Clinical value of HER2 as a prognostic and predictive factor

Patients with tumors that have HER2 protein overexpression or gene amplification:

• Have a worse prognosis in terms of disease-free and overall survival
• Obtain more benefit from trastuzumab
• Obtain equal or more benefit from anthracyclines
• Obtain equivocal benefit from taxanes
• Obtain less benefit from nonanthracycline chemotherapy and hormones

Standardization of HER2 testing

• Use of 10 percent neutral buffered formalin as a fixative
• Optimal fixation time is 6 to 12 hours
• Use of control cell lines, fixed exactly as the test sample, to calibrate the assay with each episode of testing
• Selection of well-fixed areas of tumor and benign breast tissue, without artifacts or decalcified materials
• If antigen lability is suspected, then a negative IHC result can be verified by evaluating ubiquitous antigen preservation
• Better training, improved interpretation guidelines, or quantitation by image analysis may reduce interobserver variation in IHC interpretation
• Verification that invasive tumor is being assessed

Consensus algorithm for HER2 testing

• Laboratories should confirm their concordance rates of FISH to IHC for IHC scores of 3+ and 0, or they should perform both tests on all breast cancer specimens.
• IHC can be used as a screening tool if there is at least a 90 percent concordance for IHC 3+/FISH-amplified and IHC 0/FISH-nonamplified.
• If IHC is used as a screening tool, FISH should confirm all 1+ and 2+ cases.
• If the concordance rate for IHC 1+/FISH is more than 95 percent, there may not be a need to confirm cases with FISH.
• Testing may be considered for all patients newly diagnosed with breast cancer, not just those with metastatic disease.

Liability issues for the pathologist

Basing a therapeutic decision on non-FDA-approved HER2 tests raises a number of liability issues, such as the potential for malpractice exposure should a patient experience injury from the treatment.

Quality control

Measures of quality control for HER2 testing should include the percentage of positive cases obtained and whether the percentage varies by pathologist.

“Pathologists should view the current Her-2/neu testing challenge as an emerging opportunity to play a larger and more pivotal role in clinical medicine by providing the laboratory determination responsible for the selection of patients for future targeted therapies. This larger role in pathology practice requires the ongoing education of colleagues regarding the significance of new testing as it becomes available and leadership in algorithm development to provide consistent and accurate testing. This rigorous approach to Her-2/neu testing should become the standard by which we view our role as future laboratory assays that determine therapeutic decisions become available.”

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