What question did this study set out to answer?

This study aims to determine how TP53 status and licensing complex (LC) profiles affect endocrine therapy outcomes in ER+/HER2- breast cancer patients treated with CDK4/6 inhibitors.

May 29, 2026Journal of Clinical Oncology

TP53 status and licensing complex/IFNγ transcriptional profiles to stratify endocrine-related outcomes with CDK4/6i exposure in 10,833 real-world ER+/HER2- breast cancers and a treatment-naïve subset.

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This study aims to determine how TP53 status and licensing complex (LC) profiles affect endocrine therapy outcomes in ER+/HER2- breast cancer patients treated with CDK4/6 inhibitors.
Analysed ER+/HER2- breast cancer biopsies (N=10,833; treatment-naïve subset N=1,960) with DNA and RNA sequencing.
Calculated LC and IFNγ scores, comparing quartiles to predict time on endocrine therapy (To1 and ToT).
Estimated immune microenvironment proportions using quanTIseq deconvolution.
LC score Q4 predicted shorter ToT for endocrine therapy whether or not CDK4/6i was used (HR 1.27, p<0.0001).
In TP53 wild-type tumors, LC-Q4/IFNγ-Q4 showed a trend toward shorter ToT compared to LC-Q1/IFNγ-Q1 (42.7 vs 26.5 months, HR 1.67, p=0.075).
IFNγ score quartiles significantly predicted shorter initial time on endocrine therapy with CDK4/6i exposure (14.4 vs 19.9 months, HR 1.28, p=0.0074).

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Implication

Randomized trial correlates TP53 and transcriptional profiles with endocrine therapy outcomes in ER+/HER2- breast cancer, indicating potential predictive value.

Cite This Study

Raghavan et al. (2026) studied this question.

synapsesocial.com/papers/6a192e4efab5b468c4417645 https://doi.org/10.1200/jco.2026.44.16_suppl.1032

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Implication

Randomized trial correlates TP53 and transcriptional profiles with endocrine therapy outcomes in ER+/HER2- breast cancer, indicating potential predictive value.

TP53 status and licensing complex/IFNγ transcriptional profiles to stratify endocrine-related outcomes with CDK4/6i exposure in 10,833 real-world ER+/HER2- breast cancers and a treatment-naïve subset.

Key Points

Discussion

Implication

Cite This Study

TP53 status and licensing complex/IFNγ transcriptional profiles to stratify endocrine-related outcomes with CDK4/6i exposure in 10,833 real-world ER+/HER2- breast cancers and a treatment-naïve subset.

Key Points

Discussion

Implication

Cite This Study

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