BOSTON, Mass. — Boston Cell Standards announced the publication of the CASI-01 study in Lancet: eBioMedicine, highlighting that calibration significantly improves the accuracy and reproducibility of Immunohistochemistry (IHC) testing in breast cancer. According to the study’s authors, the findings mark “pivotal advancements in precision medicine,” with broad implications for HER2-low diagnosis, companion diagnostic development, regulatory standards for IHC testing, and patient outcomes.
HER2 IHC testing is central to determining eligibility for targeted therapies such as trastuzumab and trastuzumab deruxtecan (T-DXd). As HER2-low tumors have gained clinical importance, inconsistencies in current testing methods have become more apparent. Without standardized calibration, many HER2 assays struggle to reliably detect low levels of expression, potentially preventing patients from receiving effective treatment. Some results have been described as “no more reproducible than the flip of a coin.”
“Patients with HER2-low cancers who could benefit from T-DXd may go untreated simply because the tests can’t measure expression levels precisely enough,” said Dr. Steve Bogen, MD, PhD, principal investigator of CASI-01 and CEO of Boston Cell Standards. “Calibration changes that. A patient’s treatment options should not depend on which lab performs their test.”
CASI-01 is the first international study to apply IHC calibration—using IHCalibrators from Boston Cell Standards—to evaluate HER2 testing across multiple laboratories. The findings show that calibration significantly improves analytical sensitivity and overall test reliability.
The study documented several key advancements, including quantifying the variability in HER2 results across laboratories, showing that the most widely used HER2 IHC test has a limited dynamic range for HER2-low scoring, and introducing the first objective analytic sensitivity guidance for IHC testing. The research also found that image analysis can outperform pathologist readouts in certain scenarios, and that combining sensitive IHC assays with image analysis improves dynamic range—offering a potential new benchmark for precision medicine.
“As therapies expand to include HER2-low disease, the need for precise and reproducible HER2 testing has never been greater,” said Dr. Emina Torlakovic, study co-author and board-certified anatomic and clinical pathologist. “Whereas current methods of IHC assay validation are insufficient to support the needs of precision medicine, by enabling an objective quantification of analytical sensitivity, we can now reliably evaluate the accuracy and precision of IHC assays for targeted therapies.”
The CASI-01 findings support a shift toward treating IHC not as an “unregulated stain,” but as a quantitative laboratory assay. The results bolster recent calls to adopt reference standards, calibration tools, analytic sensitivity metrics, and statistical process control—approaches already standard in other diagnostic fields.
