SRM Mass Spectrometry for Her2 Quantification in Breast Cancer
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Solution Overview
Problem
Current methods for determining Her2 protein expression in breast cancer patients are inaccurate, leading to inappropriate treatment recommendations, as they lack quantitative data predictive of sensitivity to anti-HER2 therapeutic agents like lapatinib, and result in misleading test results due to varying classification criteria among testing facilities.
Innovation Solution
A mass spectrometry-based Selected Reaction Monitoring (SRM/MRM) assay is used to quantify a specific Her2 peptide fragment in tumor samples, allowing for the calculation of Her2 protein levels and informing treatment decisions by comparing these levels to a reference value, thereby guiding the inclusion or exclusion of lapatinib in the treatment regimen.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If current methods are used to determine Her2 protein expression, then treatment recommendations can be provided, but the results are inaccurate and lack quantitative data predictive of sensitivity to anti-HER2 therapeutic agents
Solution Approach 1:
The patent replaces conventional immunohistochemistry (IHC) methods with mass spectrometry-based Selected Reaction Monitoring (SRM/MRM) assay. This substitution transitions from antibody-based detection to direct mass spectrometric quantification of Her2 peptide fragments, providing absolute quantitative measurement of Her2 protein levels with high precision and reproducibility, thereby improving both measurement accuracy and treatment recommendation reliability
Solution Approach 2:
The patent changes the measurement parameter from relative IHC staining intensity (0-3+) to absolute quantitative Her2 protein levels (amol/μg of protein). This parameter transformation enables precise determination of Her2 expression thresholds (e.g., 817 amol/μg) that predict lapatinib sensitivity, allowing for more reliable and personalized treatment recommendations
2Adaptability or versatility
If varying classification criteria are used among testing facilities, then more patients can be evaluated, but misleading test results are produced
Solution Approach 1:
The patent establishes a universal mass spectrometry-based SRM/MRM assay platform that can be applied across all testing facilities with standardized protocols. This universal method uses absolute quantitative measurement of Her2 peptide fragments (e.g., ELVSEFSR sequence) with consistent reference standards, eliminating the variability inherent in facility-specific IHC classification criteria while maintaining broad patient evaluation capability
Solution Approach 2:
The patent implements a feedback mechanism where Her2 protein quantification results are directly correlated with clinical outcomes (progression-free survival) to establish evidence-based expression thresholds. This feedback loop allows continuous refinement of treatment decision criteria based on actual patient response data, improving test result accuracy while maintaining adaptability across different patient populations
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
This approach provides accurate, quantitative Her2 protein expression levels, enabling personalized treatment strategies by predicting clinical response to lapatinib, improving progression-free survival for patients with lower Her2 levels and avoiding unnecessary exposure to its side effects in those with higher levels.
Implementation Method 1
The assay uses mass spectrometry-based Selected Reaction Monitoring (SRM), also referred to as Multiple Reaction Monitoring (MRM), to detect and quantitatively measure the amount of the specified Her2 fragment peptide
Data Source
AI summary
Methods of treating breast cancer are provided where a quantitative Her2 assay is used to identify whether a breast tumor will be responsive to treatment with anti-Her2 therapeutic agents such as lapatinib and trastuzumab, followed by selection of a suitable treatment regimen and administration of the regimen. A specific Her2 fragment peptide is precisely quantitated by SRM-mass spectrometry directly in breast tumor cells collected from breast tumor tissue that was obtained from a cancer patient and compared to a reference level in order to determine if the breast cancer patient will positively respond to treatment with a therapeutic agent that specifically targets the Her2 protein.