scholarly journals Basal-Like Phenotype in a Breast Carcinoma Case Series from Sudan: Prevalence and Clinical/Pathological Correlations

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Khalid Dafaallah Awadelkarim ◽  
Carmelo Arizzi ◽  
Elgizouli Omer Musa Elamin ◽  
Hussein M. A. Hamad ◽  
Pasquale De Blasio ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Case Series ◽  
Hierarchical Cluster ◽  
Breast Cancers ◽  
Central Sudan ◽  
Younger Age ◽  
Basal Like Breast Cancer ◽  
Her 2 ◽  
Aggressive Subtype

Basal-like breast cancer, an aggressive subtype associated with high grade, poor prognosis, and younger age, is reported frequently in Africa. We analyzed the expression of the basal cytokeratins (CKs) 5/6 and 17 in a case series from Central Sudan and investigated correlations among basal CK status, ER, PgR, and Her-2/neu, and individual/clinicopathological data. Of 113 primary breast cancers 26 (23%), 38 (34%), and 46 (41%) were, respectively, positive for CK5/6, CK17, and combined basal CKs (CK5/6 and/or CK17). Combined basal CK+ status was associated with higher grade (P<.03) and inversely correlated with ER (P<.002), PgR (P=.004) and combined ER and/or PgR (P<.0002). Two clusters based on all tested markers were generated by hierarchical cluster analysis and k-mean clustering: I: designated ``hormone receptors positive/luminal-like’’ and II: designated ``hormone receptors negative’’, including both basal-like and Her-2/neu+ tumors. The most important factors for dataset variance were ER status, followed by PgR, CK17, and CK5/6 statuses. Overall basal CKs were expressed in a fraction of cases comparable to that reported for East and West African case series. Lack of associations with age and tumor size may represent a special feature of basal-like breast cancer in Sudan.

Basal-Like Breast Cancer: A Critical Review

2008 ◽  
Vol 26 (15) ◽  
pp. 2568-2581 ◽  
Author(s):  
Emad A. Rakha ◽  
Jorge S. Reis-Filho ◽  
Ian O. Ellis
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Treatment Strategies ◽  
Myoepithelial Cells ◽  
Therapeutic Implications ◽  
Basal Like Breast Cancer ◽  
Her 2 ◽  
Triple Negative Phenotype ◽  
Definition Of ◽  
Aggressive Subtype

Recent gene expression profiling of breast cancer has identified specific subtypes with clinical, biologic, and therapeutic implications. The basal-like group of tumors is characterized by an expression signature similar to that of the basal/myoepithelial cells of the breast and is reported to have transcriptomic characteristics similar to those of tumors arising in BRCA1 germline mutation carriers. They are associated with aggressive behavior and poor prognosis, and typically do not express hormone receptors or HER-2 (“triple-negative” phenotype). Therefore, patients with basal-like cancers are unlikely to benefit from currently available targeted systemic therapy. Although basal-like tumors are characterized by distinctive morphologic, genetic, immunophenotypic, and clinical features, neither an accepted consensus on routine clinical identification and definition of this aggressive subtype of breast cancer nor a way of systematically classifying this complex group of tumors has been described. Different definitions are, therefore, likely to produce variable and contradictory results that may hamper consistent identification and development of treatment strategies for these tumors. In this review, we discuss definition, heterogeneity, morphologic spectrum, relation to BRCA1, and clinical significance of this important class of breast cancer.

scholarly journals HER-2/neu overexpression in invasive ductal breast cancer: An association with other prognostic and predictive factors

2007 ◽  
Vol 15 (1-2) ◽  
pp. 15-18 ◽  
Author(s):  
Tatjana Ivkovic-Kapicl ◽  
Slavica Knezevic-Usaj ◽  
Milana Panjkovic ◽  
Dragana Ðilas-Ivanovic ◽  
Mileta Golubovic
Keyword(s):  
Breast Cancer ◽  
Hormone Receptors ◽  
Histological Grade ◽  
Lymph Node Status ◽  
Breast Cancers ◽  
Protein Overexpression ◽  
Large Tumor ◽  
Invasive Ductal Breast Cancer ◽  
Ductal Breast Cancer ◽  
Her 2

Background: HER-2/neu is a proto-oncogene that is amplified/overexpressed in 15 to 30% of invasive breast cancers. The purpose of this study was to determine if any relationship exist between HER-2/neu protein overexpression and estrogen receptor (ER), progesterone receptor (PR), grade, size, and lymph node status in female breast cancer. Methods: A total of 100 cases of invasive ductal breast cancer were included in this study. The hormone receptors and HER-2/neu were studied immunohistochemically (IHC). Using the HER-2/neu DAKO scoring system, scores of 0, 1+ and 2+ were defined as negative and 3+ as positive. Results: HER-2/neu protein overexpression was seen in 20 (20%) of cases. HER-2/neu protein overexpression was present in 4 of 52 T1 lesions (8%), in 11 of 37 T2 lesions (30%), in 3 of 6 T3 lesions (50%), and in 2 of 5 T4 lesions (40%), (p<0.05). Protein overexpression was seen in 7 of 17 grade III tumors (41%), and 13 of 61 grade II tumors (21%). Overexpression was not detected in grade I tumors (p<0.01). Of the 20 Her-2/neu positive cases, ER- and PR-negative status was detected in 60% and 70%, respectively. Conclusion: Statistically significant correlation was found between HER-2/neu protein overexpression and large tumor size, high histological grade, and ER-, PR-negativity. There was no correlation with lymphonodal status.

Clinical significance of extranuclear expression of hormone receptors in breast cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 644-644
Author(s):  
R. Kim ◽  
M. Kaneko ◽  
K. Arihiro ◽  
M. Emi ◽  
K. Tanabe ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Signaling Pathways ◽  
Clinical Significance ◽  
Cross Talk ◽  
Hormone Receptors ◽  
Growth Factor Signaling ◽  
Breast Cancers ◽  
Er Positive ◽  
Her 2 ◽  
Positive Breast Cancer

644 Background: Hormone receptor (HR)-positive breast cancer cells grow through estrogen receptor (ER)-signaling pathways that mediate both genomic and nongenomic actions, which cross-talk with growth factors associated with resistance to tamoxifen. The aim of this study is to explore the clinical significance of extranuclear expression of ER and PR in the cross-talk between HR and growth factor signaling pathways. Methods: We examined the extranuclear expression of ER and PR in 219 primary breast cancers by immunohistochemical staining. Specimens showing such expression were further examined for the expression of pAkt and aromatase. Due to heterogeneity, staining was scored on the basis of intensity and distribution in the tumors. Results: Extranuclear expression of ER or PR was observed in 21 cases (9.5%), which included 4 cases (19.0%) for ER and 20 cases (95.2%) for PR. Among these patients, HER-2, pAkt, and aromatase-positivity were observed in 14 cases (66.6%), 13 cases (61.9%), and 14 cases (66.6%), respectively. On the basis of nuclear HR expression, 11 of these cases were categorized as ER-positive/PR-negative, while 2 were ER-negative/PR-positive. Of those 13 cases, increased pAkt staining was found in 11 cases (84.6%). In particular, among the 11 ER-positive/PR-negative, elevated pAkt and aromatase were found in 10 (90.9%; p<0.01) and 9 cases (81.8%), respectively. Conclusion: PR is more frequently expressed extranuclearly than ER in primary breast cancer, and extranuclear HRs cross-talk with the Akt/HER-2-signaling pathway and activation of aromatase, providing an explanation for the observation that aromatase inhibitors are more beneficial than tamoxifen for ER-positive/PR-negative patients. No significant financial relationships to disclose.

scholarly journals Association between ultrasound findings, tumor type, grade, and biological markers in patients with breast cancer

2019 ◽  
Vol 50 (1) ◽  
Author(s):  
Yasmine Mohamed Elsaeid ◽  
Dina Elmetwally ◽  
Salwa Mohamed Eteba
Keyword(s):  
Breast Cancer ◽  
Biological Markers ◽  
Tumor Grade ◽  
The State ◽  
Tumor Type ◽  
Breast Cancers ◽  
Duct Carcinoma ◽  
Ultrasound Findings ◽  
Her 2 ◽  
And Biological Markers

Abstract Background This prospective study included 65 female patients with primary breast cancer. Ultrasound was performed for all patients. Ultrasound findings were analyzed according to the ACR BI-RADS lexicon 5th edition and correlated with tumor type, grade, and biological markers (ER, PR, HER-2/neu, and Ki67). The purpose of this study is to assess the association between ultrasound findings, tumor type, grade, and the state of biological markers in patients with breast cancer. Results Irregular shape and speculated margins are more frequently associated with invasive duct carcinoma than DCIS (p value < 0.001). There were no association between the ultrasound findings (shape, margin, orientation, echopattern, and posterior features) and the tumor grade (p value 1.0, 0, 0.544, 1.0, and 1.0), respectively. Irregular shape is more frequently seen in ER and PR positive breast cancers (p value = 0.036 and 0.026, respectively). Non-circumscribed margins were frequently seen in PR positive breast cancers (p value = 0.068). No statistically significant difference between US descriptors and HER-2/neu-positive cases. Conclusion Irregularly shaped tumors with speculated margins are frequently seen in invasive duct carcinoma and also more frequently seen in ER-, PR-, and Ki67-positive cases. No relation between ultrasound descriptors and the tumor grade of invasive duct carcinoma. Also, there were no relation between ultrasound descriptors and the state of HER-2/neu.

scholarly journals CBP/p300: Critical Co-Activators for Nuclear Steroid Hormone Receptors and Emerging Therapeutic Targets in Prostate and Breast Cancers

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2872
Author(s):  
Aaron R. Waddell ◽  
Haojie Huang ◽  
Daiqing Liao
Keyword(s):  
Breast Cancer ◽  
Prostate Cancer ◽  
Tumor Growth ◽  
Signaling Pathways ◽  
Cell Cycle Progression ◽  
Hormone Receptors ◽  
Steroid Hormone Receptors ◽  
Breast Cancers ◽  
Creb Binding Protein ◽  
Breast And Prostate Cancer

The CREB-binding protein (CBP) and p300 are two paralogous lysine acetyltransferases (KATs) that were discovered in the 1980s–1990s. Since their discovery, CBP/p300 have emerged as important regulatory proteins due to their ability to acetylate histone and non-histone proteins to modulate transcription. Work in the last 20 years has firmly established CBP/p300 as critical regulators for nuclear hormone signaling pathways, which drive tumor growth in several cancer types. Indeed, CBP/p300 are critical co-activators for the androgen receptor (AR) and estrogen receptor (ER) signaling in prostate and breast cancer, respectively. The AR and ER are stimulated by sex hormones and function as transcription factors to regulate genes involved in cell cycle progression, metabolism, and other cellular functions that contribute to oncogenesis. Recent structural studies of the AR/p300 and ER/p300 complexes have provided critical insights into the mechanism by which p300 interacts with and activates AR- and ER-mediated transcription. Breast and prostate cancer rank the first and forth respectively in cancer diagnoses worldwide and effective treatments are urgently needed. Recent efforts have identified specific and potent CBP/p300 inhibitors that target the acetyltransferase activity and the acetytllysine-binding bromodomain (BD) of CBP/p300. These compounds inhibit AR signaling and tumor growth in prostate cancer. CBP/p300 inhibitors may also be applicable for treating breast and other hormone-dependent cancers. Here we provide an in-depth account of the critical roles of CBP/p300 in regulating the AR and ER signaling pathways and discuss the potential of CBP/p300 inhibitors for treating prostate and breast cancer.

scholarly journals The Roles of DNA Demethylases in Triple-Negative Breast Cancer

2021 ◽  
Vol 14 (7) ◽  
pp. 628
Author(s):  
Shoghag Panjarian ◽  
Jean-Pierre J. Issa
Keyword(s):  
Breast Cancer ◽  
Dna Methylation ◽  
Tumor Suppressor Genes ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Breast Cancers ◽  
Therapeutic Implications ◽  
High Propensity ◽  
Dna Methylation Profile

Triple-negative breast cancers (TNBCs) are very heterogenous, molecularly diverse, and are characterized by a high propensity to relapse or metastasize. Clinically, TNBC remains a diagnosis of exclusion by the lack of hormone receptors (Estrogen Receptor (ER) and Progesterone Receptor (PR)) as well as the absence of overexpression and/or amplification of HER2. DNA methylation plays an important role in breast cancer carcinogenesis and TNBCs have a distinct DNA methylation profile characterized by marked hypomethylation and lower gains of methylations compared to all other subtypes. DNA methylation is regulated by the balance of DNA methylases (DNMTs) and DNA demethylases (TETs). Here, we review the roles of TETs as context-dependent tumor-suppressor genes and/or oncogenes in solid tumors, and we discuss the current understandings of the oncogenic role of TET1 and its therapeutic implications in TNBCs.

The Pattern of Proline, Glutamic Acid, and Leucine-Rich Protein 1 Expression in Chinese Women with Primary Breast Cancer

2014 ◽  
Vol 29 (1) ◽  
pp. e1-e7 ◽  
Author(s):  
Yanzhi Zhang ◽  
Peng Wang ◽  
Mumu Shi ◽  
Hironobu Sasano ◽  
Monica S.M. Chan ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Glutamic Acid ◽  
Primary Breast Cancer ◽  
Chinese Women ◽  
Cancer Prognosis ◽  
Clinicopathological Parameters ◽  
Breast Cancers ◽  
Breast Cancer Patients ◽  
Ki 67 ◽  
Her 2

Background Disparities of biomarkers’ expression in breast cancer across different races and ethnicities have been well documented. Proline, glutamic acid, and leucine-rich protein 1 (PELP1), a novel ER coregulator, has been considered as a promising biomarker of breast cancer prognosis; however, the pattern of PELP1 expression in Chinese women with breast cancer has never been investigated. This study aims to provide useful reference on possible racial or ethnic differences of PELP1 expression in breast cancer by exploring the pattern of PELP1 expression in Chinese women with primary breast cancer. Methods The expression of PELP1 in primary breast cancer samples from 130 Chinese female patients was detected by immunohistochemistry and correlated to other clinicopathological parameters; for comparison, the expression of PELP1 in 26 benign breast fibroadenomas was also examined. Results The overall value of the PELP1 H-score in breast cancer was significantly higher than that in breast fibroadenoma (p<0.001). In our breast cancer patients, the ER/HER-2-positive group had significantly higher PELP1 H-scores than their negative counterparts (p=0.003 for ER and p=0.022 for HER-2); the Ki-67-high group also showed significantly higher PELP1 H-scores than the Ki-67-low group (p=0.008). No significant association between PELP1 H-scores and other clinicopathological parameters was found. Finally, the PELP1 H-score in breast cancers of the luminal B subtype was significantly higher than that in the triple negative subtype (p=0.002). Conclusion Overexpression of PELP1 in Chinese women with primary breast cancer appears to be associated with biomarkers of poor outcome; these results are similar to other reports based on Western populations.

Short Preoperative Treatment With Erlotinib Inhibits Tumor Cell Proliferation in Hormone Receptor–Positive Breast Cancers

2008 ◽  
Vol 26 (6) ◽  
pp. 897-906 ◽  
Author(s):  
Marta Guix ◽  
Nara de Matos Granja ◽  
Ingrid Meszoely ◽  
Theresa B. Adkins ◽  
Bobbye M. Wieman ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Proliferation ◽  
Tumor Cell ◽  
Growth Factor Receptor ◽  
Preoperative Treatment ◽  
Breast Cancers ◽  
Tumor Cell Proliferation ◽  
Hormone Receptor Positive ◽  
Er Positive ◽  
Her 2

Purpose To administer the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor erlotinib to patients with operable untreated breast cancer during the immediate preoperative period and to measure an antiproliferative and/or a proapoptotic effect in the post-therapy specimen and determine a biomarker profile associated with evidence of erlotinib-mediated cellular activity. Patients and Methods Newly diagnosed patients with stages I to IIIA invasive breast cancer were treated with erlotinib 150 mg/d orally for 6 to 14 days until the day before surgery. Erlotinib plasma levels were measured by tandem mass spectrometry the day of surgery. Drug-induced changes in tumor cell proliferation and apoptosis were assessed by Ki67 immunohistochemistry and terminal deoxynucleotidyl transferase–mediated deoxyuridine triphosphate-biotin nick-end labeling analysis, respectively, in biopsies from the pretherapy and surgical specimens. Biopsies were also evaluated for P-EGFR, P-HER-2, P-MAPK, P-Akt, P-S6, and S118 P-ERα. Results In drug-sensitive PC9 xenografts, 5 days of treatment with erlotinib were enough to induce a maximal inhibition of cell proliferation and induction of apoptosis. Forty-one patients completed preoperative treatment with erlotinib. Grade ≤ 2 rash and diarrhea were the main toxicities. Erlotinib inhibited tumor cell proliferation (Ki67), P-EGFR, and P-HER-2. The inhibition of proliferation occurred in estrogen receptor (ER) –positive but not in human epidermal growth factor receptor 2 (HER-2) –positive or triple-negative cancers. Treatment was associated with a significant reduction of P-MAPK, P-Akt, P-S6, and S118 P-ERα in hormone receptor–positive cancers. Conclusion A presurgical approach to evaluate cellular responses to new drugs is feasible in breast cancer. EGFR inhibitors are worthy of testing against ER-positive breast cancers but are unlikely to have clinical activity against HER-2–positive or triple-negative breast cancers.

HER-2-Amplified Breast Cancer

2018 ◽  
Author(s):  
Zahraa Al-Hilli ◽  
Judy C Boughey
Keyword(s):  
Breast Cancer ◽  
Treatment Options ◽  
Growth Factor Receptor ◽  
Standard Of Care ◽  
Breast Cancers ◽  
Aggressive Disease ◽  
Node Positive Disease ◽  
Her 2 ◽  
Epidermal Growth ◽  
Positive Breast Cancer

Amplification of the human epidermal growth factor receptor–2 (HER-2) gene is found in approximately 15 to 30% of breast cancers. Historically, HER-2 overexpression has been associated with aggressive disease and a poor prognosis. However, the use of targeted anti-HER2 therapy has revolutionized the treatment of HER-2-positive disease, and the use of the monoclonal antibody trastuzumab in combination with chemotherapy is now standard of care for tumors greater than 1 cm in size and in node-positive disease. More recently, the value of dual-agent anti-HER-2 therapy has been demonstrated in large clinical trials. This review provides an overview of HER-2-positive breast cancer, its molecular basis, methods of identification, and treatment options and strategies. This review contains 2 figures and 70 references Key words: anti-HER-2 therapy, breast cancer, HER-2-positive breast cancer, HER-2 resistance, lapatinib, neoadjuvant chemotherapy, pertuzumab, small HER-2-positive breast cancer, trastuzumab

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