Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer

Purpose: Immunohistochemistry (IHC) is a newer technique for assessing the estrogen receptor (ER) status of breast cancers, with the potential to over come many of the shortcomings associated with the traditional ligand-bindin g assay (LBA), The purpose of this study was to evaluate the ability of ER status determination by IHC, compared with LBA, to predict clinical outcome -especially response to adjuvant endocrine therapy-in a large number of pat ients with long-term clinical follow-up. Patients and Methods: ER status was evaluated in 1,982 primary breast cance rs by IHC on formalin-fixed paraffin-embedded tissue sections, using antibo dy 6F11 and standard methodology, Slides were scored on a scale representin g the estimated proportion and intensity of positive-staining tumor cells ( range, 0 to 8), Results were compared with ER values obtained by the LBA in the same tumors and to clinical outcome. Results: An IHC score of greater than 2 (corresponding to as few as 1% to 1 0% weakly positive cells) was used to define ER positivity on the basis of a univariate cut-point analysis of all possible scores and disease-free sur vival (DFS) in patients receiving any adjuvant endocrine therapy. Using thi s definition, 71% of all tumors were determined to be ER-positive by IHC, a nd the level of agreement with the LBA was 86%, In multivariate analyses of patients receiving adjuvant endocrine therapy alone, ER status determined by IHC was better than that determined by the LBA at predicting improved DF S (hazard ratios/P = 0.474/.0008 and 0.707/.3214, respectively) and equival ent at predicting overall survival (0.379/.0001 and 0.381/.0003, respective ly). Conclusion: IHC is superior to the LBA for assessing ER status in primary b reast cancer because it is easier, safer, and less expensive, and has an eq uivalent or better ability to predict response to adjuvant endocrine therap y. J Clin Oncol 17:1474-1481. (C) 1999 by American Society of Clinical Onco logy.