fulvestrant

Overview

Fulvestrant is a selective estrogen receptor degrader (SERD) that binds ESR1 and promotes its degradation, used in the treatment of hormone receptor-positive breast cancer. It lacks the partial agonist activity of tamoxifen and is employed in both first-line and endocrine-refractory settings.

Evidence in the corpus

  • In a rat AAV-CRISPR somatic editing model of ER+ breast cancer, Nf1Indel tumors (DCIS histology, 12/13 cases) regressed completely with 5-week fulvestrant treatment (4/4 rats), and 3/4 treated animals remained in remission for 8 months after cessation, demonstrating strong endocrine sensitivity driven by NF1 loss alone PMID:26437033.
  • Combined Nf1Indel/Tp53Indel rat tumors showed only modest, transient shrinkage by week 3 (p<0.05) and resumed growth by weeks 4–5 under fulvestrant, modeling endocrine-refractory disease driven by TP53 co-loss PMID:26437033.
  • GSEA of 486 fulvestrant-responsive rat differentially expressed genes showed significant enrichment of genes induced by neoadjuvant fulvestrant in human patients (GSE71791); 58 overlapping genes included PGR, AREG, SGK3, STC2, and WNT5A PMID:26437033.
  • In 216 metastatic breast cancer patients (SAFIR01/02, SHIVA, MOSCATO trials), ESR1 mutations (found in 20/143 HR+/HER2- mBCs, 14%) were exclusively in patients who had received prior endocrine therapy including fulvestrant, and all ESR1 mutations occurred in the hormone-receptor domain mediating acquired endocrine resistance PMID:28027327

Resistance mechanisms

  • Co-disruption of TP53 with NF1 converts fulvestrant-sensitive to fulvestrant-refractory ER+ breast cancer in rat models; consistent with clinical reports that TP53 mutation associates with endocrine resistance PMID:26437033.

Cancer types (linked)

Sources

  • PMID:26437033 — Bu et al. (bioRxiv 2025). Rat somatic genome editing models of ER+ breast cancer; fulvestrant sensitivity/resistance dichotomy driven by NF1 and TP53 status.

This page was processed by crosslinker on 2026-05-14. - PMID:28027327 — Lefebvre et al. 2016, metastatic breast cancer WES; ESR1 mutations (14% of HR+/HER2- mBC) exclusively in prior-endocrine-therapy patients, mediating acquired endocrine resistance.

*This page was processed by entity-page-writer on 2026-05-15.