On the other hand, we have found a significant correlation between MDM2 (T309G) polymorphism with HER2/neu status (χ (2) = 11.14, p = 0.003) and distant metastasis (p value = 0.04).
In human invasive breast cancers, high CIP4 levels was significantly associated with high tumor stage, TNBC and HER2 subtypes, and risk of progression to metastatic disease.
The logistic regression analysis for tumor invasion, lymph node metastasis and distant metastasis revealed that lymph node metastasis was most closely associated with the HER-2 genotype.
The mechanisms of ERBB2 dosage changes-gene amplification versus chromosome gain and loss-probably differ in primary and metastatic disease; however, a correction for chromosome 17 copy-number is necessary to completely distinguish between these mechanisms.
In this study, to explore the possibility that ERBB2 mutation is involved in the metastasis mechanism, we analyzed the kinase domain of ERBB2 for the detection of somatic mutations in 58 gastric adenocarcinomas with lymph node metastasis.
<i>EZH2</i> rs12670401 and rs6464926 polymorphisms, <i>EZH2</i> and <i>SMYD3</i> expression, clinical staging, lymph node metastasis, human epidermal growth factor receptor-2 (HER2) status, and metastasis may be correlated with breast cancer susceptibility and prognosis.
Conversely, of the 23 amplified PBC, 13 (57%) demonstrated a significant increase in the HER2 gene and chromosome 17 copy number in their paired metastases (P = 0.01), as defined by SISH (k = 0.54, P < 0.0001) and MLPA.
Here, we employed a spontaneous mammary tumor mouse model showing that MMTV-ErbB2(V664E) mice lacking mouse LCN2 had significantly delayed mammary tumor formation and metastasis with reduced matrix metalloproteinase-9 activity in the blood.
Treatment with 100 mg/kg of pazopanib resulted in a 73% decline in large 231-BR-HER2metastases (P < 0.0001) and a 39% decline in micrometastases (P = 0.004).
HER2 gene amplification and HER2 overexpression occur early in the development of breast cancers and are found in a high proportion of ductal carcinomas in situ (DCIS), non-invasive cancers that generally do not give rise to metastases.
However, patients treated with both trastuzumab and lapatinib after developing metastasis had significantly longer survival than patients treated with trastuzumab alone, lapatinib alone, or no HER2-targeting agent (p < 0.001).
Sequencing of the progressing metastasis allowed the identification of the ERBB2L869R mutation previously associated with resistance to lapatinib in vitro.These results support further clinical investigation aiming to demonstrate that ERBB2-mutational driven therapy can improve patient care irrespective of histology.
Risk factors for high ALN<sub>Dsum</sub> were primary tumor diameter (P = 0.0092), histopathological type (P = 0.0173), number of positive SLNs (P = 0.0012), type of metastasis (P = 0.0025), molecular type (P = 0.0037), SLN<sub>Dmax</sub> (P = 0.0001), and Her-2 status (P = 0.0093).
Intriguingly, HER2 inhibitors significantly reversed CUL4B-induced EMT in vitro and partially blocked GC metastasis in tumor xenografts with CUL4B overexpression.
Ado-trastuzumab emtansine (T-DM1/Kadcyla<sup>®</sup>;Genentech) is an antibody-drug conjugate used in the treatment of human epidermal growth factor receptor-2-positive metastasized breast cancer.
Genetic alterations of the proto-oncogene human epidermal growth factor receptor (HER-2/neu) have been shown to induce malignant transformation and metastasis.
Here, we investigated whether rVP1 exhibits any inhibitory effects on migration/metastasis and human epidermal growth factor receptor 2 (HER-2), a well-known biomarker for poor prognosis of breast cancer.
The incidence of C-erbB-2 positivity in lymph nodes with metastasis was higher than in primary sites (P < 0.01) and was significantly higher in differentiated adenocarcinoma (P < 0.01).
Conclusions The significant discordance between HER-2/neu expression in primary and metastatic tumors suggests that determination of HER-2/neu status in metastatic disease should be attempted.
The level of HER2/neu amplification tends to increase from the primary tumour to the paired metastases in a significant proportion of patients with HER2-positive MBC.