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Julian Puppe‘s paper “EZH2 is overexpressed in BRCA1-like breast tumors and predictive for sensitivity to high-dose platinum-based chemotherapy“ is published in Clinical Cancer Research.


BRCA1-mutant breast cancers are associated with poor survival highlighting the need for novel treatment options. In the present study, Puppe and colleagues show that the Polycomb-group protein EZH2 is significantly higher expressed in breast tumors with a BRCA1-mutation, BRCA1-promoter methylation or a BRCA1-like DNA Copy Number Profile indicating that BRCA1 loss is associated with high EZH2 expression levels. Importantly, EZH2 overexpression can identify breast cancer patients that benefit significantly from intensified DSB-inducing platinum-based chemotherapy. Moreover, pharmaceutical inhibition of EZH2 improves the antitumor effect of platinum drugs in Brca1-deficient breast tumors in vivo. These data indicates that EZH2 is a promising anti-cancer target in BRCA1-associated breast tumors and could be used as a predictive biomarker to categorize patients according to their likelihood to benefit from intensified DSB-inducing platinum-based chemotherapy independent of BRCA1-like status.