scholarly journals ID1 and ID4 Are Biomarkers of Tumor Aggressiveness and Poor Outcome in Immunophenotypes of Breast Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 492
Author(s):  
Marta Garcia-Escolano ◽  
Yoel G. Montoyo-Pujol ◽  
Fernando Ortiz-Martinez ◽  
Jose J. Ponce ◽  
Silvia Delgado-Garcia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Histological Grade ◽  
Tumor Development ◽  
Tumor Aggressiveness ◽  
Id Proteins ◽  
Id Genes ◽  
Grade 3 ◽  
New Treatments ◽  
Worse Prognosis

Inhibitor of differentiation (ID) proteins are a family of transcription factors that contribute to maintaining proliferation during embryogenesis as they avoid cell differentiation. Afterward, their expression is mainly silenced, but their reactivation and contribution to tumor development have been suggested. In breast cancer (BC), the overexpression of ID1 has been previously described. However, whether the remaining ID genes have a specific role in this neoplasia is still unclear. We studied the mRNA expression of all ID genes by q RT-PCR in BC cell lines and 307 breast carcinomas, including all BC subtypes. Our results showed that ID genes are highly expressed in all cell lines tested. However, ID4 presented higher expression in BC cell lines compared to a healthy breast epithelium cell line. In accordance, ID1 and ID4 were predominantly overexpressed in Triple-Negative and HER2-enriched samples. Moreover, high levels of both genes were associated with larger tumor size, histological grade 3, necrosis and vascular invasion, and poorer patients’ outcomes. In conclusion, ID1 and ID4 may act as biomarkers of tumor aggressiveness and worse prognosis in breast cancer, and they could be used as potential targets for new treatments discover.

Correlation, comparison, and combined analysis of Ki-67 and histological grade for early luminal breast cancer.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 585-585 ◽  
Author(s):  
Yoichi Naito ◽  
Satoshi Fujii ◽  
Kuniaki Itoh ◽  
Masahiko Nezu ◽  
Nobuaki Matsubara ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Histological Grade ◽  
Luminal Breast Cancer ◽  
Prognostic Impact ◽  
Ki 67 ◽  
Combined Analysis ◽  
Combination Methods ◽  
Grade 3 ◽  
Worse Prognosis

585 Background: Both Ki-67 and histological grade are established prognostic factors in patients with early breast cancer. Recent international expert consensus employs Ki-67 to classify luminal breast cancer, and histological grade is described as an alternative. We investigated the prognostic value of Ki-67, histological grade, and their combination. Methods: Patients with early breast cancer treated with surgery between January 2000 and December 2008 were retrospectively reviewed. Inclusion criteria were as follows: estrogen receptor positive, HER2 negative, available for Ki-67 and histological grade. Clinicopathological data were retrieved from medical records. Ki-67 labeling index was investigated using MIB-1 antibody and subdivided into three categories: low 0-9%; intermediate 10-19%; high >20%. Histological grade was scored between 1 and 3. Disease-free survival (DFS) was defined as time from surgery to the first documented disease recurrence or death. Ki-67 categories and histological grade were analyzed respectively and then concomitantly for prognostic impact on DFS. Results: A total of 606 patients were included. Median age was 58 and 28.1% were over 65 years. 65.4% were postmenopausal women. Progesterone receptor was positive in 84.0% of patients. 29.6% received neoadjuvant or adjuvant chemotherapy. Number of lymph node metastasis was 0 in 70.0%, 1-3 in 21.3%, and >4 in 8.7% of patients. Ki-67 categories and histological grade showed weak but significantly correlation (Spearman’s rho = 0.385, p<0.001). High Ki-67 and histological grade 3 were correlated with worse prognosis to the same extent (HR 2.518, p = 0.002 and HR 2.541, p = 0.048, respectively). For combined analysis, patients represented concomitant with high Ki-67 and histological grade 3 showed worse prognosis compared with those with Ki-67 low and histological grade 1 (HR 3.137, p = 0.021). Conclusions: Ki-67 and histological grade were significantly but weakly correlated. Combined use of these two factors could better predict recurrence of early luminal breast cancer.

scholarly journals Cancer Grade Model: a multi-gene machine learning-based risk classification for improving prognosis in breast cancer

2021 ◽  
Author(s):  
E. Amiri Souri ◽  
A. Chenoweth ◽  
A. Cheung ◽  
S. N. Karagiannis ◽  
S. Tsoka
Keyword(s):  
Breast Cancer ◽  
Machine Learning ◽  
Clinical Decision Making ◽  
Histological Grade ◽  
Tumour Size ◽  
Clinical Decision ◽  
Gene Signature ◽  
Risk Classification ◽  
Breast Cancers ◽  
Grade 3

Abstract Background Prognostic stratification of breast cancers remains a challenge to improve clinical decision making. We employ machine learning on breast cancer transcriptomics from multiple studies to link the expression of specific genes to histological grade and classify tumours into a more or less aggressive prognostic type. Materials and methods Microarray data of 5031 untreated breast tumours spanning 33 published datasets and corresponding clinical data were integrated. A machine learning model based on gradient boosted trees was trained on histological grade-1 and grade-3 samples. The resulting predictive model (Cancer Grade Model, CGM) was applied on samples of grade-2 and unknown-grade (3029) for prognostic risk classification. Results A 70-gene signature for assessing clinical risk was identified and was shown to be 90% accurate when tested on known histological-grade samples. The predictive framework was validated through survival analysis and showed robust prognostic performance. CGM was cross-referenced with existing genomic tests and demonstrated the competitive predictive power of tumour risk. Conclusions CGM is able to classify tumours into better-defined prognostic categories without employing information on tumour size, stage, or subgroups. The model offers means to improve prognosis and support the clinical decision and precision treatments, thereby potentially contributing to preventing underdiagnosis of high-risk tumours and minimising over-treatment of low-risk disease.

scholarly journals Melatonin regulates tumor aggressiveness under acidosis condition in breast cancer cell lines

2018 ◽  
Author(s):  
Nath�lia Sonehara ◽  
J�ssica Lacerda ◽  
Bruna Jardim‑Perassi ◽  
Rubens de Paula ◽  
Marina Moschetta‑Pinheiro ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines ◽  
Tumor Aggressiveness

Final Results of ECOG1100: A phase I/II study of combined blockade of the ErbB receptor network in patients with HER2- overexpressing metastatic breast cancer (MBC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1033-1033 ◽  
Author(s):  
S. L. Moulder ◽  
A. O’Neill ◽  
C. Arteaga ◽  
M. Pins ◽  
J. Sparano ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase I ◽  
Cell Lines ◽  
Dose Level ◽  
Phase Ii ◽  
Prior Exposure ◽  
Prior Chemotherapy ◽  
Group 2 ◽  
Grade 3 ◽  
Group 1

1033 Background: Activation of EGF receptor has been associated with resistance to trastuzumab in breast cancer cell lines. EGFR tyrosine kinase inhibitors inhibit HER2 phosphorylation and synergize with trastuzumab in HER2+ cell lines that co-express EGFR. Methods: Pts with MBC and HER2 overexpression by immunohistochemistry (3+) and/or HER2 gene-amplification by FISH, 0–2 prior chemotherapy regimens for met disease, LVEF 50%, and no prior trastuzumab were treated with trastuzumab 2 mg/kg/wk and gefitinib 250- 500 mg/day until disease progression, unacceptable toxicity or withdrawal of consent. The phase I portion of the trial used a 3+3 design to determine MTD. In the phase II portion of the trial, patients were stratified based upon prior chemotherapy exposure (Group 1= no prior exposure to chemotherapy, Group 2= prior exposure to 1–2 chemotherapy regimens). Response measured using RECIST criteria. The primary endpoint was to increase proportion progression free from 50 to 65% at 6 months in Group 1 and from 50 to 70% at 3 months in Group 2. Results: Phase I: DLT (Grade 3 diarrhea) occurred in 2/3 patients treated at the 500 mg/day dose level of gefitinib in combination with weekly trastuzumab. 0/3 patients treated at the 250 mg/day dose level experienced DLT. This was considered MTD and was the dose selected for the Phase II portion of the trial. Phase II: 36 eligible pts were enrolled. Most patients were ECOG PS of 0 and had visceral organ involvement. Of the patients enrolled in Group 1, one pt achieved a CR, one PR and 7 had SD (≥ 24 weeks). Median time to progression (TTP) was 2.9 months (95% CI, 2.5–4). In Group 2 no responses were observed with a median TTP of 2.5 months (95% CI, 1.5- 2.7). Most common severe toxicities were rash (grade 3, 14%) and diarrhea (grade 3, 30%). No grade 3 cardiac toxicity was encountered. Conclusions: Trastuzumab in combination with gefitinib at doses of 250 mg/day demonstrated an acceptable toxicity profile; however, during planned interim analysis, the TTP did not meet predetermined statistical endpoints required for study continuation. These results do not support the further use of this combination and have implications for other trials using trastuzumab and EGFR TK inhibitors simultaneously. [Table: see text]

scholarly journals Circulating Low Density Neutrophils of Breast Cancer Patients are Associated with their Worse Prognosis due to the Impairment of T cell Responses

2021 ◽  
Author(s):  
Diana P. Saraiva ◽  
Bruna F. Correia ◽  
Rute Salvador ◽  
Nídia de Sousa ◽  
António Jacinto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Ex Vivo ◽  
Tumor Development ◽  
Poor Response ◽  
Response To Treatment ◽  
Low Density ◽  
Breast Cancer Patients ◽  
Activation Markers ◽  
Healthy Donors ◽  
Worse Prognosis

AbstractNeutrophils are prominent immune components of solid tumors, which can protect against the onset of cancer (N1) or have pro-tumor activity (N2). Circulating neutrophils, divided into high density neutrophils (HDN) and low density neutrophils (LDN), functionally mirror those N1 and N2 cells, respectively. LDN, a rare subset in non-pathological conditions, have been extensively studied in cancer, due to their frequency in this disease and their pro-tumor phenotype. However, this has been mainly demonstrated in animal models and proper validation in humans is an urgent need. Here, we further enlighten the clinical impact of LDN in a cohort of breast cancer (BC) patients. We observed that LDN were practically absent in healthy donors’ blood, while were significantly increased in the blood of BC patients, particularly with metastatic disease. Relevant for a clinical translation, within the population of non-metastatic patients, LDN were more prevalent in patients with poor response to neoadjuvant chemotherapy than in responders. The association of a higher incidence of circulating LDN and the worse prognosis of BC patients could be explained by the pro-tumor/immunosuppressive characteristics exhibited by these cells. Namely, there are more LDN expressing the immunosuppressive marker PD-L1, than HDN. Additionally, LDN also showed increased expression of activation markers; a robust formation of neutrophil extracellular traps; an augmented phagocytic activity; and a higher capacity to release reactive oxygen species, which may contribute for tumor development and metastization. Moreover, the percentage of LDN in BC patients’ blood was negatively correlated with activated cytotoxic T lymphocytes and positively correlated with the immunosuppressive CCR4+ regulatory T cells, corroborating their impairment on the anti-tumor immune responses, which was further demonstrated ex vivo. Hence, this study reveals the potential of LDN as a clinical meaningful biomarker of BC response to treatment and opens new avenues for developing targeted immunotherapies.

scholarly journals Validation of immunophenotyping by flow cytometry in the investigation of diagnostic and prognostic markers for breast cancer

Mastology ◽  
2020 ◽  
Vol 30 (Suppl 1) ◽  
Author(s):  
Daniella Serafin Couto Vieira ◽  
Sandro Wopereis ◽  
Laura Otto Walter ◽  
Maria Claudia Santos da Silva
Keyword(s):  
Breast Cancer ◽  
Flow Cytometry ◽  
Predictive Value ◽  
Morphological Analysis ◽  
Prognostic Markers ◽  
Molecular Subtype ◽  
Histological Grade ◽  
Tumor Development ◽  
Progesterone Receptors ◽  
The Individual

Introduction: Given its high prevalence, breast cancer has a great financial impact on health systems. Currently, the diagnosis is made by morphological analysis and immunohistochemistry (IHC). However, this methodology has some limitations. Therefore, new methods should be developed to assist those in use, based on the fast and safe detection of tumor cells. Objective: To validate immunophenotyping by flow cytometry (FC) in the investigation of diagnostic and prognostic markers for breast cancer and study lymphocyte subtypes infiltrating the tumor and their relationship with tumor development. Method: A total of 52 samples of breast tumors were sectioned, macerated in phosphate-buffered saline, stained with antibodies against estradiol receptors (ER), progesterone receptors (PR), HER2, Ki67, CD3, CD4, CD8, and CD45, and analyzed by FC. All results were compared with IHC (standard method) as to sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), except for Ki67, whose analysis involved a comparison of bias between the methods and correlation between lymphocyte subtypes and tumor characteristics. Results: The comparison between FC and IHC for each marker presented the ER analysis (sensitivity: 75%, specificity: 90%, PPV: 96.7%, NPV: 47.4%); PR analysis (sensitivity: 72%, specificity: 70%, PPV: 79.3%, NPV: 60.8%); HER2 analysis (sensitivity: 80%, specificity: 90.2%, PPV: 66.7%, NPV: 94.9%). The FC Ki67 analysis proved to be equivalent to that of IHC, with the advantage of not having observational bias. No correlations were identified between the profile of the population of intratumoral lymphocytes and the molecular subtype or the histological grade of the tumor. Conclusion: The results show the ability of FC in safely and promptly detecting breast cancer markers used in clinical practice. The use of FC, together with morphological analysis and IHC, might overcome the individual limitations of each methodology, efficiently providing reliable and rapid results, which would lead to faster diagnosis and more accurate prognosis, directly benefiting the patients.

scholarly journals Impact of clinical-pathological factors on locoregional recurrence in mastectomy patients with T1-2N1 breast cancer: who can omit adjuvant radiotherapy?

2021 ◽  
Author(s):  
Xiaofang Wang ◽  
Li Zhang ◽  
Xiaomeng Zhang ◽  
Jurui Luo ◽  
Xuanyi Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Risk Factors ◽  
Tumor Size ◽  
Cox Regression ◽  
Histological Grade ◽  
Disease Free Survival ◽  
Axillary Lymph Nodes ◽  
Axillary Lymph ◽  
Entire Cohort ◽  
Grade 3

Abstract Purpose Postmastectomy radiation therapy (PMRT) in T1–T2 tumors with 1–3 positive axillary lymph nodes (ALNs) is controversial. This study was to identify prognostic factors of locoregional control (LRC) following mastectomy with or without PMRT for patients with T1-2N1 breast cancer and to discuss the selection of patients who might omit PMRT. Materials and methods Between January 2006 and December 2012, the data of 1474 postmastectomy patients staged pT1-2N1 were analyzed. PMRT was applied in 663 patients. LRC and disease-free survival (DFS) were calculated using the Kaplan–Meier method. Cox regression model was applied in the univariate and multivariate analyses to recognize the recurrence risk factors. Results With the median follow-up duration of 93 months (range, 5–168 months), 78 patients (5.3%) failed to secure LRC and 220 patients (14.9%) experienced any recurrence. The 7.7-year LRC and DFS was 94.9% and 85.4% respectively in the entire cohort. PMRT significantly improved 7.7-year LRC from 93.4% to 96.6% (p = 0.005), but not the DFS (p = 0.335). Multivariate analysis revealed that PMRT was an independent prognostic factor of LRC (p < 0.001), meanwhile, age ≤ 40 years (p = 0.012), histological grade 3 (p = 0.004), 2–3 positive nodes (p < 0.001) and tumor size of 3–5 cm (p = 0.045) were significantly associated with decreased LRC. The 7.7-year LRC for patients with 0, 1, and 2–4 risk factors was 97.7% / 98.9% (p = 0.233), 95.3% / 98.0% (p = 0.092), and 80.3% / 94.8% (p < 0.001) in the non-PMRT and PMRT group, respectively. Conclusions In patients with T1-2N1 breast cancer, clinical-pathological factors including young age, histological grade 3, 2–3 positive nodes, and tumor size of 3–5 cm were identified to be predictors of a poorer LRC following mastectomy. Patients with 0–1 risk factor might consider the omission of PMRT.

Evaluation of clinicopathological features from core needle biopsy and CT imaging as predictors of response to primary systemic therapy for operable breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 11086-11086
Author(s):  
T. Shien ◽  
S. Akashi-Tanaka ◽  
C. Shimizu ◽  
T. Hojo ◽  
K. Seki ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Multivariate Analysis ◽  
Systemic Therapy ◽  
Histological Grade ◽  
Breast Conserving Surgery ◽  
Clinicopathological Features ◽  
Tumor Type ◽  
Primary Systemic Therapy ◽  
Grade 3

11086 Background: Primary systemic therapy (PST) is standard therapy for patients with locally advanced breast cancer and increasingly used for early-stage operable disease. Clinical and pathologic responses are important prognostic parameters and clinicopathological markers to predict response to PST are needed to individualize treatment. Methods: From 1998 to 2005, 403 primary breast cancer patients were underwent curative surgical treatment after PST (Anthlacycline and/or Taxane) at NCCH. We retrospectively evaluated the clinicopathological features (age, histological type, histological grade, ER, PgR and HER-2) and classification of tumors using CT (localized tumor type and diffused tumor type) at before PST and analyzed the correlation with clinical response and pathological complete response (pCR). The log-rank statistic was used for univariate comparisons and multivariate analysis performed using Cox hazard model. Results: Overall response and pCR rate were 87% and 18%. Breast conserving surgery was performed 37% patients. Histological grade 3 (p<0.0001), ER negative (p<0.0001), PgR negative (p<0.0001), solid-tubular type (p=0.0006), age (>50) (p=0.008) and localized tumor type (p=0.02) correlated with pCR. In multivariate analysis, Histological grade 3 (p=0.01) and localized tumor type (p=0.036) were independent predictors for pCR. ER positive, histological grade 2 or 1, invasive lobular carcinoma and diffuse tumor type associated with low chemosensitivity and low breast conserving surgery rate. Conclusions: Clinical and pathological response significantly associated with ER status and histological grade. Furthermore the classification of tumor type using CT was effective to predict of response to PST. No significant financial relationships to disclose.

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