Introduction/Background Estrogen receptor (ER) status is an important biomarker in breast cancer (BC), influencing treatment decisions. Immunohistochemistry is commonly used to assess ER expression in breast cancer tissue samples. The biology of BC with a low expression level (1–10%) of ER remains a matter of confusion. Challenges can arise in terms of reproducibility, including variations in interpretation among different observers and potential differences in intra-observer evaluation. We herein investigated the inter-observer and intra-observer reproducibility of ER IHC in BC, with an emphasis on ER-low breast cancers.

Methodology Design: 100 BC cases were stained by IHC with ER 6F11 clone. All cases were evaluated by two experienced pathologists using 10% of staining tumor cells as a cutoff for positivity. The level of inter-observer agreement and intra-observer reproducibility were evaluated.

Results Results: The inter-observer reliability for ER 6F11 clone was 80%. The intra-observer agreement for ER 6F11 clone was 82.3%. The inter-observer agreement for ER 6F11 clone was high for ER-negative cases, 90%, and for ER-positive cases, 90%. For ER-low cases, the inter-observer reliability was moderate, 60%. In these cases, discrepancies were noticed with the ER positive cases 40% of cases and with ER-negative cases in 60%.

The intra-observer reliability for ER 6F11 clone was high for ER-negative cases, 92%, and for ER-positive cases, 90%. For ER-low cases, the inter-observer reliability was 65%.

Conclusion Conclusions: Our results reinforce that there is inter-observer and intra-observer variation in the evaluation of ER IHC, particularly in cases with ER low staining. Given that IHC is the primary assay used to identify ER-low BC, our results suggest that until a more consistently reproducible methodology is available, careful evaluation of ER IHC, with consensus between observers, may be required for the evaluation of ER-low BC.’

Disclosures We Don’t have any conflict of interest or any financial relationship.