Materiały źródłowe

• #1 Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8176983/

  Invasive lobular carcinoma (ILC) accounts for 10% to 15% of breast cancers in the United States, 80% of which are estrogen receptor (ER) positive, with an unusual metastatic pattern of spread to sites such as the serosa, meninges, and ovaries, among others. […] Despite the unique features of ILC, it is often lumped with hormone receptor positive invasive ductal cancers (IDC); consequently, ILC screening, treatment, and follow-up strategies are largely based on data from IDC. […] Despite both being treated as ER positive breast cancer, querying the Cancer Genome Atlas database shows distinctive molecular aberrations in ILC compared with IDC, such as Ecadherin loss (66% vs. 3%), FOXA1 mutations (7% vs. 2%), and GATA3 mutations (5% vs. 20%). […] Taken together, this suggests that ILC is biologically distinct, which may influence tumorigenesis and therapeutic strategies.

• #2 Lobular Breast Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK554578/

  Invasive lobular carcinoma is the second most common histologic form of breast cancer, representing 5% to 15% of all invasive breast cancers. It is composed of non-cohesive cells individually dispersed or organized in a single-file linear pattern in a fibrous stroma. […] It is now recognized as a biologically distinct disease from the more common invasive ductal carcinoma, with unique molecular pathogenesis and consequential implications on diagnosis and treatment. An understanding of these differences is crucial to tailor management strategies. […] Molecular studies have been instrumental in highlighting the role of E-cadherin inactivation in the development of lobular lesions and in supporting the notion that lobular carcinoma in situ and atypical lobular hyperplasia are, nonobligate precursors for the development of invasive cancer, rather than being simply risk indicators for invasive disease.

• #3 Invasive lobular carcinoma of the breast: the increasing importance of this special subtype | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-020-01384-6

  Invasive lobular carcinoma (ILC) is the most common of the breast cancer special types, accounting for up to 15% of all breast cancer cases. ILCs are noted for their lack of E-cadherin function, which underpins their characteristic discohesive growth pattern, with cells arranged in single file and dispersed throughout the stroma. […] From an evolutionary point of view, these tumours arise from a family of non-obligate precursor lesions called atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), which may be collectively termed lobular neoplasia (LN). […] The multistep model of breast cancer progression contends that although lobular carcinomas arise along the low-grade, ER-positive arm of the pathway (with low-grade, ER-positive ductal lesions), de-differentiation to higher grade lesions can occur through acquisition of alterations in oncogenes such as ERBB2 and TP53, producing a spectrum of heterogenous proliferations.

• #4 Invasive lobular carcinoma with extracellular mucin (ILCEM): clinicopathologic and molecular characterization of a rare entity | Modern Pathology

  https://www.nature.com/articles/s41379-022-01084-w

  Invasive lobular carcinoma with extracellular mucin (ILCEM) is a rare histologic subtype of breast cancer. Little is known about the pathologic or genomic signatures that distinguish ILCEM from classic invasive lobular carcinoma (ILC) or mucinous carcinoma. […] The cases of ILCEM were moderately or poorly differentiated, frequently exhibiting variant morphology that has not been previously described or emphasized, including grade 3 nuclei, diffuse signet ring cells, solid growth, tumor necrosis or apocrine features. All tumors showed absent or reduced membranous E-cadherin expression. […] Our data highlights ILCEM as a distinct variant of ILC that often presents with higher-grade and variant morphologic features and is associated with an aggressive clinical course. NGS data support an overall lobular-type molecular profile and reveal potentially targetable alterations in a subset of cases with recurrence.

• #5 Pathology Outlines – Invasive lobular carcinoma classic

  https://www.pathologyoutlines.com/topic/breastmalignantlobularclassic.html

  Invasive breast carcinoma with loss of cellular adhesion, characteristically arranged in discohesive or single file patterns […] Special subtype of invasive breast carcinoma characterized by discohesive tumor cells arranged in single files or as individual single cells […] Shows 16q loss (CDH1 gene located at 16q22.1 encodes E-cadherin, integral in formation of adherens junction responsible for cell adhesion) […] Invasiveness and loss of cellular cohesion due to abnormalities of the adherens complex, formed by cadherins and catenins […] Majority of lobular carcinomas show loss of E-cadherin expression […] Lobular carcinoma in situ is a risk factor and nonobligate precursor of invasive lobular carcinoma […] E-cadherin negative lobular carcinomas have a higher disease specific mortality than E-cadherin positive counterparts […] CDH1 loss of function through truncating mutation or promoter hypermethylation combined with loss of heterozygosity at chromosome 16, resulting in loss of protein.

• #6 Invasive lobular carcinoma of the breast: morphology, biomarkers and ’omics | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0519-x

  Invasive lobular carcinoma of the breast is the most common special morphological subtype of breast cancer, comprising up to 15% of all cases. […] Despite this, clinicians face countless challenges in the diagnosis and long-term management of patients, as they encounter a tumour that can be difficult to detect through screening, elicits a very invasive nature, a propensity for widespread metastatic colonisation and, consequently, in some studies a worse long-term poor outcome compared with invasive carcinoma of no special type. […] E-cadherin loss is responsible for the inherently discohesive phenotype associated with ILCs, and changes at the genomic level account for this loss. […] The characteristic discohesive growth pattern of ILC is the result of the dysregulation of cell-cell adhesion properties, primarily driven by the targeted disruption of the cell adhesion molecule E-cadherin.

• #7 Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8176983/

  Loss of Ecadherin in ILC is predominantly attributed to CDH1 mutation, which in 89% of cases occurred concurrently with heterozygous deletion in chromosome 16q. […] Analysis of invasive breast carcinoma cases in the Cancer Genome Atlas (TCGA) dataset revealed that 66% (107/162) of ILCs harbor mutation in CDH1 compared with only 3% (22/741) of IDCs. […] Loss of Ecadherin markedly increases cytoplasmic accumulation of p120 catenin, which plays a key role in tumor invasion. […] Patients with ILC are routinely treated with endocrine therapy, but one third of patients fail to respond to treatment and develop endocrine resistance in the long term. […] The underlying mechanism behind acquired endocrine resistance in ILC is multifactorial. […] FOXA1, an ER transcription modulator, plays a key role in cancer progression and development of endocrine resistance. […] A higher rate of FOXA1 mutations was observed in ILC compared with IDC (7% vs. 2%). […] Thus, ILC is not only a unique histological subtype with specific clinical features but also exhibits complex molecular alterations that could be potentially targeted for improved clinical outcomes.

• #8 Lobular Breast Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK554578/

  Germline CDH1 mutations and the role of genes of the phosphatidylinositol 3-kinase pathway, PIK3CA in the development of lobular breast cancer, is considered important. […] Several additional molecular factors, namely TP53, PIK3CA, FOXA1, ZNF703, FGFR1, and BCAR4, have been linked to infiltrating lobular breast cancer or the evolution of lobular carcinoma in situ to invasive cancer. […] One of the most consistent molecular alterations in invasive lobular carcinoma and its variants is the loss of expression of the cell-cell adhesion molecule E-cadherin, which contributes to the characteristic discohesive nature of lobular cells.

• #9 Invasive lobular carcinoma of the breast: we diagnose it, but do we know what it is? | Pathologica – Journal of the Italian Society of Anatomic Pathology and Diagnostic Cytopathology

  https://www.pathologica.it/article/view/862

  E-cadherin is a transmembrane calcium-dependent cell adhesion molecule found in most epithelial cells being a part of their adherens junctions. While its extracellular domain links cells to cells, its intracellular domain fixes the molecule to the cytoskeletal actin via the E-cadherin-catenin complex, including b-catenin and a-catenin; E-cadherin-bound p120 catenin being also part of the complex. […] Unfortunately, loss of E-cadherin is not only seen in ILCs and lobular neoplasia, but is an event that has been associated with increased cell motility, invasion and epithelial-mesenchymal transition. […] The lack of E-cadherin function on cell membranes can theoretically derive from several genomic events. One of these is biallelic alteration, mutation of the CDH1 gene, which can result in no protein in the cell membrane or a protein without adhesive function; such missense mutations have been recognized to be the sources of erroneous classifications as NST carcinomas.

• #10 Invasive lobular carcinoma with extracellular mucin (ILCEM): clinicopathologic and molecular characterization of a rare entity | Modern Pathology

  https://www.nature.com/articles/s41379-022-01084-w

  Most cases of ILCEM included in this and other reports have demonstrated loss of normal membranous expression of E-cadherin with or without alterations in expression of other members of the cadherin-catenin complex, a hallmark of the lobular phenotype, supporting its classification as a variant of ILC. […] Sequencing of the ILCEM cases in our series revealed genetic alterations consistent with a lobular phenotype. Most important, CDH1 alterations were identified in all but one of the sequenced cases of ILCEM, most of which had demonstrable biallelic inactivation of CDH1 due to concurrent CDH1 mutation and whole or partial 16q arm loss. […] ILCEM displayed few amplifications at genomic loci that are known to drive breast tumorigenesis and have been reported at varying frequencies in lobular and other ER+ breast carcinomas, including at 8p11-p12, 11q13, and 20q13.

• #11 Invasive lobular carcinoma of the breast: morphology, biomarkers and ’omics | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0519-x

  In contrast, approximately 90% of LNs and ILCs, including variants, completely lack E-cadherin protein expression. […] The loss of E-cadherin in ILC also results in the loss of -, – and -catenins, and p120-catenin becomes up-regulated and re-localised to the cytoplasm. […] E-cadherin deregulation occurs in the earliest morphological stage of lobular tumourigenesis (that is, ALH) and is frequently and irreversibly driven by genomic alterations targeting its gene, CDH1. […] The somatic copy number loss of 16q in ILC and ER-positive, low-grade IC-NST is extremely frequent, suggesting these tumours share a common pathway of evolution. […] Identical CDH1 genetic mutations have been detected in LCIS and in their adjacent invasive counterpart, which is a key finding implicating LCIS as a direct (but non-obligate) precursor for ILC.

• #12 Lobular Carcinoma of the Breast: A Comprehensive Review with Translational Insights

  https://www.mdpi.com/2072-6694/15/22/5491

  CDH1 mutations are the most frequent mutations seen in ILC (in up to 65% of cases). E-cadherin, a 120 kda is a transmembrane glycoprotein transcribed by the CDH1 gene. […] Loss of e-cadherin (loss of 16q) causes cytoplasmic accumulation of p120 catenin, which interacts with various effector molecules and pathways (e.g., Rho/Rock signaling pathway), thus causing anoikis resistance and tumor progression. […] The IGF1 pathway is known for its association with breast cancer progression. Binding of IGF to its receptor IGF1R further leads to activation of the PI3K and MAPK pathways. Higher IGF1/2 expression and its receptor activation is seen in ILCs compared to ductal carcinomas. E-cadherin loss increases the availability of the IGF1R receptor, thus causing increased IGF1, IGF2, and insulin signaling and, hence, leading to increased ligand binding. This ultimately leads to tumor cell motility and invasion.

• #13 Invasive lobular carcinoma of the breast: morphology, biomarkers and ’omics | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0519-x

  In contrast, approximately 90% of LNs and ILCs, including variants, completely lack E-cadherin protein expression. […] The loss of E-cadherin in ILC also results in the loss of -, – and -catenins, and p120-catenin becomes up-regulated and re-localised to the cytoplasm. […] E-cadherin deregulation occurs in the earliest morphological stage of lobular tumourigenesis (that is, ALH) and is frequently and irreversibly driven by genomic alterations targeting its gene, CDH1. […] The somatic copy number loss of 16q in ILC and ER-positive, low-grade IC-NST is extremely frequent, suggesting these tumours share a common pathway of evolution. […] Identical CDH1 genetic mutations have been detected in LCIS and in their adjacent invasive counterpart, which is a key finding implicating LCIS as a direct (but non-obligate) precursor for ILC.

• #14 Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8176983/

  Loss of Ecadherin in ILC is predominantly attributed to CDH1 mutation, which in 89% of cases occurred concurrently with heterozygous deletion in chromosome 16q. […] Analysis of invasive breast carcinoma cases in the Cancer Genome Atlas (TCGA) dataset revealed that 66% (107/162) of ILCs harbor mutation in CDH1 compared with only 3% (22/741) of IDCs. […] Loss of Ecadherin markedly increases cytoplasmic accumulation of p120 catenin, which plays a key role in tumor invasion. […] Patients with ILC are routinely treated with endocrine therapy, but one third of patients fail to respond to treatment and develop endocrine resistance in the long term. […] The underlying mechanism behind acquired endocrine resistance in ILC is multifactorial. […] FOXA1, an ER transcription modulator, plays a key role in cancer progression and development of endocrine resistance. […] A higher rate of FOXA1 mutations was observed in ILC compared with IDC (7% vs. 2%). […] Thus, ILC is not only a unique histological subtype with specific clinical features but also exhibits complex molecular alterations that could be potentially targeted for improved clinical outcomes.

• #15 Lobular Carcinoma of the Breast: A Comprehensive Review with Translational Insights

  https://www.mdpi.com/2072-6694/15/22/5491

  CDH1 mutations are the most frequent mutations seen in ILC (in up to 65% of cases). E-cadherin, a 120 kda is a transmembrane glycoprotein transcribed by the CDH1 gene. […] Loss of e-cadherin (loss of 16q) causes cytoplasmic accumulation of p120 catenin, which interacts with various effector molecules and pathways (e.g., Rho/Rock signaling pathway), thus causing anoikis resistance and tumor progression. […] The IGF1 pathway is known for its association with breast cancer progression. Binding of IGF to its receptor IGF1R further leads to activation of the PI3K and MAPK pathways. Higher IGF1/2 expression and its receptor activation is seen in ILCs compared to ductal carcinomas. E-cadherin loss increases the availability of the IGF1R receptor, thus causing increased IGF1, IGF2, and insulin signaling and, hence, leading to increased ligand binding. This ultimately leads to tumor cell motility and invasion.

• #16

  https://link.springer.com/article/10.1007/s12609-021-00412-4

  Invasive lobular carcinoma (ILC) is increasingly recognized as a distinct subtype of breast cancer with unique management challenges. […] Molecular alterations specific to or enriched in ILC may serve as treatment targets. […] ILC has specific features that may be treatment targets. Clinical trials for ILC are available and being developed. […] The defining characteristic of ILC is the absence of the adhesion protein E-cadherin, which results in a number of unique characteristics including a diffuse growth pattern in so-called single file lines. […] The absence of functional E-cadherin in ILC results from alterations in the E-cadherin gene, CDH1. […] Nearly all ILC tumors lack E-cadherin expression, which results in a number of consequences including cytosolic translocation of the catenin p120, subsequent activation of the Rho/Rho-associated kinase 1 (ROCK) pathway, and anchorage independent growth in vitro.

• #17

  https://link.springer.com/article/10.1007/s12609-021-00412-4

  Additionally, E-cadherin loss appears to result in activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway, irrespective of oncogenic mutations in PIK3CA. […] Somatic mutations in ILC differ from those in IDC, with increased prevalence of mutations in FOXA1, AKT1, PTEN, HER2, HER3, and FGFR4 seen in HR-positive, HER2-negative ILC compared to HR-positive, HER2-negative IDC. […] Recent data show that high expression of the bromodomain and extraterminal domain (BET) proteins BRD3/BRD4 are associated with worse outcomes in ILC and that resistance to BET inhibition may be driven by tyrosine kinases including fibroblast growth factor receptor (FGFR)-1. […] Indeed, FGFR-1 is thought to be necessary for tumor cell survival in the setting of endocrine resistance in ILC cell lines and is implicated in recurrent or metastatic ILC.

• #18 A review of invasive lobular carcinoma of the breast: Should it be treated like invasive ductal carcinoma?

  https://oatext.com/A-review-of-invasive-lobular-carcinoma-of-the-breast-Should-it-be-treated-like-invasive-ductal-carcinoma.php

  Other genetic abnormalities commonly implicated include mutations of the PIK3CA/AKT/PTEN and FOXA1 genes and ESR1 copy number gains, while mutations of TP53 and GATA3 are rare unlike in IDC, with the exception of the pleomorphic variant of ILC. […] ILC differs greatly from IDC in many important ways. From sensitivity of imaging techniques in their detection, to pathological and molecular characteristics, these two subtypes have significant differences that contribute to their different clinical course, responses to treatment and prognosis. […] Future trials should stratify recruitment by histological subtype and more studies are needed to evaluate the molecular characteristics of ILC.

• #19 Invasive lobular carcinoma of the breast: the increasing importance of this special subtype | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-020-01384-6

  A lineage of lobular disease evolves from a normal epithelial cell on a background of a loss of E-cadherin expression and function, and key early somatic alterations involving gain of chromosome 1q, loss of 16q, and mutations in PIK3CA, AKT1, or PTEN. […] The morphological and molecular diversity of in situ and invasive lobular lesions is likely to be a result of the subsequently arising pattern of molecular alterations that drive progression. […] ILC and its subtypes are typified by a loss of cellular adhesion, frequently the result of biallelic inactivation (i.e. gene mutation combined with gene deletion) of the CDH1 gene encoding E-cadherin, although other mechanisms of expression loss also feature. […] The capacity of neoplastic cells of ILC to create tubular structures in the absence of E-cadherin-facilitated cellular adhesion has long intrigued researchers.

• #20

  https://journals.lww.com/indianjcancer/fulltext/2018/55040/clinico_pathological_characteristics_and_treatment.7.aspx

  Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer and accounts for 10%15% of all breast cancers in the west. […] ILC differs from invasive ductal carcinoma (IDC) in clinic-pathological features, molecular biology, and natural history of the disease. […] ILC is frequently associated with older age, larger tumor size, lower histologic grade, and positive hormone receptor status. […] Genomic profiling of ILC is also distinct in terms of high frequency of CDH1 mutations, loss of phosphatase and tensin homolog, activation of AKT, and mutations in TBX3 and FOXA1. […] ILCs are more prone to spread to GI, peritoneal, and ovarian tissue. […] The role of FOXA1 and GATA3 genes in modulating the ER transcription program in ILC needs to be further investigated.

• #21 Lobular Carcinoma of the Breast: A Comprehensive Review with Translational Insights

  https://www.mdpi.com/2072-6694/15/22/5491

  CDH1 mutations are the most frequent mutations seen in ILC (in up to 65% of cases). E-cadherin, a 120 kda is a transmembrane glycoprotein transcribed by the CDH1 gene. […] Loss of e-cadherin (loss of 16q) causes cytoplasmic accumulation of p120 catenin, which interacts with various effector molecules and pathways (e.g., Rho/Rock signaling pathway), thus causing anoikis resistance and tumor progression. […] The IGF1 pathway is known for its association with breast cancer progression. Binding of IGF to its receptor IGF1R further leads to activation of the PI3K and MAPK pathways. Higher IGF1/2 expression and its receptor activation is seen in ILCs compared to ductal carcinomas. E-cadherin loss increases the availability of the IGF1R receptor, thus causing increased IGF1, IGF2, and insulin signaling and, hence, leading to increased ligand binding. This ultimately leads to tumor cell motility and invasion.

• #22 Lobular Carcinoma of the Breast: A Comprehensive Review with Translational Insights

  https://www.mdpi.com/2072-6694/15/22/5491

  ERBB2 amplifications, which exert their oncogenic effect by heterodimerization to HER3, are frequently found in ILC (in up to 15%). ERBB2 mutations, which can be nonamplified, or somatic mutations, which drive the oncogenesis by tyrosine kinase activation or dimerization of the HER2 domain, vary in frequency from 4 to 6% in ILC according to studies. […] The fibroblast growth factor signaling pathway has a distinct part to play in ILC tumor biology. Studies have shown that FGFR1 acts as an initial amplicon in ILC genetics, and inhibition of cell growth in cell lines was observed when FGFR1 was inhibited.

• #23

  https://link.springer.com/article/10.1007/s12609-021-00412-4

  Additionally, E-cadherin loss appears to result in activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway, irrespective of oncogenic mutations in PIK3CA. […] Somatic mutations in ILC differ from those in IDC, with increased prevalence of mutations in FOXA1, AKT1, PTEN, HER2, HER3, and FGFR4 seen in HR-positive, HER2-negative ILC compared to HR-positive, HER2-negative IDC. […] Recent data show that high expression of the bromodomain and extraterminal domain (BET) proteins BRD3/BRD4 are associated with worse outcomes in ILC and that resistance to BET inhibition may be driven by tyrosine kinases including fibroblast growth factor receptor (FGFR)-1. […] Indeed, FGFR-1 is thought to be necessary for tumor cell survival in the setting of endocrine resistance in ILC cell lines and is implicated in recurrent or metastatic ILC.

• #24 Lobular Carcinoma of the Breast: A Comprehensive Review with Translational Insights

  https://www.mdpi.com/2072-6694/15/22/5491

  ERBB2 amplifications, which exert their oncogenic effect by heterodimerization to HER3, are frequently found in ILC (in up to 15%). ERBB2 mutations, which can be nonamplified, or somatic mutations, which drive the oncogenesis by tyrosine kinase activation or dimerization of the HER2 domain, vary in frequency from 4 to 6% in ILC according to studies. […] The fibroblast growth factor signaling pathway has a distinct part to play in ILC tumor biology. Studies have shown that FGFR1 acts as an initial amplicon in ILC genetics, and inhibition of cell growth in cell lines was observed when FGFR1 was inhibited.

• #25 Invasive lobular carcinoma of the breast: the increasing importance of this special subtype | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-020-01384-6

  The acquisition of ERBB2 and ERBB3 mutations in ILC has been shown to be associated with an increased risk of relapse and poorer outcomes, likely representing an escape mechanism to endocrine therapy. […] The genomic mechanisms underlying therapy resistance are a burgeoning field and are already producing important data and insights into the clinical management of ILC relapse.

• #26 Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8176983/

  Loss of Ecadherin in ILC is predominantly attributed to CDH1 mutation, which in 89% of cases occurred concurrently with heterozygous deletion in chromosome 16q. […] Analysis of invasive breast carcinoma cases in the Cancer Genome Atlas (TCGA) dataset revealed that 66% (107/162) of ILCs harbor mutation in CDH1 compared with only 3% (22/741) of IDCs. […] Loss of Ecadherin markedly increases cytoplasmic accumulation of p120 catenin, which plays a key role in tumor invasion. […] Patients with ILC are routinely treated with endocrine therapy, but one third of patients fail to respond to treatment and develop endocrine resistance in the long term. […] The underlying mechanism behind acquired endocrine resistance in ILC is multifactorial. […] FOXA1, an ER transcription modulator, plays a key role in cancer progression and development of endocrine resistance. […] A higher rate of FOXA1 mutations was observed in ILC compared with IDC (7% vs. 2%). […] Thus, ILC is not only a unique histological subtype with specific clinical features but also exhibits complex molecular alterations that could be potentially targeted for improved clinical outcomes.

• #27 Lobular Breast Carcinoma – StatPearls – NCBI Bookshelf

  https://www.ncbi.nlm.nih.gov/books/NBK554578/

  Germline CDH1 mutations and the role of genes of the phosphatidylinositol 3-kinase pathway, PIK3CA in the development of lobular breast cancer, is considered important. […] Several additional molecular factors, namely TP53, PIK3CA, FOXA1, ZNF703, FGFR1, and BCAR4, have been linked to infiltrating lobular breast cancer or the evolution of lobular carcinoma in situ to invasive cancer. […] One of the most consistent molecular alterations in invasive lobular carcinoma and its variants is the loss of expression of the cell-cell adhesion molecule E-cadherin, which contributes to the characteristic discohesive nature of lobular cells.

• #28 A review of invasive lobular carcinoma of the breast: Should it be treated like invasive ductal carcinoma?

  https://oatext.com/A-review-of-invasive-lobular-carcinoma-of-the-breast-Should-it-be-treated-like-invasive-ductal-carcinoma.php

  Other genetic abnormalities commonly implicated include mutations of the PIK3CA/AKT/PTEN and FOXA1 genes and ESR1 copy number gains, while mutations of TP53 and GATA3 are rare unlike in IDC, with the exception of the pleomorphic variant of ILC. […] ILC differs greatly from IDC in many important ways. From sensitivity of imaging techniques in their detection, to pathological and molecular characteristics, these two subtypes have significant differences that contribute to their different clinical course, responses to treatment and prognosis. […] Future trials should stratify recruitment by histological subtype and more studies are needed to evaluate the molecular characteristics of ILC.

• #29 Invasive lobular carcinoma of the breast: morphology, biomarkers and ’omics | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0519-x

  The acquisition of the mesenchymal phenotype is accompanied by cadherin switching (loss of E-cadherin and activation of N-cadherin), which is driven by transcriptional regulators of E-cadherin, including SNAIL and TWIST. […] The loss of E-cadherin is also associated with the process of epithelial to mesenchymal transition (EMT) where cells lose polarity and adhesion to become more migratory and invasive during embryonic morphogenesis and wound healing. […] The functional role of EMT in driving the invasive nature of ILC remains unlikely.

• #30 Invasive lobular carcinoma of the breast: morphology, biomarkers and ’omics | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0519-x

  The acquisition of the mesenchymal phenotype is accompanied by cadherin switching (loss of E-cadherin and activation of N-cadherin), which is driven by transcriptional regulators of E-cadherin, including SNAIL and TWIST. […] The loss of E-cadherin is also associated with the process of epithelial to mesenchymal transition (EMT) where cells lose polarity and adhesion to become more migratory and invasive during embryonic morphogenesis and wound healing. […] The functional role of EMT in driving the invasive nature of ILC remains unlikely.

• #31

  https://www.aurorahealthcare.org/services/cancer/breast-cancer/invasive-lobular-carcinoma

  Invasive lobular carcinoma is a type of breast cancer that has spread outside the milk glands of the breast. […] Invasive lobular carcinoma starts within the milk glands (lobules) of your breast, and later invades surrounding breast tissue and possibly other parts of your body. […] Unlike some other types of breast cancer, ILC grows in a scattered pattern and may not present as a distinct lump. This creates challenges in detection with imaging tests like mammograms or self-exams. […] The invasive lobular carcinoma grade is a classification system used to judge the characteristics of cancer cells when examined under a microscope. This system helps doctors predict the speed at which your cancer cells may grow and spread to nearby tissue or other parts of your body. […] Invasive lobular carcinoma is graded on a scale ranging from one to three:

• #32 Invasive Lobular Carcinoma | MD Anderson Cancer Center

  https://www.mdanderson.org/cancer-types/breast-cancer/invasive-lobular-carcinoma.html

  Invasive lobular carcinoma (ILC) is a rare type of breast cancer that grows in the lobes of the breast, where milk is produced. […] When cells in the TDLUs first mutate and become cancerous, a few lose the ability to produce a molecule called E-cadherin. This molecule helps healthy breast cells stay attached to their surroundings. […] The lack of E-cadherin is a defining feature of ILC. […] Unlike ductal carcinomas, ILCs usually do not form a lump. Instead, the cancer cells grow in straight lines. […] As a low-grade cancer, the prognosis for early-stage ILC is generally good. However, the disease has a higher chance of returning after 10 years than invasive ductal carcinoma. […] Most ILCs are positive for the estrogen and progesterone receptors and negative for the HER2 receptor. They are called hormone-receptor positive breast cancers.

• #33 Metastatic Breast Lobular Carcinoma to Unusual Sites: A Report of Three Cases and Review of Literature | Abdallah | Journal of Medical Cases

  https://www.journalmc.org/index.php/JMC/article/view/3538/2866

  Invasive lobular carcinoma of the breast is the second most common type of invasive breast carcinoma. Invasive lobular carcinoma has an unusual pattern of metastases, which poses a diagnostic challenge for both clinicians and pathologists. […] Breast invasive lobular carcinoma has a high frequency of distant metastases. The most common sites of metastases are the bone, lung, pleura, soft tissue and liver. Metastases to the female genital tract are rare; and metastases to the gastrointestinal (GI) tract are even rarer. […] One of the most consistent molecular alterations in invasive lobular carcinoma is the loss of the adhesion molecule E-cadherin. This explains the characteristic non-cohesive pattern of the tumor cells. Inactivation of this gene occurs as an early event in oncogenesis, as a result of somatic, truncating mutations, loss of heterozygosity (LOH) and promoter methylation. The lost E-cadherin facilitates the seeding of the tumor cells to remote sites.

• #34 How Pathology Affects Appearance, Features of Invasive Lobular Carcinoma That Every Imaging Physician Should Know | Journal of Nuclear Medicine

  https://jnm.snmjournals.org/content/62/supplement_1/2035

  Invasive lobular carcinoma (ILC) is the second most common histology of breast malignancy, accounting for approximately 10-15% of cases. The classic histologic appearance is of uniform tumor cells in a single-file line infiltrating the breast parenchyma, usually in part due to the lack of E-cadherin, without causing significant desmoplastic response. These features decrease the degree of architectural distortion and mass-forming tendencies of this tumor histology, thus causing challenge in both a clinical and radiologic diagnosis. It is important for the imaging physician to recognize the pathologic and histologic basis that leads to challenging in detecting ILC on imaging, especially on typical modalities such as bone scan and FDG PET/CT where uptake and metabolic uptake is often low level, potentially leading to higher numbers of false negative examinations.

• #35 Invasive Lobular Breast Cancer – Susan G. Komen®

  https://www.komen.org/breast-cancer/diagnosis/invasive-lobular-breast-cancer/

  Invasive lobular cancer or infiltrating lobular carcinoma (ILC) is invasive breast cancer that begins in the lobules of the breast. The lobules are small, round sacs in the breast that produce milk for breastfeeding. […] With ILC, the cancer cells in the lobules invade nearby breast tissue and may travel from the breast to other parts of the body. […] Compared to IDC, ILC tends to have a larger tumor size, but a lower tumor grade at diagnosis. […] Under a microscope, invasive lobular cancer (ILC) cells most often appear in a single file order. Because ILC tumors grow in this way, there may not be a mass (lump) present. This can make ILC harder to find on a mammogram than some other breast cancers. […] ILC tends to be hormone receptor-positive and HER2-negative. […] Some findings show chemotherapy (in addition to hormone therapy) may not benefit all people with hormone receptor-positive, HER2-negative ILC.

• #36 Invasive lobular carcinoma – Libre Pathology

  https://librepathology.org/w/index.php?title=Invasive_lobular_carcinoma&mobileaction=toggle_view_desktop

  Invasive lobular carcinoma, abbreviated ILC, is the second most common form of Invasive breast cancer. […] May be associated with a CDH1 mutation – seen in diffuse type gastric cancer. […] Commonly have low grade nuclear features. […] E-cadherin -ve. […] ER and PR +ve. […] HER2 -ve. […] CK7 +ve.

• #37 Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8176983/

  Long-term survival and clinical outcomes in patients with ILC are worse than in stage and grade matched patients with IDC; therefore, nuanced criteria are needed to better define treatment goals and protocols tailored to ILC’s unique biology. […] ILC also differs in response to systemic therapy, with studies showing ILC as less sensitive to chemotherapy. […] The classic subtype of ILC is composed of discohesive, small, round to ovoid cells with minimal cytoplasm and occasional cytoplasmic inclusions. […] Loss of membranous Ecadherin expression as detected by immunohistochemistry (IHC) is seen in 90% of cases, with concomitant loss of membranous p120 (increased cytoplasmic expression) and beta-catenin due to disruption of the Ecadherin complex. […] The morphology and immunophenotype of ILC is due to inactivation of the cell-cell adhesion molecule Ecadherin.

• #38 Invasive Lobular Carcinoma — Cancer Stat Facts

  https://seer.cancer.gov/statfacts/html/ilc.html

  Like IDC/NST, ILC can metastasize to the bones, brain, liver, and lungs. However, ILC can also spread to unique sites such as the gastrointestinal tract, gynecological organs, the peritoneum, and in rarer cases leptomeninges and orbital tissues. […] Though ILC is hardly a rare cancer, at 15% of breast cancers, for decades, there has been very little research. The standard of care for early-stage hormone receptor positive ILC is the same as treatment of hormone receptor positive non-lobular tumors. More research is needed to identify ILC-specific treatment protocols.

• #39 Invasive Lobular Breast Cancer – Susan G. Komen®

  https://www.komen.org/breast-cancer/diagnosis/invasive-lobular-breast-cancer/

  CDH1 inherited gene mutations increase the risk of breast cancer. […] CDH1 gene mutations appear to be related more often to ILC than invasive ductal cancer (IDC). […] The use of MHT containing estrogen plus progestin may be more strongly linked to the risk of ILC than to the risk of IDC. […] Hormone receptor-positive breast cancers can recur more than 10 years after diagnosis, while such late recurrences are rare for hormone receptor-negative cancers. […] The most important factors related to survival for ILC are cancer stage and tumor grade. […] While invasive lobular cancer (ILC) can metastasize to these sites, it can also spread to sites not common with other breast cancers. For example, ILC sometimes may metastasize to the ovaries or the gastrointestinal tract (including the stomach, colon and rectum).

• #40 Metastatic Breast Lobular Carcinoma to Unusual Sites: A Report of Three Cases and Review of Literature | Abdallah | Journal of Medical Cases

  https://www.journalmc.org/index.php/JMC/article/view/3538/2866

  Invasive lobular carcinoma has a distinctive metastatic patterns, including multiple metastasis sites, higher risk for liver metastases. It has a higher tendency for meningeal, peritoneal, gastrointestinal or GI tract and uterine metastases. […] Our recommendations is to have a higher index of suspicion in any case with a history of current breast cancer, especially invasive lobular carcinoma when developing GI tract or genital tract symptoms, even if mild or subtle, and to biopsy any developed GI tract or genital tract lesions with performing an extensive immunostaining panel including breast specific antibodies.

• #41 Infiltrative pattern of metastatic invasive lobular breast carcinoma in the abdomen: a pictorial review | Insights into Imaging | Full Text

  https://insightsimaging.springeropen.com/articles/10.1186/s13244-021-01120-4

  Invasive lobular carcinoma (ILC) has a greater tendency to metastasize to the peritoneum, retroperitoneum, and gastrointestinal (GI) tract as compared to invasive carcinoma of no special type (NST). […] ILC metastases are often infiltrative and subtle, rendering them difficult to detect on imaging as compared to mass-forming lesions. […] The infiltrative pattern of growth of ILC is the result of loss of E-cadherin, the cell-to-cell adhesion molecule, which is related to changes at the genomic level. […] Metastatic ILC can present with late relapse many years after remission. […] Metastatic spread to the GI tract is more common in ILC than in NST. […] When metastatic disease progresses and involves all layers of the stomach, it appears as linitis plastica, in which the stomach is poorly distensible and diffusely thickened. […] ILC has a higher tendency to metastasize to the peritoneum and retroperitoneum compared with NST.

• #42 Metastatic Breast Lobular Carcinoma to Unusual Sites: A Report of Three Cases and Review of Literature | Abdallah | Journal of Medical Cases

  https://www.journalmc.org/index.php/JMC/article/view/3538/2866

  Invasive lobular carcinoma has a distinctive metastatic patterns, including multiple metastasis sites, higher risk for liver metastases. It has a higher tendency for meningeal, peritoneal, gastrointestinal or GI tract and uterine metastases. […] Our recommendations is to have a higher index of suspicion in any case with a history of current breast cancer, especially invasive lobular carcinoma when developing GI tract or genital tract symptoms, even if mild or subtle, and to biopsy any developed GI tract or genital tract lesions with performing an extensive immunostaining panel including breast specific antibodies.

• #43 Invasive Lobular Carcinoma: Symptoms, Treatment, Research | BCRF

  https://www.bcrf.org/about-breast-cancer/invasive-lobular-carcinoma/

  A loss of CDH1 is the most prevalent gene alteration that distinguishes invasive lobular carcinoma from invasive ductal carcinoma. […] Loss of E-cadherin function is associated with increased tumor development, invasiveness, and metastasis (spreading to distant sites in the body). […] Invasive lobular carcinoma has generally been treated like HR-positive invasive ductal carcinoma, but there are marked differences in how the two types of invasive carcinoma respond to hormone therapies. […] Recent studies profiling lobular tumors suggest that some common genetic mutations cause a poorer response to hormone therapies and drive resistance. […] A more profound understanding of the biology that distinguishes this disease subtype is critical for improving lobular breast cancer treatment. […] Researchers are striving to increase participation of patients with lobular breast cancer in clinical trials as well as designing clinical trials specifically focused on this subtypeachieving these goals is critical to advancing our understanding of lobular breast cancer and moving treatments and disease management forward.

• #44 Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8176983/

  Loss of Ecadherin in ILC is predominantly attributed to CDH1 mutation, which in 89% of cases occurred concurrently with heterozygous deletion in chromosome 16q. […] Analysis of invasive breast carcinoma cases in the Cancer Genome Atlas (TCGA) dataset revealed that 66% (107/162) of ILCs harbor mutation in CDH1 compared with only 3% (22/741) of IDCs. […] Loss of Ecadherin markedly increases cytoplasmic accumulation of p120 catenin, which plays a key role in tumor invasion. […] Patients with ILC are routinely treated with endocrine therapy, but one third of patients fail to respond to treatment and develop endocrine resistance in the long term. […] The underlying mechanism behind acquired endocrine resistance in ILC is multifactorial. […] FOXA1, an ER transcription modulator, plays a key role in cancer progression and development of endocrine resistance. […] A higher rate of FOXA1 mutations was observed in ILC compared with IDC (7% vs. 2%). […] Thus, ILC is not only a unique histological subtype with specific clinical features but also exhibits complex molecular alterations that could be potentially targeted for improved clinical outcomes.

• #45 Invasive Lobular Carcinoma: Symptoms, Treatment, Research | BCRF

  https://www.bcrf.org/about-breast-cancer/invasive-lobular-carcinoma/

  A loss of CDH1 is the most prevalent gene alteration that distinguishes invasive lobular carcinoma from invasive ductal carcinoma. […] Loss of E-cadherin function is associated with increased tumor development, invasiveness, and metastasis (spreading to distant sites in the body). […] Invasive lobular carcinoma has generally been treated like HR-positive invasive ductal carcinoma, but there are marked differences in how the two types of invasive carcinoma respond to hormone therapies. […] Recent studies profiling lobular tumors suggest that some common genetic mutations cause a poorer response to hormone therapies and drive resistance. […] A more profound understanding of the biology that distinguishes this disease subtype is critical for improving lobular breast cancer treatment. […] Researchers are striving to increase participation of patients with lobular breast cancer in clinical trials as well as designing clinical trials specifically focused on this subtypeachieving these goals is critical to advancing our understanding of lobular breast cancer and moving treatments and disease management forward.

• #46

  https://link.springer.com/article/10.1007/s12609-021-00412-4

  Additionally, E-cadherin loss appears to result in activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway, irrespective of oncogenic mutations in PIK3CA. […] Somatic mutations in ILC differ from those in IDC, with increased prevalence of mutations in FOXA1, AKT1, PTEN, HER2, HER3, and FGFR4 seen in HR-positive, HER2-negative ILC compared to HR-positive, HER2-negative IDC. […] Recent data show that high expression of the bromodomain and extraterminal domain (BET) proteins BRD3/BRD4 are associated with worse outcomes in ILC and that resistance to BET inhibition may be driven by tyrosine kinases including fibroblast growth factor receptor (FGFR)-1. […] Indeed, FGFR-1 is thought to be necessary for tumor cell survival in the setting of endocrine resistance in ILC cell lines and is implicated in recurrent or metastatic ILC.

• #47 Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8176983/

  Long-term survival and clinical outcomes in patients with ILC are worse than in stage and grade matched patients with IDC; therefore, nuanced criteria are needed to better define treatment goals and protocols tailored to ILC’s unique biology. […] ILC also differs in response to systemic therapy, with studies showing ILC as less sensitive to chemotherapy. […] The classic subtype of ILC is composed of discohesive, small, round to ovoid cells with minimal cytoplasm and occasional cytoplasmic inclusions. […] Loss of membranous Ecadherin expression as detected by immunohistochemistry (IHC) is seen in 90% of cases, with concomitant loss of membranous p120 (increased cytoplasmic expression) and beta-catenin due to disruption of the Ecadherin complex. […] The morphology and immunophenotype of ILC is due to inactivation of the cell-cell adhesion molecule Ecadherin.

• #48 What is invasive lobular carcinoma? | MD Anderson Cancer Center

  https://www.mdanderson.org/cancerwise/What-is-invasive-lobular-carcinoma-8-insights-on-lobular-breast-cancer.h00-159539745.html

  Invasive lobular carcinoma is different from ductal carcinoma. […] One of the hallmarks of lobular breast cancer is that it loses its anchoring protein, Mouabbi says. The cancer cells dont link with surrounding cells so they grow in lines. […] Lobular breast cancer tends to spread to unusual sites, such as the lining of the gastrointestinal and urinary tracts. […] Individuals with a family member who has also been diagnosed with the disease are at a higher risk of the same diagnosis, Mouabbi says. […] Many patients with invasive lobular carcinoma receive the standard-of-care chemotherapy, but the comprehensive review showed there isnt much clinical benefit. […] There are other therapies for invasive lobular carcinoma, but theyre not widely used yet. […] We found that lobular breast cancers are universally driven by the CDH1 mutation, Mouabbi says. […] To define more personalized approaches, Mouabbi says its critical to conduct clinical trials specific to lobular breast cancer.

• #49

  https://link.springer.com/article/10.1007/s12609-021-00412-4

  Additionally, E-cadherin loss appears to result in activation of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/Akt signaling pathway, irrespective of oncogenic mutations in PIK3CA. […] Somatic mutations in ILC differ from those in IDC, with increased prevalence of mutations in FOXA1, AKT1, PTEN, HER2, HER3, and FGFR4 seen in HR-positive, HER2-negative ILC compared to HR-positive, HER2-negative IDC. […] Recent data show that high expression of the bromodomain and extraterminal domain (BET) proteins BRD3/BRD4 are associated with worse outcomes in ILC and that resistance to BET inhibition may be driven by tyrosine kinases including fibroblast growth factor receptor (FGFR)-1. […] Indeed, FGFR-1 is thought to be necessary for tumor cell survival in the setting of endocrine resistance in ILC cell lines and is implicated in recurrent or metastatic ILC.

• #50 Behind the Breakthroughs: Advancing Our Understanding of Invasive Lobular Breast Cancer | Breast Cancer Research Foundation

  https://www.bcrf.org/blog/invasive-lobular-breast-cancer-research-2021/

  There are clinical trials now running specifically for patients with ILC, which came out of benchwork that said, OK, there is this overexpression of genes X, Y, and Z, and we need to test this in a clinical trial. […] Metastasis in ILC is a very big topic for us. There are clearly unique features of the metastasis. It recurs later. And it goes to different sites in the body unusual sites, like the peritoneal metastasis that goes to the ovary. We dont understand it yet, but we hope that we can set up models and work with patient advocates. […] We do think there is a subset of patients with ILC whose tumors are immune infiltrated. And if not, can we try to get the immune cells into the tumor? We have an active program to try to see if there are specific biomarkers in ILC patients to determine whose tumors might actually respond to immunotherapy.

• #51 Invasive Lobular Carcinoma: Symptoms, Treatment, Research | BCRF

  https://www.bcrf.org/about-breast-cancer/invasive-lobular-carcinoma/

  We now know that lobular breast cancer tumors have enormous pathological and molecular diversity that affects how they form and respond to treatment. […] Progress in understanding the intricacies of the diseases biology has led researchers to develop new lobular carcinoma models for use in laboratory studies that subsequently inform new clinical trials. […] BCRF is at the forefront of lobular breast cancer research and continues to support work to: Investigate the drivers of lobular carcinoma development and growth.

• #52 What is invasive lobular carcinoma? | MD Anderson Cancer Center

  https://www.mdanderson.org/cancerwise/What-is-invasive-lobular-carcinoma-8-insights-on-lobular-breast-cancer.h00-159539745.html

  Invasive lobular carcinoma is different from ductal carcinoma. […] One of the hallmarks of lobular breast cancer is that it loses its anchoring protein, Mouabbi says. The cancer cells dont link with surrounding cells so they grow in lines. […] Lobular breast cancer tends to spread to unusual sites, such as the lining of the gastrointestinal and urinary tracts. […] Individuals with a family member who has also been diagnosed with the disease are at a higher risk of the same diagnosis, Mouabbi says. […] Many patients with invasive lobular carcinoma receive the standard-of-care chemotherapy, but the comprehensive review showed there isnt much clinical benefit. […] There are other therapies for invasive lobular carcinoma, but theyre not widely used yet. […] We found that lobular breast cancers are universally driven by the CDH1 mutation, Mouabbi says. […] To define more personalized approaches, Mouabbi says its critical to conduct clinical trials specific to lobular breast cancer.

• #53 Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8176983/

  Invasive lobular carcinoma (ILC) accounts for 10% to 15% of breast cancers in the United States, 80% of which are estrogen receptor (ER) positive, with an unusual metastatic pattern of spread to sites such as the serosa, meninges, and ovaries, among others. […] Despite the unique features of ILC, it is often lumped with hormone receptor positive invasive ductal cancers (IDC); consequently, ILC screening, treatment, and follow-up strategies are largely based on data from IDC. […] Despite both being treated as ER positive breast cancer, querying the Cancer Genome Atlas database shows distinctive molecular aberrations in ILC compared with IDC, such as Ecadherin loss (66% vs. 3%), FOXA1 mutations (7% vs. 2%), and GATA3 mutations (5% vs. 20%). […] Taken together, this suggests that ILC is biologically distinct, which may influence tumorigenesis and therapeutic strategies.

• #54 Invasive lobular carcinoma of the breast: morphology, biomarkers and ’omics | Breast Cancer Research | Full Text

  https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-015-0519-x

  Invasive lobular carcinoma of the breast is the most common special morphological subtype of breast cancer, comprising up to 15% of all cases. […] Despite this, clinicians face countless challenges in the diagnosis and long-term management of patients, as they encounter a tumour that can be difficult to detect through screening, elicits a very invasive nature, a propensity for widespread metastatic colonisation and, consequently, in some studies a worse long-term poor outcome compared with invasive carcinoma of no special type. […] E-cadherin loss is responsible for the inherently discohesive phenotype associated with ILCs, and changes at the genomic level account for this loss. […] The characteristic discohesive growth pattern of ILC is the result of the dysregulation of cell-cell adhesion properties, primarily driven by the targeted disruption of the cell adhesion molecule E-cadherin.

• #55

  https://link.springer.com/article/10.1007/s12609-021-00412-4

  Invasive lobular carcinoma (ILC) is increasingly recognized as a distinct subtype of breast cancer with unique management challenges. […] Molecular alterations specific to or enriched in ILC may serve as treatment targets. […] ILC has specific features that may be treatment targets. Clinical trials for ILC are available and being developed. […] The defining characteristic of ILC is the absence of the adhesion protein E-cadherin, which results in a number of unique characteristics including a diffuse growth pattern in so-called single file lines. […] The absence of functional E-cadherin in ILC results from alterations in the E-cadherin gene, CDH1. […] Nearly all ILC tumors lack E-cadherin expression, which results in a number of consequences including cytosolic translocation of the catenin p120, subsequent activation of the Rho/Rho-associated kinase 1 (ROCK) pathway, and anchorage independent growth in vitro.

• #56 Comprehensive Review of Molecular Mechanisms and Clinical Features of Invasive Lobular Cancer

  https://pmc.ncbi.nlm.nih.gov/articles/PMC8176983/

  Loss of Ecadherin in ILC is predominantly attributed to CDH1 mutation, which in 89% of cases occurred concurrently with heterozygous deletion in chromosome 16q. […] Analysis of invasive breast carcinoma cases in the Cancer Genome Atlas (TCGA) dataset revealed that 66% (107/162) of ILCs harbor mutation in CDH1 compared with only 3% (22/741) of IDCs. […] Loss of Ecadherin markedly increases cytoplasmic accumulation of p120 catenin, which plays a key role in tumor invasion. […] Patients with ILC are routinely treated with endocrine therapy, but one third of patients fail to respond to treatment and develop endocrine resistance in the long term. […] The underlying mechanism behind acquired endocrine resistance in ILC is multifactorial. […] FOXA1, an ER transcription modulator, plays a key role in cancer progression and development of endocrine resistance. […] A higher rate of FOXA1 mutations was observed in ILC compared with IDC (7% vs. 2%). […] Thus, ILC is not only a unique histological subtype with specific clinical features but also exhibits complex molecular alterations that could be potentially targeted for improved clinical outcomes.

• #57 Invasive Lobular Carcinoma: Symptoms, Treatment, Research | BCRF

  https://www.bcrf.org/about-breast-cancer/invasive-lobular-carcinoma/

  A loss of CDH1 is the most prevalent gene alteration that distinguishes invasive lobular carcinoma from invasive ductal carcinoma. […] Loss of E-cadherin function is associated with increased tumor development, invasiveness, and metastasis (spreading to distant sites in the body). […] Invasive lobular carcinoma has generally been treated like HR-positive invasive ductal carcinoma, but there are marked differences in how the two types of invasive carcinoma respond to hormone therapies. […] Recent studies profiling lobular tumors suggest that some common genetic mutations cause a poorer response to hormone therapies and drive resistance. […] A more profound understanding of the biology that distinguishes this disease subtype is critical for improving lobular breast cancer treatment. […] Researchers are striving to increase participation of patients with lobular breast cancer in clinical trials as well as designing clinical trials specifically focused on this subtypeachieving these goals is critical to advancing our understanding of lobular breast cancer and moving treatments and disease management forward.

• #58 Behind the Breakthroughs: Advancing Our Understanding of Invasive Lobular Breast Cancer | Breast Cancer Research Foundation

  https://www.bcrf.org/blog/invasive-lobular-breast-cancer-research-2021/

  Invasive lobular carcinoma (ILC) is the second most common form of invasive breast cancer accounting for 10 to 15 percent of invasive breast cancer diagnoses and affecting nearly 40,000 people each year it has unfortunately been understudied and misunderstood. […] ILC, also known as lobular breast cancer, originates in the milk-producing glands of the breast and presents differently than other invasive breast cancers, making it more difficult to detect by traditional screening and self-exam. Recent research has not only shown that ILC is its own distinct subtype of breast cancer, but also that it may not respond as well to standard treatments, recur later, and metastasize in unusual ways. […] It has become obvious now that there are many molecular and clinical features that are different between ductal and lobular cancer. We need to study it more to really understand them and find ways to personalize medicine for patients was ILC.

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