scholarly journals Preclinical Evaluation of 18F-Labeled Anti-HER2 Nanobody Conjugates for Imaging HER2 Receptor Expression by Immuno-PET

2016 ◽  
Vol 57 (6) ◽  
pp. 967-973 ◽  
Author(s):  
G. Vaidyanathan ◽  
D. McDougald ◽  
J. Choi ◽  
E. Koumarianou ◽  
D. Weitzel ◽  
...  
Keyword(s):  
Receptor Expression ◽  
Her2 Receptor ◽  
Preclinical Evaluation

Molecular profiling of triple-negative endometrial cancers (TNEC) and triple-negative breast cancers (TNBC) to reveal unique expression profiles.

2015 ◽  
Vol 33 (28_suppl) ◽  
pp. 159-159
Author(s):  
Nathaniel L. Jones ◽  
Joanne Xiu ◽  
Sandeep K. Reddy ◽  
Jason Dennis Wright ◽  
William M. Burke ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Endometrial Cancer ◽  
Protein Expression ◽  
Triple Negative ◽  
Expression Profiles ◽  
Receptor Expression ◽  
Mutation Rates ◽  
Breast Cancers ◽  
Her2 Receptor ◽  
Molecular Features

159 Background: “Triple negative” has been used to characterize a subtype of breast cancer that lacks estrogen, progesterone, and HER2 receptor expression. They are aggressive cancers with limited treatment options. It’s unknown if similar phenotype found in other cancer types, like endometrial cancer, harbor similar molecular alterations and prognosis. We aim to compare molecular features between TNEC and TNBC. Methods: A total of 3133 endometrial cancer samples were evaluated by Caris Life Sciences (Phoenix, AZ) from Mar, 2011 to Jul, 2014 by multiplatform profiling, which included a combination of sequencing (Sanger or NGS), protein expression (IHC), and/or gene amplification (CISH or FISH). 545 TNEC and 2049 TNBC were identified based on reported pathology and compared using Fisher exact tests. Results: Compared to an incidence of 15-20% TNBC in breast cancer, 17% (545/3133) TNEC was seen in our cohort, of which 13% were endometrioid, 22% serous, 26% carcinosarcoma, 7% clear cell, and 22% other. Compared with TNBC, TNEC showed 1.9 exonic mutations per case while TNBC showed 1.2 mutations per case. As shown in the table, AR expression is lower in TNEC than TNBC. TP53 mutation was common in both but more frequent in TNBC. While BRCA1/2 mutation rates were similar, low MGMT and ERCC1 were more common in TNEC, suggesting increased aberrant DNA repair. DNA synthesis protein expression was higher in TNEC including TS, RRM1, and TOPO2A, although TNBC had higher TOPO1. PD-1 expression was more common in TNEC suggesting immune pathway involvement. PI3K/AKT/mTor, MAPK and Wnt pathways were more involved in TNEC with greater PTEN, PIK3CA, FBXW7, KRAS and CTNNB1 mutations. Conclusions: Our study reveals significantly higher overall mutation rates in TNEC than TNBC, and specifically higher activations of multiple molecular pathways including PI3K/Akt/mTor, MAPK and Wnt. Further studies are warranted to validate these findings in clinical trials.

Biological behavior of HER2+ breast cancer: Differences based in hormone receptor expression.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e12120-e12120
Author(s):  
Maria Joao Ribeiro Da Silva ◽  
Miguel Henriques Abreu ◽  
Sergio Xavier Azevedo ◽  
Tiago Alpoim ◽  
Susana Sousa ◽  
...  
Keyword(s):  
Hormone Receptors ◽  
Disease Free Survival ◽  
Clinicopathological Characteristics ◽  
Receptor Expression ◽  
Biological Behavior ◽  
Her2 Receptor ◽  
Adjuvant Trastuzumab ◽  
Her2 Breast Cancer ◽  
The Impact

e12120 Background: Breast carcinoma is a heterogeneous disease whose therapeutic approach idepends on the classification into molecular subtypes. Despite the impact the expression of hormone receptors (HR) among patients with overexpression of HER2 is already the target of some studies, there is a lack of analysis in the era of treatment with adjuvant trastuzumab. Methods: This stydy consists in a retrospective analysis of cases of tumors with overexpression of the HER2 receptor (HER2 +), and HR- treated at an oncological center, comparing their biological behavior with cases of HR +/ HER2 + tumors, thus controlling for classic prognosis. Results: We analised a total of 420 patients, of whom 210 with HR+/HER2+ tumors and 210 HR- / HER2 +, with median ages of 52 years and 53 years, respectively. They accounted for 89.5% of cases of stage I to III disease. The groups were balanced in clinical characteristics. There was a higher proportion of undifferentiated and inflammatory tumors in the RH-/ HER2 + group, and in this group higher rates of complete pathological responses to treatment were observed (50.8% vs. 30.0%, p < 0.001). During the follow-up 30 recurrences occurred, 18 in the HR- / HER2 + group, and 12 in the HR + / HER2 +. There was lower disease-free survival in the HR-/HER2 +, on average 69.1 months, compared to 74.3 months in the group HR+/HER2 + (p = 0.001). The first metastatic site involved visceral location in 13 cases (72.2%) in HR- / HER2 + tumors (CNS involved in 8 cases), and in 8 cases (66.6%) in HR + / HER2 + tumors (CNS in 1 case). There was an association between relapse and response to primary systemic treatment (p = 0.003), with no relation demonstrated with other clinicopathological characteristics. In the global sample, there were 28 deaths, corresponding to 17 in the HR-/HER2 +, and 11 in the HR+/HER2 + group. There were significant diferences in OS, showing worse prognosis of HR- disease (mean of 70.7 months vs. 106.6 months, p = 0.001). There was an association of mortality with the presentation as an inflammatory tumor and involvement of the CNS. Conclusions: This study supports the concept of two distinct entities according to the expression in HER2 + disease, justifying therapeutic approaches and eventually different follow-up strategies.

scholarly journals Quantitative Analysis of HER2 Receptor Expression In Vivo by Near-Infrared Optical Imaging

2010 ◽  
Vol 9 (4) ◽  
pp. 7290.2010.00018 ◽  
Author(s):  
Victor Chernomordik ◽  
Moinuddin Hassan ◽  
Sang Bong Lee ◽  
Rafal Zielinski ◽  
Amir Gandjbakhche ◽  
...  
Keyword(s):  
Quantitative Analysis ◽  
Optical Imaging ◽  
Near Infrared ◽  
Receptor Expression ◽  
Her2 Receptor

scholarly journals Real-world data on discordance between estrogen, progesterone, and HER2 receptor expression on diagnostic tumor biopsy versus tumor resection material

2019 ◽  
Vol 175 (2) ◽  
pp. 451-458 ◽  
Author(s):  
A. M. Sofie Berghuis ◽  
Carolien H. M. van Deurzen ◽  
Hendrik Koffijberg ◽  
Leon W. M. M. Terstappen ◽  
Stefan Sleijfer ◽  
...  
Keyword(s):  
Real World ◽  
Tumor Resection ◽  
Receptor Expression ◽  
Her2 Receptor ◽  
Real World Data ◽  
Tumor Biopsy ◽  
World Data

scholarly journals Synthesis, Preclinical Validation, Dosimetry, and Toxicity of 68Ga-NOTA-Anti-HER2 Nanobodies for iPET Imaging of HER2 Receptor Expression in Cancer

2013 ◽  
Vol 54 (5) ◽  
pp. 776-784 ◽  
Author(s):  
C. Xavier ◽  
I. Vaneycken ◽  
M. D'huyvetter ◽  
J. Heemskerk ◽  
M. Keyaerts ◽  
...  
Keyword(s):  
Receptor Expression ◽  
Her2 Receptor

scholarly journals Dose-Reduced Trastuzumab Emtansine: Active and Safe in Acute Hepatic Dysfunction

2015 ◽  
Vol 8 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Adam Sharp ◽  
Stephen R.D. Johnston
Keyword(s):  
Breast Cancer ◽  
Metastatic Disease ◽  
Hepatic Dysfunction ◽  
Metastatic Breast ◽  
Receptor Expression ◽  
Trastuzumab Emtansine ◽  
Breast Cancers ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Cancer Subtypes

Breast cancer is the most common cancer in women worldwide. The majority of deaths attributed to breast cancer are a result of metastatic disease, and 30% of early breast cancers (EBC) will develop distant disease. The 5-year survival of patients with metastatic disease is estimated at 23%. Breast cancer subtypes continue to be stratified histologically on oestrogen, progesterone and human epidermal growth factor-2 (HER2) receptor expression. HER2-positive breast cancers represent 25% of all breast cancer diagnoses. The therapies available for metastatic breast cancer (MBC) are expanding, in particular within the field of HER2-positive disease, with the approval of trastuzumab, pertuzumab, lapatinib and trastuzumab emtansine (TDM-1). Recently, TDM-1 has been shown to improve progression-free survival in HER2 MBC when compared to capecitabine and lapatinib in clinical studies. Its main toxicities are deranged liver function tests and thrombocytopenia. There have also been cases of acute liver failure. Therefore, its use in acute hepatic dysfunction, to our knowledge, has been neither studied nor reported. We report a patient with progressive HER2-positive MBC who had previously responded to multiple HER2-targeted therapies that presented with acute hepatic dysfunction. She was treated with dose-reduced TDM-1 safely, with clear evidence of rapid biochemical, clinical and radiological response. This allowed dose escalation of TDM-1, and the patient maintains an ongoing response.

scholarly journals Relative Prognostic Value of Human Epidermal Growth Factor Receptor 2 (HER2) Expression in Operable Oesophagogastric Cancer

ISRN Surgery ◽  
2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
David S. Y. Chan ◽  
Fiona Campbell ◽  
Paul Edwards ◽  
Bharat Jasani ◽  
Geraint T. Williams ◽  
...  
Keyword(s):  
Prognostic Significance ◽  
Growth Factor Receptor ◽  
High Specificity ◽  
Endoscopic Biopsy ◽  
Receptor Expression ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Receptor ◽  
Her2 Positive ◽  
Predictive Values

Aims. The aim of this study was to determine the prognostic significance of HER2 receptor expression in operable oesophagogastric adenocarcinoma. Methods. Eighty-five consecutive patients diagnosed with oesophagogastric adenocarcinoma [18 oesophageal (OC), 32 junctional (JC) and 35 gastric (GC)] undergoing potentially curative resection were studied retrospectively. Immunohistochemistry was used to determine HER2 status at endoscopic biopsy and resection specimen. The primary outcome measure was survival. Results. Twenty (24%) patients had HER2 positive tumours which was commoner in JC (14/32, 44% versus 2/18, 11% in OC and 4/35, 11% in GC, P=0.003). The sensitivity, specificity, positive and negative predictive values of HER2 status at endoscopic biopsy were 56%, 93%, 63%, 91% respectively (weighted Kappa=0.504, P<0.0001). Five-year survival in OC HER2 positive negative was 100% and 36% (P=0.167) compared with 14% and 44% (P=0.0726) in JC and 50% and 46% (P=0.942) in GC respectively. Conclusions. Endoscopic biopsy had a high specificity and negative predictive value in determining HER2 status. Patients with JC had a significantly higher rate of HER2 overexpression and this was associated with a nonsignificant poorer survival trend. A larger study is needed to confirm these findings because of the implications for neoadjuvant and adjuvant chemotherapy regimens.

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