Invasive Ductal Carcinoma Research Articles

This study explores the differential diagnostic value of conventional dimensional ultrasound (US) and automated breast volume scanner (ABVS) for breast ductal carcinoma in situ (DCIS) patients. A total of 986 female patients who underwent breast tumor surgery in our hospital from December 2019 to December 2022 were included. Clinical, US, ABVS, and pathological information were collected from all of the patients. Pathological results were used to separate patients into 3 groups: benign, DCIS, and invasive ductal carcinoma (IDC). Single-factor and multivariate analyses were conducted to evaluate the characteristics of DCIS. Of the 986 patients with breast tumors included in this study, 498, 193, and 295 were diagnosed with benign, DCIS, and IDC tumors, respectively. Compared with benign tumors, DCIS tumors were characterized by higher age at onset and breast imaging-reporting and data system (BI-RADS) grades, together with high rates of extension to the nipple, microcalcification, convergence sign, abundant blood supply, and nipple discharge proportion. Relative to IDC patients, DCIS tumors exhibited lower BI-RADS grades, aspect ratio values, and Ki-67 index values together with lower rates of irregular morphology, unclear boundaries, posterior echo attenuation, convergence sign, enhanced peripheral echo, nipple discharge, and palpable masses, and higher rates of extension to the nipple. Higher microcalcification rates in DCIS tumors were observed than the proportion of non-calcification in IDC cases. Conventional US and ABVS images of DCIS tumors exhibit certain distinctive characteristics that can aid in the differential diagnosis of DCIS.

Sentinel lymph node biopsy (SLNB) is a pivotal technique employed to assess the necessity for axillary lymph node dissection (ALND), evaluated during the preoperative phase through clinical and radiological findings. The preoperative identification of sentinel lymph node metastasis has gained paramount importance in the surgical management of breast cancer. Tumor budding (TB) has emerged as a significant prognostic marker across various cancers, including breast cancer, where it is instrumental in detecting lymph node metastasis. This study aims to investigate the role of tumor budding in predicting sentinel lymph node metastasis in preoperative breast biopsies.We included patients diagnosed with breast cancer, specifically those with invasive ductal carcinoma (IDC), who underwent preoperative needle biopsy and subsequent evaluation of postoperative surgical specimens, as well as SLNB at our medical center. The histological slides of these cases were reevaluated, and tumor cell clusters comprising up to four cells were classified as TB. Lymph nodes exhibiting tumor cell involvement, limited to macrometastasis, were classified as positive.A total of 65 patients were enrolled in the study. Among these, 36 patients exhibited TB in their preoperative biopsies, while 29 did not. The median tumor sizes were 20 mm (range: 6-50 mm) in the TB-positive group and 19 mm (range: 2-50 mm) in the TB-negative group (p=0.3). Sentinel lymph node metastasis was detected in 18 patients with TB, compared to only five patients without TB, a difference that was statistically significant (p=0.006). We conclude that evaluating tumor budding in breast tru-cut specimens, in conjunction with clinical and radiological findings, may enhance the preoperative assessment of breast cancer cases requiring SLNB.

Context Immunohistochemical (IHC) testing of estrogen receptors (ER), progesterone receptors (PR), HER2 and Ki-67 on breast cancer samples is carried out in the majority of clinical departments to predict response to therapies and to determine prognosis. Issues surrounding the reproducibility of testing are well documented and guidelines recommend laboratories participate in external quality assessment (EQA) in order to ensure reliability of results. Objective To assess the reproducibility of IHC testing for these markers in hospitals from the south, north, and centre of Vietnam, estimated to be approximately half of all clinical hospitals in the country performing these tests. Design As cases are referred for testing between hospitals, an EQA ring study was designed that included the testing of samples from all participating laboratories. Participants were provided with unstained slides of invasive breast carcinomas with different expression levels for ER, PR, HER2 and Ki-67. Results There was a significant level of reproducibility for all four biomarkers, with ER testing giving the least variation in results (kappa 0.822, coefficient of variation [CV] 4.8%) and Ki-67 the greatest variation (kappa 0.647 CV 17%). However, 328/392 (84%) and 317/392 (81%) of the Ki-67 evaluations were in agreement when employing the clinically relevant cut points of ≥30% and ≥20%, respectively. The reproducibility of testing for HER2-low expression was relatively poor (kappa 0.323, 95% CI 0.223–0.424), compared to overall agreement for HER2 testing (kappa 0.794, 95% CI 0.753–0.836). Conclusion This is the first EQA ring study held within Vietnam for ER, PR, HER2 and Ki-67 and sets the base line as to the current level of reproducibility in the country. Continued participation in the program will help ensure the reliability of testing for clinical use.

Background: Dextrocardia is a rare congenital anomaly in which the heart is positioned in the right hemithorax, often accompanied by complex structural abnormalities involving the cardiac chambers and great vessels. In oncology, this condition poses therapeutic challenges, particularly regarding cardiotoxicity risk. A thorough anatomical evaluation is essential to ensure the safety of invasive procedures and systemic cancer therapies. Research Questions: This case report explores how congenital cardiac anatomical variations influence clinical decision-making and cardio-oncology monitoring strategies. Approach: We describe a 35-year-old woman with left-sided invasive ductal carcinoma (HER2-, ER/PR+, Ki-67: 10%) and complex congenital heart disease: dextrocardia, congenitally corrected transposition of the great arteries, pulmonary stenosis, and ventricular septal defect. Pre-treatment evaluation included chest X-ray (Fig.1a), ECG (Fig. 1b), transthoracic echocardiography (Fig. 2), and cardiac MRI (Fig. 3). She underwent mastectomy, radiotherapy, and six cycles of docetaxel/cyclophosphamide chemotherapy. Cardiac function was monitored with serial echocardiograms and cardiac biomarkers (troponin, NT-proBNP). The patient developed heart failure with preserved ejection fraction (HFpEF) during chemotherapy. Clinical management with a loop diuretic and ACE inhibitor led to symptom resolution and clinical stabilization. The patient remained hemodynamically stable, with no drop in left ventricular ejection fraction. Discussion: Docetaxel and cyclophosphamide can be safely administered in dextrocardia, provided standard precautions are observed along with attention to altered cardiac anatomy. In cases with associated congenital heart disease, detailed cardiac imaging is crucial prior to chemotherapy. Serial monitoring with cardiac biomarkers allows early detection of cardiotoxicity. Interestingly, in this patient, dextrocardia led to reduced cardiac exposure during left-sided breast radiotherapy, possibly affording additional protection against radiation-induced myocardial fibrosis, coronary artery disease, and late cardiotoxicity. Conclusion: This case highlights the value of personalized oncology care in patients with congenital heart defects. While dextrocardia does not inherently preclude chemotherapy with agents such as docetaxel and cyclophosphamide, detailed imaging and vigilant clinical and laboratory monitoring are essential to optimize treatment safety and efficacy.

In most cases, invasive ductal carcinoma (IDC) of the breast is identifiable when it presents with classic infiltrative growth patterns. However, a subset of IDC can present in a very sneaky way, significantly mimicking the appearance of ductal carcinoma in situ (DCIS). In this condition, it is much easier to miss the invasive component without pulling ancillary staining when morphologic findings are extremely compatible with DCIS, especially the diagnosis of DCIS was made on the previous biopsy. Here, we report the case of a 55-year-old female patient who was found to have microcalcifications at the 11:00 o’clock position in the right posterior breast during a routine mammographic examination. A biopsy of the calcification area performed at an outside hospital reported high-grade DCIS (ER+, PR−). Histologic examination of the subsequent mastectomy specimen at our institution showed two separate areas that closely resembled DCIS. Immunohistochemical (IHC) staining showed that all myoepithelial markers—smooth muscle myosin heavy chain (SMMHC), p63, CK5/6, and S100—were retained at the periphery of the expanded acini in one of the areas. Unexpectedly and surprisingly, myoepithelial markers were completely lost at the periphery of a subset of the DCIS-looking acini in another area, a finding that was immunohistochemically consistent with the diagnosis of invasive ductal carcinoma admixed with DCIS. Knowing that invasive ductal carcinoma of the breast can exhibit a DCIS-like morphology, especially in cases where a prior biopsy has already established a diagnosis of DCIS, will enhance the awareness of pathologists to recognize invasive ductal carcinoma that mimics DCIS. In turn, this will prevent misdiagnosis and undertreatment of patients with invasive ductal carcinoma of the breast.

To evaluate the diagnostic efficacy of 7G image-guided vacuum-assisted biopsy (VAB) in predicting pathological complete response (pCR) after neoadjuvant systemic therapy (NST) in HER2+ or triple-negative (TN) breast cancer (BC) showing complete response (CR) or almost-CR on MRI. A prospective study was conducted from June 2018 to October 2022 on 25 HER2+ or TN operable BC patients who achieved CR or almost-CR on post-NST MRI. Presurgery, stereotactic or US-guided 7G VAB of the tumor bed was performed, and the pathological findings were compared with surgical results to evaluate the negative predictive value (NPV), accuracy, sensitivity, positive predictive value (PPV), and specificity in predicting residual disease. All tumors were invasive ductal carcinoma, with TN BC accounting for 52% (13/25) and HER2+ for 48% (12/25). MRI showed CR in 60% (15/25) of cases and almost-CR in 40% (10/25). Stereotactic VAB was performed in 84% (21/25) of cases and US-VAB in 16% (4/25), using 7G needles (average 10 samples) in all the cases. Posttreatment changes were demonstrated in all cases. Pathological CR was observed in 80% (20/25) of VAB cases and 84% (21/25) of surgical cases. Vacuum-assisted biopsy had a 100% NPV (95% CI, 83.2-100.0), 97.6% accuracy (95% CI, 92.9-100.0), 100% sensitivity (95% CI, 39.8-100.0), 80% PPV (95% CI, 28.4-99.5), and 95.2% specificity (95% CI, 76.2-99.9). Image-guided VAB with 7G needles in HER2+ or TN BC with CR or almost-CR in post-NST MRI demonstrated a 100% NPV for detecting residual carcinoma when sample correlation and representativeness were ensured. Additional studies with larger patient cohorts are needed to confirm these promising results and to potentially omit surgery through image-guided VAB in selected TN BC and HER2+ BC cases.

Despite advancements in screening and treatment, the incidence of breast cancer (BC) and associated mortality are projected to increase. Therefore, developing a companion diagnostic for BC remains important. Herein, we explore the urinary proteome for biomarkers of BC: 130 urine samples from (1) newly diagnosed breast cancer (BC), n = 46, (2) benign breast disease (BBD), n = 36, (3) symptom control (SC), n = 30, and (4) healthy control (HC), n = 18. The BC class included preinvasive: ductal carcinoma in situ (DCIS) (n = 3), invasive ductal carcinoma (IDC) (n = 23), and IDC accompanied by DCIS (n = 8) classes. Protein profiling was performed using ThermoScientific ProteomeDiscoverer and analyzed using MetaboAnalyst v6.0, DAVID, and STRING v12.0. Analyses identified 346 significantly (p < 0.05) differentially expressed proteins (DEP) across BC, BBD, SC, and HC. Multivariate Receiver Operating Characteristic curves (five proteins) suggested Area Under the Curve values of 0.985, 0.989, and 0.999 distinguishing BC from BBD, SC, and HC, respectively. DEP elevated in BC included beta-glucuronidase isoform 1, fibrinogen gamma chain, alpha-actinin-1, peptidase inhibitor 16, cysteine-rich C-terminal protein 1 isoform X1, guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1, vascular cell adhesion protein 1, ATP-dependent translocase ABCB1, and tumor protein p63-regulated gene 1 isoform X1. BC types were differentiated based on calpain-2 and cystatin-C expression (p < 0.05). Thus, BC has distinct urinary-protein profiles based on clinical diagnosis, which could be used in real-time noninvasive BC monitoring.

The Nottingham grading system, developed by Elston and Ellis, is the recommended method for grading invasive breast carcinoma. A previous study demonstrated the mean concordance for 35 breast pathologists in classifying 58 images as glandular (acinar)/tubule formation (G/TF) based on the World Health Organization definition was only 64%. To determine if an expanded description of G/TF according to the original definition and current use of the Nottingham grading system would improve recognition of G/TF among breast pathologists and pathologists in training. Fifty-eight images with one structure circled were classified as G/TF or non-G/TF by Dr Ian Ellis. Images were sent as a PowerPoint (Microsoft) file to the breast pathologists who participated in the original study and to 21 trainees. Participants were asked to classify the structures based on the expanded description and were also provided with the 58 images from the first study with annotation. Among the participating 28 of the original 35 breast pathologists, the mean concordance increased from 64% (range, 40%-97%) to 94% (range, 86%-100%). Trainees had a mean concordance of 90% (range, 52%-100%). The expanded description assisted in the recognition of G/TF for both breast pathologists and trainees. The most important impact on grading will likely be for carcinomas with complex cribriform patterns or micropapillary patterns with "inverted tubules." Participants endorsed that the expanded description of G/TF and the annotated images would be helpful reference material for pathologists.

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer, but distinct treatment strategies are limited. Better characterization of the genomic and transcriptomic landscape is critical to elucidate ILC tumor biology, improve histologic classification, and define precision medicine treatment approaches. We retrospectively analyzed de-identified next-generation sequencing data of 4,613 metastatic patients from the Tempus database including 637 with ILC, 91 with mixed lobular/ductal histology, and 3,885 with invasive breast carcinoma of no special type (IBC-NST). Samples were profiled using the Tempus xT assays. Mutations in CDH1 occurred in 71% of patients with ILC (453/637). The median tumor mutational burden was significantly higher in CDH1-mutant ILC samples compared with wild-type (WT) CDH1 samples (P = 0.008). Mutations in PIK3CA (55% vs. 28%), ERBB2 (13% vs. 4.3%), and TBX3 (12% vs. 3.8%) were enriched in CDH1-mutant ILC versus CDH1-WT ILC. CDH1 expression was similar between CDH1-mutant ILC and CDH1-WT ILC samples (P = 0.11). Patients with CDH1-mutant mixed histology or IBC-NST had lower CDH1 expression than those with CDH1-WT mixed histology or IBC-NST (P < 0.001). ILC had a different distribution of PAM50 subtypes compared with IBC-NST and mixed histologies (P < 0.001). Our real-world data illustrate the distinct molecular landscape of CDH1-mutant metastatic ILC, and therapies targeting ERBB2 and PIK3CA should be further investigated in CDH1-mutant ILC. ILC differs from mixed and IBC-NST at a transcriptional level, suggesting the possibility of using CDH1 RNA expression levels to improve classification of ILC.

Background: The E26 transformation-specific (ETS) transcription factor Friend Leukemia Integration 1 (FLI1) has been linked to breast cancer aggressiveness, stromal remodeling, and immune modulation, yet the regulatory mechanisms governing its activity remain poorly defined. Of note, various studies have shown that EWS-FLI1-mediated transcription programs are facilitated via direct recruitment and binding of the NuRD-LSD1 complex, regulating its associated gene targets. Furthermore, LSD1 inhibition exhibited reverse transcriptional profiles driven by ETS-FLI and reduced in vivo tumorigenesis in cancers. Methods: We evaluated FLI1 expression across multiple invasive breast carcinoma (IBC) cohorts to determine its prognostic significance and associations with stromal features. In parallel, we investigated FLI1 regulation in humanized breast cancer mouse models treated with an LSD1 inhibitor. Results: High FLI1 expression was associated with advanced histological grade in IBC, consistent with an oncogenic function. FLI1-high tumors also exhibited elevated stromal and immune scores, indicating a role in remodeling the tumor microenvironment. Additionally, LSD1 inhibition downregulated FLI1 target genes involving angiogenesis and invasion. Conclusions: These findings highlight the dual role of FLI1: tumor-intrinsic FLI1 promotes proliferation and invasion, whereas its transcriptional regulation in tumor and endothelial compartments likely reflects LSD1 dependence. Collectively, our results support a mechanistic model in which LSD1–FLI1 crosstalk is involved in immune and stromal remodeling, positioning FLI1 as both a marker of tumor aggressiveness and a potential predictor of response to epigenetic therapies in breast cancer.

Background and Objectives: In early-stage HER2-positive breast cancer, ado-trastuzumab emtansine (T-DM1) has been adopted as the preferred adjuvant approach for patients left with residual invasive disease despite neoadjuvant therapy. The influence of different neoadjuvant regimens on subsequent outcomes in real-world settings remains uncertain. Materials and Methods: From 2019 to 2025, 102 patients treated with adjuvant T-DM1 following surgery after neoadjuvant chemotherapy were retrospectively assessed. Neoadjuvant regimens included doxorubicin plus cyclophosphamide followed by trastuzumab-paclitaxel, doxorubicin plus cyclophosphamide with pertuzumab–trastuzumab–docetaxel, or docetaxel–carboplatin–trastuzumab–pertuzumab. Clinical features, treatment response, survival, and toxicity were evaluated. Results: The mean age of the cohort was 49.7 years, and the majority of patients (80.4%) were aged 40 years or older. Hormone receptor positivity was 82.0%, and invasive ductal carcinoma accounted for 97.1% of cases. Regional responses included 39.2% with axillary pCR despite residual breast lesions, and 5.9% with breast pCR accompanied by axillary disease. Kaplan–Meier analysis demonstrated disease-free survival rates of 100%, 95.2%, and 92.2% at 1, 3, and 5 years, respectively. Adverse events were predominantly grade 1–2, while grade 3–4 toxicities occurred in under 5% of the cohort. Baseline characteristics varied across regimens, reflecting real-world treatment preferences, but survival outcomes remained comparable. Conclusions: Adjuvant T-DM1 was associated with high survival rates and manageable toxicity across different neoadjuvant regimens, underscoring its consistent benefit in routine clinical practice.

Abstract Introduction Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterised by skin involvement, with or without muscle disease. A known paraneoplastic entity, approximately one-third of DM cases are associated with malignancy, particularly within three years of diagnosis. Among the autoantibodies, anti-TIF1-γ is most strongly associated with cancer-associated DM. This case describes a middle-aged woman presenting with inflammatory myopathy and atypical ulcerative skin lesions, ultimately diagnosed as paraneoplastic DM linked to recurrent breast cancer. The case highlights an uncommon cutaneous presentation in a patient with a known cancer-associated myositis autoantibody, offering insight into diagnostic nuances and management challenges in paraneoplastic syndromes. Case description A 42-year-old African female presented to the rheumatology outpatient clinic with a one-month history of difficulty standing from a squatting position and combing her hair. She had a prior history of hormone receptor–positive breast cancer, treated with lumpectomy eight months earlier in her home country. Clinical examination revealed symmetrical proximal muscle weakness (MMT-8 score: 117/150), Gottron’s papules, and calcinosis over the buttocks. Painful ulcerative skin lesions were noted, which are uncommon in TIF1-γ–associated DM. Cutaneous Dermatomyositis Severity Index (CDASI) scores were 19/100 (activity) and 2/32 (damage). Serum CPK was modestly elevated at 394 IU/L. The patient reported new-onset pain in the left axillary region, where lymphadenopathy was noted. PET-CT revealed multiple FDG-avid level I axillary lymph nodes and diffuse increased FDG uptake in skeletal muscles. Biopsy of the axillary nodes confirmed metastatic recurrence of invasive ductal carcinoma of the breast. Myositis line immunoassay (LIA) was positive for anti-TIF1-γ antibody. A diagnosis of paraneoplastic dermatomyositis associated with recurrent breast malignancy was established. She was initiated on systemic corticosteroids (oral prednisolone), topical corticosteroids, and sunscreen. Oncologists commenced adjuvant chemotherapy with doxorubicin and cyclophosphamide. She completed two cycles locally and opted to continue further treatment in her home country. Discussion This case illustrates the classical association of dermatomyositis with underlying malignancy, underscoring the diagnostic and management complexity in paraneoplastic presentations. TIF1-γ is one of the most common myositis-specific autoantibodies associated with cancer, particularly in adults over 40. Its presence warrants an extensive malignancy screen, even in patients with a known cancer history. Interestingly, our patient displayed ulcerative skin lesions—a feature more typical of anti-MDA5–associated DM. While ulceration is rarely associated with anti-TIF1-γ, it is still documented in the setting of paraneoplastic DM, reflecting a potentially overlapping phenotype or immune activation profile. The modest elevation of CPK despite significant muscle weakness and PET-CT muscle uptake emphasises the importance of correlating clinical, biochemical, and imaging data. While the standard treatment for idiopathic DM includes corticosteroids and immunosuppressants, in paraneoplastic DM, cancer control is central to managing myositis. Here, malignancy-targeted therapy was prioritised, alongside immunosuppression for symptom relief. This case raises important clinical questions: should skin ulceration in the context of TIF1-γ prompt clinicians to consider alternative or coexisting antibody profiles? How should treatment be tailored in patients with dual autoimmune and oncological pathology? Through this case, we advocate for vigilance in cancer surveillance in DM, especially in those with TIF1-γ antibodies, and for awareness of atypical cutaneous signs that may expand the known phenotype. Key learning points • TIF1-γ autoantibody is a key marker of cancer-associated dermatomyositis, especially in adults over 40. Its presence should prompt thorough malignancy screening, even in patients with a past history of cancer in remission. • Skin ulceration is uncommon but possible in anti-TIF1-γ–positive DM and should not exclude this diagnosis. It is more typically seen with anti-MDA5 but may also reflect severe immune activation in paraneoplastic contexts. • Clinical-imaging-biochemical discordance can occur, as seen with mildly elevated CPK despite significant clinical weakness and muscle FDG uptake on PET-CT. Comprehensive assessment is crucial. • Management of paraneoplastic DM focuses on malignancy control. Immunosuppression is supportive but less effective without oncological treatment. Early coordination with oncology is essential. • Case-based learning objectives for the conference: • To explore evolving phenotypes in antibody-associated myositis • To identify key features distinguishing idiopathic from paraneoplastic DM • To discuss practical approaches for malignancy screening and coordination between rheumatology and oncology • To reflect on treatment dilemmas in immunosuppression versus tumor-targeted therapy

Comparative Evaluation of Advanced Deep Learning, Image-to-Text Models, and Radiomics for Predicting Tumor Budding and Tumor-Stroma Ratio from Breast Ultrasound in Invasive Ductal Carcinoma.

Background/Objectives: Breast cancer is a leading cause of cancer-related mortality among women worldwide. Small nucleolar RNAs (snoRNAs) represent a class of non-coding RNAs with potential as novel biomarkers applicable to improve diagnostic and prognostic applications. Methods: We performed a comprehensive evaluation of the snoRNA-related gene expression by qPCR using benign and tumor tissue samples associated with invasive breast carcinomas of no special type (NST). Selected candidate snoRNAs, i.e., SCARNA2, SCARNA3, SNORD15B, SNORD94, SNORA68, and SNHG1, along with RNU2-1 snRNA, were further validated and their associations with clinicopathological parameters were examined. External datasets and plasma samples were used for additional validation. Results: SCARNA2 was identified as the most promising snoRNA biomarker candidate, showing a positive association with better progression-free survival (PFS) in our data (13.3-month survival difference between low- and high-expression groups) and with both PFS and overall survival in external RNA-seq datasets. SNORD94, SNORD15B, SCARNA3, and RNU2-1 snRNA were also indicated as putative tumor suppressors. SNORD94 was associated with better progression-free survival (PFS) in our data as well (12.4-month survival difference between low- and high expression groups). Greater downregulation in the low-expression tumor subgroup compared to benign samples further supports the prognostic potential of SCARNA2 and SNORD94. Evidence for SNHG1 and SNORA68 as putative oncogenes was less conclusive. Conclusions: Several small nucleolar RNAs were found to be dysregulated in breast cancer specimens, supporting their further evaluation as potential biomarkers. In particular, SCARNA2, SNORD94, SNORD15B, SCARNA3, and RNU2-1 snRNA merit further investigation to determine their clinical relevance and biological roles in breast cancer.

Gene expression studies are fundamental in molecular biology, offering insights into development, disease progression, and therapeutic targets. To address the need for precise analysis of large datasets, we developed THRESHOLD, a novel tool that introduces the concept of gene saturation. Unlike traditional methods focused on absolute or binary expression levels, THRESHOLD quantifies the consistency of gene expression across patients, revealing co-regulation patterns critical for understanding disease mechanisms and stratifying patients by molecular signatures. The tool offers several features, including user-defined parameters, statistical comparisons, and interactive data visualization. THRESHOLD has uncovered compelling insights into disease progression using TCGA cancer datasets. For instance, bladder urothelial carcinoma demonstrated increasing upregulated gene saturation in progressive cancer stages (P < .00001). Moreover, THRESHOLD identified heightened gene saturation in patients with earlier onset of prostate adenocarcinoma (P < .0001) and revealed a critical fusion transcript, SLC45A2-AMACR, implicated in prostate adenocarcinoma progression, recurrence, and metastasis. Additionally, novel biomarkers and potential candidates for drug therapies were identified through protein–protein interaction networks and functional analyses of saturation data in colon adenocarcinoma and breast invasive carcinoma. THRESHOLD offers a new approach for studying gene expression dynamics and patient stratification. The tool is publicly available at Zenodo: https://zenodo.org/records/15287195.

Intratumoral heterogeneity (ITH) of HER2 expression and HER3 upregulation have been associated with resistance to HER2-targeted therapies. However, their predictive role in the neoadjuvant setting remains controversial. We retrospectively analyzed 59 patients with HER2-positive invasive breast carcinoma treated with neoadjuvant chemotherapy and anti-HER2 agents at the Agostino Gemelli University Hospital (2018-2020). HER2 ITH was assessed on pre-treatment biopsies and residual tumors (when applicable) by immunohistochemistry and SISH. HER3 expression was also evaluated using IHC and categorized as negative, low, or high. The association with pathological complete response (pCR) and event-free survival (EFS) was assessed. pCR was achieved in 49.2% of patients. HER2 ITH was present in 23.7% of biopsies and was significantly associated with a lower pCR rate (p = 0.005). In multivariate analysis, HER2 ITH (OR 0.156, p = 0.030), HER2 score (3 + vs 2 + , OR 9.63, p = 0.044), and PgR negativity (OR 0.306, p = 0.029) emerged as independent predictors of pCR. HER3 expression did not significantly correlate with pCR or EFS, although a non-significant trend toward reduced EFS was observed in HER3-high cases. HER2 ITH negatively impacts pathological response to neoadjuvant therapy in HER2-positive breast cancer and may serve as a potential predictive biomarker. HER3 expression, while not significantly associated with outcome in this cohort, warrants further investigation as a possible contributor to therapeutic resistance. Standardized assessment protocols for both markers could improve patient stratification, guide treatment intensification, and support the integration of novel targeted agents in HER2-positive breast cancer.

Background/AimNeo-lymphangiogenesis induces lymphatic invasion of cancer cells, significantly increasing the metastatic potential of breast carcinomas (BCs). Among the molecules that are implicated in lymphangiogenesis, podoplanin (PDPN, gene locus: 1p36.21) - a transmembrane receptor glycoprotein - is expressed exclusively in lymphatic vessels. The current study explored the impact of PDPN-dependent mean lymphatic micro-vessel density (mLMVD) in invasive ductal (inDBC) and invasive lobular breast adenocarcinomas (inLBC).Materials and MethodsA set of thirty (n=30) paraffin-embedded invasive BC tissue sections (22 inDBCs and 8 inLBCs, respectively) were analyzed by applying a combination of immunocytochemistry (IHC) and digital image analysis (DIA) assays.ResultsHigh and moderate mLMVD rates (defined by the mean number of lymphatic domains with emboli in five optical fields under 400X magnification) were detected in 5/30 (16.6%) and 6/30 (20%) cases (total 11/30 (36.6%), respectively. In these cases, PDPN demonstrated strong cytoplasmic/membranous staining intensity. The remaining 19 cases (63.4%) demonstrated low levels of mLMVD. mLMVD was significantly correlated with the stage of the examined malignancies (p=0.019), whereas a marginal association with the grade of differentiation was identified (p=0.042). No significant correlation was observed with histological subtype (p=0.234) or tumor size (p=0.085).ConclusionNeo-lymphangiogenesis in BCs is a critical histological feature in the progression of the malignancy and is correlated with an aggressive phenotype (advanced stage). PDPN expression in lymphatic micro vessels is a reliable biomarker for evaluating lymphangiogenic activity in BCs, independently of their histotype, especially when assessed with precise DIA techniques.

Early prediction of response to neoadjuvant chemotherapy (NAC) is essential for personalized treatment planning in breast carcinoma. Previous studies have relied on human-annotated regions of interest for digital pathology analysis rather than directly leveraging whole-slide images (WSIs). This study aimed to evaluate the predictive value of pretreatment core needle biopsy (CNB) WSIs for pathological complete response (pCR) to NAC using an artificial intelligence (AI)-based approach. We analyzed 130 patients with invasive ductal carcinoma who underwent anthracycline- or taxane-based NAC followed by surgery. From each pretreatment CNB WSI, five regions with the highest cellular density were selected to extract image patches. A fusion-based classification model was developed, integrating image data with clinical metadata, including age, hormone receptor status, and Ki-67 labeling index. The model achieved an accuracy of 92.3%, comparable to those using expert annotations. Omitting either image or clinical data significantly reduced performance, underscoring their complementary roles. Optimal performance was achieved using five image patches of 1,000×1,000 pixels, balancing histological detail and computational efficiency. Our AI-based model accurately predicted pCR to NAC in breast carcinoma using only a limited number of high-cellularity image patches and basic clinical metadata, without requiring expert annotation. This approach may facilitate earlier treatment decisions and improve preoperative outcome prediction.

Prognostic significance of ductal carcinoma <i>in situ</i> coexisting with invasive ductal carcinoma: Biological behavior, immune response and survival outcomes

Patient: Male, 43-year-oldFinal Diagnosis: Invasive breast carcinomas of no special type (NST)Symptoms: Areola ulcer • breast cancerClinical Procedure: Axillary lymph node dissection • mastectomy • radiation therapySpecialty: OncologyObjective: Rare diseaseBackgroundAbemaciclib is a selective cyclin-dependent kinase inhibitor that has been approved as an adjuvant treatment for advanced hormone-positive, human epidermal growth factor receptor-2 (HER2)-negative breast cancer and is usually used in combination with an aromatase inhibitor. This report describes the case of a 43-year-old man with a grade 2, stage IIIc, hormone receptor-positive, HER2-negative, invasive ductal carcinoma of the left breast successfully managed with left mastectomy, radiation therapy, and postoperative oral tamoxifen and abemaciclib.Case ReportA 43-year-old man presented to our Dermatology Department with a primary concern of non-healing erosion in the left areola that persisted despite 3 months of topical ointment application. Tissue diagnosis confirmed breast cancer, and the patient was referred to the Breast Surgery Department. Imaging studies and detailed tissue analysis revealed a grade 2, hormone receptor-positive, HER2-negative, invasive ductal carcinoma of the left breast. The preoperative stage was cT4bN1aM0 (tumor with skin involvement, limited axillary node metastases, no distant spread), corresponding to stage IIIB. The patient underwent surgery (left mastectomy with axillary lymph node dissection; levels I–III). The pathological stage was IIIC (pT4bN3aM0: skin involvement with extensive nodal metastases and no distant disease). We administered postoperative adjuvant chemotherapy with sequential administration of anthracycline and taxane, and postoperative radiation therapy, followed by postoperative adjuvant endocrine therapy with tamoxifen and abemaciclib. To date, no signs of recurrence have been observed.ConclusionsThis report describes a rare case of advanced male breast cancer and a successful outcome following postoperative treatment that included abemaciclib.