Lobular Breast Cancer

2017 ◽  
Author(s):  
Anita Mamtani ◽  
Tari A King

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer, with a unique pathogenesis and distinct clinical biology. These cancers display a characteristic loss of E-cadherin, and the vast majority are estrogen receptor positive (ER+), with a low-to-intermediate grade. These features generally portend a favorable prognosis, but there is a propensity for late recurrences and metastasis to atypical locations. These infiltrative tumors can be more clinically challenging than the more common ductal cancers. Their insidious nature can make them more difficult to diagnose, and they may show a differing response to standard therapies, keeping with the predominantly ER+ phenotype. Although ILC patients comprise a small minority in large breast cancer trials, most fundamentals of locoregional and systemic therapy presently remain shared between all cancer types. Recognizing the nuances of treating ILC remains important, and the recent discovery of novel mutations that are more frequently expressed in ILC holds promise for further investigations into lobular-specific targeted therapies. This review 3 figures, 8 tables and 50 references Key words: aromatase inhibitors, breast cancer, breast conservation, chemotherapy, E-cadherin, invasive lobular carcinoma, mastectomy, The Cancer Genome Analysis 

2017 ◽  
Author(s):  
Anita Mamtani ◽  
Tari A King

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer, with a unique pathogenesis and distinct clinical biology. These cancers display a characteristic loss of E-cadherin, and the vast majority are estrogen receptor positive (ER+), with a low-to-intermediate grade. These features generally portend a favorable prognosis, but there is a propensity for late recurrences and metastasis to atypical locations. These infiltrative tumors can be more clinically challenging than the more common ductal cancers. Their insidious nature can make them more difficult to diagnose, and they may show a differing response to standard therapies, keeping with the predominantly ER+ phenotype. Although ILC patients comprise a small minority in large breast cancer trials, most fundamentals of locoregional and systemic therapy presently remain shared between all cancer types. Recognizing the nuances of treating ILC remains important, and the recent discovery of novel mutations that are more frequently expressed in ILC holds promise for further investigations into lobular-specific targeted therapies. This review 3 figures, 8 tables and 50 references Key words: aromatase inhibitors, breast cancer, breast conservation, chemotherapy, E-cadherin, invasive lobular carcinoma, mastectomy, The Cancer Genome Analysis 


2019 ◽  
Author(s):  
Nilgun Tasdemir ◽  
Kai Ding ◽  
Kevin M. Levine ◽  
Tian Du ◽  
Emily A. Bossart ◽  
...  

AbstractBACKGROUNDInvasive lobular carcinoma (ILC) is a histological subtype of breast cancer with distinct molecular and clinical features from the more common subtype invasive lobular carcinoma (IDC). We have previously shown that human ILC cells lines have a remarkably unique ability to grow in ultra-low attachment (ULA) suspension cultures as compared to IDC cells, the mediators of which remain unknown.METHODSUsing flow cytometry and immunoblotting in human ILC and IDC cell lines, we measured levels of apoptosis and cell proliferation in attached (2D) and suspension (ULA) cultures. siRNA-mediated knockdown and pharmacological inhibitors were utilized to assess the effects of known regulators of anchorage-independence. Reverse Phase Protein Arrays and RNA-Sequencing were performed to identify novel proteomic and transcriptomic mediators of ULA growth in ILC cells.RESULTSWe show that human ILC cell lines exhibit enhanced anoikis resistance and cell proliferation in ULA cultures as compared to IDC cells. Transient restoration of E-cadherin did not impact the 2D or ULA growth of human ILC cell lines, while transient E-cadherin knockdown in IDC cells partially rescued their growth defect in ULA culture. Inhibition of the Rho/ROCK, p120-catenin or YAP/Hippo pathways previously implicated in anoikis resistance did not have a major effect on the ULA growth of ILC cells. Proteomic comparison of ILC and IDC cell lines identified unique induction of PI3K/Akt and p90-RSK pathways in ULA culture in ILC cells. Transcriptional profiling uncovered unique upregulation of the Inhibitors of Differentiation family transcription factors ID1 and ID3 in ILC ULA culture, the knockdown of which diminished anchorage-independent growth. We find that ID1 and ID3 expression is higher in human ILC tumors as compared to IDC and correlated with a worse disease-specific survival uniquely in the ILC cohort.CONCLUSIONOur comprehensive study of 2D and ULA growth in human ILC cell lines revealed anoikis resistance, cell proliferation and novel mediators of anchorage-independence and provides possible mechanistic insights and clinical implications for metastatic dissemination of ILC. High expression in human ILC tumors and association with clinical outcome implicate ID1 and ID3 as novel drivers and therapeutic targets for lobular breast cancer.


2018 ◽  
Author(s):  
Nilgun Tasdemir ◽  
Emily Bossart ◽  
Zheqi Li ◽  
Zhu Li ◽  
Kevin M. Levine ◽  
...  

AbstractInvasive lobular carcinoma (ILC) is the second most common subtype of breast cancer following invasive ductal carcinoma (IDC) and characterized by the loss of E-cadherin-mediated adherens junctions. Despite displaying unique histological and clinical features, ILC still remains a chronically understudied disease with limited knowledge on the available laboratory research models. To this end, herein we report a comprehensive 2D and 3D phenotypic characterization of four Estrogen Receptor-positive human ILC cell lines - MDA-MB-134, SUM44, MDA-MB-330 and BCK4. Compared to the IDC cell lines MCF7, T47D and MDA-MB-231, ultra-low attachment culture conditions revealed a remarkable anchorage-independence ability that was unique to the ILC cells, a feature not evident in soft agar gels. 3D Collagen I and Matrigel culture indicated a generally loose morphology for the ILC cell lines, which exhibited differing preferences for adhesion to ECM proteins in 2D. Furthermore, ILC cells had limited migration and invasion ability in wound-scratch and transwell assays with the exception of haptotaxis to Collagen I. Transcriptional comparison of the cell lines confirmed the decreased cell proliferation and E-cadherin-mediated intercellular junctions in ILC, while uncovering the induction of novel pathways related to cyclic nucleotide phosphodiesterase activity, ion channels, drug metabolism and alternative cell adhesion molecules such as N-cadherin, some of which were also differentially regulated in ILC versus IDC tumors. Altogether, these studies will serve as an invaluable resource for the breast cancer research community and facilitate further functional discoveries towards understanding ILC, identifying novel drug targets and ultimately improving the outcome of patients with ILC.Authors’ ContributionsConception and design:N. Tasdemir, NE. Davidson, S. OesterreichDevelopment of methodology:N. Tasdemir, L. Zhu, GC. Tseng, S. OesterreichAcquisition of data (performed experiments, processed data, etc.):N. Tasdemir, E. Bossart, Z. Li, Z. LiAnalysis and interpretation of data (e.g. biological interpretation, statistical analysis, computational analysis):N. Tasdemir, Z. Li, KM. Levine, NE. Davidson, S. OesterreichWriting, review and/or revision of the manuscript:N. Tasdemir, Z. Li, KM. Levine, BM. Jacobson, GC. Tseng, NE. Davidson, S. OesterreichStudy supervision:NE. Davidson and S. Oesterreich


Author(s):  
Anak Agung Ngurah Gunawan ◽  
I Wayan Supardi ◽  
S. Poniman ◽  
Bagus G. Dharmawan

<p>Medical imaging process has evolved since 1996 until now. The forming of Computer Aided Diagnostic (CAD) is very helpful to the radiologists to diagnose breast cancer. KNN method is a method to do classification toward the object based on the learning data which the range is nearest to the object. We analysed two types of cancers IDC dan ILC. 10 parameters were observed in 1-10 pixels distance in 145 IDC dan 7 ILC. We found that the Mean of Hm(yd,d) at 1-5 pixeis the only significant parameters that distingguish IDC and ILC. This parameter at 1-5 pixels should be applied in KNN method. This finding need to be tested in diffrerent areas before it will be applied in cancer diagnostic.</p>


2017 ◽  
Author(s):  
Anne Kuritzky ◽  
Laila Khazai ◽  
Roberto Diaz ◽  
Christine Laronga

The identification of an axillary metastasis in the absence of a primary breast cancer can pose a diagnostic and therapeutic dilemma. The clinician should first use more sensitive imaging modalities, such as breast magnetic resonance imaging, to attempt to find the primary index lesion. If the primary cancer remains occult and the molecular markers are consistent with a breast origin, then the recommended treatment includes multimodality therapy including surgery, chemotherapy/endocrine treatment, and radiation. Historically, the modified radical mastectomy was the standard of practice. Recently, in the era of improved adjuvant therapies, breast-conserving surgery with irradiation is also being considered. Multiple retrospective reviews have shown no difference in survival or recurrence with these two surgical pathways. However, due to the rare nature of this clinical presentation, no multiinstitutional or prospective clinical trial data are available.  Key words: axillary lymph node dissection, axillary metastasis, breast cancer, breast conservation, local recurrence, occult primary tumor, radiotherapy 


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