scholarly journals Fibulin-2 expression associates with vascular invasion and patient survival in breast cancer

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249767
Author(s):  
Tor A. Klingen ◽  
Ying Chen ◽  
Hans Aas ◽  
Elisabeth Wik ◽  
Lars A. Akslen
Keyword(s):  
Breast Cancer ◽  
Vascular Invasion ◽  
Screening Program ◽  
Univariate Analysis ◽  
Basement Membranes ◽  
Blood Vessel Invasion ◽  
Elastic Fibers ◽  
Luminal Breast Cancer ◽  
Interval Cancers ◽  
Cancer Subtypes

Stromal elastosis is related to good prognosis in breast cancer and fibulin-2 helps to stabilize elastic fibers in basement membranes. Here, we examined the level of perivascular fibulin-2 expression in relation to elastosis content, vascular invasion, molecular subtypes, tumour detection mode, and patient prognosis in breast cancer. We performed a population based retrospective study of invasive breast cancers from the Norwegian Breast Screening Program (Vestfold County, 2004–2009) including 200 screen-detected and 82 interval cancers. Perivascular fibulin-2 staining was semi-quantitatively graded based on immunohistochemistry (1–3) and dichotomized as high expression (grade 2–3) and low expression (grade 1). Elastosis content was graded on a 4-tiered scale and dichotomized as high (score 3) and low (score 0–2) expression, whereas lymphatic (LVI) and blood vessel invasion (BVI) were recorded as absent or present by immunohistochemistry. High perivascular fibulin-2 expression was strongly related to stromal elastosis (p<0.001), and inversely associated with BVI and LVI (p<0.001 for both). High fibulin-2 was associated with luminal breast cancer subgroups (p<0.001) and inversely with interval cancers compared with screen-detected tumours (p<0.001). By univariate analysis, low perivascular fibulin-2 was associated with reduced recurrence-free survival (p = 0.002) and disease specific survival (p = 0.019). Low perivascular fibulin-2 expression was strongly related to vascular invasion, low stromal elastosis, non-luminal breast cancer subtypes, interval presentation, and adverse prognosis.

Tumour cell invasion into blood vessels is significantly related to breast cancer subtypes and decreased survival

2016 ◽  
Vol 70 (4) ◽  
pp. 313-319 ◽  
Author(s):  
Tor A Klingen ◽  
Ying Chen ◽  
Ingunn M Stefansson ◽  
Gøril Knutsvik ◽  
Karin Collett ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Screening Program ◽  
Interval Cancer ◽  
Population Based ◽  
Blood Vessel Invasion ◽  
Breast Cancers ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Increased Risk ◽  
Basic Features

AimsVascular invasion in breast cancer is associated with increased risk of recurrence, metastases and death from disease. However, there are few studies discriminating between blood vessel invasion (BVI) and lymphatic vessel involvement (LVI).MethodsA population-based series of 282 breast cancers was examined (200 screen-detected and 82 interval patients) with respect to BVI and LVI in addition to basic features and molecular subtypes, using CD31 and D2-40 antibodies. This series is part of the prospective Norwegian Breast Cancer Screening Program.ResultsThe frequency of LVI and BVI was 25% and 15%, respectively. BVI was associated with HER2-positive and basal-like tumours, and several features of aggressive breast cancer, whereas LVI showed weaker associations. BVI was the strongest factor to predict interval cancer presentation. BVI showed significant associations with recurrence-free survival and disease-specific survival in univariate and multivariate analyses, whereas LVI was not significant.ConclusionsOur findings indicate that BVI by tumour cells is strongly associated with aggressive tumour features including a basal-like phenotype, and BVI was an independent prognostic factor in contrast to what was found for LVI.

scholarly journals Genomic Signatures in Luminal Breast Cancer

Breast Care ◽  
2020 ◽  
Vol 15 (4) ◽  
pp. 355-365
Author(s):  
Julian Puppe ◽  
Tabea Seifert ◽  
Christian Eichler ◽  
Henryk Pilch ◽  
Peter Mallmann ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Throughput Sequencing ◽  
Early Stage ◽  
Intrinsic Subtype ◽  
Luminal Breast Cancer ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Cancer Subtypes ◽  
Molecular Tests ◽  
Immunohistochemical Markers

Background: Breast cancer is a very heterogeneous disease and luminal breast carcinomas represent the hormone receptor-positive tumors among all breast cancer subtypes. In this context, multigene signatures were developed to gain further prognostic and predictive information beyond clinical parameters and traditional immunohistochemical markers. Summary: For early breast cancer patients these molecular tools can guide clinicians to decide on the extension of endocrine therapy to avoid over- and undertreatment by adjuvant chemotherapy. Beside the predictive and prognostic value, a few genomic tests are also able to provide intrinsic subtype classification. In this review, we compare the most frequently used and commercially available molecular tests (OncotypeDX®, MammaPrint®, Prosigna®, EndoPredict®, and Breast Cancer IndexSM). Moreover, we discuss the clinical utility of molecular profiling for advanced breast cancer of the luminal subtype. Key Messages: Multigene assays can help to de-escalate systemic therapy in early-stage breast cancer. Only the Oncotype DX® and MammaPrint®test are validated by entirely prospective and randomized phase 3 trials. More clinical evidence is needed to support the use of genomic tests in node-positive disease. Recent developments in high-throughput sequencing technology will provide further insights to understand the heterogeneity of luminal breast cancers in early-stage and metastatic disease.

scholarly journals Tumorigenic and Metastatic Role of CD44−/low/CD24−/low Cells in Luminal Breast Cancer

Cancers ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1239 ◽  
Author(s):  
Rajeev Vikram ◽  
Wen Cheng Chou ◽  
Shih-Chieh Hung ◽  
Chen-Yang Shen
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Breast Cancer Subtypes ◽  
Diagnostic Tools ◽  
Breast Cancer Cell Lines ◽  
Luminal Breast Cancer ◽  
Cancer Subtypes ◽  
Tumorigenic Potential ◽  
Mcf 7

Cells with high CD44 but low CD24 expression (CD44high/CD24−/low) and high aldehyde dehydrogenase activity (ALDHbr) are widely considered to be drivers of metastasis, therapy resistance and tumor recurrence in breast cancer. However, the role of the CD44high/CD24−/low and ALDHbr phenotypes in identifying tumorigenic cells in breast cancer remains controversial due to the discrepancy in their distribution and tumorigenic potential in intrinsic breast cancer subtypes. In this study, we analyzed the cells expressing these markers in six different breast cancer cell lines representing major breast cancer subtypes (T47D, MCF-7, BT-474, AU-565, Hs578T and MDA-MB-231). CD44high/CD24−/low, ALDHbr and CD44−/low/CD24−/low cell populations were isolated by flow cytometry and analyzed for hallmark stem cell characteristics of differentiation, migration, invasiveness and metastasis using in vitro and in vivo techniques. Our results demonstrate that the CD44−/low/CD24−/low cell population, which is enriched in luminal cell lines (T47D, MCF-7 and BT-474), possesses metastatic and tumorigenic properties. We also show that, contrary to previous claims, the expression of the ALDH1 isoform ALDH1A1 does not affect the tumorigenic potential of cell lines with high ALDH activity (BT-474 and AU-565). Further transcriptomic and clinical studies are needed to determine the potential of these markers as early diagnostic tools and treatment targets.

Breast cancer subtype and screening sensitivity in the Quebec Mammography Screening Program

2018 ◽  
Vol 26 (3) ◽  
pp. 154-161
Author(s):  
Linda Perron ◽  
Sue-Ling Chang ◽  
Jean-Marc Daigle ◽  
Nathalie Vandal ◽  
Isabelle Theberge ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Mammography Screening ◽  
Triple Negative ◽  
Screening Program ◽  
Luminal A ◽  
Her2 Positive ◽  
Cancer Subtypes ◽  
Luminal B ◽  
Mammography Screening Program ◽  
Screening Sensitivity

Objective In mammography screening, interval cancers present a problem. The metric ‘screening sensitivity’ monitors both how well a programme detects cancers and avoids interval cancers. To our knowledge, the effect of breast cancer surrogate molecular subtypes on screening sensitivity has never been evaluated. We aimed to measure the 2-year screening sensitivity according to breast cancer subtypes. Methods We studied 734 women with an invasive breast cancer diagnosed between 2003 and 2007 after participating in one regional division of Quebec’s Mammography Screening Program. They represented 83% of all participating women with an invasive BC diagnosis in that region for that period. Tumours were categorized into ‘luminal A-like’, ‘luminal B-like’, ‘triple-negative’ and ‘HER2-positive’ subtypes. We used logistic regression and marginal standardization to estimate screening sensitivity, sensitivity ratios (SR) and sensitivity differences. We also assessed the mediating effect of grade. Results Adjusted 2-year screening sensitivity was 75.4% in luminal A-like, 66.1% in luminal B-like, 52.9% in triple-negative and 45.3% in HER2-positive, translating into sensitivity ratios of 0.88 (95% confidence interval [CI] = 0.78–0.98) for luminal B-like, 0.70 (CI = 0.56–0.88) for triple-negative and 0.60 (CI = 0.39–0.93) for HER2-positive, when compared with luminal A-like. Grade entirely mediated the subtype-sensitivity association for triple negative and mediated it partly for HER2-positive. Screening round (prevalent vs. incident) did not modify results. Conclusion There was substantial variation in screening sensitivity according to breast cancer subtypes. Aggressive phenotypes showed the lowest sensitivity, an effect that was mediated by grade. Tailoring screening according to women’s subtype risk factors might eventually lead to more efficient programs.

scholarly journals Parity, hormones and breast cancer subtypes - results from a large nested case-control study in a national screening program

2017 ◽  
Vol 19 (1) ◽  
Author(s):  
Merete Ellingjord-Dale ◽  
Linda Vos ◽  
Steinar Tretli ◽  
Solveig Hofvind ◽  
Isabel dos-Santos-Silva ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Case Control Study ◽  
Screening Program ◽  
Case Control ◽  
Breast Cancer Subtypes ◽  
Cancer Subtypes ◽  
Nested Case Control ◽  
Control Study

scholarly journals Distinguishing luminal breast cancer subtypes by Ki67, progesterone receptor or TP53 status provides prognostic information

2013 ◽  
Vol 27 (4) ◽  
pp. 554-561 ◽  
Author(s):  
Linda P Feeley ◽  
Anna M Mulligan ◽  
Dushanthi Pinnaduwage ◽  
Shelley B Bull ◽  
Irene L Andrulis
Keyword(s):  
Breast Cancer ◽  
Progesterone Receptor ◽  
Breast Cancer Subtypes ◽  
Luminal Breast Cancer ◽  
Prognostic Information ◽  
Cancer Subtypes ◽  
Tp53 Status

scholarly journals Stromal NRG1 in luminal breast cancer defines pro-fibrotic and migratory cancer-associated fibroblasts

Oncogene ◽  
2021 ◽  
Author(s):  
Mireia Berdiel-Acer ◽  
Ana Maia ◽  
Zhivka Hristova ◽  
Simone Borgoni ◽  
Martina Vetter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumour Progression ◽  
Phase 1 ◽  
Single Agent ◽  
Therapy Resistance ◽  
Luminal Breast Cancer ◽  
Cancer Associated Fibroblasts ◽  
Cancer Subtypes ◽  
Elevated Expression ◽  
Hyaluronan Synthase 2

AbstractHER3 is highly expressed in luminal breast cancer subtypes. Its activation by NRG1 promotes activation of AKT and ERK1/2, contributing to tumour progression and therapy resistance. HER3-targeting agents that block this activation, are currently under phase 1/2 clinical studies, and although they have shown favorable tolerability, their activity as a single agent has proven to be limited. Here we show that phosphorylation and activation of HER3 in luminal breast cancer cells occurs in a paracrine manner and is mediated by NRG1 expressed by cancer-associated fibroblasts (CAFs). Moreover, we uncover a HER3-independent NRG1 signaling in CAFs that results in the induction of a strong migratory and pro-fibrotic phenotype, describing a subtype of CAFs with elevated expression of NRG1 and an associated transcriptomic profile that determines their functional properties. Finally, we identified Hyaluronan Synthase 2 (HAS2), a targetable molecule strongly correlated with NRG1, as an attractive player supporting NRG1 signaling in CAFs.

scholarly journals Stromal NRG1 in luminal breast cancer defines pro-fibrotic and migratory cancer-associated fibroblasts

2020 ◽  
Author(s):  
Mireia Berdiel-Acer ◽  
Ana Maia ◽  
Zhivka Hristova ◽  
Simone Borgoni ◽  
Martina Vetter ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumour Progression ◽  
Phase 1 ◽  
Single Agent ◽  
Therapy Resistance ◽  
Luminal Breast Cancer ◽  
Cancer Associated Fibroblasts ◽  
Autocrine Signaling ◽  
Cancer Subtypes ◽  
Elevated Expression

AbstractHER3 is highly expressed in luminal breast cancer subtypes. Its activation by NRG1 promotes activation of AKT and ERK1/2, contributing to tumour progression and therapy resistance. HER3-targeting agents that block this activation, are currently under phase 1/2 clinical studies, and although they have shown favorable tolerability, their activity as a single agent has proven to be limited. Here we show that phosphorylation and activation of HER3 in luminal breast cancer cells occurs in a paracrine manner and is mediated by NRG1 expressed by cancer-associated fibroblasts (CAFs). Moreover, we uncover an autocrine role of NRG1 in CAFs. This occurs independently of HER3 and results in the induction of a strong migratory and pro-fibrotic phenotype, describing a subset of CAFs with elevated expression of NRG1 and an associated transcriptomic profile that determines their functional properties. Finally, we identified Hyaluronan Synthase 2 (HAS2), a targetable molecule strongly correlated with NRG1, as an attractive player supporting NRG1 - autocrine signaling in CAFs.

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