Frequent Upregulation Of HER2 Protein In Hormone Receptor-Positive HER2-Negative Breast Cancer After Short-Term...

Area of Science:

• Oncology
• Molecular Biology
• Clinical Trials

Background:

• Endocrine resistance develops in 20-25% of hormone-receptor positive (HR+) breast cancer (BC) patients.
• HER family receptor tyrosine kinases (RTKs) can be upregulated as an escape mechanism during endocrine therapy (ET).
• Short-term neoadjuvant ET (NET) provides an opportunity to study early endocrine escape mechanisms in individual tumors.

Approach:

• A single-arm, phase II clinical trial evaluated 4 weeks of NET in early-stage HR+/HER2- BC patients.
• The primary objective was to assess NET-induced changes in HER1-4 proteins using immunohistochemistry (IHC).
• Upregulation was defined as an increase of ≥1 in IHC score post-NET.

Key Points:

• HER2 was upregulated in 48.6% of evaluable tumors after NET (p=0.025).
• Three patients showed HER2-positive status at surgery, recommended for trastuzumab-based therapy.
• HER3 and/or HER4 were downregulated in 54.2% of tumors; HER1 remained unchanged.
• Short-term NET reduced tumor proliferation rates but not tumor volume.

Conclusions:

• Short-term NET frequently and preferentially upregulates HER2 over other HER-family RTKs in early-stage HR+/HER2- BC.
• This strategy may identify tumors using HER2 as an early endocrine escape pathway.
• NET can serve as a method to discover individual tumor escape mechanisms.