Invasive Lobular Carcinoma Of Breast Research Articles

CDH1 methylation analysis in invasive lobular breast carcinomas with and without gene mutation.

The proposed role of CDH1 (E-cadherin gene) methylation as a mechanism of gene inactivation in invasive lobular carcinoma (ILC) remains inconclusive. For many years, CDH1 promoter hypermethylation has been regarded as a mechanism for gene inactivation in ILC. However, this assumption has primarily relied on non-quantitative assays, which have reported CDH1 methylation frequencies ranging from 26 to 93% at CpG sites within the island region. Few studies employing quantitative methods and covering CpG island shores, regions of relatively low CpG density situated proximal to conventional promoter CpGs, have been conducted, revealing lower percentages of methylation ranging from 0 to 51%. Therefore, using the quantitative pyrosequencing method, we examined CDH1 methylation in the island region and shores in E-cadherin deficient ILC cases (15 with CDH1 mutation and 22 non-mutated), 19 cases of invasive breast carcinomas non-special type (IBC-NSTs), and five cases of usual ductal hyperplasia (UDH). Our analysis revealed CDH1 methylation frequencies ranging from 3 to 64%, with no significant increase in methylation levels in any group of ILCs (median = 12%) compared to IBC-NST (median = 15%). In addition, considering the poorly studied association between the number of tumor-infiltrating lymphocytes (TILs) and CDH1 methylation in breast cancer, we undertook a thorough analysis within our dataset. Our findings revealed a positive correlation between CDH1 methylation and the presence of TILs (r = 0.5; p-value < 0.05), shedding light on an aspect of breast cancer biology warranting further investigation. These findings challenge CDH1 methylation as a CDH1 inactivation mechanism in ILC and highlight TILs as a potential confounding factor in gene methylation.

Abstract PO5-02-13: Distinct differences in the prognostic implication of tumor size for invasive lobular carcinoma of breast when compared to invasive ductal carcinoma

Abstract Purpose Invasive lobular carcinoma (ILC) is the second common types of breast cancer and its clinicopathological feature and outcomes differ from invasive ductal carcinoma (IDC). However, in terms of survival outcomes, there are conflicting data on the prognostic implication of the ILC when compared to that of IDC. This study aims to evaluate the survival outcomes of patients diagnosed with ILC at single center and compared them with those of IDC. Methods We reviewed the data of the 13,034 IDC patients and 935 ILC patients who were treated between January 2005 and December 2022 at Seoul National University Hospital. We investigated the overall treatment outcomes of two histologic types with a special focus on the tumor size and lymph nodes. Result ILC exhibited distinct characteristics compared to IDC, including a larger tumor size (2.6 ± 1.8 vs. 1.9 ± 1.1 cm, p &amp;lt; 0.001) and a higher hormone receptor positivity (97.4% vs. 79.3%, p &amp;lt; 0.001). Additionally, the presence of lymphovascular emboli was lower in ILC (8.0% vs. 24.6%, p &amp;lt; 0.001). While IDC patients showed slightly better overall survival (OS) than ILC (10-year OS, ILC 89.9% vs. IDC 91.1%, the difference was not statistically significant (p = 0.85). However, distant metastasis-free survival (DMFS) was significantly higher in ILC (10-year DMFS, ILC 93.2% vs. IDC 89.9%, p = 0.001). Age at diagnosis, tumor size, presence of lymphovascular emboli, high expression of Ki-67, and higher pathologic N stage were poor prognostic markers for ILC. Multivariate analysis for DMFS showed that age, high expression of Ki-67 and higher pathologic N stage were poor prognostic markers for ILC. Tumor size was not an independent prognostic factor for DMFS (HR: 0.92, 95% CI: 0.72-1.17, p = 0.491) and for OS (HR: 1.18, 95% CI: 0.99-1.41, p = 0.060) in ILC. Conclusion Our data suggest that the tumor size, which is a well-known prognostic factor in IDC, carries distinctly different prognostic implication in ILC. These observation indicate that adjuvant treatment decisions based on tumor size can be tailored to different histologic subtypes of breast cancer. Citation Format: Ik Beom Shin, Eunhye Kang, Ji-Jung Jung, Hawjeong Lee, Jin Young Byeon, Yunhee Choi, Changjin Lim, Jong-Ho Cheun, Hong-Kyu Kim, Han-Byoel Lee, Wonshik Han, Hyeong-Gon Moon. Distinct differences in the prognostic implication of tumor size for invasive lobular carcinoma of breast when compared to invasive ductal carcinoma [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO5-02-13.

Abstract GS03-04: Novel Mechanisms of CDH1 Inactivation in Breast Invasive Lobular Carcinoma Unveiled by the Integration of Artificial Intelligence and Genomics

Abstract Background: Invasive lobular carcinoma (ILC) of the breast is the second most common histologic subtype of breast cancer (BC), following invasive ductal carcinoma of no special type (IDC-NST). The hallmark histologic feature of ILC is cellular discohesiveness, the result of bi-allelic inactivation of CDH1, and represents an important genotypic-phenotypic correlation in BC. Although most ILCs harbor CDH1 loss-of function mutations associated to loss-of-heterozygosity (LOH) of the wild type-allele, a subset of ILCs lack these alterations despite displaying a typical lobular phenotype. Here, we sought to identify alternative molecular mechanisms converging on CDH1 inactivation by employing an integrative artificial intelligence (AI) and genomics approach. Materials and Methods: A genomics-driven AI-based algorithm using hematoxylin and eosin (H&amp;E) whole slide images (WSIs) as input, previously developed to detect bi-allelic CDH1 mutations (inactivating mutation associated to LOH) in BC was employed. WSIs of 1,057 BCs including ILCs (n=187) and non-lobular BCs (n=870) previously subjected to FDA-cleared tumor/normal targeted sequencing were subjected to analysis with the AI-based algorithm. Cases predicted to harbor CDH1 bi-allelic mutations by the AI-model but lacking CDH1 bi-allelic mutations by targeted sequencing were assessed through targeted sequencing data re-analysis, CDH1 gene promoter methylation evaluation and/or whole genome sequencing analysis. Results: AI-based analysis WSIs corresponding to 1,057 BCs resulted in the identification of 34 cases found to lack CDH1 bi-allelic mutations by targeted sequencing but predicted to harbor these genetic alterations by the AI-based model. CDH1 gene promoter methylation assessment revealed CDH1 promoter methylation in 18 cases. Targeted sequencing data reanalysis revealed other genetic mechanisms of CDH1 inactivation including CDH1 homozygous deletions (n=3), intragenic deletion with LOH (n=1), and likely pathogenic non-coding CDH1 alterations associated with LOH (n=2). WGS analysis of an ILC revealed a novel deleterious CDH1 fusion stemming from translocation t(13;16), resulting in loss of the 5’UTR, transcription start site and exons 1 and 2 of CDH1, associated with complete loss of E-cadherin protein expression. Taken together, we identified alternative/novel mechanisms of bi-allelic CDH1inactivation in 74% (25/34) cases analyzed. Conclusions: By applying an AI-based algorithm trained to detect a genetic alteration (i.e., CDH1 bi-allelic mutations), we were able to identify alternative epigenetic and genetic molecular mechanisms of CDH1 inactivation in ILCs, including novel non-coding CDH1 genetic alterations and a new inactivating CDH1 fusion gene. These findings indicate that molecular mechanisms affecting a single gene or process converging on the same phenotype can be unveiled by the integration of AI and genomics, highlighting the robustness of this approach for the discovery of novel biology. Citation Format: Fresia Pareja, Higinio Dopeso, Yikan Wang, Andrea Gazzo, David Brown, Pier Selenica, Jan Bernhard, Fatemeh Derakhshan, Edaise M. da Silva, Lorraine Colon-Cartagena, Thais Basili, Antonio Marra, Jillian Sue, Qiqi Ye, Arnaud Da Cruz Paula, Selma Yeni, Xin Pei, Hunter Green, Kaitlyn Gill, Yingjie Zhu, Matthew Lee, Ran Godrich, Adam Casson, Britta Weigelt, Nadeem Riaz, Hanna Y Wen, Edi Brogi, Matthew Hanna, Diana Mandelker, Jeremy Kunz, Brandon Rothrock, Sarat Chandarlapaty, Christopher Kanan, Gerard Oakley III, David Klimstra, Thomas Fuchs, Jorge Reis-Filho. Novel Mechanisms of CDH1 Inactivation in Breast Invasive Lobular Carcinoma Unveiled by the Integration of Artificial Intelligence and Genomics [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr GS03-04.

Abstract PO4-17-03: Neoadjuvant chemotherapy in invasive lobular carcinoma of the breast: A retrospective study on survival outcomes

Abstract Background: Neoadjuvant chemotherapy (NAC) is a well-established component of breast cancer management. Invasive lobular carcinoma (ILC) and invasive ductal carcinoma (IDC) are often treated similarly, but many studies are demonstrating a major difference in treatment responses according to the histopathological type of cancer. Aim: To evaluate the overall survival of patients with ILC after NAC compared with adjuvant chemotherapy. Methods: This retrospective cohort study included patients treated for breast ILC between 1998 and 2016 at the Center for Breast Diseases of de CHU de Québec – Université Laval, a tertiary breast cancer center. The primary outcomes were the overall survival (OS) and the recurrence-free survival (RFS) of ILC patients receiving NAC compared with patients who received only adjuvant chemotherapy. The follow-up was censored at the last hospital contact. The secondary outcomes were the locoregional recurrence, pathological complete response (pCR), and pCR impact on survival. Results: During the study period, 265 women were treated for ILC, of which 72 had NAC, and 193 had adjuvant therapy. No significant differences were observed regarding the patient’s characteristics (age, BMI, smoking, menopausal status, and use of hormonal replacement therapy). A T4 disease was found in 29.2% of the NAC group (vs. 0 in the adjuvant group), but the N2-3 rate was lower in the NAC group (5.6% vs. 22.3%, P=0.011). More patients in the NAC group underwent mastectomy (65.3% vs. 29.5%, P&amp;lt; 0.0001) and axillary dissection (80.6% vs. 50.8%, P&amp;lt; 0.0001). Three (4.2%) patients in the NAC group achieved a pCR. The rates of radiotherapy (P=0.851) and hormonal therapy (P=0.694) were similar between the two groups. The mean follow-up was 8 years. After adjustment for age, T, N, surgery type, radiotherapy, and hormonal therapy, the NAC group showed significantly lower 10-year OS (56.2% vs. 80.7%, P&amp;lt; 0.0001) and RFS (51.8% vs. 72.7%, P=0.0004) compared with the adjuvant group. There were no differences in the 10-year local recurrence rate (90.6% vs. 93.5%, P=0.11). In a Cox regression analysis of RFS considering the previously mentioned covariables, more events in the NAC group (OR=2.52, 95%CI: 1.39-4.58, P=0.002) and patients with N2-N3 (OR=3.68, 95%IC: 2.00-6.80, P&amp;lt; 0.01). Conclusion: Despite the general belief that ILC and IDC should be treated similarly, this study strongly suggests that ILC seems to have a poorer response to NAC. Patients diagnosed with ILC might benefit from a more aggressive surgical approach followed by adjuvant chemotherapy, no matter the severity of the disease. Additional long-term prospective comparative studies are needed to support this statement and improve the management of these patients. Citation Format: Virginie Gauthier, Anne-Julie Simard, Christine Desbiens, Brigitte Poirier, Julie Lemieux, Dominique Boudreau, Dominique Leblanc, Claudya Morin, Jean-Charles Hogue, Éric Poirier. Neoadjuvant chemotherapy in invasive lobular carcinoma of the breast: A retrospective study on survival outcomes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-17-03.

Comparison of Clinicopathological Features of Pleomorphic and Invasive Lobular Breast Carcinomas.

Accounting for about 15% of invasive lobular carcinomas and 1% of breast carcinomas, pleomorphic lobular carcinoma is known to be a rare histological subtype of invasive lobular carcinoma. Yet, it is more aggressive and produces a worse prognosis than other breast cancers. Ultimately, the present study compares the clinicopathological features of pleomorphic and invasive lobular breast carcinomas. In the study, we retrospectively evaluated the data of 262 patients with histological subtypes of classical and pleomorphic lobular cancers having been recruited for surgical operations. After resorting to Kolmogorov-Smirnov and Shapiro-Wilk tests to check the normality of distribution, the categorical and continuous variables were compared between the groups using the chi-square test and independent samples t test, respectively. In all analyses, we considered a P-value of <.05 to be statistically significant. Our findings revealed that the groups with lobular and pleomorphic groups significantly differed by Ki-67 value, estrogen receptor negativity, grade, multicentricity, multifocality, surgical margin positivity, completion mastectomy, and metachronous contralateral tumor (P < .05). We discovered that pleomorphic type was associated with higher grades, estrogen receptor negativity, and Ki-67 expression. The incidence of metachronous breast cancer was high in the pleomorphic group, which may be a noteworthy finding to be considered in follow-ups. In addition, the high rates of multicentricity and multifocality of tumors in the pleomorphic group may be associated with increased surgical margin positivity and a higher likelihood of mastectomy. In a nutshell, our findings may guide patients and surgeons regarding the type of intervention and reconstruction options to be adopted in prospective surgeries.

Differences in Histological Subtypes of Invasive Lobular Breast Carcinoma According to Immunohistochemical Molecular Classification.

The aim of this study was to compare the differences between histological and molecular subtypes of invasive lobular carcinoma (ILC) of the breast, in order to be able to predict the behavior and prognosis of the disease, as well as to effectively determine therapy. This study included 263 cases of breast ILC diagnosed over a seven-year period. The diagnosis of invasive lobular carcinoma is based on the characteristic growth pattern and phenotype of cancer cells with the respective subtypes: classic, alveolar, solid, tubulolobular, pleomorphic and mixed lobular type. The examined cases were divided into five groups according to molecular classification based on the expression of ER, PR, HER2 and Ki67 immunohistochemical markers. It was found that the pleomorphic subtype occurred statistically significantly less often as the luminal A subtype compared to others (p = 0.00027), and the HER2-enriched subtype occurred statistically significantly more often in the pT4 stage (p = 0.024). The results of this study significantly singled out the luminal A subtype, and among them classic ILC, as the subtype with the most favorable expression ratio of the investigated predictive/prognostic immunohistochemical markers.

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.

Concurrent use of fam-trastuzumab-deruxtecan-nxki and larotrectinib in metastatic breast cancer: A case report

A 60-year-old female presented in 2010 with left breast invasive lobular carcinoma, estrogen receptor (ER)+ (98%), progesterone receptor (PR)+ (98%), Her2 (2+), Ki67 (8%), Stage IIIC, T2 N3. She had lumpectomy, adjuvant chemo and radiation, took anastrozole until July 2019 when she had metastasis to bone. She started on palbociclib and fulvestrant. Imaging showed minimal improvement. In March 2022, her bone pain worsened and blood counts dropped and became transfusion dependent, bone marrow biopsy showed breast cancer metastases, ER+ (35%), PR−, Her2 (2+). PDL1 was negative, NTRK 1 was positive. She started on larotrectinib for her NTRK1 mutation, which showed some improvement and added fam-trastuzumab-deruxtecan-nxki for her Her2neu weekly positive, resulting in normalization of her blood counts. She has been on this combination which has never been reported, for over a year and has remained in remission with no significant toxicity. Targeting these two mutations simultaneously with possible additive effect can open some new trial ideas.

266 (PB-082) Poster - Systematic profiling of primary invasive lobular breast carcinoma defines distinct candidates for PD-1/PD-L1 targeting immunotherapy

266 (PB-082) Poster - Systematic profiling of primary invasive lobular breast carcinoma defines distinct candidates for PD-1/PD-L1 targeting immunotherapy

Genomic and epigenomic basis of breast invasive lobular carcinomas lacking CDH1 genetic alterations

CDH1 (E-cadherin) bi-allelic inactivation is the hallmark alteration of breast invasive lobular carcinoma (ILC), resulting in its discohesive phenotype. A subset of ILCs, however, lack CDH1 genetic/epigenetic inactivation, and their genetic underpinning is unknown. Through clinical targeted sequencing data reanalysis of 364 primary ILCs, we identified 25 ILCs lacking CDH1 bi-allelic genetic alterations. CDH1 promoter methylation was frequent (63%) in these cases. Targeted sequencing reanalysis revealed 3 ILCs harboring AXIN2 deleterious fusions (n = 2) or loss-of-function mutation (n = 1). Whole-genome sequencing of 3 cases lacking bi-allelic CDH1 genetic/epigenetic inactivation confirmed the AXIN2 mutation and no other cell-cell adhesion genetic alterations but revealed a new CTNND1 (p120) deleterious fusion. AXIN2 knock-out in MCF7 cells resulted in lobular-like features, including increased cellular migration and resistance to anoikis. Taken together, ILCs lacking CDH1 genetic/epigenetic alterations are driven by inactivating alterations in other cell adhesion genes (CTNND1 or AXIN2), endorsing a convergent phenotype in ILC.

ERBB2-amplified lobular breast carcinoma exhibits concomitant CDK12 co-amplification associated with poor prognostic features.

Most invasive lobular breast carcinomas (ILBCs) are luminal-type carcinomas with an HER2-negative phenotype (ERBB2 or HER2 un-amplified) and CDH1 mutations. Rare variants include ERBB2-amplified subtypes associated with an unfavorable prognosis and less response to anti-HER2 targeted therapies. We analyzed the clinicopathological and molecular features of ERBB2-amplified ILBC and compared these characteristics with ERBB2-unamplified ILBC. A total of 253 patients with ILBC were analyzed. Paraffin-embedded formalin-fixed tumor samples from 250 of these patients were added to a tissue microarray. Protein expression of prognostic, stem cell and breast-specific markers was tested by immunohistochemistry (IHC). Hybrid capture-based comprehensive genomic profiling (CGP) was performed for 10 ILBCs that were either fluorescent in situ hybridization (FISH) or IHC positive for HER2 amplification/overexpression and 10 ILBCs that were either FISH or IHC negative. Results were compared with a CGP database of 44,293 invasive breast carcinomas. The CGP definition of ERBB2 amplification was five copies or greater. A total of 17 of 255 ILBC (5%) were ERBB2 amplified. ERBB2-amplified ILBC had higher tumor stage (p < 0.0001), more frequent positive nodal status (p = 0.00022), more distant metastases (p = 0.012), and higher histological grade (p < 0.0001), and were more often hormone receptor negative (p < 0.001) and more often SOX10 positive (p = 0.005). ERBB2 short variant sequence mutations were more often detected in ERBB2-unamplified tumors (6/10, p = 0.027), whereas CDH1 mutations/copy loss were frequently present in both subgroups (9/10 and 7/10, respectively). Amplification of pathogenic genes were more common in HER2-positive ILBC (p = 0.0009). CDK12 gene amplification (≥6 copies) was detected in 7 of 10 ERBB2-amplified ILBC (p = 0.018). There were no CDK12 gene amplifications reported in 44,293 invasive breast carcinomas in the FMI Insights CGP database. ERBB2-amplified ILBC is a distinct molecular subgroup with frequent coamplification of CDK12, whereas ERBB2 sequence mutations occur only in ERBB2-unamplified ILBC. CDK12/ERBB2 co-amplification may explain the poor prognosis and therapy resistance of ERBB2-amplified ILBC.

Systems approach for congruence and selection of cancer models towards precision medicine.

Cancer models are instrumental as a substitute for human studies and to expedite basic, translational, and clinical cancer research. For a given cancer type, a wide selection of models, such as cell lines, patient-derived xenografts, organoids and genetically modified murine models, are often available to researchers. However, how to quantify their congruence to human tumors and to select the most appropriate cancer model is a largely unsolved issue. Here, we present Congruence Analysis and Selection of CAncer Models (CASCAM), a statistical and machine learning framework for authenticating and selecting the most representative cancer models in a pathway-specific manner using transcriptomic data. CASCAM provides harmonization between human tumor and cancer model omics data, systematic congruence quantification, and pathway-based topological visualization to determine the most appropriate cancer model selection. The systems approach is presented using invasive lobular breast carcinoma (ILC) subtype and suggesting CAMA1 followed by UACC3133 as the most representative cell lines for ILC research. Two additional case studies for triple negative breast cancer (TNBC) and patient-derived xenograft/organoid (PDX/PDO) are further investigated. CASCAM is generalizable to any cancer subtype and will authenticate cancer models for faithful non-human preclinical research towards precision medicine.

Ptosis revealing breast carcinoma about a case

Aims/Purpose: The purpose of our work is to describe the clinical and therapeutic aspects of a clinical case of ptosis revealing breast carcinoma.Methods: We report the case of a 61‐year‐old patient, with no pathological history, who presented to the ophthalmological emergency department for a unilateral left ptosis, of rapidly progressive onset.Results: This is a 61‐year‐old patient, with no pathological history, who presents to the ophthalmological emergency department for a unilateral left ptosis of rapidly progressive onset. Ophthalmological examination noted visual acuity at 10/10 in 2 eyes and Parinaud 2 in near vision in 2 eyes, complete ophthalmoplegia of oculomotor nerve (III) with severe ptosis on the left and relative left afferent pupillary deficit. The ophthalmological examination of the right eye was unremarkable. The general examination revealed a right breast mass. Cerebral angio‐MRI revealed four metastatic lesions on the left, above and under tentorial. A mammography showed a diffuse invasive lesion classified ACR 5 (American College of Radiology) on the right. A breast biopsy with histopathological study confirmed the diagnosis of poorly differentiated and invasive lobular carcinoma of the right breast. The patient is currently undergoing chemotherapy treatment.Conclusions: Acute ptosis is an emergency. Thus, a well‐conducted interrogation as well as a thorough general and ophthalmological examination make it possible to orient the etiological assessment and to take early and adequate management of a pathology that may be life‐threatening for the patient.

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.

Invasive Lobular Carcinoma of Breast with Extracellular Mucin: A Novel Entity

Invasive carcinoma of no special type (NST) or ductal carcinoma is the most common type of invasive breast cancers. Invasive lobular carcinoma (ILC) is the most common special variant amongst breast cancers that lacks some of the common features associated with breast cancers e.g. absence of desmoplastic reaction and infrequent mitosis. Some cases of ILC produce intracellular mucin that pushes the nucleus to one side, creating the characteristic signet ring cell morphology. Extracellular mucin secretion is essentially described in association with mucinous breast carcinoma and ductal carcinoma. Very few cases of ILC showing extracellular mucin has been reported in literature. Herein, such a rare case of classic lobular carcinoma is described, in a 70-year-old female who presented to the Surgical department of our hospital. Keywords: Breast cancer, Extracellular mucin, Invasive lobular carcinoma

2328P Alternative molecular mechanisms underpinning breast invasive lobular carcinoma identified by genomics-driven artificial intelligence model

2328P Alternative molecular mechanisms underpinning breast invasive lobular carcinoma identified by genomics-driven artificial intelligence model

Prognostic value of axillary lymph node metastases in invasive lobular breast carcinoma

BackgroundAxillary lymph node involvement is a well-established prognostic factor for recurrence in breast cancer, specifically the number of nodes affected and the ratio of the number of affected nodes to the number of harvested nodes for non-specific invasive breast cancer (invasive ductal carcinoma). However, there is limited information on the impact of lymph node involvement in the case of invasive lobular carcinoma. Objectivesour study aimed to evaluate the prognostic impact of lymph node involvement on overall survival and distant metastatic-free survival according to the number of nodes affected and the ratio of positive nodes (LNR) for patients managed for invasive lobular carcinoma. MethodsThis is a monocentre, comparative, observational study of patients managed for invasive lobular carcinoma at the Gynaecology Department of the University Hospital Center of Tours between January 1, 2007 and December 31, 2018.The LNR cut-off values used were: low risk if LNR ≤ 0.2; intermediate risk if LNR > 0.2 and ≤ 0.65, and high risk for LNR >0.659. ResultsOur study demonstrated a significant difference in overall survival and distant metastasis free survival (p < 0.0001). The 5-years Overall survival was 94 % for N0 patients, 92.4 % for low-risk patients, 85.6 % for intermediate-risk patients and 58.5 % for high-risk patients. The 5-year distant metastasis-free survival was 98.2 % for N0 patients, 95.9 % for low-risk patients, 80.1 % for intermediate-risk patients, and 60.3 % for high-risk patients.Multivariate analysis identified age, invasive lobular histologic type, presence of clinical inflammation, and intermediate and high risk classes of LNR ratio as independent factors affecting overall survival. For metastatic-free survival, the presence of clinical inflammation, the presence of LVSI and the low, intermediate, or high-risk classes of LNR ratio were identified as independent factors. However, age and invasive lobular histologic type did not appear to be independent factors affecting metastatic-free survival. ConclusionOur study highlights the significant prognostic impact of lymph node involvement in patients with invasive lobular carcinoma. The LNR ratio can be used as a reliable predictor of overall survival and metastatic-free survival in these patients.

Clinical and pathological characteristics of metastatic tumors to the urinary bladder

Metastatic carcinoma to the urinary bladder is a rare and under-recognized condition in surgical pathology. In this study, we identified 8 cases of true bladder metastasis at our institution in the past 20 years, excluding secondary tumors via direct extension or serosal implantation. The most common tumor type is malignant melanoma (3/8), followed by clear cell renal cell carcinoma (2/8), adenocarcinoma of the gastrointestinal tract (2/8), and breast invasive lobular carcinoma (1/8). There are 6 cases of endoscopically exophytic metastasis and 2 cases of diffuse metastasis, commensurate with 6 patients with hematuria and 2 patients with urinary obstruction as respective clinical symptoms. Exophytic bladder metastasis usually presents with similar clinical features as urothelial carcinoma, while diffuse metastasis often masquerades as a urinary tract infection. In the latter circumstance, a markedly thickened bladder wall discerned via imaging study is the best indication for the bladder biopsy to circumvent the misdiagnosis. Histologically, the metastatic tumors can also mimic conventional urothelial carcinoma or its histological variants, and thus pose a potential diagnostic challenge to pathologists. The lack of an in situ component in primary bladder cancer may hint at bladder metastasis. Accurate diagnosis of bladder metastasis requires heightened alertness to this rare condition in addition to a multidisciplinary approach.

FDG Localization in Acellular Dermal Matrix, a Potential Cause of Nonpernicious Uptake Following Breast Reconstruction Surgery.

A 47-year-old woman with invasive lobular carcinoma of the left breast underwent prophylactic double mastectomy which also incidentally revealed follicular lymphoma of the right breast. Reconstruction was achieved with bilateral silicone implants and acellular dermal matrix (ADM), a biological scaffold material providing mechanical support. Twelve days thereafter, staging PET/CT demonstrated symmetric moderate FDG uptake corresponding to location of the ADM slings, suspected to reflect cellular engraftment onto the ADM and confirmed by near-complete resolution at 3-month follow-up study. FDG uptake related to ADM should be recognized as reflecting expected cellular incorporation into the matrix, rather than recurrent tumor or infection.

Optimized Modeling of Metastatic Triple-Negative Invasive Lobular Breast Carcinoma.

Invasive lobular carcinoma (ILC) is a common breast cancer subtype that is often diagnosed at advanced stages and causes significant morbidity. Late-onset secondary tumor recurrence affects up to 30% of ILC patients, posing a therapeutic challenge if resistance to systemic therapy develops. Nonetheless, there is a lack of preclinical models for ILC, and the current models do not accurately reproduce the complete range of the disease. We created clinically relevant metastatic xenografts to address this gap by grafting the triple-negative IPH-926 cell line into mouse milk ducts. The resulting intraductal xenografts accurately recapitulate lobular carcinoma in situ (LCIS), invasive lobular carcinoma, and metastatic ILC in relevant organs. Using a panel of 15 clinical markers, we characterized the intratumoral heterogeneity of primary and metastatic lesions. Interestingly, intraductal IPH-926 xenografts express low but actionable HER2 and are not dependent on supplementation with the ovarian hormone estradiol for their growth. This model provides a valuable tool to test the efficiency of potential new ILC therapeutics, and it may help detect vulnerabilities within ILC that can be exploited for therapeutic targeting.