HER2/neu

Overview

HER2/neu (human epidermal growth factor receptor 2) is a protein involved in cell growth and differentiation, encoded by the ERBB2 gene. It is a membrane-bound receptor tyrosine kinase that plays a critical role in the regulation of cell proliferation. HER2/neu is notably overexpressed or gene-amplified in approximately 20-30% of breast cancers, which influences tumor behavior and treatment response. Tracking HER2/neu status is essential for guiding targeted therapies, particularly trastuzumab, and for prognostic assessment in breast cancer management.¹³

Scientific Background

HER2/neu is a 185 kDa transmembrane receptor tyrosine kinase that belongs to the epidermal growth factor receptor (EGFR) family. It regulates cell growth, survival, and differentiation through intracellular signaling pathways. Normally expressed at low levels in epithelial tissues, HER2/neu gene amplification leads to protein overexpression, driving oncogenic processes such as increased proliferation and tumor aggressiveness. The HER2 gene is located on chromosome 17q21, and its amplification often co-occurs with alterations in nearby genes like topoisomerase II, which can affect chemotherapy sensitivity. HER2-positive tumors tend to have higher proliferation rates, lower estrogen and progesterone receptor levels, and a greater propensity for metastasis, especially to the brain and viscera. HER2 status is closely related to other biomarkers such as hormone receptors (ER, PR) and p53 mutations, influencing prognosis and treatment strategies.¹²

Measurement and Testing

HER2/neu status is primarily assessed by immunohistochemistry (IHC) to detect protein overexpression on tumor tissue and by fluorescence in situ hybridization (FISH) or other in situ hybridization techniques to detect gene amplification. IHC is the most common initial test due to its speed and cost-effectiveness, with FISH used to confirm equivocal cases. Factors such as tissue fixation, sample quality, and interpretation criteria can affect test accuracy. Testing is recommended for all invasive breast cancers at diagnosis to guide treatment decisions, especially regarding HER2-targeted therapies.²⁴

Reference Ranges

HER2/neu results are reported qualitatively rather than quantitatively. HER2-positive status is defined by strong protein overexpression (IHC 3+) or gene amplification by FISH. HER2-negative includes IHC scores of 0 or 1+ and no gene amplification. An IHC score of 2+ is considered equivocal and requires confirmatory FISH testing. There are no normal reference ranges since HER2 is typically expressed at low levels in normal tissue. HER2 positivity occurs in about 20-30% of breast cancers, with no significant variation by age or ethnicity, though tumor subtype influences prevalence. Interpretation guides treatment eligibility and prognosis.⁴⁵

High Values

Elevated HER2/neu expression or gene amplification is caused by oncogenic amplification of the ERBB2 gene. This leads to aggressive tumor behavior characterized by rapid cell proliferation, higher histologic grade, and increased metastatic potential, especially to the central nervous system and visceral organs. HER2-positive breast cancers often show relative resistance to hormonal therapies but increased sensitivity to certain chemotherapies like doxorubicin due to co-amplification of topoisomerase II. Clinically, high HER2 is associated with poorer prognosis if untreated but predicts responsiveness to HER2-targeted therapies such as trastuzumab, which significantly improve outcomes.¹⁵

Low Values

Low or normal HER2/neu expression indicates absence of gene amplification and is typical of most breast cancers. These tumors generally have slower growth rates, higher hormone receptor expression, and better prognosis. Low HER2 levels mean that HER2-targeted therapies are not effective, and treatment focuses on hormonal or other chemotherapy options. Deficiency of HER2 is not pathological in itself but reflects a different tumor biology with less aggressive behavior.⁴

Improving Biomarker Levels

Since HER2/neu overexpression is a genetic alteration in cancer cells, it is not modifiable by lifestyle or supplements. Management focuses on targeted therapies such as monoclonal antibodies (trastuzumab, pertuzumab) and tyrosine kinase inhibitors that specifically inhibit HER2 signaling. Early detection and accurate HER2 testing enable timely initiation of these treatments, which improve survival and reduce recurrence. Research continues into novel agents and combination therapies to overcome resistance and improve outcomes.¹⁵

Importance of Tracking

Monitoring HER2/neu status is critical for personalized cancer treatment. It informs prognosis, guides the use of HER2-targeted therapies, and helps predict treatment response. Accurate HER2 testing at diagnosis and during disease progression can influence clinical decisions, optimize therapy, and improve patient outcomes. Tracking HER2 also aids in identifying patients at higher risk for aggressive disease and metastasis, enabling closer surveillance and tailored interventions.³⁴

Disclaimer

The information provided in this document is for educational purposes only and does not constitute medical advice. It is essential to consult with a qualified healthcare professional for any health concerns or before making any decisions related to your health or treatment.