However, the molecular association of HER2 gene mutation with HER2 gene amplification and/or protein expression in cancer tissues has not been clearly defined.
Consistently, we show that the addition of the p110β inhibitor to BYL719 prevents the PIP3 rebound and induces greater antitumor efficacy in HER2-amplified and PIK3CA mutant cancers.
In stratification analysis, these associations consistently manifested in ER-positive breast cancer: in ER positive, PR-positive subtype, genotypes with the six-repeats allele (OR, 1.42; 95% CI, 1.06-1.90), long alleles (OR, 1.77; 95% CI, 1.17-2.67) or a high dose of biallelic repeats (OR, 1.67; 95% CI, 1.19-2.33) were associated with cancer risk; in ER positive, HER2-negative subtype, they were susceptible factors with the ORs being 1.46 (95% CI, 1.06-2.02), 2.06 (95% CI, 1.28-3.32) and 1.85 (95% CI, 1.26-2.71), respectively.
Epidermal growth factor receptor (EGFR) and ErbB2 in particular are mutated in many epithelial tumors, and clinical studies suggest that they play roles in cancer development and progression.
However, we did not find a significant association between the distribution of genotypes or alleles and cancer characteristics for the HER2Ile655Val polymorphism.
Overall, we detected somatic cancer-driver events in 11 of 40 (27.5%) IE cases and 13 of 36 (36.1%) DE cases, including hotspot mutations in KRAS, ERBB2, PIK3CA and CTNNB1.
Breast cancer is the leading malignancy among Filipino women, with about 23.50% of cases characterized by human epidermal growth factor receptor-2 (HER2) overexpression.
Monoclonal antibodies (mAbs) and small molecule inhibitors targeting EGFR and HER2 tyrosine kinase activities exhibit clinical benefits in the treatment of several types of cancers, but their clinical efficacy is limited by the occurrence of drug resistance.
A significant risk association of HER-2Ile655Val polymorphism was observed in different types of cancer using various genetic models (co-dominant heterogeneous Ile/Val vs Ile/Ile; OR=1.1, 95% CI = 1.01-1.16, P = 0.01 and dominant; OR = 1.12, 95% CI = 1.03-1.20, P = 0.0003).
Human epidermal growth factor receptor 2 (HER2 or ErbB2) can be overexpressed, amplified and/or mutated in malignant tumors, and is a candidate for therapeutic targeting.
The aim of this study was to investigate the degree to which HER2 amplification in terms of HER2 gene copy numbers in HER2+IHC2+ cancers affected the outcome in a community setting.
Genetic polymorphism not only affects cancer susceptibility but also influences malignant phenotype; examples include single-nucleotide polymorphism in the HER-2 and MMP-9 genes.
In conclusion, using G129R-based fusion proteins to target mammary carcinomas and to tackle multiple hallmarks of cancer at the same time was an effective strategy for treating HER2-postive mammary cancer in this mouse tumor model.