scholarly journals Claudin-Low Breast Cancer Inflammatory Signatures Support Polarization of M1-Like Macrophages with Protumoral Activity

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2248
Author(s):  
Mayra Cecilia Suárez-Arriaga ◽  
Alfonso Méndez-Tenorio ◽  
Vadim Pérez-Koldenkova ◽  
Ezequiel M. Fuentes-Pananá
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative ◽  
Tumor Subtype ◽  
Blood Monocytes ◽  
Adverse Clinical Outcome ◽  
M1 Macrophages ◽  
Peripheral Blood Monocytes ◽  
Gm Csf ◽  
Th1 Immune Response

We previously reported that triple-negative breast cancer (BRCA) cells overexpress the cytokines GM-CSF, G-CSF, MCP-1, and RANTES, and when monocytes were 3-D co-cultured with them, M1-like macrophages were generated with the ability to induce aggressive features in luminal BRCA cell lines. These include upregulation of mesenchymal and stemness markers and invasion. In this study, we stimulated peripheral blood monocytes with the four cytokines and confirmed their capacity to generate protumoral M1-like macrophages. Using the METABRIC BRCA database, we observed that GM-CSF, MCP-1, and RANTES are associated with triple-negative BRCA and reduced overall survival, particularly in patients under 55 years of age. We propose an extended M1-like macrophage proinflammatory signature connected with these three cytokines. We found that the extended M1-like macrophage signature coexists with monocyte/macrophage, Th1 immune response, and immunosuppressive signatures, and all are enriched in claudin-low BRCA samples, and correlate with reduced patient overall survival. Furthermore, we observed that all these signatures are also present in mesenchymal carcinomas of the colon (COAD) and bladder (BLCA). The claudin-low tumor subtype has an adverse clinical outcome and remains poorly understood. This study places M1 macrophages as potential protumoral drivers in already established cancers, and as potential contributors to claudin-low aggressiveness and poor prognosis.

scholarly journals Association between circulating tumor cells and peripheral blood monocytes in metastatic breast cancer

2019 ◽  
Vol 11 ◽  
pp. 175883591986606 ◽  
Author(s):  
Ugo De Giorgi ◽  
Michal Mego ◽  
Emanuela Scarpi ◽  
Antonio Giordano ◽  
Mario Giuliano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Metastatic Breast Cancer ◽  
Tumor Cells ◽  
Triple Negative ◽  
Metastatic Breast ◽  
Monocyte Count ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Lymphocyte Ratio

Background: We retrospectively evaluated the correlation between a baseline measurement of circulating tumor cells (CTCs) and inflammation-based scores in patients with metastatic breast cancer (MBC). Methods: The optimal value of inflammation-based scores as the neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR), monocyte–lymphocyte ratio (MLR) and systemic immune-inflammation index (SII) to predict survival was determined and compared with CTC <5 or ⩾5 per 7.5 ml of blood. Results: In the overall population of 516 women with MBC, CTCs correlated with peripheral blood monocytes ( p = 0.008) and neutrophils ( p = 0.038). In triple-negative tumors, CTCs correlated with monocyte count ( p = 0.009); in HER2+ tumors, CTCs correlated with neutrophil count ( p = 0.009), with a trend versus monocyte count ( p = 0.061), whereas no correlation was found in HER2– estrogen receptor-positive (ER+) tumors. In multivariate analysis only monocytes were associated with ⩾5 CTCs (OR = 2.72, 95% CI 1.09–6.80, p = 0.033). In multivariable analysis for predictors of overall survival, CTC (⩾5 versus <5), number of metastatic sites (>1 versus 1), tumor subtypes (triple-negative versus HER2– ER+ tumors) and MLR only remained significant. Conclusions: CTC and MLR are predictors of overall survival in MBC. CTC correlates with monocytes, in particular in triple-negative tumors.

scholarly journals Clinical, pathological, and PAM50 gene expression features of HER2-low breast cancer

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Francesco Schettini ◽  
Nuria Chic ◽  
Fara Brasó-Maristany ◽  
Laia Paré ◽  
Tomás Pascual ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Overall Survival ◽  
High Activity ◽  
Triple Negative ◽  
Her2 Expression ◽  
Drug Conjugates ◽  
Molecular Features ◽  
Biological Heterogeneity ◽  
Antibody Drug

AbstractNovel antibody-drug conjugates against HER2 are showing high activity in HER2-negative breast cancer (BC) with low HER2 expression (i.e., 1+ or 2+ and lack of ERBB2 amplification). However, the clinical and molecular features of HER2-low BC are yet to be elucidated. Here, we collected retrospective clinicopathological and PAM50 data from 3,689 patients with HER2-negative disease and made the following observations. First, the proportion of HER2-low was higher in HR-positive disease (65.4%) than triple-negative BC (TNBC, 36.6%). Second, within HR-positive disease, ERBB2 and luminal-related genes were more expressed in HER2-low than HER2 0. In contrast, no gene was found differentially expressed in TNBC according to HER2 expression. Third, within HER2-low, ERBB2 levels were higher in HR-positive disease than TNBC. Fourth, HER2-low was not associated with overall survival in HR-positive disease and TNBC. Finally, the reproducibility of HER2-low among pathologists was suboptimal. This study emphasizes the large biological heterogeneity of HER2-low BC, and the need to implement reproducible and sensitive assays to measure low HER2 expression.

Applicability of PD-L1 tests to tailor triple-negative breast cancer treatment in Brazil

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Kátia Ramos Moreira Leite ◽  
Carlos Henrique Barrios ◽  
Antônio Carlos Buzaid ◽  
Débora Gagliato ◽  
Helenice Gobbi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Median Overall Survival ◽  
Triple Negative ◽  
Breast Cancer Treatment ◽  
Main Text ◽  
Critical Questions ◽  
Online Panel ◽  
Active Interest

Abstract Background Triple-negative breast cancer (TNBC) is a heterogeneous disease that represents 10–20% of breast cancer cases. The prognosis for advanced TNBC is usually poor, with a median overall survival of approximately 18 months or less. Main text New targeted therapies such as anti-PD-L1 agents are emerging as an option to treat advanced TNBC. A panel of 6 national experts with an active interest in breast cancer convened online. Panel members had either clinical or pathology experience in breast cancer. The experts pre-defined critical questions in the management of PD-L1 in TNBC, and a literature review was performed for selected topics before the online meeting. Conclusion The experts led active discussions involving a multidisciplinary team comprising pathologists and clinical oncologists. The meeting served to discuss the most relevant issues. A total of 10 critical questions for PD-L1+ TNBC were debated and are presented in this review. This article discusses the current landscape for PD-L1 tests in TNBC in Brazil.

IL-4 down-regulates IL-2-, IL-3-, and GM-CSF-induced cytokine gene expression in peripheral blood monocytes

1994 ◽  
Vol 68 (6) ◽  
pp. 293-298 ◽  
Author(s):  
F. H. M. Cluitmans ◽  
B. H. J. Esendam ◽  
J. E. Landegent ◽  
R. Willemze ◽  
J. H. F. Falkenburg
Keyword(s):  
Gene Expression ◽  
Peripheral Blood ◽  
Cytokine Gene Expression ◽  
Cytokine Gene ◽  
Blood Monocytes ◽  
Peripheral Blood Monocytes ◽  
Gm Csf

scholarly journals Lipoplatin Treatment in Lung and Breast Cancer

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Manuela Fantini ◽  
Lorenzo Gianni ◽  
Carlotta Santelmo ◽  
Fabrizio Drudi ◽  
Cinzia Castellani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Cancer Patients ◽  
Triple Negative ◽  
Response Rate ◽  
Toxicity Profile ◽  
Phase 2 ◽  
Breast Cancer Patients ◽  
Phase 3 ◽  
Cisplatin Analogues

The introduction of cisplatin in cancer treatment represents an important achievement in the oncologic field. Many types of cancers are now treated with this drug, and in testicular cancer patients major results are reached. Since 1965, other compounds were disovered and among them carboplatin and oxaliplatin are the main Cisplatin analogues showing similar clinical efficacy with a safer toxicity profile. Lipoplatin is a new liposomal cisplatin formulation which seems to have these characteristics. Lipoplatin was shown to be effective in NSCLC both in phase 2 and phase 3 trials, with the same response rate of Cisplatin, a comparable overall survival but less toxicity. A new protocol aiming to elucidate the double capacity of Lipoplatin to act as a chemotherapeutic and angiogenetic agent in triple-negative breast cancer patients is upcoming.

Development of prognostic nomograms using institutional data for patients with triple-negative breast cancer

2021 ◽  
Author(s):  
Jie-Yu Zhou ◽  
Kang-Kang Lu ◽  
Wei-Da Fu ◽  
Hao Shi ◽  
Jun-Wei Gu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Predictive Accuracy ◽  
Area Under The Curve ◽  
Disease Free Survival ◽  
Discriminative Ability ◽  
Free Survival ◽  
Disease Free

Background: Triple-negative breast cancer (TNBC) is an aggressive disease. Nomograms can predict prognosis of patients with TNBC. Methods: A total of 745 eligible TNBC patients were recruited and randomly divided into training and validation groups. Endpoints were disease-free survival and overall survival. Concordance index, area under the curve and calibration curves were used to analyze the predictive accuracy and discriminative ability of nomograms. Results: Based on the training cohort, neutrophil-to-lymphocyte ratio, positive lymph nodes, tumor size and tumor-infiltrating lymphocytes were used to construct a nomogram for disease-free survival. In addition, age was added to the overall survival nomogram. Conclusion: The current study developed and validated well-calibrated nomograms for predicting disease-free survival and overall survival in patients with TNBC.

Surgery provides survival benefit over systemic therapy alone for stage IV triple negative breast cancer: A propensity matched analysis of the National Cancer Database.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e13054-e13054
Author(s):  
Lifen Cao ◽  
Jonathan T. Bliggenstorfer ◽  
Kavin Sugumar ◽  
Christopher W. Towe ◽  
Pamela Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Systemic Therapy ◽  
Survival Benefit ◽  
Triple Negative ◽  
Stage Iv ◽  
National Cancer Database ◽  
Propensity Matching ◽  
N Stage ◽  
Metastatic Sites

e13054 Background: Conflicting data exist regarding benefit of surgery of the primary site for stage IV breast cancer, in which systemic therapy is standard of care and patient characteristics may bias treatment decisions. Metastatic triple negative breast cancer (TNBC) is an aggressive subtype with limited therapy options and poor prognosis. Our aim was to assess whether surgery for the primary tumor in stage IV TNBC provides a survival advantage over systemic therapy alone. Methods: The National Cancer Database was queried for patients with de-novo stage IV TNBC who received systemic therapy alone or systemic therapy and surgery of the primary breast site 2004-2016. Patients receiving surgery for metastatic tumor sites or with incomplete follow up data were excluded. 1:1 propensity matching was performed for demographics, comorbidities, clinical T and N stage, and metastatic sites to minimize confounding factors. Survival outcomes were analyzed using a stratified log-rank test and Cox proportional hazard regression analysis. Results: Of 2989 patients, 782 (26.21%) underwent surgery plus systemic therapy and 2207 (73.84%) were treated with systemic therapy alone. The majority of all patients were aged 51-70 with low co-morbidity, and treated in metropolitan areas. Patients treated at academic facilities (OR = 0.67, p = 0.025), with multiple metastatic sites (OR = 0.59, p < 0.001), or advanced clinical N stage (OR = 0.55, p < 0.001) were less likely to undergo surgery. Of those who completed surgery, 58% had unilateral mastectomy, and 63% had axillary lymph node dissection. Propensity matching identified 507 ‘paired’ patients with similar characteristics in the surgery and systemic therapy alone groups. After multivariable adjustment, surgery was associated with superior overall survival compared with systemic therapy alone (HR 0.73, P < 0.001). Older age (HR = 1.47, p < 0.001), greater comorbidity (HR = 1.28, p < 0.001) and multiple metastatic sites (HR = 1.53, p < 0.001) significantly decreased overall survival in the matched cohort. Median survival was shortest in the systemic therapy alone group (12.8 months, 95% CI 11.3-14.5) and longest in those undergoing systemic therapy plus simple mastectomy (18 months, 95% CI 14.3-21.2), though approximately 4 months of median survival was added for all patients undergoing any surgery vs. systemic therapy alone (p = 0.0001). Conclusions: In stage IV TNBC, surgical resection of the primary tumor site in addition to systemic therapy may provide a survival benefit in selected patients. Though in this retrospective study the sequence of treatment was unknown, surgery could be considered for low disease burden as in other malignancies with oligometastatic disease. Additional research is needed to determine if these findings persist in prospective studies and for other hormone-receptor subtypes.

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