Boston Cell Standards: Calibration Transforms Accuracy in HER2-Low Breast Cancer Testing

International Study Published in Lancet: eBioMedicine

BOSTON--(BUSINESS WIRE)--Boston Cell Standards today announced the publication of the CASI-01 study in Lancet: eBioMedicine demonstrating that calibration dramatically improves the accuracy and reproducibility of Immunohistochemistry (IHC) testing in breast cancer. Study authors concluded that the findings point to “pivotal advancements in precision medicine,” with potential far-reaching implications for HER2-low diagnosis, companion diagnostic development, regulatory reform for IHC clinical testing, and improved patient outcomes.

The Challenge: Inconsistent HER2-Low Testing

HER2 IHC testing guides eligibility for targeted therapies such as trastuzumab and trastuzumab deruxtecan (T-DXd). However, the growing importance of identifying HER2-low tumors has revealed critical weaknesses in current testing methods. Without standardized calibration, HER2 assays often fail to consistently detect low-expression levels—leaving some patients without access to effective treatment. Test results are viewed as “no more reproducible than the flip of a coin.”¹

“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.”

Study Design and Key Findings

CASI-01 is the first international study to apply IHC calibration (using IHCalibrators® from Boston Cell Standards) to evaluate HER2 testing across multiple laboratories. Results showed that calibrated IHC dramatically enhances test reliability and analytical sensitivity.

The study’s findings have industry-changing implications, as they:

• Quantified the variability in HER2 testing across clinical laboratories;
• Revealed that the most widely used HER2 IHC test has poor assay dynamic range for HER2-low scores;
• Introduced the first objective, quantitative analytic sensitivity guidance for IHC testing;
• Showed that image analysis can, in some cases, outperform pathologist readouts in accuracy;
• Demonstrated that combining more sensitive IHC tests with image analysis improves assay dynamic range, pointing to a potential new standard in 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, board-certified anatomic and clinical pathologist and hematopathologist; director of Canadian Biomarker Quality Assurance academic program; and division head of Hematopathology, Dept. of Pathology & Laboratory Medicine, Saskatchewan Health Authority and University of Saskatchewan. “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 study supports a long-discussed shift from viewing IHC as an “unregulated stain” to treating it as a quantitative laboratory assay.² The research findings support recent proposals to adopt reference standards, calibration, analytic sensitivity metrics, and statistical process control—methods already routine in other diagnostic disciplines.

About Boston Cell Standards

Boston Cell Standards is a privately held diagnostics technology company that provides the only integrated platform for improving the accuracy and standardization of immunohistochemistry (IHC) testing used for diagnosing and treating cancer patients. BCS empowers laboratories and clinicians to deliver dependable and consistent patient test results, yielding better patient outcomes and accelerating the adoption of precision medicine.

1. Rimm D, Dacic S, Schnitt S. The Pathologists’ Conundrum. Arch Pathol Lab Med. 2023;147:17-18. https://doi.org//10.5858/arpa.2022-0226-ED.
2. Magnani B, Taylor C. Opinion: IHC should be regulated as an assay. Arch Pathol Lab Med. 2023;147:1229-1231. https://doi.org/10.5858/arpa.2023-0048-ED
2. Bell M, Chiriboga L et al. Immunohistocheistry as an assay. Letter to the editor. Journal of Histotechnology 2023; 46 (4): 156-157. https://doi.org/10.1080/01478885.2023.2278384
2. Miller DV. The chemistry in immunohistochemistry. Arch Pathol Lab Med. 2023; 147 (11): 1232-1233. https://doi.org/10.5858/arpa.2023-0254-ED