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| 100 | 1 | _ | |a Hoppe, Reiner |0 0000-0003-2213-9612 |b 0 |
| 245 | _ | _ | |a Lessons learned from a candidate gene study investigating aromatase inhibitor treatment outcome in breast cancer. |
| 260 | _ | _ | |a London |c 2025 |b Nature Publ. Group |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a The 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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| 700 | 1 | _ | |a Lo, Wing-Yee |b 2 |
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| 700 | 1 | _ | |a Wang, Qin |b 6 |
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| 700 | 1 | _ | |a Lush, Michael |b 8 |
| 700 | 1 | _ | |a Kalari, Krishna R |b 9 |
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| 700 | 1 | _ | |a Wang, Liewei |0 0000-0003-3818-8531 |b 11 |
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| 700 | 1 | _ | |a He, Wei |b 19 |
| 700 | 1 | _ | |a Larson, Nicole L |b 20 |
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