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Development and validation of multivariate predictors of primary endocrine resistance to tamoxifen and aromatase inhibitors in luminal breast cancer reveal drug-specific differences

ABSTRACT: In the WSG-ADAPT trial (NCT01779206), HR+/HER2-EBC patients underwent pre-operative short-term endocrine therapy (pET). Treatment response was determined by immunohistochemical in-situ labeling of cycling cells (G1 to M-phase) with Ki67 before and after pET. We performed targeted next generation sequencing and Infinium MethylationEPIC-based DNA methylation analysis post-pET in a discovery cohort (n=364, responder (R) and non-responder (NR) pairs matched for clinicopathologic features) and a validation cohort (n=270, unmatched). Predictive indices of endocrine resistance under both treatments were constructed using lasso penalized logistic regression. Further details in J Clin Invest. 2025. https://doi.org/10.1172/JCI177813.

ORGANISM(S): Homo sapiens

PROVIDER: GSE261142 | GEO | 2025/07/17

REPOSITORIES: GEO

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Development and validation of multivariate predictors of primary endocrine resistance to tamoxifen and aromatase inhibitors in luminal breast cancer reveal drug-specific differences [HumanMethylationEPICv2]

Project description:In the WSG-ADAPT trial (NCT01779206), HR+/HER2-EBC patients underwent pre-operative short-term endocrine therapy (pET). Treatment response was determined by immunohistochemical in-situ labeling of cycling cells (G1 to M-phase) with Ki67 before and after pET. We performed Infinium MethylationEPICv2-based DNA methylation analysis post-pET in a validation cohort2 (n=176, unmatched). Predictive indices of endocrine resistance under both treatments were calculated as described in J Clin Invest. 2025. https://doi.org/10.1172/JCI177813.

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