Recommendations for scoring (readout) and interpretation of IHC test to determine ER status in breast cancers

IHC: immunohistochemistry; ER: estrogen receptor; SOP: standard operating procedure; PgR: progesterone receptor.
* Hormone receptor testing should only be done with a validated method and with appropriate laboratory procedures, including ongoing assay monitoring and pathologist competency assessment.
¶ Refer to UpToDate graphic on invasive breast cancer histopathologic concordance with ER staining.
Δ Steps to consider including in SOP:

• Re-review of controls
• A second reviewer to confirm interpretation
• Validated quantitative digital image analysis to confirm interpretation
• Comparison of result with any prior patient-specific results
• Retesting the same sample if analytic issues suspected (eg, controls did not work as expected)
• Repeating the test on a different block or subsequent specimen if there are no internal controls, preanalytic issues are suspected, or result is unusual or unexpected

◊ If no internal controls are present but external controls are positive, include comment: "No internal controls are present, but external controls are appropriately positive. If needed, testing another specimen that contains internal controls may be warranted for confirmation of ER status."
§ For ER-low-positive results, include comment: "The cancer in this sample has a low level (1 to 10%) of ER expression by IHC. There are limited data on the overall benefit of endocrine therapies for patients with these results, but they currently suggest possible benefit, so patients are considered eligible for endocrine treatment. There are data that suggest invasive cancers with these results are heterogeneous in both behavior and biology and often have gene expression profiles more similar to ER-negative cancers."