What question did this study set out to answer?

This research aims to explore the effects of co-targeting KAT6 and the estrogen receptor in ER+/HER2− metastatic breast cancer using prifetrastat and fulvestrant.

April 19, 2026Cancer Research

Abstract CT174: Unlocking endocrine resistance: Co-targeting KAT6 and ER with prifetrastat (PF-07248144) and fulvestrant drives tumor and ctDNA response in ER+/HER2− metastatic breast cancer

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Authors

LLLi LiuPfizer (United States)RLRachel M. LaymanThe University of Texas MD Anderson Cancer Center XMXinmeng Jasmine MuBroad Institute

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Implication

Phase 1/2a study demonstrates early ctDNA clearance in ER+/HER2− metastatic breast cancer, suggesting effective intervention strategies.

Key Points

This research aims to explore the effects of co-targeting KAT6 and the estrogen receptor in ER+/HER2− metastatic breast cancer using prifetrastat and fulvestrant.
Patients with ER+/HER2− metastatic breast cancer received either prifetrastat alone or with fulvestrant.
Serial blood and tumor biopsies were collected for analysis before and after treatment.
H3K23 acetylation levels were measured, and tumor gene expression was profiled using RNA sequencing.
ctDNA mutation burden was assessed using Guardant 360 assay.
All treatment groups showed over 50% reduction of H3K23 acetylation.
Prifetrastat 5 mg QD plus fulvestrant led to significant gene expression changes in tumor suppressors and cell cycle genes.
Early ctDNA clearance rates were highest with prifetrastat 5 mg QD plus fulvestrant, showing 26% overall clearance and specific rates for resistance-associated mutations.
Clearance correlated with durable clinical responses regardless of baseline mutation status.

Cite This Study

Liu et al. (2026) studied this question.

synapsesocial.com/papers/69e473ff010ef96374d8fb6c https://doi.org/10.1158/1538-7445.am2026-ct174

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Implication

Phase 1/2a study demonstrates early ctDNA clearance in ER+/HER2− metastatic breast cancer, suggesting effective intervention strategies.

Abstract CT174: Unlocking endocrine resistance: Co-targeting KAT6 and ER with prifetrastat (PF-07248144) and fulvestrant drives tumor and ctDNA response in ER+/HER2− metastatic breast cancer

Discussion

Member takes

Implication

Key Points

Cite This Study

Abstract CT174: Unlocking endocrine resistance: Co-targeting KAT6 and ER with prifetrastat (PF-07248144) and fulvestrant drives tumor and ctDNA response in ER+/HER2− metastatic breast cancer

Discussion

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Implication

Key Points

Cite This Study

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