Evidence map›Paper›PMID 42174712›Full record

ArticleBreast cancer research : BCR2026

TP53 mutation is associated with shorter treatment duration with CDK4/6 inhibitors, but not with immune checkpoint inhibitors, in ER-positive/HER2-negative breast cancer: real-world perspective.

Masanori Oshi, Makoto Sugimori, Kei Kawashima, Shipra Gandhi, Akimitsu Yamada, Kazutaka Narui, Takashi Ishikawa, Itaru Endo, Kazuaki Takabe

Abstract read
In one paragraph

Article in Breast cancer research : BCR, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors.

Masanori OshiDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA. oshi.mas.wc@yokohama-cu.ac.jp.
Makoto SugimoriDivision of Cancer Genome Medicine, Yokohama City University Medical Center, Yokohama, Japan.
Kei KawashimaDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.
Shipra GandhiWinship Cancer Institute of Emory University, Atlanta, GA, USA.
Akimitsu YamadaDepartment of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Kazutaka NaruiDepartment of Breast and Thyroid Surgery, Yokohama City University Medical Center, Yokohama, Kanagawa, Japan.
Takashi IshikawaDepartment of Breast Surgery and Oncology, Tokyo Medical University, Tokyo, Japan.
Itaru EndoDepartment of Gastroenterological Surgery, Yokohama City University Graduate School of Medicine, Yokohama, Kanagawa, Japan.
Kazuaki TakabeDepartment of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA.

Funding

Impact of Circulating Myeloid Cell Clusters on Anti-Tumor ImmunityR01CA250412 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI ABRAMS, SCOTT I., EVANS, SHARON S · 2021 to 2025
$3.4M
Functional Significance of individual p53 mutations in determining the role of estrogen receptor beta in triple negative breast cancerR01CA251545 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI DAS, GOKUL M. · 2021 to 2025
$2.9M
Leveraging the GTP Biosynthetic Pathway for Anti-Tumor TherapiesR37CA248018 · NCI · ROSWELL PARK CANCER INSTITUTE CORP · PI Anna Bianchi-Smiraglia · 2021 to 2026
$2.3M
Multiparametric photoacoustic and ultrasonic imaging of the breast in cranial-caudal viewR01EB029596 · NIBIB · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI XIA, JUN · 2020 to 2023
$1.4M
Japan Society for the Promotion of Science 21K15535Japan Society for the Promotion of Science 23K14600NCI NIH HHS R01 CA250412NCI NIH HHS R01 CA251545NCI NIH HHS R37 CA248018NIBIB NIH HHS R01 EB029596NIH HHS R01CA250412NIH HHS R01CA251545NIH HHS , R01EB029596, W81XWH-19-1-0674 and W81XWH-19-1-0111NIH HHS R37CA248018NIH HHS R37CA248018, R01CA250412, R01CA251545, R01EB029596, W81XWH-19-1-0674 and W81XWH-19-1-0111
6 · The paper itself

Abstract

backgroundTP53 mutation is a critical driver of breast cancer, yet its relationship with treatment outcomes for breast cancer remains unclear. This study investigates the association between TP53 mutation and response to CDK4/6 inhibitors (CDK4/6i) and immune checkpoint inhibitors (ICI) in breast cancer using real-world data from the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) cohort, focusing on age-related differences.

methodsMETABRIC (n = 1355) was used for initial survival analysis, and gene set enrichment analysis (GSEA) was performed to identify pathways enriched in TP53-mutated ER-positive/HER2-negative breast cancers. Clinical and genomic data of metastatic breast cancer (mBC) patients in Japan were analyzed in the C-CAT (n = 1668) cohort. Treatment duration was used as a real-world surrogate endpoint reflecting treatment exposure and potential clinical benefit. Patients were stratified by age into four groups: Adolescents and Young Adults (AYA; 15-39 years), perimenopausal (40-54 years), menopausal (55-64 years), and older (≥ 65 years).

resultsTP53 mutations were associated with poor prognosis in the METABRIC cohort. GSEA showed TP53-mutated tumors were enriched with gene sets related to cell proliferation and immune response, while TP53 wild-type tumors enriched for estrogen response pathways. In the C-CAT cohort, TP53 mutations were linked to shorter CDK4/6i treatment duration with similar trends observed for both abemaciclib and palbociclib. However, TP53 mutations were not associated with ICI treatment duration. Patients in the AYA group had the shortest treatment duration, with TP53 mutation prevalence decreasing with age. In age-stratified analyses, TP53 mutation was associated with shorter treatment duration in perimenopausal, menopausal, and older groups but not in the AYA group. However, formal interaction testing did not detect a significant interaction between TP53 mutation and age group.

conclusionTP53 mutation is associated with shorter CDK4/6i treatment duration, highlighting the importance of considering both genomic and age-related clinical context when interpreting treatment duration in ER-positive/HER2-negative breast cancer.

Indexed as

Breast NeoplasmsCyclin-Dependent Kinase 6Immune Checkpoint InhibitorsMutationProtein Kinase InhibitorsTumor Suppressor Protein p53AdolescentAdultAgedCyclin-Dependent Kinase 4Erb-b2 Receptor Tyrosine KinasesFemaleHumansMiddle AgedPiperazinesPyridinesCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6ERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesImmune Checkpoint InhibitorspalbociclibPiperazinesProtein Kinase InhibitorsPyridinesReceptors, EstrogenTP53 protein, humanTumor Suppressor Protein p53Adolescents and young adultsBreast cancerCDK4/6 inhibitorImmune checkpoint inhibitorTP53Treatment duration

Identifiers

PMID42174712
PMCPMC13371642

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.