learning and an auxiliary network. Single-Task Meta Learning was proposed to endow the model with generalization ability, and the auxiliary network was used to enhance the feature characteristics of breast pathology images. The experimental results demonstrate that the STMLAN model proposed in this study improves accuracy by at least 1.85% in challenging multi-classification tasks compared to the existing methods. Furthermore, the Silhouette Score corresponding to the features learned by the model has increased by 31.85%, reflecting that the proposed model can learn more discriminative features, and the generalization ability of the overall model is also improved.

Abstract 2521: New predictive markers for dasatinib responsiveness in triple-negative breast cancer: A biomarker discovery study

Abstract Triple negative breast cancer is the most heterogeneous and aggressive type of breast tumor type and is characterized by the lack of expression of clinical biomarkers (ER, PR, and HER2) and targeted therapies. In this regard, different clinical trials have failed, unable to stratify these patients to find an effective response to specific therapy. This study aimed to identify biomarkers exclusively expressed in the basal mammary compartment that can help us to subclassify the triple-negative breast cancer subtype. Based on computational analysis from single-cell RNA sequencing data, we have identified a list of basal identity-associated genes (BC-markers). Subsequent histological validation confirmed the expression pattern of these markers in a cohort of 50 samples, which has allowed us to stratify triple-negative breast cancer patients into BC-TNBC and luminal-like subtypes. Importantly, the expression of these markers correlated with poorer prognosis in TNBC patients. Functional analysis revealed that TAGLN played a significant role in cell proliferation and migration, potentially impacting tumor aggressiveness. Moreover, the expression of these BC-markers is associated with a mesenchymal phenotype which corresponds to the previously described Lehmannn’s mesenchymal-like signature. In this study, TAGLN appeared to influence dasatinib sensitivity, suggesting its potential as a predictive biomarker for dasatinib response in TNBC patients. Citation Format: Daniel Ortega-Álvarez, David Tebar, Marta Casado, Elena Castillo, Cristina Guardia, David Olivares-Osuna, Eva Musulén, Elisabetta Mereu, Ginés Luengo, Eva M. Galán-Moya, Veronica Rodilla. New predictive markers for dasatinib responsiveness in triple-negative breast cancer: A biomarker discovery study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 2521.

Stochastic Spin‐Orbit‐Torque Synapse and its Application in Uncertainty Quantification

AbstractStochasticity plays a significant role in the low‐power operation of a biological neural network. In an artificial neural network, stochasticity also contributes to critical functions such as the uncertainty quantification (UQ) for estimating the probability for the correctness of prediction. This UQ is vital for cutting‐edge applications, including medical diagnostics, autopilots, and large language models. Thanks to nonlinear variation of analogous Hall resistance with high computing velocity and low dissipation, a stochastic spin‐orbit‐torque (SOT) device exhibits significant potential for implementing the UQ. However, up until now, the application of UQ for stochastic SOT devices remains unexplored. In this study, based on SOT‐induced stochastic magnetic domain wall (DW) motion with varying velocity, a SOT synapse is fabricated that can emulate stochastic weight update following the Spike‐Timing‐Dependent‐Plasticity (STDP) rule. Furthermore, a stochastic SNN is set up, which, when compared to its deterministic counterpart, demonstrates a clear advantage in quantifying uncertainty for diagnosing the type of breast tumor (benign or malignant).

Abstract A086: Retrospective study on postoperative adjuvant radiotherapy in primary malignant angiosarcoma of the breast patients following mastectomy or breast-conserving surgery using SEER database

Abstract Primary Angiosarcoma of the breast (PAOB) is one of the rarest types of breast tumors, representing less than 0.2% of all breast tumors. These tumors are also associated with a poor prognosis. Mastectomy or breast-conserving surgery (BCS) are considered the best therapeutic techniques in patients with (PAOB). However, there is a debate about the need for postoperative radiotherapy (RT). PAOB is a rare tumor, therefore best management techniques are based only on expert opinion and clinical experience, which are scarce. The aim of this paper is to study the effectiveness of postoperative radiotherapy (RT) for PAOB over a long period. Patients with primary angiosarcoma of the breast (PAOB), who underwent a mastectomy and breast-conserving surgery (BCS), were identified through the Surveillance, Epidemiology, and End Results (SEER) database from 2000 to 2020. Descriptive analyses were conducted to evaluate the clinical characteristics of patients with PAOB.Age, ethnicity, year of diagnosis, grade, tumor extent, lymph node (LN) metastasis and Postoperative radiotherapy (RT) were incorporated.Cancer-specific survival (CSS) was calculated using the Kaplan Meier and compared using the log rank test. Univariate and multivariate Cox proportional hazards regressions were performed to evaluate the prognostic power of factors on (CSS). A total of 542 women with primary angiosarcoma of the breast (PAOB) were included in this study. Most women (82.8%) underwent mastectomy, while (17.2%) underwent breast conserving surgery (BCS). Postoperative radiotherapy (RT) was performed on 102 women (18.8%), with 27 (29.0%) in the BCS group and 75 (16.7%) in the mastectomy group.Postoperative radiotherapy (RT) was more likely to be performed in women with adverse risk factors, such as a larger tumor size in the mastectomy group and a higher tumor grade in both groups.Lymph node (LN) metastasis was rarely found in PAOB, only 11 patients had positive lymph node (LN) metastasis. Among those, 9 patients underwent mastectomy, and 2 patients underwent BCS. Additionally, lymph node involvement increased the chance of postoperative RT in the mastectomy group. In both groups, the need for postoperative radiotherapy (RT) increased as the tumor size became more than (3cm).However, this pattern was less obvious in the BCS group.In multivariate analysis, there weren’t any significant prognostic factors impact on Cancer-specific survival (CSS) in the mastectomy group, also, postoperative radiotherapy RT had no impact (P = 0.656).In the BCS group,age, tumor size and lymph node (LN) metastasis were significant predictive factors on Cancer-specific survival (CSS),meanwhile postoperative radiotherapy (RT) had no effect on (CSS) (P = 0.152). PAOB patients with more adverse prognostic factors received postoperative radiotherapy (RT).There was no statistically significant difference in CSS between radiotherapy (RT) group and non-(RT) group,regardless of whether the procedure is a mastectomy or a breast-conserving surgery (BCS).Further trials are needed to reach more accurate evaluations. Citation Format: Ramez M. Odat, Ismail A. Ibrahim, Mohamed Ahmed Ali, Sara A. Haddadin, Bashar M. Al Zoubi, Mohamed Nezar Abohalawa, Alexander Leeper. Retrospective study on postoperative adjuvant radiotherapy in primary malignant angiosarcoma of the breast patients following mastectomy or breast-conserving surgery using SEER database [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A086.

Abstract A012: Molecular profiling of neoductgenesis in early stage breast cancer for the development of novel diagnostic biomarkers

Abstract Ductal carcinoma in situ (DCIS) is the most common precancerous finding in mammography screens. DCIS generally has a good prognosis, and only 20-25% of the cases progress to invasive breast carcinoma (IBC) even if left untreated. Breast pathologists and radiologists have suggested that there are currently more than one kind of DCIS under the same diagnosis. A subset of DCIS cases with reduced survival rate are associated with casting-type calcifications that can be histologically detected within closely packed, contorted, newly formed ducts, a phenomenon called neoductgenesis. Tumors with neoductgenesis are often erroneously diagnosed as DCIS, while in fact, they are associated with higher degree of metastasis and should be considered invasive carcinomas. This tumor category currently lacks specific histopathological markers and the biological processes leading to metastasis via neoductgenesis remain poorly characterised. To reveal new information of this breast tumor type, we are currently conducting comprehensive characterization of FFPE tissue samples of DCIS cases with and without neoductgenesis using imaging mass cytometry analysis and immunohistochemistry of specific tumor areas. Preliminary results on immunofluorescence staining suggest that neoductgenesis is associated with changes in the expression of specific myoepithelial marker proteins compared to areas with pure DCIS. In addition, we are analysing the three-dimensional ductal architecture of these lesions. The information obtained from this study can lead to development of new diagnostic tools for the identification of early breast cancers with a higher risk of spreading. Early detection of these cases is important to ensure the effectiveness and timeliness of treatment, and at the same time to improve the patients' quality of life. Citation Format: Laura Lehtinen, Leena Koskinen, Markus Peurla, Emilia Huotari, Otto Kauko, Peter Dean, Pauliina Hartiala, Pia Boström, Emilia Peuhu. Molecular profiling of neoductgenesis in early stage breast cancer for the development of novel diagnostic biomarkers [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Breast Cancer Research; 2023 Oct 19-22; San Diego, California. Philadelphia (PA): AACR; Cancer Res 2024;84(3 Suppl_1):Abstract nr A012.

Global transcriptomic analysis of breast cancer and normal mammary epithelial cells infected with Borrelia burgdorferi.

The bacterial spirochete Borrelia burgdorferi, the causative agent of Lyme Disease, can disseminate and colonize various tissues and organs, orchestrating severe clinical symptoms including arthritis, carditis, and neuroborreliosis. Previous research has demonstrated that breast cancer tissues could provide an ideal habitat for diverse populations of bacteria, including B. burgdorferi, which is associated with a poor prognosis. Recently, we demonstrated that infection with B. burgdorferi enhances the invasion and migration of triple-negative MDA-MB-231 cells which represent a type of breast tumor with more aggressive cancer traits. In this study, we hypothesized that infection by B. burgdorferi affects the expression of cancer-associated genes to effectuate breast cancer phenotypes. We applied the high-throughput technique of RNA-sequencing on B. burgdorferi-infected MDA-MB-231 breast cancer and normal-like MCF10A cells to determine the most differentially expressed genes (DEG) upon infection. Overall, 142 DEGs were identified between uninfected and infected samples in MDA-MB-231 while 95 DEGs were found in MCF10A cells. A major trend of the upregulation of C-X-C and C-C motif chemokine family members as well as genes and pathways was associated with infection, inflammation, and cancer. These genes could serve as potential biomarkers for pathogen-related tumorigenesis and cancer progression which could lead to new therapeutic opportunities.

Predicting histopathological types and molecular subtype of breast tumors: A comparative study using amide proton transfer-weighted imaging, intravoxel incoherent motion and diffusion kurtosis imaging

PurposeTo evaluate the predictive performance of multiparameter and histogram features derived from amide proton transfer-weighted imaging (APTWI), intravoxel incoherent motion (IVIM) and diffusion kurtosis imaging (DKI) for histopathological types of breast tumors. MethodsRegion of interest (ROI) was delineated by outlining the largest slice of the tumor on the false-color images of the DKI, IVIM and APTWI parameters, and extracted the histogram features. Receiver operating characteristic (ROC) curve was used to evaluate the performance of parameters in predicting benign and malignant breast lesions, molecular prognostic biomarkers, lymph node status, and subtypes of breast lesions. The Spearman correlation coefficient was used to determine the correlations between each parameter and clinical-pathological factors. ResultsAll 52 breast lesions were enrolled in this prospective study, including 8 benign lesions and 44 breast cancers. To diagnose malignant and benign breast lesions, the value of APT (min) performed best, with the AUC reaching 0.983. According to the different imaging methods, the APTWI performed best. To predict the positive status of ER, PR, Ki67, the value of Dapp (uniformity), Dapp (uniformity), f (entropy) performed best, with the AUC values reaching 0.743, 0.770, 0.848, respectively. For the identification of Luminal B, HER2-enriched, and TNBC breast cancers, Kapp (max), f (kurtosis), and Dapp (uniformity) performed best, with AUC values reaching 0.679, 0.826, 0.771, respectively. ConclusionThis study found the APTWI, IVIM and DKI parameters could diagnose breast cancer. The histogram features of DKI and IVIM, based on tumor heterogeneity, may help to predict breast cancer subtypes.

Ferroptosis: the emerging player in remodeling triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a highly heterogeneous breast tumor type that is highly malignant, invasive, and highly recurrent. Ferroptosis is a unique mode of programmed cell death (PCD) at the morphological, physiological, and molecular levels, mainly characterized by cell death induced by iron-dependent accumulation of lipid peroxides, which plays a substantial role in a variety of diseases, including tumors and inflammatory diseases. TNBC cells have been reported to display a peculiar equilibrium metabolic profile of iron and glutathione, which may increase the sensitivity of TNBC to ferroptosis. TNBC possesses a higher sensitivity to ferroptosis than other breast cancer types. Ferroptosis also occurred between immune cells and tumor cells, suggesting that regulating ferroptosis may remodel TNBC by modulating the immune response. Many ferroptosis-related genes or molecules have characteristic expression patterns and are expected to be diagnostic targets for TNBC. Besides, therapeutic strategies based on ferroptosis, including the isolation and extraction of natural drugs and the use of ferroptosis inducers, are urgent for TNBC personalized treatment. Thus, this review will explore the contribution of ferroptosis in TNBC progression, diagnosis, and treatment, to provide novel perspectives and therapeutic strategies for TNBC management.

A case report and literature review on a rare subtype of triple-negative breast cancer in children

BackgroundTriple-negative breast cancer (TNBC) is a type of breast tumor with a poor prognosis because it lacks or expresses low levels of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2). TNBC is more common in middle-aged and older women, and cases of TNBC in children are rarely reported. This is the only case of childhood SBC in our hospital in more than 70 years, and the disease is extremely rare internationally. We analyzed and studied the disease and TNBC from both clinical and pathological aspects and found that SBC is very different from TNBC.Case presentationWe report a case of secretory breast cancer (SBC), a subtype of TNBC, in an 8-year-old girl from our institution. The child presented with a single mass in the left breast only, with no skin rupture and no enlargement of the surrounding lymph nodes. The child underwent two surgeries and was followed up for one year with a good prognosis.ConclusionsSBC is highly prevalent among the multiple pathological types of pediatric breast cancer. Almost all pediatric SBC patients are characterized by the ETV6-NTRK3 fusion gene, which has a good prognosis and a 10-year survival rate of more than 90% when compared with other TNBC subtypes. According to the patient, we performed local mass resection and a postoperative pathological diagnosis of SBC (a subtype of BL-TNBC). The TNBC case had a good prognosis and differed from basal TNBC in several aspects, including clinical presentation, treatment, and prognosis. It is necessary to exclude SBC from BL-type TNBC, enhance understanding of the disease, and individualize the treatment plan, so as to avoid medical errors.

A prospective comparative study of preoperative and postoperative clinicopathological correlation of fibroadenoma of breast: A study protocol

Fibroadenoma of the breast most often arises during the late teens and early reproductive years. It is the most prevalent tumor in women &lt; 30 years. After the age of 40 to 45, fibroadenomas are rarely observed as new masses in women. Fibroadenomas are made up of both epithelial and stromal components. Fibroadenoma is the most frequent type of breast tumor. It is crucial to diagnose preoperatively, both clinically and pathologically, by using F.N.A.C. Postoperatively, Fibroadenoma is confirmed histopathology. However, malignant transformation is very rare in Fibroadenoma of the breast. Early identification, accurate analysis, and appropriate management are advantageous. The current study's goal is to examine preoperative and postoperative clinicopathological aspects of Fibroadenoma and to assess any differences between preoperative and postoperative diagnosis in patients admitted to Jawaharlal Nehru Medical College, Sawangi (M), Wardha, Maharashtra, India.

Comparison of Pericanalicular and Intracanalicular Fibroadenoma Mammae Growth Pattern on Various Age Range

Background: Fibroadenoma mammae is the most common type of benign breast tumor in women. Fibroadenoma mammae can occur on various ages, there is no much data recorded about anatomical pathology especially regarding the distribution of fibroadenoma mammae growth pattern in Siaga Medika Purbalingga Hospital. Study in Indonesia that focus on this topic also remain scarce.Objective: To analyze comparison between the growth pattern in fibroadenoma mammae patients with age range 11-50 years.Method: This cross-sectional study with data collected restrospectively based on medical records and histopatological examination in Siaga Medika Purbalingga Hospital. Statistical analysis was done using JASP 0.14.1.0.Results: The majority of patients with fibroadenoma mammae were in the age range 21-30 years (48.9%) with pericanalicular pattern (66%). The four groups had different two growth pattern (p &lt;0.001). Odds ratio showed 3.4 that means patient with age ≤30 years has chance 3.4x to diagnose with pericanalicular fibroadenoma mammae than patient with age &gt;30 years.Conclusion: Incidence of pericanalicular and intracanalicular fibroadenoma mammae growth pattern in Siaga Medika Purbalingga Hospital patients can be affected by age.

A phase I/II trial investigating safety and efficacy of autologous TAC01-HER2 in relapsed or refractory solid tumors.

2519 Background: Despite recent therapeutic developments for patients with advanced, metastatic, unresectable HER2+ solid cancers, significant unmet medical needs still exist, especially in tumors other than breast and gastric. The T cell antigen coupler (TAC) technology is a novel approach to modifying T cells, allowing them to recognize and treat HER2+ solid tumors. The TAC receptor redirects T cells to tumor cells, and upon tumor cell recognition, co-opts the natural T cell receptor (TCR) to yield safer anti-tumor responses versus chimeric antigen receptor (CAR) T cells. In preclinical studies, TAC T cells led to complete tumor clearance in mouse models of human cancer, without any TAC-related toxicities. Methods: In the ongoing clinical trial (NCT04727151), TAC01-HER2 treatment of HER2+ solid tumors is hypothesized to result in safe and effective anti-tumor responses. Subjects undergo leukapheresis, bridging therapy (if needed) while their TAC01-HER2 are engineered, lymphodepletion chemotherapy (LDC), and finally TAC01-HER2 infusion. In phase I dose escalation, the primary objective is to evaluate the safety of TAC01-HER2 at increasing doses of 0.3, 0.8, 3, and 8 x 106 cells/kg in HER2+ solid tumors (1+, 2+ or 3+ as identified by immunohistochemistry) in adult subjects who have progressed after ≥2 lines of systemic therapy. Dose limiting toxicities (DLTs) are assessed up to 28 days from cell infusion. In Phase II, dose expansion groups will further evaluate the safety, efficacy, and pharmacokinetics of the optimal TAC01-HER2 dose in HER2+ breast and other solid tumor types. Results: As of 10 Feb 2023, 18 patients have been treated in Cohorts 1-4 with breast, colorectal, gall bladder, gastroesophageal junction, gastric, esophageal, lung, and ovarian cancers. One DLT event of grade 3 pneumonitis has been reported in one subject in Cohort 4 (8 x 106 cells/kg). No neurotoxicity has been reported. Most subjects treated at Cohorts 3 and 4 experienced Grade ≤2 CRS which resolved with standard therapy. Twelve subjects have reported a total of 21 serious adverse events, 17 unrelated to TAC01-HER2 except for one Grade 3 pneumonitis, one Grade 1 and two Grade 2 CRS. Most adverse events were related to LDC or the underlying malignancy. At Cohort 2 (0.8 x 106 cells/kg), a partial response was observed in a subject with refractory metastatic gastric adenocarcinoma (3+ HER2) at 1st scan, with a 35% reduction in measurable disease and clinical benefit was maintained for 4 months. A 55% disease control rate was observed at Cohorts 2-4 at 1st scan. Conclusions: Dose escalation of TAC01-HER2 is ongoing, with seven subjects treated and three more scheduled in Cohort 4. These results in a heavily pre-treated cancer population show manageable safety and promising clinical activity with a novel T cell therapy that may have broad clinical applicability in HER+ cancers. Clinical trial information: NCT04727151 .

Evaluation of hematopoietic- and neurologic-expressed sequence 1-like (HN1L) protein levels in tissue and plasma of breast cancer patients

Objectives: Breast cancer is the second leading cause of cancer deaths among women. Therefore, there is a need for new approaches that increase the success of treatment in breast cancer. Cancer stem cells (CSCs) are associated with treatment resistance and metastasis, which are important problems in cancer treatment including breast tumors. In this study, the Hematopoietic- and neurologic-expressed sequence 1-like (HN1L), also known as Jupiter microtubule associated homolog 2 (JPT2) protein levels which is involved in the self-renewal of CSCs were evaluated in common and rare breast tumor types. Methods: In this context, HN1L protein levels were measured from plasma of 17 patients and from tumor and normal tissues of 9 patients by enzyme linked immunosorbent assay method. Results: Mean HN1L levels were measured as 1.63 ± 0.88 ng/mL in plasma samples, 2.18 ± 0.75 ng/mL in tumor tissue samples and 2.71 ± 0.88 ng/mL in normal tissue samples. A significant difference was observed between mean HN1L levels in plasma and normal tissue (p &amp;lt; 0.05). Correlation of HN1L protein levels with clinicopathological characteristics were analyzed. Accordingly, HN1L levels were positively correlated with tumor size and invasion status (r=0.425; p &amp;lt; 0.05 and r=0.449; p &amp;lt; 0.05, respectively). Conclusions: We believe that the importance of HN1L in management of breast cancers will be demonstrated more thoroughly when further studies are conducted with increased number of patients.