Proteomics based selection achieves complete response to HER2 therapy in HER2 IHC 0 breast cancer

Area of Science:

• Oncology
• Molecular Biology
• Proteomics

Background:

• Trastuzumab deruxtecan (T-DXd) shows efficacy in HER2-negative cancers, but patient selection remains challenging.
• Current HER2 assays (IHC, FISH) may inaccurately assess HER2 expression in unamplified tumors.

Purpose of the Study:

• To investigate the utility of a proteomic assay in identifying HER2 expression in a HER2-negative patient.
• To explore potential biomarkers for predicting T-DXd response in traditionally HER2-negative breast cancer.

Main Methods:

• Case study of a heavily pre-treated triple-negative breast cancer patient with HER2 IHC 0.
• Utilized a CLIA-certified reverse-phase protein array (RPPA) for proteomic analysis.
• Quantified total HER2 protein expression and HER2 activation (pY1248).

Main Results:

• The patient, initially HER2 IHC 0, showed moderate HER2 protein expression (HER2^Total 2+, 42%) and activation (HER2^Y1248 1+, 23%) via RPPA.
• Achieved a complete response to T-DXd therapy.
• Proteomic findings suggested eligibility for T-DXd despite conventional HER2-negative status.

Conclusions:

• Proteomics-based assays may offer a more accurate method for quantifying HER2 expression and activation in HER2 unamplified/IHC 0 settings.
• This approach could identify patients eligible for HER2-directed therapies like T-DXd who might otherwise be excluded.
• Highlights the potential of advanced proteomic techniques for personalized cancer treatment selection.