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000298978 1001_ $$00000-0003-2213-9612$$aHoppe, Reiner$$b0
000298978 245__ $$aLessons learned from a candidate gene study investigating aromatase inhibitor treatment outcome in breast cancer.
000298978 260__ $$aLondon$$bNature Publ. Group$$c2025
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000298978 520__ $$aThe role of germline genetics in adjuvant aromatase inhibitor (AI) treatment efficacy in ER-positive breast cancer is poorly understood. We employed a two-stage candidate gene approach to examine associations between survival endpoints and common germline variants in 753 endocrine resistance-related genes. For a discovery cohort, we screened the Breast Cancer Association Consortium database (n ≥ 90,000 cases) and retrieved 2789 AI-treated patients. Cox model-based analysis revealed 125 variants associated with overall, distant relapse-free, and relapse-free survival (p-value ≤ 1E-04). In validation analysis using five independent cohorts (n = 8857), none of the six selected candidates representing major linkage blocks at CELA2B/CASP9, NR1I2/GSK3B, LRP1B, and MIR143HG (CARMN) were validated. We discuss potential reasons for the failed validation and replication of published findings, including study/treatment heterogeneity and other limitations inherent to genomic treatment outcome studies. For the future, we envision prospective longitudinal studies with sufficiently long follow-up and endpoints that reflect the dynamic nature of endocrine resistance.
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000298978 7001_ $$aWinter, Stefan$$b1
000298978 7001_ $$aLo, Wing-Yee$$b2
000298978 7001_ $$00000-0001-7065-1237$$aMichailidou, Kyriaki$$b3
000298978 7001_ $$00000-0002-4351-9326$$aBolla, Manjeet K$$b4
000298978 7001_ $$00000-0002-5452-9933$$aKeeman, Renske$$b5
000298978 7001_ $$aWang, Qin$$b6
000298978 7001_ $$00000-0003-4591-1214$$aDennis, Joe$$b7
000298978 7001_ $$aLush, Michael$$b8
000298978 7001_ $$aKalari, Krishna R$$b9
000298978 7001_ $$00000-0002-4383-270X$$aGoetz, Matthew P$$b10
000298978 7001_ $$00000-0003-3818-8531$$aWang, Liewei$$b11
000298978 7001_ $$aCairns, Junmei$$b12
000298978 7001_ $$00000-0002-4911-7985$$aWeinshilboum, Richard$$b13
000298978 7001_ $$aShepherd, Lois$$b14
000298978 7001_ $$00000-0001-6139-0696$$aChen, Bingshu E$$b15
000298978 7001_ $$aHäberle, Lothar$$b16
000298978 7001_ $$aRuebner, Matthias$$b17
000298978 7001_ $$aBeckmann, Matthias W$$b18
000298978 7001_ $$aHe, Wei$$b19
000298978 7001_ $$aLarson, Nicole L$$b20
000298978 7001_ $$aArmasu, Sebastian M$$b21
000298978 7001_ $$aSchroth, Werner$$b22
000298978 7001_ $$aChowbay, Balram$$b23
000298978 7001_ $$00000-0002-1128-4729$$aKhor, Chiea Chuen$$b24
000298978 7001_ $$00000-0003-3728-6535$$aAbubakar, Mustapha$$b25
000298978 7001_ $$aAntoniou, Antonis C$$b26
000298978 7001_ $$aBrüning, Thomas$$b27
000298978 7001_ $$aCastelao, Jose E$$b28
000298978 7001_ $$0P:(DE-He78)c259d6cc99edf5c7bc7ce22c7f87c253$$aChang-Claude, Jenny$$b29
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000298978 7001_ $$00000-0002-9458-0282$$aDörk, Thilo$$b31
000298978 7001_ $$00000-0002-9935-3169$$aEccles, Diana M$$b32
000298978 7001_ $$00000-0002-5100-623X$$aFigueroa, Jonine D$$b33
000298978 7001_ $$aGago-Dominguez, Manuela$$b34
000298978 7001_ $$00000-0001-6880-0301$$aGarcía-Sáenz, José A$$b35
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000298978 7001_ $$aHack, Carolin C$$b37
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000298978 7001_ $$aHan, Sileny$$b39
000298978 7001_ $$aHooning, Maartje J$$b40
000298978 7001_ $$00000-0001-6889-1493$$aHuebner, Hanna$$b41
000298978 7001_ $$aAbctb Investigators$$b42
000298978 7001_ $$aJohn, Esther M$$b43
000298978 7001_ $$aKo, Yon-Dschun$$b44
000298978 7001_ $$00000-0001-5012-7438$$aKristensen, Vessela N$$b45
000298978 7001_ $$00000-0001-5541-0347$$aLinn, Sabine$$b46
000298978 7001_ $$aMargolin, Sara$$b47
000298978 7001_ $$aMavroudis, Dimitrios$$b48
000298978 7001_ $$00000-0002-0916-2976$$aNevanlinna, Heli$$b49
000298978 7001_ $$aNeven, Patrick$$b50
000298978 7001_ $$aObi, Nadia$$b51
000298978 7001_ $$aPark-Simon, Tjoung-Won$$b52
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000298978 7001_ $$00000-0002-7684-3122$$aRashid, Muhammad U$$b54
000298978 7001_ $$00000-0002-1634-7397$$aRomero, Atocha$$b55
000298978 7001_ $$00000-0002-0485-0120$$aSaloustros, Emmanouil$$b56
000298978 7001_ $$00000-0001-8285-4111$$aSawyer, Elinor J$$b57
000298978 7001_ $$aTapper, William J$$b58
000298978 7001_ $$aTomlinson, Ian$$b59
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000298978 7001_ $$00000-0003-0932-9104$$aWinqvist, Robert$$b61
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