letrozole

Overview

Letrozole is a third-generation non-steroidal aromatase inhibitor that blocks CYP19A1-mediated estrogen synthesis. It is used as adjuvant and neoadjuvant endocrine therapy for hormone receptor-positive breast cancer and as a benchmark comparator in endocrine-response research.

Evidence in the corpus

• GSEA of fulvestrant-responsive gene signatures in rat ER+ breast cancer models showed significant enrichment of genes induced by neoadjuvant letrozole in human patients (GSE5462 dataset); the overlap of 58 genes — including PGR, AREG, SGK3, and KLF10/TIEG1 — confirms cross-species transcriptional concordance under aromatase inhibition and fulvestrant treatment PMID:26437033.

Resistance mechanisms

• No direct letrozole resistance mechanisms reported in the current corpus; cited as a benchmark comparator for endocrine-response gene signatures PMID:26437033.

Cancer types (linked)

• BRCA

Sources

• PMID:26437033 — Bu et al. (bioRxiv 2025). Rat somatic genome editing models of ER+ breast cancer; letrozole (GSE5462) used as benchmark neoadjuvant endocrine-therapy transcriptomic reference dataset.

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