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Introduction: Tumor biological factors of breast cancer (BC) such as hormone receptor (HR) status, HER2 status, and grade can differ in the metastatic cascade from primary to lymph node (LN) metastasis and to distant metastatic tissue. Systematic data regarding therapeutic consequences are yet limited., Methods: We conducted a prospectively planned, retrospective cohort study comparing BC phenotype in tissue from primary tumors (PTs), locoregional LN metastases, and disease recurrence (DR). HR and HER2 as well as tumor grade in PTs and DR were obtained by a database search. No centralized biomarker testing was performed. The impact of changes in tumor biological factors on post-recurrence survival (PRS) and overall survival was analyzed., Results: PriMet comprises 635 patients (LN tissue in 142 patients). Discrepancies for HR or HER2 status between PT and DR were observed in 18.7 and 21.6% of cases, respectively. For HR status, positivity of PT and negativity of DR was seen more often (13.2%) than vice versa (5.5%). For HER2 status, negativity of the primary and positivity of DR was seen more often (14.9%) than vice versa (6.7%). Discordance was more often observed between PT and LN metastasis compared to LN versus DR. However, numbers were small. Compared to concordant non-triple-negative (TN) disease, concordant TN disease showed significantly inferior PRS., Conclusion: We demonstrate receptor discordance to occur relatively frequently between PT, LN metastasis, and DR and to impact patient prognosis. However, clinical consequences of receptor discordance need to be drawn with caution considering clinical aspects as well as tumor biology., Competing Interests: C. Kolberg-Liedtke has received honoraria/travel support by Phaon Scientific, Novartis, Pfizer, Celgene, Roche, AstraZeneca, Lilly, HEXAL, Amgen, Eisai, and SonoScape and has received research funding by Roche, Novartis, and Pfizer (CKL). O. Gluz has received lecture/consultancy fees from Celgene, Roche, Genomic Health, Amgen, Pfizer, Novartis, Lilly, Nanostring, Eisai, and MSD, and assistance with travel costs from Celgene, Roche, and Daiichi-Sankyo. N. Harbeck has received honoraria for lectures and/or consulting from Agendia, Amgen, Astra Zeneca, BMS, Celgene, Daiichi-Sankyo, Genomic Health, Lilly, MSD, Novartis, Odonate, Pierre Fabre, Pfizer, Roche, Sandoz/Hexal, and Seattle Genetics. R. Wuerstlein, M. Freudenberger, E. Bensmann, A. du Bois, U. Nitz, E. Pelz, M. Warm, M. Ortmann, E. Sultova, S.Y. Brucker, R.E. Kates, and T. Fehm state that they have no conflict of interest regarding the paper., (Copyright © 2020 by S. Karger AG, Basel.)