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000303115 1001_ $$aZhang, Guokun$$b0
000303115 245__ $$aA predictive endocrine resistance index accurately stratifies luminal breast cancer treatment responders and non-responders.
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000303115 520__ $$aEndocrine therapy (ET) with tamoxifen (TAM) or aromatase inhibitors (AI) is highly effective against hormone receptor (HR) positive early breast cancer (BC), but resistance remains a major challenge. The primary objectives of our study were to understand the underlying mechanisms of primary resistance and to identify potential biomarkers.We selected >800 patients in three sub-cohorts (Discovery, N=364, matched pairs), Validation 1, N=270, Validation 2, N= 176) of the West German Study Group (WSG) Adjuvant Dynamic marker-Adjusted Personalized Therapy (ADAPT) trial who underwent short-term pre-operative TAM or AI treatment. Treatment response was assessed by immunohistochemical labeling of proliferating cells with Ki67 before and after ET. We performed comprehensive molecular profiling, including targeted next-generation sequencing (NGS) and DNA methylation analysis using EPIC arrays, on post-treatment tumor samples.TP53 mutations were strongly associated with primary resistance to both TAM and AI. In addition, we identified distinct DNA methylation patterns in resistant tumors, suggesting alterations in key signaling pathways and tumor microenvironment composition. Based on these findings and patient age, we developed the Predictive Endocrine ResistanCe Index (PERCI). PERCI accurately stratified responders and non-responders in both treatment groups in all three sub-cohorts and predicted progression-free survival in an external validation cohort and in the combined sub-cohorts.Our results highlight the potential of PERCI to guide personalized endocrine therapy and improve patient outcomes.WSG-ADAPT, ClinicalTrials.gov NCT01779206, Registered 2013-01-25, retrospectively registered.
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000303115 650_7 $$2Other$$aBioinformatics
000303115 650_7 $$2Other$$aBreast cancer
000303115 650_7 $$2Other$$aClinical Research
000303115 650_7 $$2Other$$aClinical trials
000303115 650_7 $$2Other$$aEpigenetics
000303115 650_7 $$2Other$$aOncology
000303115 7001_ $$aJurinovic, Vindi$$b1
000303115 7001_ $$aBartels, Stephan$$b2
000303115 7001_ $$aChristgen, Matthias$$b3
000303115 7001_ $$aChristgen, Henriette$$b4
000303115 7001_ $$aKandt, Leonie Donata$$b5
000303115 7001_ $$aMishieva, Lidiya$$b6
000303115 7001_ $$aNi, Hua$$b7
000303115 7001_ $$aRaap, Mieke$$b8
000303115 7001_ $$aKlein, Janin$$b9
000303115 7001_ $$aKatzke, Anna-Lena$$b10
000303115 7001_ $$aHofmann, Winfried$$b11
000303115 7001_ $$aSteinemann, Doris$$b12
000303115 7001_ $$aKates, Ronald E$$b13
000303115 7001_ $$aGluz, Oleg$$b14
000303115 7001_ $$aGraeser, Monika$$b15
000303115 7001_ $$aKuemmel, Sherko$$b16
000303115 7001_ $$aNitz, Ulrike$$b17
000303115 7001_ $$0P:(DE-He78)4301875630bc997edf491c694ae1f8a9$$aPlass, Christoph$$b18$$udkfz
000303115 7001_ $$aLehmann, Ulrich$$b19
000303115 7001_ $$aZu Eulenburg, Christine$$b20
000303115 7001_ $$aMansmann, Ulrich$$b21
000303115 7001_ $$0P:(DE-He78)3c4679d03b730156fae20c4948722efe$$aGerhauser, Clarissa$$b22$$udkfz
000303115 7001_ $$aHarbeck, Nadia$$b23
000303115 7001_ $$aKreipe, Hans H$$b24
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