Integration of Pathological Criteria and Immunohistochemical Evaluation for Invasive Lobular Carcinoma Diagnosis: Recommendations From the European Lobular Breast Cancer Consortium.

Invasive lobular carcinoma (ILC) is the second most frequent type of breast cancer (BC) and its peculiar morphology is mainly driven by inactivation of CDH1, the gene coding for E-cadherin cell adhesion protein. ILC-specific therapeutic and disease-monitoring approaches are gaining momentum in the clinic, increasing the importance of accurate ILC diagnosis. Several essential and desirable morphologic diagnostic criteria are currently defined by the World Health Organization, the routine use of immunohistochemistry (IHC) for E-cadherin is not recommended. Disagreement in the diagnosis of ILC has been repeatedly reported, but interpathologist agreement increases with the use of E-cadherin IHC. In this study, we aimed to harmonize the pathological diagnosis of ILC by comparing 5 commonly used E-cadherin antibody clones (NCH-38, EP700Y, Clone 36, NCL-L-E-cad [Clone 36B5], and ECH-6). We determined their biochemical specificity for the E-cadherin protein and IHC staining performance according to type and location of mutation on the CDH1 gene. Western blot analysis on mouse cell lines with conditional E-cadherin expression revealed a reduced specificity of EP700Y and NCL-L-E-cad for E-cadherin, with cross-reactivity of Clone 36 to P-cadherin. The use of IHC improved interpathologist agreement for ILC, lobular carcinoma in situ, and atypical lobular hyperplasia. The E-cadherin IHC staining pattern was associated with variant allele frequency and likelihood of nonsense-mediated RNA decay but not with the type or position of CDH1 mutations. Based on these results, we recommend the indication for E-cadherin staining, choice of antibodies, and their interpretation to standardize ILC diagnosis in current pathology practice.

Chromatin accessibility landscape and active transcription factors in primary human invasive lobular and ductal breast carcinomas.

BACKGROUND: Invasive lobular breast carcinoma (ILC), the second most prevalent histological subtype of breast cancer, exhibits unique molecular features compared with the more common invasive ductal carcinoma (IDC). While genomic and transcriptomic features of ILC and IDC have been characterized, genome-wide chromatin accessibility pattern differences between ILC and IDC remain largely unexplored. METHODS: Here, we characterized tumor-intrinsic chromatin accessibility differences between ILC and IDC using primary tumors from The Cancer Genome Atlas (TCGA) breast cancer assay for transposase-accessible chromatin with sequencing (ATAC-seq) dataset. RESULTS: We identified distinct patterns of genome-wide chromatin accessibility in ILC and IDC. Inferred patient-specific transcription factor (TF) motif activities revealed regulatory differences between and within ILC and IDC tumors. EGR1, RUNX3, TP63, STAT6, SOX family, and TEAD family TFs were higher in ILC, while ATF4, PBX3, SPDEF, PITX family, and FOX family TFs were higher in IDC. CONCLUSIONS: This study reveals the distinct epigenomic features of ILC and IDC and the active TFs driving cancer progression that may provide valuable information on patient prognosis.

Gastric metastasis before diagnosis of primary invasive lobular breast carcinoma: a rare case presentation from Pakistan.

Metastatic spread of invasive lobular breast carcinoma to stomach is rare especially before diagnosis of primary breast cancer. Incorrect diagnosis might result in delay of appropriate treatment for breast cancer. Recognition of this possibility enables better clinical management. A 62-year-old female presented with upper gastrointestinal symptoms and weight loss and was referred to a gastroenterologist for investigation. At the time of initial diagnosis of stomach cancer, patient was asymptomatic for breast cancer. Multiple gastric biopsies taken showed features suspicious of metastatic breast cancer. Consequently, the initial provisional diagnosis of stomach cancer changed into metastatic invasive lobular breast carcinoma. These findings were corroborated radiologically. The patient was treated with letrozole and zoledronic acid as first-line therapy for one year. Residual metastatic breast cancer was present in the gastric mucosa. The patient was treated with endocrine therapy containing ribociclib and treatment was ineffective confirmed by PET-CT scan. But her symptoms have resolved completely despite her presentation with stage IV. We present rare case of initial presentation of gastric metastasis before diagnosis of a primary invasive lobular breast carcinoma. Correct diagnosis and appropriate treatment were accomplished through initial clinical suspicion, accurate histological examination, and endoscopy together with analysis of disease-specific biomarkers.

Heterogeneity in risk factors for ductal and lobular breast carcinomas: A case-control study.

Invasive ductal carcinoma (IDC) and invasive lobular carcinoma (ILC) of the breast are the most common histological subtypes of breast cancer. However, the associations and heterogeneity between histological subtypes and their risk factors are not well established. This study aimed to investigate risk factors for IDC and ILC. This case-control study included 1,009 incident breast cancer cases and 1,009 hospital controls, frequency-matched by age. Data were obtained from the patients' medical files and an interview administered via a questionnaire. Multinomial logistic regression was used and odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. The heterogeneity of the associations was assessed using the Wald test. Family history of breast cancer was associated with IDC (OR 2.64, 95% CI: 1.97-3.55) but not ILC (OR 0.81, 95% CI: 0.42-1.57; p for heterogeneity <0.001). Conversely, a history of miscarriage was associated with ILC (OR 1.71, 95% CI: 1.17-2.51) but not IDC (OR 1.18, 95% CI: 0.95-1.46; p for heterogeneity = 0.04). Similarly, type 2 diabetes was associated with ILC but not IDC (p for heterogeneity = 0.02). Age at first delivery and breastfeeding were significantly associated with IDC but not ILC, though p values for heterogeneity did not reach the significance level. Deliberate weight loss and age at menarche were significantly associated with ILC but not IDC (p for heterogeneity ≥0.27). Smoking, history of benign breast disease and BMI were associated with both subtypes. The present study supports the hypothesis that IDC and ILC are etiologically distinct tumours.

Orbital and conjunctival metastasis from lobular breast carcinoma.

This article examines the clinical presentation of ocular metastasis from an infiltrating lobular breast carcinoma. We examined a conjunctival biopsy from a 69-year-old woman who developed unilateral conjunctival inflammation together with a neurotrophic corneal ulcer and proptosis. Infiltrating lobular breast carcinoma (ILBC) was diagnosed using routine histology and immunohistochemistry. She had a past history of a hormone receptor-positive infiltrating ILBC 11 years ago with cutaneous and diffuse osteoblastic metastases, and she was kept under treatment with lezotrol. Treatment was initiated with systemic corticosteroids but an annular conjunctival perilimbal infiltration was found to have spread, which did not respond either to local radiotherapy (total dose 60 Gy, 2 Gy per day). A new extensive corneal epithelial defect recurred, and because it had not responded to matrix therapy agent (RGTA, Cacicol®) eye drops, autologous serum eye drops and a therapeutic contact lens, a permanent total tarsorrhaphy was performed. Progression of the diffuse bone metastases was detected and the treatment with lezotrol was replaced by fulvestrant.Infiltrating lobular breast carcinoma is a rare cause of conjunctival metastasis. This aggressive malignancy did not respond to external beam radiotherapy.

Gastric and Colorectal Metastases of Lobular Breast Carcinoma: A Case Report.

BACKGROUND: Occurrence of gastric metastasis as the first symptom of breast carcinoma with a long period of latency before presentation of the primary breast carcinoma is rare. CASE REPORT: A patient with gastric metastasis as the first symptom of lobular breast carcinoma, treated by neoadjuvant preoperative chemoradiotherapy and total gastrectomy, with complete local control. Fourteen months after presentation of the gastric metastasis a primary lobular breast carcinoma was discovered, treated by radiotherapy, chemotherapy and hormonal treatment with complete local response. Twenty-three months after diagnosis of breast cancer multiple colorectal metastases from the breast cancer occurred, which were treated by chemotherapy and hormonal treatment. Eighty-six months after diagnosis of gastric metastasis the patient died due to progression of cancer. CONCLUSIONS: Metastases to gastrointestinal or gynaecological tracts are more likely in invasive lobular carcinoma than invasive ductal cancer. The pathologist should determine whether or not they check estrogen and progesterone receptor status not simply by signet ring cell morphology but also by consideration of clinic-pathological correlation of the patient, such as the presence of a past history of breast cancer, or the colorectal localization of poorly differentiated carcinoma, which may occur less frequently than in the stomach.

Nomograms to predict the long-term prognosis for non-metastatic invasive lobular breast carcinoma: a population-based study.

Invasive lobular breast carcinoma (ILC) is one potential subset that "clinicopathologic features" can conflict with "long-term outcome" and the optimal management strategy is unknown in such discordant situations. The present study aims to predict the long-term, overall survival (OS) and cancer-specific survival (CSS) of ILC. The clinical information of patients with non-metastatic ILC was retrieved from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2020. A total of 31451 patients were enrolled and divided into the training cohort (n=22,017) and validation cohort (n=9434). The last follow-up was December, 31, 2020 and the median follow-up period was 99 months (1-203). Age, marriage, estrogen (ER) status, progesterone (PR) status, grade, tumor size, lymph node ratio (LNR) and combined summary (CS) stage were prognostic factors for both OS and CSS of ILC, whereas chemotherapy and radiation were independent protect factors for OS. The nomograms exhibited satisfactory discriminative ability. For the training and validation cohorts, the C-index of the OS nomogram was 0.765 (95% CI 0.762-0.768) and 0.757 (95% CI 0.747-0.767), and the C-index of the CSS nomogram were 0.812 (95% CI 0.804-0.820) and 0.813 (95% CI 0.799-0.827), respectively. Additionally, decision curve analysis (DCA) demonstrated that the nomograms had superior predictive performance than traditional American Joint Committee on Cancer (AJCC) TNM stage. The novel nomograms to predict long-term prognosis based on LNR are reliable tools to predict survival, which may assist clinicians in identifying high-risk patients and devising individual treatments for patients with ILC. Our findings should aid public health prevention strategies to reduce cancer burden. We provide two R/Shiny apps ( https://ilc-survival2024.shinyapps.io/osnomogram/ ; https://ilc-survival2024.shinyapps.io/cssnomogram/ ) to visualize findings.

Gastric metastasis and peritoneal carcinosis revealing primary breast cancer: an unusual presentation.

Breast cancer is the most frequent cancer among women. Gastrointestinal tract metastases are uncommon and might be misidentified as primary carcinoma.A noteworthy case-study involved 53-year-old-woman complaining from epigastric pain, ascites and overall health decline. Initial investigations were inconclusive, prompting laparoscopic peritoneal biopsies which revealed independent cell proliferation. Subsequently, a second look upper digestive endoscopy showed multiple gastric ulcerations suggestive of gastric carcinoma. Histologic examination confirmed independent cell proliferation with estrogen receptors expression, a characteristic feature of breast carcinoma. Further investigations led to bilateral invasive lobular breast carcinoma diagnosis. Epirubicin cycophosphamide was prescribed after progression under letrozole ribocilib therapy.This case aims to raise awareness among clinicians about the importance of ruling out breast cancer in patients with peritoneal carcinosis and paying attention to digestive symptoms in breast cancer patients with careful gastric endoscopic examination to avoid misdiagnosis.

[Box: see text].

Gastric Metastasis from Invasive Lobular Breast Cancer, Resembling Primary Gastric Cancer.

Invasive lobular carcinoma (ILC) is the second most common subtype of invasive breast cancer and sometimes presents with an unusual metastatic pattern. Its gastric metastasis is difficult to differentiate from primary adenocarcinoma. This report presents a case of breast ILC for which the initial presentation was gastric metastasis. A 62-y-old woman presented with gastric outlet obstruction secondary to a gastric mass that had been diagnosed on upper gastrointestinal endoscopy and biopsy. The patient had been referred for 18F-FDG PET/CT for staging. The baseline 18F-FDG PET/CT scan demonstrated extensive axillary nodal and gastric metastases with a breast mass, which raised suspicion of a primary breast carcinoma. Distinguishing primary gastric adenocarcinoma from metastatic breast ILC is essential, considering that the 2 diagnoses lead to divergent treatments. Therefore, this entity needs to be considered in the differential diagnosis in clinical practice.

Construction of immune score and its prognostic value in invasive lobular carcinoma of the breast using computational pathology analysis.

BACKGROUND: Previous studies have shown that high level of TILs in invasive lobular carcinoma (ILC) is associated with poor prognosis, contrary to that in TNBC and HER2-positive breast cancer. METHODS: The densities of six immune cell markers and three immune checkpoints in the ILC microenvironment were detected by computational pathology analysis. Then, the LASSO cox regression model was used to construct an immune score (IS) and further evaluate its prognostic value. RESULTS: In our ILC cohort, the low density of CD4, CD8, CD20, CD56, CD68, FOXP3, PD-1, and PD-L1 had significantly longer disease-free survival (DFS) and overall survival (OS); however, the low density of CTLA-4 was associated with shorter DFS and OS. Based on this, an IS was constructed, and patients with low-IS had significantly prolonged DFS (p < 0.0001) and OS (p < 0.0001). Multivariate analysis revealed that IS was an independent prognostic indicator for DFS and OS. Further analysis showed that IS may increase the prognostic value of TNM stage. We further explored the prognostic role of CD68 and FOXP3 in the transcriptional level and the corresponding ISm in the METABRIC dataset, and found that low proportion of CD68 and FOXP3 and their ISm were associated with longer OS, and ISm was also an independent prognostic factor for OS. CONCLUSION: IS was a promising biomarker to distinguish the prognosis in ILC patients.

68Ga-FAPI PET/CT as an Alternative to 18F-FDG PET/CT in the Imaging of Invasive Lobular Breast Carcinoma.

Accurate staging of invasive lobular carcinoma (ILC), a subtype of breast cancer, is vital for effective clinical management. Although 18F-FDG PET/CT is a commonly used tool, its efficacy varies across different histologic subtypes. To mitigate this challenge, our investigation delves into the potential utility of 68Ga-fibroblast activation protein inhibitor (FAPI) PET/CT as an alternative for staging ILC, aiming to address a significant research gap using a more expansive patient cohort than the smaller samples commonly found in the existing literature. Methods: In this retrospective analysis, women diagnosed with primary ILC of the breast underwent both 18F-FDG PET/CT and 68Ga-FAPI PET/CT. Both modalities were compared across all lesion locations with the used reference standard. The interval between scans was 1 wk, without any intervening treatments. Lesions were categorized visually, and tracer activity was analyzed using SUVmax, tumor-to-background uptake ratio, and uptake ratios. Both modalities were compared across various parameters, and statistical analysis was performed using SPSS 22.0. A P value of less than 0.05 was chosen to determine statistical significance. Results: The study included 23 female ILC patients (mean age, 51 y) with hormone-positive, human epidermal growth factor receptor type 2-negative tumors. Most (65%) had the luminal A subtype. 68Ga-FAPI PET/CT outperformed 18F-FDG PET/CT, with higher tumoral activity and tumor-to-background uptake ratios (P < 0.001). Primary tumors showed significantly increased uptake with 68Ga-FAPI PET/CT (P < 0.001), detecting additional foci, including multicentric cancer. Axillary lymph node metastases were more frequent and had higher uptake values with 68Ga-FAPI PET/CT (P = 0.012). Moreover, 68Ga-FAPI PET/CT identified more lesions, including bone and liver metastases. Pathologic features did not significantly correlate with imaging modalities, but a positive correlation was observed between peritumoral lymphocyte ratio and 68Ga-FAPI PET/CT-to-18F-FDG PET/CT uptake ratios (P = 0.026). Conclusion: This study underscores 68Ga-FAPI PET/CT's superiority over 18F-FDG PET/CT for ILC. 68Ga-FAPI PET/CT excels in detecting primary breast masses, axillary lymph nodes, and distant metastases; can complement 18F-FDG PET/CT in ILC; and holds potential as an alternative imaging method in future studies.

CDH1 gene mutation, a challenging surgical topic: Case report and literature review.

INTRODUCTION: Gastric cancer is one of the top 5 cancers worldwide. Most gastric cancers are classified as sporadic with the exception of around 3 % that are associated with specific syndromes or genes. Hereditary diffuse gastric cancer is a very rare type of gastric cancer, associated with loss of function of a tumor suppressor gene CDH1 which has a high penetrance that can reach 90 % over a lifetime. CASE PRESENTATION: Here we present the case of a 31 years old male patient carrying the CDH1 gene who presented for prophylactic total gastrectomy and D1 lymphadenectomy followed by a roux en y esophago-jejunostomy for digestive tract reconstruction. The patient had a preoperative negative gastroscopy for gastric cancer. On final pathology, few 2 mm foci of signet ring cells involving the lamina propria (T1a) were identified. CLINICAL DISCUSSION: Randomized clinical trial data concerning HDGC is lacking. Individuals who meet the genetic testing criteria developed by the IGCLC, testing should be obtainable from the legal age of consent that range from 16 to 18 years of age. CDH1 is the main gene that is tested. The mainstay treatment of choice for HDGC is total gastrectomy and Roux-en-Y esophago-jejunostomy in asymptomatic patients but should only be undertaken after baseline endoscopy. CONCLUSION: Genetic testing for CDH1 should be carried in high-risk populations. Due to its high penetrance, any person carrying the CDH1 gene should be managed by a prophylactic gastrectomy and D1 lymphadenectomy with close follow up for any future breast neoplasm.

The Alveolar Variant of Lobular Carcinoma and Its Mimickers: A Case Series.

Invasive lobular carcinoma (ILC) is the most common special type of invasive breast cancer (IBC), accounting for 5-15% of IBCs. The distinct histomorphology of ILC reflects a special tumor biology, the hallmark of which is the lack of E-cadherin expression. However, the occasional presence of E-cadherin expression and the presence of IBC of no special type (IBC, NST)-like morphologies in ILC and vice versa make the diagnosis challenging.  We present two cases of the alveolar variant of ILC, a diagnostically challenging entity. The first case is an 81-year-old female with two discrete right breast masses at 1 o'clock and 9 o'clock positions.  The second case is a 61-year-old female with two discrete left breast masses located at 11 o'clock and 12 o'clock positions. Core needle biopsies and subsequent mastectomy were performed in both cases. On histology, three tumor foci were identified in the first case. The 1 o'clock focus showed IBC, NST, grade 3/3, ductal carcinoma in situ (DCIS) and lobular carcinoma in situ (LCIS). The 9 o'clock focus revealed ILC, classic and alveolar variants, grade 2/3, while a nearby third incidental focus was ILC, alveolar variant, both supported by lack of E-cadherin and ß-catenin immunostaining.  The second case showed ILC, alveolar variant, grade 1 with LCIS component in the 11 o'clock lesion on both biopsy and mastectomy specimens. The lesion at the 12 o'clock position was diagnosed as IBC, NST, grade 2 with high-grade DCIS and LCIS components.  It is challenging to distinguish the alveolar variant of ILC from IBC, NST, and in situ lesions because of the overlapping morphology and occasional E-cadherin expression. Altered adherence of lobular cells may also be due to loss of α-, ß-, and γ-catenins, and cytoplasmic re-localization of p120-catenin. Therefore, in ILC, the lack of ß-catenin can be used as an adjunct along with E-cadherin. Myoepithelial markers such as p63 and smooth muscle myosin heavy chain (SMMHC) can be used to distinguish the alveolar variant of ILC from LCIS.

Automated feathered edge blood smear analysis: early diagnosis of carcinocythemia in a case of disseminated intravascular coagulation with multi-organ failure.

Carcinocythemia, known as the presence of circulating tumor cells in the peripheral blood, is difficult to detect when the carcinoma cells are minimally present. We describe a case of a 56-year-old patient presenting with disseminated intravascular coagulation (DIC) and multiple organ failure. Despite initial suspicion of sepsis, a peripheral blood smear showed the presence of atypical cells, mainly located at the feathered edge, leading to a presumptive diagnosis of carcinocythemia of unknown primary origin. The presence of a high-fluorescent cell population detected by our hematology analyzer (Sysmex XN-9100) and immunohistochemical staining with pancytokeratin AE1/AE3 confirmed the carcinoma cell origin. The patient died 4 days after referral to our hospital. Postmortem examination revealed a pleomorphic lobular breast carcinoma (triple-negative, androgen receptor-negative). Given the clinical acuity of patients with carcinocythemia, early diagnosis is essential to guide management. This case underscores the importance of optimizing current workflows relying on complex flagging algorithms and enhanced digital imaging to aid in the early detection of such rare condition. When patients present with DIC of unknown origin and high fluorescent signals are detected on the hematology analyzer, carcinocythemia should actively be ruled out by extensive microscopic peripheral blood examination.

FDG and Non-FDG Radiopharmaceuticals for PET Imaging in Invasive Lobular Breast Carcinoma.

Invasive lobular cancer (ILC) is the second most frequent histological type of breast cancer (BC) and includes a heterogeneous spectrum of diseases with unique characteristics, especially the infiltrative growth pattern and metastatic spread. [18F]fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (FDG-PET/CT) is extensively used in oncology and BC patient evaluation. Its role in ILCs is considered suboptimal due to its low FDG avidity. Therefore, ILCs could benefit from molecular imaging with non-FDG tracers that target other specific pathways, contributing to precision medicine. This narrative review aims to summarize the current literature on the use of FDG-PET/CT in ILC and to discuss future opportunities given by the development of innovative non-FDG radiotracers.

The uncharted role of HER2 mutant alleles in breast cancer.

Somatic HER2 mutations are a novel class of therapeutic targets across different cancer types. Treatment with the tyrosine kinase inhibitor (TKI) neratinib as a single agent continues to be evaluated in HER2-mutant metastatic disease. However, responses are heterogeneous, with frequent early progression. Herein, we discuss the under-explored effects of individual HER2 mutant alleles on therapeutic response, a role for HER2 mutation in metastatic propensity, and differences in patient outcomes in ER+ invasive lobular carcinoma (ILC) versus invasive ductal carcinoma (IDC). The preclinical efficacy of additional agents is also discussed, particularly the pan-HER inhibitor poziotinib.

Descriptive Study and Surgical Management Among Infiltrating Lobular Carcinoma Patients Admitted to King Abdulaziz Medical City From 2000 to 2017: A Retrospective Cross-Sectional Study.

INTRODUCTION: Invasive lobular carcinoma (ILC) is the second most common histologic type of breast carcinoma. The etiology of ILC is unknown; however, many contributing risk factors have been suggested. Treatment of ILC can be divided into local and systemic. Our objectives were to assess the clinical presentations, risk factors, radiological findings, pathological types, and surgical options for patients with ILC treated at the national guard hospital. Identify the factors associated with metastasis and recurrence. METHODS: Retrospective cross-sectional descriptive study at a tertiary care center in Riyadh. All adult patients aged 16 years and above, from different nationalities, and both genders, were diagnosed with ILC from 2000 to 2017 and followed up at KAMC. The sampling technique was a non-probability consecutive technique. Among 1066 patients identified, 91 patients were diagnosed with ILC over seventeen years study period. RESULTS: The median age at the primary diagnosis was 50. On the clinical examination, 63 (71%) cases were found to have palpable masses which was the most suspicious finding. On radiology, the most encountered finding was speculated masses which were seen in 76 (84%). Regarding the pathology, unilateral breast cancer was seen in 82 while bilateral breast cancer was found only in eight. For the biopsy, a core needle biopsy was the most commonly used in 83 (91%) patients. The most documented surgery for ILC patients was a modified radical mastectomy. Metastasis in different organs was identified with the musculoskeletal system being the commonest site. Different significant variables were compared between patients with or without metastasis. Skin changes, post-operative invasion, estrogen, progesterone, and HER2 receptors were significantly associated with metastasis. Patients with metastasis were less likely to have conservative surgery. Regarding the Recurrence and five years survival, out of 62 cases, 10 had recurrence within five years, which was more prevalent in patients who had fine needle aspiration, excisional biopsy, and nulliparous patients. CONCLUSION: To our knowledge, this is the first study to exclusively describe ILC in Saudi Arabia. The results of this current study are highly important, as these results provide baseline data of ILC in the capital city of Saudi Arabia.

Expression analysis of novel long non-coding RNAs for invasive ductal and invasive lobular breast carcinoma cases.

AIM: Long non-coding RNAs (LncRNAs) serve as important regulatory molecules of gene expression and protein functionality at multiple biological levels, and their deregulation plays a key role in tumorigenesis including in breast cancer metastasis. Therefore, in this study, we aim to compare the expression of novel lncRNAs in the landscape of invasive ductal carcinoma (IDC) and invasive lobular (ILC) carcinoma of breast. MAIN METHODS: We have designed an in-silico approach to find the lncRNAs that regulate the breast cancer. Then, we used the clinical samples to carry out the verification of our in silico finding. In the present study, the tissues of breast cancer were deparaffinized. RNA was extracted by the TRIzole method. After synthesizing cDNA from the extracted RNA, expression levels of lncRNAs were analyzed by qPCR using primers specifically designed and validated for the targeted lncRNAs. In this study, breast biopsy materials from 41 female patients with IDC and 10 female patients with ILC were examined histopathological and expression changes of candidate lncRNAs were investigated in line with the findings. The results were analyzed using IBM SPSS Statistics 25 version. RESULTS: The mean age of the cases was 53.78 ± 14.96. The minimum age was 29, while the maximum age was 87. While 27 of the cases were pre-menopausal, 24 cases were post-menopausal. The number of hormone receptor-positive cases was found to be 40, 35, and 27 for ER, PR, and cerb2/neu, respectively. While the expressions of LINC00501, LINC00578, LINC01209, LINC02015, LINC02584, ABCC5-AS1, PEX5L-AS2, SHANK2-AS3 and SOX2-OT showed significant differences (p < 0.05), the expressions of LINC01206, LINC01994, SHANK2-AS1, and TPRG1-AS2 showed no significant differences (p > 0.05). In addition, it was determined that the regulation of all lncRNAs could be able to involve in the development of cancer such as the NOTCH1, NFKB, and estrogen receptor signalings. CONCLUSION: As a result, it was thought that the discovery of novel lncRNAs might be an important player in the diagnosis, prognosis and therapeutic development of breast cancer.

Evaluation of an Artificial Intelligence System for Detection of Invasive Lobular Carcinoma on Digital Mammography.

Introduction Early breast cancer detection with screening mammography has been shown to reduce mortality and improve breast cancer survival. This study aims to evaluate the ability of an artificial intelligence computer-aided detection (AI CAD) system to detect biopsy-proven invasive lobular carcinoma (ILC) on digital mammography. Methods This retrospective study reviewed mammograms of patients who were diagnosed with biopsy-proved ILC between January 1, 2017, and January 1, 2022. All mammograms were analyzed using cmAssist® (CureMetrix, San Diego, California, United States), which is an AI CAD for mammography. The AI CAD sensitivity for detecting ILC on mammography was calculated and further subdivided by lesion type, mass shape, and mass margins. To account for the within-subject correlation, generalized linear mixed models were implemented to investigate the association between age, family history, and breast density and whether the AI detected a false positive or true positive. Odds ratios, 95% confidence intervals, and p-values were also calculated. Results A total of 124 patients with 153 biopsy-proven ILC lesions were included. The AI CAD detected ILC on mammography with a sensitivity of 80%. The AI CAD had the highest sensitivity for detecting calcifications (100%), masses with irregular shape (82%), and masses with spiculated margins (86%). However, 88% of mammograms had at least one false positive mark with an average number of 3.9 false positive marks per mammogram. Conclusion The AI CAD system evaluated was successful in marking the malignancy in digital mammography. However, the numerous annotations confounded the ability to determine its overall accuracy and this reduces its potential use in real-life practice.

Case report: A rare case of tumor-to-tumor metastasis: metastatic lobular breast carcinoma to clear cell renal cell carcinoma.

Tumor-to-tumor metastasis is a rare phenomenon. Although renal cell carcinoma is the most common recipient tumor, metastatic lobular breast carcinoma to clear cell renal cell carcinoma is even rarer, with only one case reported to date. We present a 66-year-old female patient with an invasive lobular carcinoma history who was admitted to the hospital with a right renal mass. The patient received partial nephrectomy. The final established diagnosis is lobular breast carcinoma metastasizing to clear cell renal cell carcinoma (ccRCC). Thus, although rare, the simultaneous or consecutive find of a renal mass in follow-up should be carefully evaluated, especially in high-risk patients, including women with an advanced breast cancer history, as in this scenario.