World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website https://wjon.elmerpub.com

Original Article

Volume 16, Number 4, August 2025, pages 347-356

Clinical Utility of Targeted Next-Generation Sequencing for Determining Human Epidermal Growth Factor Receptor 2 Status and Optimizing Targeted Therapy in Breast Cancer

Figures

Figure 1.
Figure 1. Distribution of ERBB2 CNAs according to HER2 IHC (4B5) expression status. Comparison of ERBB2 CNAs (FC) among patients with HER2 IHC (4B5) scores of 3+, 2+, 1+, and 0. The Kruskal-Wallis test was performed to assess the significance of differences in continuous data among the multiple groups (*). The Games-Howell test was applied to the post hoc tests for multiple comparisons (†). All tests were two-tailed, and P < 0.05 was considered significant. CNA: copy number alteration; ERBB2: erb-b2 receptor tyrosine kinase 2; FC: fold change; HER2: human epidermal growth factor receptor 2; IHC: immunohistochemistry.
Figure 2.
Figure 2. Landscape of additional gene mutations and proposed targeted therapies by targeted NGS, HER2, and ER status. ERBB2 CNA, HER2 status determined by HER2 IHC (4B5) and FISH, ER status, and additional gene mutations in ERBB2, ESR1, PIK3CA, AKT1, and PTEN along with the recommended targeted therapies based on OncoKB therapeutic evidence levels are depicted in color tiles. AKT1: serine/threonine kinase 1; CNA: copy number alteration; ER: estrogen receptor; ERBB2: erb-b2 receptor tyrosine kinase 2; FISH: fluorescence in situ hybridization; HER2: human epidermal growth factor receptor 2; IHC: immunohistochemistry; NGS: next-generation sequencing; PTEN: phosphatase and tensin homolog.
Figure 3.
Figure 3. Mutations in ERBB2, ESR1, PIK3CA, AKT1, and PTEN detected in 41 patients. Lollipop plots, which show amino acid changes, are illustrated for ERBB2, ESR1, PIK3CA, AKT1, and PTEN. AKT1: serine/threonine kinase 1; ERBB2: erb-b2 receptor tyrosine kinase 2; ESR1: estrogen receptor 1; HER2: human epidermal growth factor receptor 2; IHC: immunohistochemistry; PIK3CA: phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha; PTEN: phosphatase and tensin homolog.

Tables

Table 1. Patient Background
 
VariablesNumber of patients (%)
*Union for International Cancer Control (UICC) TNM classification, eighth edition.
Age
  Median (range)57 (28 - 84)
T classification*
  T115 (37)
  T221 (51)
  T34 (10)
  T41 (2)
N classification*
  N022 (54)
  N114 (34)
  N23 (7)
  N32 (5)
M classification*
  M040 (98)
  M11 (2)
Estrogen receptor status
  Negative22 (54)
  Positive19 (46)
Progesterone receptor
  Negative26 (63)
  Positive15 (37)
Ki67 labeling index
  < 25%19 (46)
  ≥ 25%22 (53)

 

Table 2. Concordance Between ERBB2 CNA Evaluated by Targeted Next-Generation Sequencing and HER2 IHC (4B5)
 
Number of patients
HER2 IHC (4B5)Total
Score 1 - 3Score 0
CI: confidence interval; CNA: copy number alteration; ERBB2: erb-b2 receptor tyrosine kinase 2; HER2: human epidermal growth factor receptor 2; IHC: immunohistochemistry.
ERBB2 CNA evaluated by targeted next-generation sequencing> 1.00-fold change15217
≤ 1.00-fold change111324
Total261541
Positive percent agreement57.7%
Negative percent agreement86.7%
Overall percent agreement68.3%
Cohen’s kappa (95% CI)0.39 (0.14 - 0.64)