Immune landscape in ER+ breast cancer subtypes identifies a differential role for macrophages
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE193911 | GEO | 2023/01/29
REPOSITORIES: GEO
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Project description:Invasive lobular carcinoma (ILC) is the second most frequent histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for 5-15% of all breast cancers. Although clinical outcomes of ILC and IDC seem similar, the molecular processes underlying ILC are still largely unknown. To explore this, we have performed a comprehensive proteomics analysis of a large ILC patient cohort. These data are generated in the context of the RATHER consortium (http://www.ratherproject.com/)
2015-03-07 | GSE66647 | GEO
Project description:One-third of all ER+ breast tumors treated with endocrine therapy fail to respond, and the remainder are likely to relapse in the future. Almost all data on endocrine resistance has been obtained in models of invasive ductal carcinoma (IDC). However, invasive lobular carcinomas (ILC) comprise up to 15% of newly diagnosed invasive breast cancers diagnosed each year and, while the incidence of IDC has remained relatively constant during the last 20 years, the prevalence of ILC continues to increase among postmenopausal women. We report a new model of Tamoxifen (TAM)-resistant invasive lobular breast carcinoma cells that provides novel insights into the molecular mechanisms of endocrine resistance. SUM44 cells express ER and are sensitive to the growth inhibitory effects of antiestrogens. Selection for resistance to 4-hydroxytamoxifen led to the development of the SUM44/LCCTam cell line, which exhibits decreased expression of estrogen receptor alpha (ERα) and increased expression of the estrogen-related receptor gamma (ERRγ). Knockdown of ERRγ in SUM44/LCCTam cells by siRNA restores TAM sensitivity, and overexpression of ERRγ blocks the growth-inhibitory effects of TAM in SUM44 and MDA-MB-134 VI lobular breast cancer cells. ERRγ-driven transcription is also increased in SUM44/LCCTam, and inhibition of activator protein 1 (AP1) can restore or enhance TAM sensitivity. These data support a role for ERRγ/AP1 signaling in the development of TAM resistance, and suggest that expression of ERRγ may be a marker of poor Tamoxifen response.
2008-11-01 | GSE12708 | GEO
Project description:As part of the RATHER (RAtional THERapy for breast cancer: individualized treatment for difficult-to-treat breast cancer subtypes) consortium, expression profiling of 144 untreated primary invasive lobular carcinoma (ILC) breast cancer tissues and 15 ILC cell lines was performed using microarray. Gene expression profiling of 144 ILC breast cancers and 15 ILC cell lines
2016-01-05 | E-GEOD-68057 | biostudies-arrayexpress
Project description:Invasive lobular carcinoma (ILC) is a histological subtype of breast cancer with distinct molecular and clinical features from the more common subtype invasive ductal carcinoma (IDC). ILC cells exhibit anchorage-independent growth in ultra-low attachment (ULA) suspension cultures, which is largely attributed to the loss of E-cadherin. In addition to anoikis resistance, herein we show that human ILC cell lines exhibit enhanced cell proliferation in ULA cultures as compared to IDC cells. Proteomic comparison of ILC and IDC cell lines identified induction of PI3K/Akt and p90-RSK pathways specifically in ULA culture in ILC cells. Further 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 the anchorage-independent growth of ILC cell lines through cell cycle arrest. We find that ID1 and ID3 expression is higher in human ILC tumors as compared to IDC, correlated with worse prognosis uniquely in patients with ILC and associated with upregulation of angiogenesis and matrisome-related genes. Altogether, our comprehensive study of anchorage independence in human ILC cell lines provides mechanistic insights and clinical implications for metastatic dissemination of ILC and implicates ID1 and ID3 as novel drivers and therapeutic targets for lobular breast cancer.
2020-06-23 | GSE130650 | GEO
Project description:Estrogen receptor-positive (ER+) invasive lobular breast cancer (ILC) comprises about ~15% of breast cancer. ILC’s unique genotypic (loss of wild type E-cadherin expression) and phenotypic (small individual round cancer cells that grow in discontinuous nests) are thought to contribute to a distinctive pattern of metastases to serosal membranes. Unlike invasive ductal carcinoma (IDC), ILC metastases often intercalate into the mesothelial layer of the peritoneum and other serosal surfaces. While ER activity is a known driver of ILC proliferation, very little is known about how additional nuclear receptors contribute to ILC’s distinctive biology. In ER+ IDC, we showed previously that glucocorticoid receptor (GR) activity inhibits pro-proliferative gene expression and cell proliferation. Here we examined ER+ ILC models and find that GR activation similarly reduces S-phase entry gene expression and ILC proliferation. While slowing tumor growth rate, our data also suggest that GR activation results in an enhanced metastatic phenotype through increasing integrin-encoding gene expression, extracellular matrix protein adhesion, and mesothelial cell clearance. Moreover, in an intraductal mouse mammary gland model of ILC, we found that GR expression is associated with increased metastases despite slowed primary mammary tumor growth. Taken together, our findings suggest GR-mediated gene expression may contribute to the unusual characteristics of ILC biology.
2023-09-04 | GSE241993 | GEO
Project description:Estrogen receptor-positive (ER+) invasive lobular breast cancer (ILC) comprises about ~15% of breast cancer. ILC’s unique genotypic (loss of wild type E-cadherin expression) and phenotypic (small individual round cancer cells that grow in discontinuous nests) are thought to contribute to a distinctive pattern of metastases to serosal membranes. Unlike invasive ductal carcinoma (IDC), ILC metastases often intercalate into the mesothelial layer of the peritoneum and other serosal surfaces. While ER activity is a known driver of ILC proliferation, very little is known about how additional nuclear receptors contribute to ILC’s distinctive biology. In ER+ IDC, we showed previously that glucocorticoid receptor (GR) activity inhibits pro-proliferative gene expression and cell proliferation. Here we examined ER+ ILC models and find that GR activation similarly reduces S-phase entry gene expression and ILC proliferation. While slowing tumor growth rate, our data also suggest that GR activation results in an enhanced metastatic phenotype through increasing integrin-encoding gene expression, extracellular matrix protein adhesion, and mesothelial cell clearance. Moreover, in an intraductal mouse mammary gland model of ILC, we found that GR expression is associated with increased metastases despite slowed primary mammary tumor growth. Taken together, our findings suggest GR-mediated gene expression may contribute to the unusual characteristics of ILC biology.
2023-09-04 | GSE241992 | GEO
Project description:Invasive lobular breast cancer (ILC) is the second most common histological sub-type of breast cancer. Although the majority of ILC are strongly hormone receptor positive and are of low-intermediate grade, they present a number of clinical challenges. These challenges include limitations in physical exam and breast imaging for early detection, decreased response to chemotherapy and prospective evidence for differences in the benefit from specific adjuvant endocrine treatment regimens when compared to invasive ductal cancer (IDC). In addition to loss of e-cadherin, ILCs possess genetic alterations that are suggestive of a unique estrogen receptor(ER) axis, including an increase in the frequency of FOXA1 mutations and decrease in GATA3 truncating mutations. We performed a randomized Phase II clinical trial, Palbociclib and Endocrine therapy for Lobular breast cancer Preoperative Study (PELOP), in which patients were stratified by histological subtype and found that the magnitude of the difference between the benefit from letrozole compared tamoxifen is significantly higher in ILC versus IDC. To elucidate the mechanism underlying this divergent response we comprehensively studied the ER axis in experimental models of ILC and IDC and clinical samples and show that ILC harbors a unique ER transcriptional axis that stems from increased FOXA1 chromatin binding and an altered chromatin state. These findings provide insights to the unique pattern of response to endocrine treatment in ILC and mechanisms of resistance to endocrine treatment, and offer new treatment strategies to improve outcomes for patients with this breast cancer subtype."
2022-08-31 | GSE152366 | GEO
Project description:Invasive lobular breast cancer (ILC) is the second most common histological sub-type of breast cancer. Although the majority of ILC are strongly hormone receptor positive and are of low-intermediate grade, they present a number of clinical challenges. These challenges include limitations in physical exam and breast imaging for early detection, decreased response to chemotherapy and prospective evidence for differences in the benefit from specific adjuvant endocrine treatment regimens when compared to invasive ductal cancer (IDC). In addition to loss of e-cadherin, ILCs possess genetic alterations that are suggestive of a unique estrogen receptor(ER) axis, including an increase in the frequency of FOXA1 mutations and decrease in GATA3 truncating mutations. We performed a randomized Phase II clinical trial, Palbociclib and Endocrine therapy for LObular breast cancer Preoperative Study (PELOP), in which patients were stratified by histological subtype and found that the magnitude of the difference between the benefit from letrozole compared tamoxifen is significantly higher in ILC versus IDC. To elucidate the mechanism underlying this divergent response we comprehensively studied the ER axis in experimental models of ILC and IDC and clinical samples and show that ILC harbors a unique ER transcriptional axis that stems from increased FOXA1 chromatin binding and an altered chromatin state. These findings provide insights to the unique pattern of response to endocrine treatment in ILC and mechanisms of resistance to endocrine treatment, and offer new treatment strategies to improve outcomes for patients with this breast cancer subtype."
2022-08-31 | GSE152365 | GEO
Project description:Invasive lobular breast cancer (ILC) is the second most common histological sub-type of breast cancer. Although the majority of ILC are strongly hormone receptor positive and are of low-intermediate grade, they present a number of clinical challenges. These challenges include limitations in physical exam and breast imaging for early detection, decreased response to chemotherapy and prospective evidence for differences in the benefit from specific adjuvant endocrine treatment regimens when compared to invasive ductal cancer (IDC). In addition to loss of e-cadherin, ILCs possess genetic alterations that are suggestive of a unique estrogen receptor(ER) axis, including an increase in the frequency of FOXA1 mutations and decrease in GATA3 truncating mutations. We performed a randomized Phase II clinical trial, Palbociclib and Endocrine therapy for LObular breast cancer Preoperative Study (PELOP), in which patients were stratified by histological subtype and found that the magnitude of the difference between the benefit from letrozole compared tamoxifen is significantly higher in ILC versus IDC. To elucidate the mechanism underlying this divergent response we comprehensively studied the ER axis in experimental models of ILC and IDC and clinical samples and show that ILC harbors a unique ER transcriptional axis that stems from increased FOXA1 chromatin binding and an altered chromatin state. These findings provide insights to the unique pattern of response to endocrine treatment in ILC and mechanisms of resistance to endocrine treatment, and offer new treatment strategies to improve outcomes for patients with this breast cancer subtype."
2022-08-31 | GSE152364 | GEO
Project description:Invasive lobular breast cancer (ILC) is the second most common histological sub-type of breast cancer. Although the majority of ILC are strongly hormone receptor positive and are of low-intermediate grade, they present a number of clinical challenges. These challenges include limitations in physical exam and breast imaging for early detection, decreased response to chemotherapy and prospective evidence for differences in the benefit from specific adjuvant endocrine treatment regimens when compared to invasive ductal cancer (IDC). In addition to loss of e-cadherin, ILCs possess genetic alterations that are suggestive of a unique estrogen receptor(ER) axis, including an increase in the frequency of FOXA1 mutations and decrease in GATA3 truncating mutations. We performed a randomized Phase II clinical trial, Palbociclib and Endocrine therapy for LObular breast cancer Preoperative Study (PELOP), in which patients were stratified by histological subtype and found that the magnitude of the difference between the benefit from letrozole compared tamoxifen is significantly higher in ILC versus IDC. To elucidate the mechanism underlying this divergent response we comprehensively studied the ER axis in experimental models of ILC and IDC and clinical samples and show that ILC harbors a unique ER transcriptional axis that stems from increased FOXA1 chromatin binding and an altered chromatin state. These findings provide insights to the unique pattern of response to endocrine treatment in ILC and mechanisms of resistance to endocrine treatment, and offer new treatment strategies to improve outcomes for patients with this breast cancer subtype.
2022-08-31 | GSE152363 | GEO