KEY TAKEAWAYS
- The study aimed to assess the prognostic impact of HER2 gene amplification in early-stage HER2-positive breast cancer patients treated with trastuzumab.
- Researchers observed a nonlinear association between HER2 biomarkers and RFS; further investigation is ongoing.
Overexpression of human epidermal growth factor receptor 2 (HER2) due to HER2 gene amplification is a key driver in breast cancer tumorigenesis.
Caroline Rönnlund and her team aimed to investigate the prognostic significance of HER2 biomarkers using manual scoring and digital image analysis (DIA) algorithms, specifically assessing HER2 copy numbers, HER2/CEP17 ratios, and ERBB2 mRNA levels. The focus is on early-stage HER2-positive breast cancer patients treated with trastuzumab.
Researchers performed an inclusive analysis in a retrospective study involving 371 early HER2-positive breast cancer patients who received adjuvant trastuzumab. HER2 re-testing was conducted on whole tumor sections, and digitized tumor tissue slides underwent manual scoring and assessment using uPath HER2 Dual ISH image analysis with a breast algorithm. The Xpert® Breast Cancer STRAT4 Assay was employed to target ERBB2 mRNA levels. In situ hybridization assessed HER2 copy number and HER2/CEP17 ratio, along with ERBB2 mRNA levels, which were then explored with recurrence-free survival (RFS).
About the analysis, patients with tumors displaying the highest and lowest manually counted HER2 copy number levels experienced worse RFS compared to those with intermediate levels (HR = 2.7, CI 1.4-5.3, P = 0.003, and HR = 2.1, CI 1.1-3.9, P = 0.03, respectively). A similar trend was noted for the HER2/CEP17 ratio, and the DIA algorithm substantiated these findings. Furthermore, patients with tumors exhibiting the highest and lowest values of ERBB2 mRNA had significantly poorer prognoses (HR = 2.7, CI 1.4-5.1, P = 0.003 and HR = 2.8, CI 1.4-5.5, P = 0.004, respectively) compared to those with intermediate levels.
The study concluded that the association between any of the three HER2 biomarkers and RFS was nonlinear. Tumors with the highest levels of HER2 gene amplification or ERBB2 mRNA demonstrated a worse prognosis compared to those with intermediate levels. This finding underscores the significance of further exploration in future clinical trials focusing on HER2-targeted therapy.
The study received open-access funding from the Karolinska Institute. This study was supported by grants from Region Stockholm Sweden, the Swedish Cancer Society, MedTechLabs, the Cancer Society in Stockholm, the Swedish Breast Cancer Association, and the Swedish Society.
Source: https://pubmed.ncbi.nlm.nih.gov/38321542/
Rönnlund C, Sifakis EG, Schagerholm C, et.al(2024). Prognostic impact of HER2 biomarker levels in trastuzumab-treated early HER2-positive breast cancer. Breast Cancer Res. 2024 Feb 7;26(1):24. doi: 10.1186/s13058-024-01779-9. PMID: 38321542; PMCID: PMC10848443.
