Evidence map›Paper›PMID 42214155›Full record

Observational studyBreast (Edinburgh, Scotland)2026

Interplay between HER2-Low status, hormone receptor expression, and therapeutic response to cyclin-dependent kinase 4/6 inhibitors as first-line treatment in luminal-like metastatic breast cancer: The CYCLHER study.

Letizia Pontolillo, Elisabetta Munzone, Paolo Vigneri, Mirco Pistelli, Antonella Palazzo, Nicla La Verde, Marco Mazzotta, Ida Paris, Daniele Alesini, Daniele Santini and 19 more

Registry-linked trialAbstract readMulticenter StudyObservational Study
PubMed Full text at PMC Publisher
In one paragraph

Observational study in Breast (Edinburgh, Scotland), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06243432 (Estrogen Receptors and HER2 Levels' Expression in Luminal Metastatic Breast Cancer), which is not on this 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.

NCT06243432 unknown statusnot on this map

Estrogen Receptors and HER2 Levels' Expression in Luminal Metastatic Breast Cancer: Correlation to Therapeutic Efficacy of Cycline-Dependent Kinase Inhibitors(CDK4/6) as First Line Treatment. CYCLHER Study

TypeobservationalSponsorFondazione Policlinico Universitario Agostino Gemelli IRCCSRan2023 to 2025Enrolled600ConditionsAdvanced Breast Carcinoma
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

29 authors.

Letizia PontolilloDepartment of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Elisabetta MunzoneDivision of Medical Senology, IEO European Institute of Oncology IRCCS, Milan, Italy.
Paolo VigneriDepartment of Clinical and Experimental Medicine, University of Catania, Catania, Italy; University Oncology Department, Humanitas Istituto Clinico Catanese, Catania, Italy.
Mirco PistelliOncological Clinic, Università Politecnica delle Marche, AOU delle Marche, Ancona, Italy.
Antonella PalazzoComprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Nicla La VerdeDepartment of Oncology, ASST Fatebenefratelli-Sacco, Luigi Sacco University Hospital, Milan, Italy.
Marco MazzottaDepartment of Medical Oncology, Medical Oncology Unit, Sandro Pertini Hospital, Rome, Italy.
Ida ParisDepartment of Woman and Child Health, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Daniele AlesiniS. Spirito e Nuovo Regina Margherita Cancer Center, Ospedale Santo Spirito in Sassia, Rome, Italy.
Daniele SantiniDepartment of Medico-Surgical Sciences and Biotechnology, Polo Pontino, Sapienza University of Rome, Rome, Italy.
Katia CannitaMedical Oncology Unit, Department of Oncology, "Giuseppe Mazzini" Hospital, Teramo, Italy.
Armando OrlandiComprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Emanuela MagnolfiMedical Oncology, P.O. SS Trinità, ASL Frosinone, Sora, Italy.
Laura GiacintiMedical Oncology - P.O. S. Giuseppe - Marino, Rome, Italy.
Mimma RaffaeleOncologia Presidio Cassia S Andrea- Breast Unit - ASL Roma 1, Rome, Italy.
Luisa CarbogninPrecision Medicine in Senology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Angela SantoroGynecologic and Breast Pathology Unit, Department of Women's, Children's and Public Health Sciences, "A. Gemelli" University Hospital Foundation IRCCS, Rome, Italy.
Alessandro RossiPrecision Medicine in Senology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy.
Giorgia ArcuriComprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Claudia SangalliClinical Trial Office, IEO European Institute of Oncology IRCCS, Milan, Italy.
Ornella GarroneMedical Oncology Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy.
Antonio MulèGynecologic and Breast Pathology Unit, Department of Women's, Children's and Public Health Sciences, "A. Gemelli" University Hospital Foundation IRCCS, Rome, Italy.
Carmine ValenzaDivision of Early Drug Development, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Rossana BerardiOncological Clinic, Università Politecnica delle Marche, AOU delle Marche, Ancona, Italy.
Giampaolo TortoraDepartment of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Emilio BriaDepartment of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy; Medical Oncology, Ospedale Isola Tiberina- Gemelli Isola, Rome Italy.
Giuseppe CuriglianoDivision of Early Drug Development, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
Diana GiannarelliBiostatistical Unit, Comprehensive Cancer Center, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.
Alessandra FabiPrecision Medicine in Senology Unit, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. Electronic address: alessandra.fabi@policlinicogemelli.it.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundIn hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer (mBC), the prognostic significance of estrogen receptor (ER), progesterone receptor (PgR), and HER2 immunohistochemical expression levels in patients treated with cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) remains unclear. The CYCLHER study was designed to evaluate treatment outcomes and identify biologically driven prognostic factors.

methodsCYCLHER (NCT06243432) is a retrospective, multicenter study conducted across 16 Italian oncology centers. Patients with HR+/HER2- mBC who received first-line endocrine therapy (ET) plus CDK4/6i between November 2016 and May 2023 were included. ER, PgR and HER2 status were assessed on metastatic or primary tumor samples. The primary endpoint was real-world progression-free survival (rwPFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), duration of response (DoR), and attrition rate. Optimal cut-off values for ER and PgR expression were determined using Cut-off Finder v1.0.

resultsAmong 597 eligible patients, median rwPFS was 28.1 months at a median follow-up of 41 months. HER2-low status emerged as a negative prognostic factor, being independently associated with shorter rwPFS compared to HER2-0 (p = 0.02). ER ≥ 87% and PgR ≥60% were associated with improved rwPFS, DCR, and 5-year OS rates. A prognostic score derived from the three biomarkers identified four groups with significantly different rwPFS outcomes (global log-rank p < 0.0001). The first-to-second line attrition rate was 16.2% (95% CI 12.4-20.0). The identified biomarkers did not significantly impact treatment outcomes in the second-line setting.

conclusionsCYCLHER confirms the prognostic relevance of ER, PgR, and HER2 expression in patients with HR+/HER2-mBC treated with CDK4/6i. HER2-low status was associated with poorer outcomes, supporting its potential role as a negative prognostic marker. The proposed score may facilitate personalized treatment strategies and enhance risk stratification in clinical practice.

Indexed as

Breast NeoplasmsCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6Erb-b2 Receptor Tyrosine KinasesProtein Kinase InhibitorsReceptors, EstrogenReceptors, ProgesteroneAdultAgedAminopyridinesBiomarkers, TumorFemaleHumansItalyMiddle AgedPrognosisAminopyridinesBiomarkers, TumorCDK4 protein, humanCDK6 protein, humanCyclin-Dependent Kinase 4Cyclin-Dependent Kinase 6ERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesProtein Kinase InhibitorsPurinesReceptors, EstrogenReceptors, ProgesteroneribociclibAdvanced breast cancerCDK4/6 inhibitorsHER2-LowHR expressionReal-world data

Identifiers

PMID42214155
PMCPMC13241962

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Registered trials

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.