PTEN expression in Palestinian women with breast cancer, particularly in triple-negative subtype.

27 Background: According to data from the Palestinian Ministry of Health, breast cancer is the most common malignancy affecting Palestinian women, being 30% of all cancers affecting female patients, 60% of them present with metastasis, very few studies were conducted to explore characteristics of this cancer in this population. Triple-negative breast cancer (TNBC) has distinct clinical and pathologic features. The fact that this type is more aggressive despite lacking the expression of growth promotion receptors, suggest other players, as defect in tumor suppressors such as PTEN gene. To our knowledge this is the first study in English literature correlating TNBC to loss of PTEN protein expression. The aim of this study is to establish data about the clinicopathological characteristics of breast cancer in Palestinian women, and to study the status of PTEN protein expression by immunohistochemistry in breast cancer and specifically in TNBC. Methods: 100 confirmed cases of breast cancer, were collected from different pathology centers, clinicopathological data; age, grade, stage for each case were specified. Each case was evaluated for the expression of hormone receptors, Her-2 status, and for PTEN protein expression by immunohistochemistry (IHC) to see if a certain pattern is noted. Results: Out of the 100 cases, the mean age at presentation was 53.3 years, 69.84% of the cases presented with advanced stage and 53% were high grade, 58% were ER positive and 46% were PR positive. HER-2 positive breast cancer were 26%. 30% of all breast cancer cases were TNBC subtype. Loss of PTEN expression was seen in 44% of cases. 60% of TNBC cases lost PTEN expression, which was statistically significant (p + 0.035), no significant correlation between PTEN loss and ER, PR, HER-2, grade or stage. Conclusions: Palestinian women have high incidence of TNBC in comparison to White population, and presented with high grade, and advanced stage tumors. There is a significant correlation between PTEN loss and TNBC that needs more research and study.

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Comparing MicroRNA Profilings of Purified HER-2-Negative and HER-2-Positive Cells Validates miR-362-5p/Sema3A as Characteristic Molecular Change in Triple-Negative Breast Cancers

Disease Markers ◽

10.1155/2019/6057280 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12 ◽

Cited By ~ 1

Author(s):

Xiaoqing Zhang ◽

Qi He ◽

Leiqin Sun ◽

Yanfei Zhang ◽

Shengying Qin ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Real Time ◽

Differential Expression ◽

Real Time Pcr ◽

Therapeutic Target ◽

Triple Negative ◽

Quantitative Real Time Pcr ◽

Her 2 ◽

Tnbc Subtype

Background. HER-2 is a key molecule serving as the therapeutic target, prognostic biomarker, and classification marker in breast cancer. Accurate microRNA profilings had not been conducted in purified tumor cells of HER-2-negative and HER-2-positive tissue specimens obtained from breast cancer patients. Methods. (i) Differential expression microRNA discovery using laser capture microdissection- (LCM-) assisted specimen preparation and microRNA array chips on HER-2 overexpressing and triple-negative breast carcinoma (TNBC) subtype tissues, (ii) differential expression microRNA validation by quantitative real-time PCR, and (iii) independent validation on tissue microarray. Results. Five microRNAs (miR-20a-5p, miR-221-3p, miR-362-5p, miR-502-3p, and miR-222-3p) were screened and validated as upregulated microRNAs in TNBC cells comparing to HER-2 overexpressing cells using a microRNA array (5 cases in each group) and quantitative real-time PCR (20 cases in each group). The expression difference of miR-362-5p had the most significant statistical significance (p=0.0016) among the five microRNAs. The expression of miR-362-5p and its target gene Sema3A was further analyzed using in situ hybridization (ISH) and immunohistochemistry on standard tissue sections (n=150). 70.8% of HER-2-negative cells showed moderate expression of miR-362-5p whereas 20.4% HER-2-negative cells correlated with strong expression of miR-362-5p (p<0.0001). The proportion of patients with moderate/strong miR-362-5p expression in luminal, HER-2 overexpressing, and TNBC subtypes were 53.2%, 22.2%, and 74.3%, respectively (p=0.0002). High miR-362-5p expressers had shorter overall survival in the univariate analysis (p=0.046). There was a significant negative correlation between miR-362-5p and Sema3A expression (p<0.0001). The patients with negative/weak Sema3A protein expression had poorer prognosis than those with moderate (HR: 3.723, p=0.021) or strong (HR: 3.966, p=0.013) Sema3A protein expression in the multivariate analysis. Conclusions. miR-362-5p/Sema3A might provide a promising therapeutic pathway and represents a candidate therapeutic target of the TNBC subtype.

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Metabotropic glutamate receptor 1 is associated with unfavorable prognosis in ER-negative and triple-negative breast cancer

Scientific Reports ◽

10.1038/s41598-020-79248-4 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Anna E. M. Bastiaansen ◽

A. Mieke Timmermans ◽

Marcel Smid ◽

Carolien H. M. van Deurzen ◽

Esther S. P. Hulsenboom ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Glutamate Receptor ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Metabotropic Glutamate Receptor ◽

Metabotropic Glutamate ◽

Metabotropic Glutamate Receptor 1 ◽

Novel Target ◽

Cancer Tissues

AbstractNew therapies are an urgent medical need in all breast cancer subgroups. Metabotropic glutamate receptor 1 (mGluR1) is suggested as a potential new molecular target. We examined the prevalence mGluR1 expression in different clinically relevant breast cancer subgroups and determined its association with prognosis. In this retrospective cohort, 394 consecutive primary breast cancer tissues were incorporated into a tissue microarray and immunohistochemically stained for mGluR1. The prevalence of mGluR1 protein expression in different breast cancer subgroups was evaluated and correlated with metastasis-free survival (MFS) and overall survival (OS). In total, 56% (n = 219) breast cancer tissues had mGluR1 expression. In estrogen receptor (ER)-negative tumors, 31% (n = 18/58) had mGluR1 expression that was significantly associated with MFS (HR 5.00, 95% CI 1.03–24.35, p = 0.046) in multivariate analysis, independently from other prognostic factors. Of the 44 triple-negative breast cancer (TNBC), 25% (n = 11) expressed mGluR1. mGluR1 expression in TNBC was significantly associated with shorter MFS (HR 8.60, 95% CI 1.06–20.39, p = 0.044) and with poor OS (HR 16.07, 95% CI 1.16–223.10, p = 0.039). In conclusion, mGluR1 is frequently expressed in breast cancer. In ER-negative breast cancer and in TNBC mGluR1 protein expression is an unfavorable prognostic marker. This study provides rationale to explore mGluR1 as a novel target for breast cancer treatment, especially for the more aggressive TNBC.

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Her-2/neu Gene Amplification and Protein Expression in Primary Male Breast Cancer

Breast Cancer Research and Treatment ◽

10.1023/b:brea.0000019953.92921.7e ◽

2004 ◽

Vol 84 (3) ◽

pp. 215-223 ◽

Cited By ~ 75

Author(s):

Christian Rudlowski ◽

Nicolaus Friedrichs ◽

Andree Faridi ◽

Lazlo Füzesi ◽

Roland Moll ◽

...

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Gene Amplification ◽

Male Breast Cancer ◽

Male Breast ◽

Her 2 ◽

Primary Male

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Loss of PTEN expression is associated with aggressive behavior and poor prognosis in Middle Eastern triple-negative breast cancer

Breast Cancer Research and Treatment ◽

10.1007/s10549-015-3430-3 ◽

2015 ◽

Vol 151 (3) ◽

pp. 541-553 ◽

Cited By ~ 25

Author(s):

Shaham Beg ◽

Abdul K. Siraj ◽

Sarita Prabhakaran ◽

Zeenath Jehan ◽

Dahish Ajarim ◽

...

Keyword(s):

Breast Cancer ◽

Aggressive Behavior ◽

Triple Negative Breast Cancer ◽

Poor Prognosis ◽

Triple Negative ◽

Middle Eastern ◽

Pten Expression

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Trial in progress: A phase 1, multicenter, open-label, dose-exploration and dose-expansion study evaluating the safety, tolerability, pharmacokinetics, and efficacy of AMG650 in subjects with advanced solid tumors.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.tps5600 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. TPS5600-TPS5600

Author(s):

Ramaswamy Govindan ◽

Amanda Rose Townsend ◽

Kathy D. Miller ◽

Inderjit Mehmi ◽

Yasutoshi Kuboki ◽

...

Keyword(s):

Breast Cancer ◽

Plasma Concentration ◽

Adverse Events ◽

Solid Tumors ◽

Triple Negative ◽

Phase 1 ◽

Locally Advanced ◽

Maximum Plasma ◽

High Grade ◽

Serous Ovarian Cancer

TPS5600 Background: KIF18A is a mitotic kinesin motor protein that regulates chromosome positioning during cell division and is overexpressed in a subset of human cancers. TP53 mutant unstable aneuploid cancer cells with chromosomal instability (CIN) features are dependent on KIF18A motor activity to prevent lethal multipolar cell division. Preclinical data demonstrate that treatment with AMG 650; an oral, first in class, selective small molecule inhibitor of KIF18A may be safe and tolerable. We are conducting a first-in-human phase 1 study with AMG 650 in adult subjects with locally advanced or metastatic solid tumors with TP53MUT, triple negative breast cancer (TNBC), high grade serous ovarian cancer (HGSOC) or serous like endometrial cancers and other solid tumors. Methods: In this phase 1, multicentric, dose escalation and dose expansion study we evaluate the safety and tolerability of AMG 650 monotherapy in patients with advanced/metastatic solid tumors (NCT04293094). The main objective is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) based on emerging safety, efficacy, and pharmacodynamics (PD) data prior to reaching the MTD. Key inclusion criteria include the presence of measurable disease and diagnosis of advanced/metastatic triple negative breast cancer (TNBC), high-grade serous ovarian cancer (HGSOC), serous-like endometrial cancer or other solid tumors with documented TP53 mutations. In the dose expansion phase, participants with locally advanced or metastatic TNBC or HGSOC will be treated with the preliminary RP2D identified from the dose exploration part of the study. Primary endpoints include the incidence of Dose Limiting Toxicities (DLTs),Treatment-Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), Treatment-related Adverse Events and the evaluation of the number of participants who experience a clinically significant change from baseline in vital signs, electrocardiogram and laboratory tests parameters. Secondary endpoints include Objective Response Rate, Duration of Response, Progression-free Survival, Clinical Benefit Rate, Time to Response, Time to Progression, Overall Survival (OS), Maximum Plasma Concentration (Cmax) of AMG 650, Time to Maximum Plasma Concentration (Tmax) of AMG 650 as well as Area Under the Plasma Concentration-time Curve (AUC) Over the Dosing Interval for AMG 650. Continuous monitoring of toxicity is conducted. The study began enrolling pts in March 2020 and is ongoing. For more information, please contact Amgen Medical Information: [email protected] Clinical trial information: NCT04293094.

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Reproductive and hormonal risk factors for postmenopausal luminal, HER-2-overexpressing, and triple-negative breast cancer

Cancer ◽

10.1002/cncr.23786 ◽

2008 ◽

Vol 113 (7) ◽

pp. 1521-1526 ◽

Cited By ~ 80

Author(s):

Amanda I. Phipps ◽

Kathleen E. Malone ◽

Peggy L. Porter ◽

Janet R. Daling ◽

Christopher I. Li

Keyword(s):

Breast Cancer ◽

Risk Factors ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Her 2

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Correlation Between HER-2 Gene Amplification or Protein Expression and Clinical Pathological Features of Breast Cancer

Cancer Biotherapy & Radiopharmaceuticals ◽

10.1089/cbr.2018.2576 ◽

2019 ◽

Vol 34 (1) ◽

pp. 42-46

Author(s):

Pengfei Shi ◽

Cheng Chen ◽

Yufeng Yao

Keyword(s):

Breast Cancer ◽

Protein Expression ◽

Gene Amplification ◽

Pathological Features ◽

Her 2

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How shall we treat locally advanced triple negative breast cancer?

F1000Research ◽

10.12688/f1000research.20509.2 ◽

2020 ◽

Vol 8 ◽

pp. 1649

Author(s):

Paulo Luz ◽

David Dias ◽

Ana Fortuna ◽

Luis Bretes ◽

Beatriz Gosalbez

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Locally Advanced ◽

Surrogate Marker ◽

Metastatic Breast ◽

Complete Response ◽

Number Of Patients ◽

Her 2 ◽

Near Future

Triple negative breast cancer (TNBC) has been shown to respond to neoadjuvant chemotherapy (NACT). It has been established that achieving pathological complete response (pCR) for certain aggressive subtypes of breast cancer, including HER-2 (over-expressed) and TNBC, provides an important surrogate marker for predicting long-term clinical response and survival outcomes. How to increase the number of patients that achieve pCR remains challenging. Platinum-based NACT seems to be part of the solution and capecitabine, an active drug in metastatic breast cancer, but not a standard one in earlier stages may have found its place in the adjuvant setting. In the near future immunotherapy can play a role in early TNBC

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Antiangiogenic therapy for breast cancer with triple negative phenotype

Modern Oncology ◽

10.26442/18151434.2021.1.200763 ◽

2021 ◽

Vol 23 (1) ◽

pp. 88-92

Author(s):

Inna P. Ganshina ◽

Kristina A. Ivanova ◽

Olga O. Gordeeva ◽

Aleksandr V. Arkhipov ◽

Liudmila G. Zhukova

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Malignant Tumors ◽

Antiangiogenic Therapy ◽

Treatment Strategies ◽

Her 2 ◽

Triple Negative Phenotype ◽

The Impact ◽

Negative Phenotype

Triple-negative breast cancer is 1024% of all cases of breast cancer and is characterized by the absence of estrogen, progesterone, and HER-2 receptors in the tumor. The therapy of this illness is a difficult clinical case. In contrast to hormone-positive and HER-2-positive phenotypes, in which we successfully use targeted drugs (antiestrogens and anti-HER-2 drugs), for triple-negative breast cancer we have not had such targets for a long time. Thus, despite the impressive results of immunotherapy of triple-negative breast cancer, there remains a fairly large group of patients with negative PD-L1 status, for whom it is necessary to develop other treatment strategies. One of the approaches in the treatment of malignant tumors includes not the impact on tumor cells, but the process of angiogenesis. Antiangiogenic drugs have positively proven themselves in the treatment of a large number of malignant tumors but are underestimated for breast cancer (including triple-negative phenotype). The use of bevacizumab in combinations with cytostatic drugs in breast cancer therapy (including triple-negative breast cancer) has been studied in a large number of clinical trials but was undeservedly forgotten in some countries due to the revoked FDA registration. This review presents the role of bevacizumab in the treatment of patients with triple-negative breast cancer and suggests the conditions when the administration of this drug is justified and leads to better results.

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