Invasive Ductal Breast Cancer Research Articles

Overexpression of WT1 in all molecular subtypes of breast cancer and its impact on survival: exploring oncogenic and tumor suppressor roles of distinct WT1 isoforms.

Breast cancer is a highly heterogeneous solid tumor, posing challenges in developing targeted therapies effective for all mammary carcinoma subtypes. WT1 emerges as a promising target for breast cancer therapy due to its potential oncogenic role in various cancer types. Previous works have yielded inconsistent results. Therefore, further studies are needed to clarify the behavior of this complex gene in breast cancer. In this study, we examined WT1 expression in both Formalin Fixed Paraffin Embedded breast tumors (n = 41) and healthy adjacent tissues (n = 41) samples from newly diagnosed cases of ductal invasive breast cancer. The fold change in gene expression between the tumor and healthy tissue was determined by calculating 2-∆∆Ct. Disease-free survival analysis was computed using the Kaplan-Meier method. To identify the expression levels of different WT1 isoforms, we explored the ISOexpresso database. Relative quantification of the WT1 gene revealed an overexpression of WT1 in most cases. The percentage of patients surviving free of disease at 8years of follow-up was lower in the group overexpressing WT1 compared to the group with down-regulated WT1. Interestingly, this overexpression was observed in all molecular subtypes of invasive breast cancer, underscoring the significance of WT1 as a potential target in all these subtypes. The observed WT1 down-expression in a few cases of invasive breast cancer, associated with better survival outcomes, may correspond to the down-regulation of a particular WT1-KTS (-) isoform: the WT1 A isoform (EX5-/KTS-). The co-expression of this WT1 oncogenic isoform with a regulated WT1- tumor suppressor isoform, such as the major WT1 F isoform (EX5-/KTS +), could also explain such survival outcomes. Due to its capacity to adopt dual roles, it becomes imperative to conduct individual molecular expression profiling of the WT1 gene. Such an approach holds great promise in the development of personalized treatment strategies for breast cancer.

A tricky singular papular peri‐cicatricial mammarian lesion

AbstractBreast cancer represents the most common malignancy in women worldwide. In most cases, metastasis is the leading cause of mortality. Early diagnosis is still challenging despite standardised, government‐led screening programs, but is crucial in achieving improved survival rates. Additionally, a deeper understanding of the metastatic potential of breast cancer is critical for developing therapeutic interventions to combat widespread disease. Cutaneous metastasis from underlying breast carcinoma is uncommon as the first manifestation of visceral malignancies and is commonly observed in advanced‐stage malignancies, often associated with poor prognosis, and a prompt, precise tissue diagnosis is mandatory. A high index of suspicion in oncologic patients is required to diagnose these lesions, as they can mimic benign skin manifestations and clinical findings may be subtle and going unnoticed. We report on a case of a 76‐year‐old female patient presenting to our non‐invasive diagnostic outpatient clinic with an unusual cutaneous presentation, as an early sign of locally advanced invasive ductal carcinoma breast cancer recurrence. The aim of our article is to underline the importance of the dermatologist in the multi‐disciplinary oncologic diagnostic process, including non‐invasive imaging evaluation of cutaneous lesions, especially insidious breast carcinomas. Dynamic optical coherence tomography (D‐OCT) is not routinely used due to its cost, therefore lesion's aspect has not been completely described, consequently, the correct evaluation of skin architecture appearance can add important information, especially in cutaneous oncology where it can help in early diagnosis or cancer recurrency. OCT may contribute to the detection of subclinical cutaneous manifestations of cancer or recurrence, in particular, when they are difficult to differentiate clinically from benign lesion. In the case we described, OCT of suspected lesion showed the loss of the DEJ with solid nests and irregular vessels.

MRI-based tumor shrinkage patterns after early neoadjuvant therapy in breast cancer: correlation with molecular subtypes and pathological response after therapy

BackgroundMRI-based tumor shrinkage patterns (TSP) after neoadjuvant therapy (NAT) have been associated with pathological response. However, the understanding of TSP after early NAT remains limited. We aimed to analyze the relationship between TSP after early NAT and pathological response after therapy in different molecular subtypes.MethodsWe prospectively enrolled participants with invasive ductal breast cancers who received NAT and performed pretreatment DCE-MRI from September 2020 to August 2022. Early-stage MRIs were performed after the first (1st-MRI) and/or second (2nd-MRI) cycle of NAT. Tumor shrinkage patterns were categorized into four groups: concentric shrinkage, diffuse decrease (DD), decrease of intensity only (DIO), and stable disease (SD). Logistic regression analysis was performed to identify independent variables associated with pathologic complete response (pCR), and stratified analysis according to tumor hormone receptor (HR)/human epidermal growth factor receptor 2 (HER2) disease subtype.Results344 participants (mean age: 50 years, 113/345 [33%] pCR) with 345 tumors (1 bilateral) had evaluable 1st-MRI or 2nd-MRI to comprise the primary analysis cohort, of which 244 participants with 245 tumors had evaluable 1st-MRI (82/245 [33%] pCR) and 206 participants with 207 tumors had evaluable 2nd-MRI (69/207 [33%] pCR) to comprise the 1st- and 2nd-timepoint subgroup analysis cohorts, respectively. In the primary analysis, multivariate analysis showed that early DD pattern (OR = 12.08; 95% CI 3.34–43.75; p < 0.001) predicted pCR independently of the change in tumor size (OR = 1.37; 95% CI 0.94–2.01; p = 0.106) in HR+/HER2− subtype, and the change in tumor size was a strong pCR predictor in HER2+ (OR = 1.61; 95% CI 1.22–2.13; p = 0.001) and triple-negative breast cancer (TNBC, OR = 1.61; 95% CI 1.22–2.11; p = 0.001). Compared with the change in tumor size, the SD pattern achieved a higher negative predictive value in HER2+ and TNBC. The statistical significance of complete 1st-timepoint subgroup analysis was consistent with the primary analysis.ConclusionThe diffuse decrease pattern in HR+/HER2− subtype and stable disease in HER2+ and TNBC after early NAT could serve as additional straightforward and comprehensible indicators of treatment response.Trial registration: Trial registration at https://www.chictr.org.cn/. Registration number: ChiCTR2000038578, registered September 24, 2020.

Radiologic patterns of distant organ metastasis in advanced breast cancer patients: Prospective review of computed tomography images.

Breast cancer (BC) metastases to the abdomen and pelvis affect the liver, mesentery, retroperitoneum, peritoneum, bladder, kidney, ovary, and uterus. The study documented the radiological pattern and features of the chest, bone, abdominal and pelvic (AP) metastases among advanced BC patients. The aim is to document the radiological pattern and features of breast cancer metastasis in the chest, abdomen, pelvis and bones. Chest, abdominal, and pelvic computed tomography scan images of 36 patients with advanced BC were collated from Cape Coast Teaching Hospital and RAAJ Diagnostics. The images were prospectively assessed for metastasis to the organs of the chest, AP soft tissues, and bones. Radiologic features of metastasis of the lungs, liver, lymph nodes (LNs), and bones were documented. Patients' demographics, clinical data, and histopathology reports were also collected. The data were captured using UVOSYO and exported to Microsoft Excel templates. The data obtained were descriptively analyzed. Only 2.8% of BCs exhibited metaplastic BC, whereas 97.2% had invasive ductal BC. Triple-negative cases were 55.6%. Of 36 patients, 31 (86.1%), 21 (58.3%), and 14(38.8%) were diagnosed of chest, AP, and bone tissues metastasis, respectively. LN involvement was reported in 26 (72.2%) patients. Majority, 21 (58.3%) were diagnosed of multiple sites metastasis with 15 (41.7%) showing single site. Lungs (77.4%, 24/31) and liver (47.6%, 10/21) were the most affected distant organs. Most bone metastases were lytic lesions (92.9%, 13/14) with the vertebrae (85.7%, 12/14) been the most affected. According to the study, advanced BC patients have a higher-than-average radiologic incidence of lung, liver, bone, and LN metastases.

Whole-tumor histogram models based on quantitative maps from synthetic MRI for predicting axillary lymph node status in invasive ductal breast cancer

PurposeTo investigate the potential of using histogram analysis of synthetic MRI (SyMRI) images before and after contrast enhancement to predict axillary lymph node (ALN) status in patients with invasive ductal carcinoma (IDC). MethodsFrom January 2022 to October 2022, a total of 212 patients with IDC underwent breast MRI examination including SyMRI. Standard T2 weight images, DCE-MRI and quantitative maps of SyMRI were obtained. 13 features of the entire tumor were extracted from these quantitative maps, standard T2 weight images and DCE-MRI. Statistical analyses, including Student’s t-test, Mann-Whiney U test, logistic regression, and receiver operating characteristic (ROC) curves, were used to evaluate the data. The mean values of SyMRI quantitative parameters derived from the conventional 2D region of interest (ROI) were also evaluated. ResultsThe combined model based on T1-Gd quantitative map (energy, minimum, and variance) and clinical features (age and multifocality) achieved the best diagnostic performance in the prediction of ALN between N0 (with non-metastatic ALN) and N+ group (metastatic ALN ≥ 1) with the AUC of 0.879. Among individual quantitative maps and standard sequence-derived models, the synthetic T1-Gd model showed the best performance for the prediction of ALN between N0 and N+ groups (AUC = 0.823). Synthetic T2_entropy and PD-Gd_energy were useful for distinguishing N1 group (metastatic ALN ≥ 1 and ≤ 3) from the N2-3 group (metastatic ALN > 3) with an AUC of 0.722. ConclusionsWhole-tumor histogram features derived from quantitative parameters of SyMRI can serve as a complementary noninvasive method for preoperatively predicting ALN metastases.

Radiomic Machine Learning in Invasive Ductal Breast Cancer: Prediction of Ki-67 Expression Level Based on Radiomics of DCE-MRI.

Our study aimed to investigate the potential of radiomics with DCE-MRI for predicting Ki-67 expression in invasive ductal breast cancer. We conducted a retrospective study including 223 patients diagnosed with invasive ductal breast cancer. Radiomics features were extracted from DCE-MRI using 3D-Slicer software. Two Ki-67 expression cutoff values (20% and 29%) were examined. Patients were divided into training (70%) and test (30%) sets. The Elastic Net method selected relevant features, and five machine-learning models were established. Radiomics models were created from intratumoral, peritumoral, and combined regions. Performance was assessed using ROC curves, accuracy, sensitivity, and specificity. For a Ki-67 cutoff value of 20%, the combined model exhibited the highest performance, with area under the curve (AUC) values of 0.838 (95% confidence interval (CI): 0.774-0.897) for the training set and 0.863 (95% CI: 0.764-0.949) for the test set. The AUC values for the tumor model were 0.816 (95% CI: 0.745-0.880) and 0.830 (95% CI: 0.724-0.916), and for the peritumor model were 0.790 (95% CI: 0.711-0.857) and 0.808 (95% CI: 0.682-0.910). When the Ki-67 cutoff value was set at 29%, the combined model also demonstrated superior predictive ability in both training set (AUC: 0.796; 95% CI: 0.724-0.862) and the test set (AUC: 0.823; 95% CI: 0.723-0.911). The AUC values for the tumor model were 0.785 (95% CI: 0.708-0.861) and 0.784 (95% CI: 0.663-0.882), and for the peritumor model were 0.773 (95% CI: 0.690-0.844) and 0.729 (95% CI: 0.603-0.847). Radiomics with DCE-MRI can predict Ki-67 expression in invasive ductal breast cancer. Integrating radiomics features from intratumoral and peritumoral regions yields a dependable prognostic model, facilitating pre-surgical detection and treatment decisions. This holds potential for commercial diagnostic tools.

Procena rizika u korelaciji sa gojaznošću i laboratorijskim monitoringom najčešćih tipova karcinoma dojke kod žena u Kantonu Sarajevo

Abstract: Introduction: Breast cancer (BC) is a malignant disease that predominantly affects women, with known genetic components such as mutations in tumor suppressor genes BRCA1 and BRCA2. Other risk factors include unhealthy lifestyles, lack of physical activity, and consumption of alcohol and cigarettes. Aging also plays a role in BC development, with hormonal influences such as estrogen and progesterone promoting cancer growth. Material and Methods: Research was conducted using data collection tools for risk factors and tumor markers from primary healthcare unit records. The sample comprised 200 women, divided into two groups based on BC diagnosis, with complete medical documentation. Male BC cases were excluded. Results: Statistical significance was found between genetic components, family history, aging, obesity, alcohol and cigarette consumption, longer hormone exposure, and female BC development using the Chi-Square test, confirmed by Fisher's Exact test. Tumor markers CA 15-3, CEA, CA 19-9, and CA 125 were useful for BC screening and metastasis detection, as determined by the One Sample T-test. In Sarajevo Canton, invasive ductal BC was the most common type among women, while lobular carcinoma in situ was the least common. Conclusion: Correlations between risk factors, including aging, unhealthy lifestyles, and hormone exposure, and increased BC risk were confirmed. Tumor markers CA 15-3, CEA, CA 19-9, and CA 125 were effective in diagnosis, screening, and metastasis detection in females, with sensitivity for regression detection at 81.8% and specificity at 100%.

LncRNA CARMN suppresses EMT through inhibiting transcription of MMP2 activated by DHX9 in breast cancer.

Long non-coding RNAs (lncRNAs) have been shown to drive cancer progression. However, the function of lncRNAs and the underlying mechanism in early-stage breast cancer(BC) have rarely been investigated. Datasets of pre-invasive ductal carcinoma in situ (DCIS), invasive ductal BC (IDC) and normal breast tissue from TCGA and GEO databases were used to conduct bioinformatics analysis. LncRNA CARMN was identified as a tumor suppressor in early-stage BC and related to a better prognosis. CARMN over-expression inhibited MMP2 mediated migration and EMT in BC. Further analysis showed that CARMN was located in the nucleus and functioned as an enhancer RNA (eRNA) in mammary epithelial cell. Mechanically, CARMN binding protein DHX9 was identified by RNA pull-down and mass spectrometry (MS) assays and it also bound to the MMP2 promoter to activate its transcription. As a decoy, CARMN competitively bound to DHX9 and blocked MMP2 transcriptional activation, thereby inhibiting metastasis and EMT of BC cells. These findings reveal the important role of CARMN as a tumor suppressor in the metastasis and a potential biomarker for progression in early-stage BC.

Exploring the Prognostic Value of CS15-3 Tumor Marker in Breast Cancer Recurrence.

The most prevalent tumor marker for breast cancer is CS15-3. This marker's elevated serum levels have been proven to predict a patient's risk of developing the condition again. The purpose of this study was to ascertain the sensitivity of blood CS15-3 levels in the identification of breast cancer recurrence. A prospective cohort follow-up analytical study was conducted at Basra Oncology Center from early 2016 to the end of 2022. The study included 178 females aged ≥18 years with histologically confirmed invasive ductal breast cancer. CS15-3 had been evaluated for all included cases on two occasions: the first, at the time of diagnosis or remission, and the second, at the time of progression. The tumor marker (CS15-3) was evaluated using a Cobas e411 analyzer (Roche Diagnostics International Ltd). The mean age showed no significant difference between the groups (P=0.581). The duration of progression was higher among those with the luminal group (40.60± 42.08). Those with bony and liver metastasis were mostly among luminal (50.0%) and HER 2+ (52.4%) groups respectively. At the time of diagnosis CS15-3 tumor marker showed no significant difference between the three groups, while at the time of progression, the luminal group showed higher means (120.74± 95.07) compared to others with a significant mean difference of (-99.84± 94.43). Age, disease stages, and co-morbidity have no significant influence on the distribution between groups of luminal. The duration of progression was higher among those in the luminal group. Osseous and hepatic secondaries are mostly among luminal and hormonal receptors positive. Initially, at the time of diagnosis CS15-3 marker expressed no significant difference between the groups, whereas at the time of progression, the luminal group expressed a higher means of level of the CS15-3 marker.

Association of Race, Ethnicity, Language, and Insurance with Time to Treatment Initiation Among Women with Breast Cancer at an Urban, Academic, Safety-Net Hospital.

Initial treatment for nonmetastatic breast cancer is resection or neoadjuvant systemic therapy, depending on tumor biology and patient factors. Delays in treatment have been shown to impact survival and quality of life. Little has been published on the performance of safety-net hospitals in delivering timely care for all patients. We conducted a retrospective study of patients with invasive ductal or lobular breast cancer, diagnosed and treated between 2009 and 2019 at an academic, safety-net hospital. Time to treatment initiation was calculated for all patients. Consistent with a recently published Committee on Cancer timeliness metric, a treatment delay was defined as time from tissue diagnosis to treatment of greater than 60 days. A total of 799 eligible women with stage 1-3 breast cancer met study criteria. Median age was 60 years, 55.7% were non-white, 35.5% were non-English-speaking, 18.9% were Hispanic, and 49.4% were Medicaid/uninsured. Median time to treatment was 41 days (IQR 27-56 days), while 81.1% of patients initiated treatment within 60 days. The frequency of treatment delays did not vary by race, ethnicity, insurance, or language. Diagnosis year was inversely associated with the occurrence of a treatment delay (OR: 0.944, 95% CI 0.893-0.997, p value: 0.039). At our institution, race, ethnicity, insurance, and language were not associated with treatment delay. Additional research is needed to determine how our safety-net hospital delivered timely care to all patients with breast cancer, as reducing delays in care may be one mechanism by which health systems can mitigate disparities in the treatment of breast cancer.

Histologic tumor type as a determinant of survival in hormone receptor-positive, HER2-negative, pT1-3 invasive ductal and lobular breast cancer

PurposeThe aim of the study was to compare the difference in survival between invasive ductal (IDC) and lobular carcinoma (ILC).MethodsData of patients (n = 1843) with a hormone receptor-positive, HER2-negative, pT1-3 IDC or ILC cancer without distant metastasis, treated at the Ghent University Hospital over the time period 2001–2015, were analyzed.ResultsILC represented 13.9% of the tumors, had a higher percentage of pT3 and pN3 stages than IDC, lymphovascular space invasion (LVSI) was less present and Ki-67 was mostly low. 73.9% of ILCs were grade 2, whereas IDC had more grade 1 and grade 3 tumors. Kaplan–Meier curves and log-rank testing showed a significant worse DFS for ILC with pN ≥ 1 than for their IDC counterpart. In a multivariable Cox regression analysis the histologic tumor type, ductal or lobular, was a determinant of DFS over 120 months (IDC as reference; hazard ratio for ILC 1.77, 95% CI 1.08–2.90) just as the ER Allred score (hazard ratio 0.84, 95% CI 0.78–0.91), LVSI (hazard ratio 1.75, 95% CI 1.12–2.74) and pN3 (hazard ratio 2.29, 95% CI 1.03–5.09). Determinants of OS over ten years were age (hazard ratio 1.05, 95% CI 1.02–1.07), LVSI (hazard ratio 3.62, 95% CI 1.92–6.82) and the ER Allred score (hazard ratio 0.80, 95% CI 0.73–0.89).ConclusionThe histologic tumor type, ductal or lobular, determines DFS in hormone receptor-positive, HER2-negative, pT1-3 breast cancer besides the ER Allred score, LVSI and pN3.

39P Prognostic significance of hypoxic microenvironment biomarkers in invasive ductal breast cancer

39P Prognostic significance of hypoxic microenvironment biomarkers in invasive ductal breast cancer

Repeated electroporation enhances the responsiveness to cisplatin-based intra-tumoral chemotherapy in murine breast cancer: revival of the electro-chemotherapy concept

Background and aims: Electroporation demonstrated certain modulable actions on tumoral cell membrane permeability to increase the intracellular bioavailability of chemotherapeutic drugs. The current in vivo study aimed to investigate the synergic effect of concomitant electroporation application to the intratumoral administration of cisplatin on murine invasive ductal adenocarcinoma breast cancer. Methods: The fragments of the extracted tumor were implanted subcutaneously in healthy female Balb/C mice. Having reached the determined tumoral volume, the mice were randomly divided into five groups, including control, intratumoral cisplatin injection, tumoral electroporation application, electrochemotherapy (ECT), and double course ECT. The normalized tumoral volume and the inhibition ratios were calculated during a 30-day follow-up period. The data were tested by ANONA, and a statistically significant level was set at P&lt;0.05. Results: The inhibition ratio was significantly different between the intra-tumoral cisplatin administration and tumoral electroporation application groups compared to the control group (P&lt;0.05). ECT displayed superior results in comparison to the two later groups (P&lt;0.05). The double-course ECT group even represented a significant difference compared to the ECT group (P&lt;0.05). Conclusion: Concomitant ECT to the cisplatin intratumoral administration indicated contributive anti-tumoral impacts in an in vivo murine model of invasive ductal adenocarcinoma breast cancer. ECT promises further applications to overcome the occurrence of therapeutic resistance to chemotherapeutic drugs.

Breast and colorectal cancer risks among over 6,000 CHEK2 pathogenic variant carriers: A comparison of missense versus truncating variants

Background and aimsHeterozygous truncating pathogenic variants (PVs) in CHEK2 confer a 1.5 to 3-fold increased risk for breast cancer and may elevate colorectal cancer risks. Less is known regarding missense variants. Here we compared the cancer associations with truncating and missense PVs in CHEK2 across breast and colorectal cancer. MethodsThis was a retrospective analysis of 705,797 patients who received single laboratory multigene panel testing between 2013 and 2020. Multivariable logistic regression models determined cancer risk associated with CHEK2 variants as odds ratios (ORs) and 95% confidence intervals (CIs) after adjusting for age at diagnosis, cancer history, and ancestry. Breast and colorectal cancer analyses were performed using 6255 CHEK2 PVs, including truncating PVs (N = 4505) and missense PVs (N = 1750). ResultsCHEK2 PVs were associated with an increased risk of ductal invasive breast cancer (p < 0.001) and ductal carcinoma in situ (DCIS) (p < 0.001), with no statistically significant differences when truncating PVs (p < 0.001) and missense PVs (p < 0.001) were evaluated separately. All CHEK2 variants assessed conferred little to no risk of colorectal cancer. ConclusionsIn our large cohort, CHEK2 truncating and missense PVs conferred similar risks for breast cancer and did not seem to elevate risk for colorectal cancer.

THU495 Glutamate Metabolic Enzymes GLUD1/2 And GPX4 Are Associated with Tumor Size In Black Women With Invasive Lobular Breast Cancer

Abstract Disclosure: T. Young: None. T.C. Abalum: None. N. Hodgins: None. S. Persaud: None. A.I. Fernandez: None. A.O. Olukoya: None. A.M. Rozeboom: None. R.B. Riggins: None. Background and Objective: Invasive Lobular Breast Cancer (ILC) is a special histologic type of breast cancer with unique genetic and biological features. ILC may be less dependent on glucose metabolism than the more common histologic type, invasive ductal breast cancer (IDC), instead relying more on lipid and amino acid metabolism. Our lab has previously published that expression of metabotropic glutamate receptors is increased in more rapidly growing and therapy-resistant cell line models of ILC. We hypothesized that increased expression of glutamate transporters and regulatory enzymes is associated with poor prognostic features. Methods and Analysis: We used multispectral immunohistochemical staining to measure the expression of four functionally related proteins: CD98, GLUD1/2, GPX4, and SLC7A11 in a cohort of 72 women with ILC (23.5% Black, 64.7% White, 11.8% Other). The cohort was in a two-fold redundant tissue microarray (TMA) format comprised of primary tumors collected by the Georgetown University Histopathology and Tissue Shared Resource. SLC7A11 and CD98 form a heterodimer that exports glutamate from, and imports cystine to, the cell. GLUD1/2 are two isoenzymes that convert glutamate into α-ketoglutarate to replenish the TCA cycle, or recycle ammonia to support amino acid synthesis. GPX4 is an enzyme that protects cells from lipid peroxidation-induced death. We compared expression of these proteins with clinical, pathological, and demographic variables (overall survival, hormone receptor expression, tumor size, race, age) using t test/ANOVA, Kaplan-Meier survival analysis, and linear regression. Results: In the 68 evaluable cases, the percentage of ILC tumor cells stained positive for GLUD1/2 and GPX4 was significantly higher than for CD98 or SLC7A11 (P&amp;lt;0.001), so further analyses focused on these. Women with a combination of high (above median) GLUD1/2+ (&amp;gt;49%) and GPX4+ (&amp;gt;54%) expression had a trend toward decreased survival (Hazard Ratio, HR 3.53, P=0.159). GPX4, GLUD1/2, and estrogen receptor (ER) expression were associated with tumor size in the entire cohort (R2 = 0.124, P = 0.041), but this relationship was markedly stronger in Black women (R2 = 0.487, P = 0.040). In univariate analyses, GLUD1/2 (R2 = 0.43, P&amp;lt;0.01) and GPX4 (R2 = 0.27, P&amp;lt;0.05) expression were each associated with tumor size in Black women, but not in the entire cohort. GPX4 expression and tumor size were both significantly higher (P&amp;lt;0.05) in Black women over 60 years of age, compared to those under 60. Conclusion: GLUD1/2 and GPX4 expression may be prognostic in ILC, as our results show that tumor size increases with higher expression of these proteins (especially among Black women). Limitations of this study include small sample size and lack of an independent cohort for validation. Future studies will include analysis of these proteins in a TMA comprised of tissue from women with IDC. Presentation: Thursday, June 15, 2023

S4309 Uncovering the Ulcer: A Rare Case of Invasive Ductal Breast Cancer Metastasis to the Stomach

S4309 Uncovering the Ulcer: A Rare Case of Invasive Ductal Breast Cancer Metastasis to the Stomach

Aquaglyceroporins in Human Breast Cancer.

Aquaporins are water channels that facilitate passive water transport across cellular membranes following an osmotic gradient and are essential in the regulation of body water homeostasis. Several aquaporins are overexpressed in breast cancer, and AQP1, AQP3 and AQP5 have been linked to spread to lymph nodes and poor prognosis. The subgroup aquaglyceroporins also facilitate the transport of glycerol and are thus involved in cellular metabolism. Transcriptomic analysis revealed that the three aquaglyceroporins, AQP3, AQP7 and AQP9, but not AQP10, are overexpressed in human breast cancer. It is, however, unknown if they are all expressed in the same cells or have a heterogeneous expression pattern. To investigate this, we employed immunohistochemical analysis of serial sections from human invasive ductal and lobular breast cancers. We found that AQP3, AQP7 and AQP9 are homogeneously expressed in almost all cells in both premalignant in situ lesions and invasive lesions. Thus, potential intervention strategies targeting cellular metabolism via the aquaglyceroporins should consider all three expressed aquaglyceroporins, namely AQP3, AQP7 and AQP9.

CD105 expression in cancer-associated fibroblasts: a biomarker for bone metastasis in early invasive ductal breast cancer patients.

Introduction: Bone metastasis is one of the causes that mainly decrease survival in patients with advanced breast cancer. Therefore, it is essential to find prognostic markers for the occurrence of this type of metastasis during the early stage of the disease. Currently, cancer-associated fibroblasts, which represent 80% of the fibroblasts present in the tumor microenvironment, are an interesting target for studying new biomarkers and developing alternative therapies. This study evaluated the prognostic significance of the CD105 expression in cancer-associated fibroblasts in early breast cancer patients. Methods: Immunohistochemistry was used to assess CD105 expression in invasive ductal breast carcinomas (n = 342), analyzing its association with clinical and pathological characteristics. Results: High CD105 expression in cancer-associated fibroblasts was associated with an increased risk of metastatic occurrence (p = 0.0003), particularly bone metastasis (p = 0.0005). Furthermore, high CD105 expression was associated with shorter metastasis-free survival, bone metastasis-free survival, and overall survival (p = 0.0002, 0.0006, and 0.0002, respectively). CD105 expression also constituted an independent prognostic factor for metastasis-free survival, bone metastasis-free survival, and overall survival (p = 0.0003, 0.0006, and 0.0001, respectively). Discussion: The high CD105 expression in cancer-associated fibroblasts is an independent prognostic marker for bone metastasis in early breast cancer patients. Therefore, the evaluation of CD105(+) CAFs could be crucial to stratify BCPs based on their individual risk profile for the development of BM, enhancing treatment strategies and outcomes.

Riluzole Suppresses Growth and Enhances Response to Endocrine Therapy in ER+ Breast Cancer.

Resistance to endocrine therapy in estrogen receptor-positive (ER+) breast cancer remains a significant clinical problem. Riluzole is FDA-approved for the treatment of amyotrophic lateral sclerosis. A benzothiazole-based glutamate release inhibitor with several context-dependent mechanism(s) of action, riluzole has shown antitumor activity in multiple malignancies, including melanoma, glioblastoma, and breast cancer. We previously reported that the acquisition of tamoxifen resistance in a cellular model of invasive lobular breast cancer is accompanied by the upregulation of GRM mRNA expression and growth inhibition by riluzole. We tested the ability of riluzole to reduce cell growth, alone and in combination with endocrine therapy, in a diverse set of ER+ invasive ductal and lobular breast cancer-derived cell lines, primary breast tumor explant cultures, and the estrogen-independent, ESR1-mutated invasive lobular breast cancer patient-derived xenograft model HCI-013EI. Single-agent riluzole suppressed the growth of ER+ invasive ductal and lobular breast cancer cell lines in vitro, inducing a histologic subtype-associated cell cycle arrest (G0-G1 for ductal, G2-M for lobular). Riluzole induced apoptosis and ferroptosis and reduced phosphorylation of multiple prosurvival signaling molecules, including Akt/mTOR, CREB, and Fak/Src family kinases. Riluzole, in combination with either fulvestrant or 4-hydroxytamoxifen, additively suppressed ER+ breast cancer cell growth in vitro. Single-agent riluzole significantly inhibited HCI-013EI patient-derived xenograft growth in vivo, and the combination of riluzole plus fulvestrant significantly reduced proliferation in ex vivo primary breast tumor explant cultures. Riluzole may offer therapeutic benefits in diverse ER+ breast cancers, including lobular breast cancer.

Exploring the potential of humanin as a biomarker for early breast cancer detection: a study of serum levels and diagnostic performance

Introduction Breast cancer is a leading cause of cancer death in women worldwide, and early detection is crucial for effective treatment. Mitochondrial dysfunction has been linked to cancer development and progression. Humanin, a mitochondrial-derived peptide, has been shown to have cytoprotective effects and may be involved in breast cancer development. In this study, we aimed to investigate the potential of humanin as a biomarker for breast cancer. Methods We recruited 45 female patients diagnosed with primary invasive ductal breast cancer and 45 healthy volunteers. Serum humanin levels were measured using ELISA, and other cancer markers were measured using an Advia Centaur Immunology Analyser. Results Our results showed that serum humanin levels were significantly higher in breast cancer patients than in healthy controls (p = 0.008). ROC curve analysis indicated that humanin could effectively discriminate between patients and healthy individuals, with a sensitivity of 62.5% and a specificity of 77.5%. Conclusion This suggests that humanin may be a potential new biomarker for breast cancer screening and early detection. Further research is needed to fully understand the relationship between humanin and breast cancer and to develop new diagnostic and therapeutic strategies.