Quantifying HER2 and TROP2 in Breast Cancer for Therapy Guidance

In this study, the researchers aimed to develop a standardized method to accurately measure the levels of two proteins, HER2 and TROP2, in breast cancer tissues. These proteins are important because they can be targeted by specific therapies known as antibody-drug conjugates (ADCs). The researchers sought to create a reliable assay that could help identify patients who would benefit from these therapies and guide the choice of treatment based on protein levels in tumors.

Accurate measurement of HER2 and TROP2 is crucial because these proteins play a significant role in breast cancer treatment. HER2-targeted therapies have shown effectiveness in improving survival rates for certain breast cancer patients. TROP2 is also a promising target for new treatments. Understanding the levels of these proteins can help doctors select the most appropriate therapy, potentially leading to better patient outcomes. This research is significant for the medical community, as it could lead to more personalized cancer treatment options.

The researchers developed a multiplex quantitative immunofluorescence (QIF) assay, a method that uses fluorescent markers to measure protein levels. They optimized this assay using tissue samples arranged on slides, known as tissue microarrays. They validated the assay by comparing it to known protein concentrations measured through a technique called mass spectrometry. The assay was then applied to 323 breast cancer samples to measure HER2 and TROP2 levels.

The study found that the assay could reliably measure HER2 and TROP2 levels across a wide range of expressions. HER2 was present in about 85% of the samples, including 51% of those with a specific type of breast cancer called triple-negative. TROP2 was detectable in over 96% of all samples. The study also discovered a weak inverse relationship between the levels of HER2 and TROP2, meaning when one was high, the other tended to be low.

The development of this assay provides a new tool for accurately assessing HER2 and TROP2 levels in breast cancer tissues. This could help oncologists decide which ADC therapy might be most effective for a patient, based on the specific protein levels in their cancer. The findings could lead to more personalized treatment plans and improve outcomes for breast cancer patients.

The researchers suggest that future studies should focus on validating the clinical usefulness of this assay in real-world settings. They propose further research to determine the exact thresholds of HER2 and TROP2 levels that predict the best response to ADC therapies. This could refine patient selection for these treatments and enhance personalized medicine approaches in breast cancer care.

This research was supported by the Breast Cancer Research Foundation (grant 23-138) and the National Institutes of Health (awards P30CA016359 and F30CA287869). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Yale University also provided funding and support for this research.