LOSS OF ESTROGEN-RECEPTOR IN RECURRENT BREAST-CANCER IS ASSOCIATED WITH POOR RESPONSE TO ENDOCRINE THERAPY

Purpose: Up to 30% to 40% of metastases from hormone receptor-positive primary breast cancer do not respond to endocrine therapy. We studied how often hormone receptor status changes between primary and recurre nt tumors and whether such a change might explain unresponsiveness to endocrine therapy. Patients and Methods: Primary breast cancer samples and matched asynchronous recurrences were studied from 50 patients wh o had not received any adjuvant therapy, Estrogen receptor (ER) and pr ogesterone receptor (PR) status was determined immunohistochemically f rom histologically representative formalin-fixed paraffin-embedded tum or samples, ER status was ascertained by mRNA in situ hybridization. R esults: Thirty-five (70%) of 50 primary tumors were positive for ER an d 30 (60%) for PR, Hormone receptor status of the recurrent tumor diff ered from that of the primary tumor in 18 cases (36%), Discordant case s were due to the loss of ER (n = 6), loss of PR (n = 6), or loss of b oth receptors (n = 6), Receptor-negative primary tumors were always ac companied by receptor-negative recurrences, Among 27 patients with PR- positive primary tumors, toss of ER was a significant predictor (P = . 0085) of poor response to subsequent endocrine therapy, Only one of ei ght patients (12.5%) with lost ER expression responded to tamoxifen th erapy, whereas the response rate was 74% (14 of 19) for patients whose recurrent tumors retained ER expression. Conclusion: Loss of ER expre ssion in recurrent breast cancer should be considered as or cause for poor response to endocrine therapy in primarily ER-positive patients, We conclude that analysis of recurrent tumor sampler; may improve the predictive value of ER and PR assays. (C) 1996 by American Society of Clinical Oncology.