Evidence map›Paper›PMID 40038334›Full record

Trial reportNature communications2025

Determinants of response and molecular dynamics in HER2+ER+ breast cancers from the NA-PHER2 trial receiving HER2-targeted and endocrine therapies.

Maurizio Callari, Matteo Dugo, Marco Barreca, Balázs Győrffy, Barbara Galbardi, Lucia Vigano, Alberta Locatelli, Chiara Dall'Ara, Marina Ferrarini, Giancarlo Bisagni and 12 more

Registry-linked trialAbstract readClinical Trial, Phase II
In one paragraph

Trial report in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02530424 ("Neo-Adjuvant Treatment With the CDK4,6 Inhibitor Palbociclib in HER2-positive and ER-positive Breast Cancer), which is not on this map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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.

NCT02530424 phase2completednot on this map

"Neo-Adjuvant Treatment With the CDK4,6 Inhibitor Palbociclib in HER2-positive and ER-positive Breast Cancer: Effect on Ki67 and Apoptosis Before, During and After Treatment "

TypeinterventionalSponsorFondazione MichelangeloRan2015 to 2019Enrolled102ConditionsBreast NeoplasmsArmsTrastuzumab, Pertuzumab, Palbociclib, Fulvestrant
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Trial
  2. Article
  3. Article
  4. Review
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

22 authors.

Maurizio CallariFondazione Michelangelo, Milan, Italy.ORCID http://orcid.org/0000-0001-5239-0918
Matteo DugoIRCCS San Raffaele Hospital, Milan, Italy.ORCID http://orcid.org/0000-0001-9786-2763
Marco BarrecaFondazione Michelangelo, Milan, Italy.ORCID http://orcid.org/0000-0002-9152-236X
Balázs GyőrffyDept. of Bioinformatics, Semmelweis University, Budapest, Hungary.
Barbara GalbardiIRCCS San Raffaele Hospital, Milan, Italy.
Lucia ViganoIRCCS San Raffaele Hospital, Milan, Italy.ORCID http://orcid.org/0000-0003-4538-4354
Alberta LocatelliIRCCS San Raffaele Hospital, Milan, Italy.ORCID http://orcid.org/0000-0003-0251-6433
Chiara Dall'AraIRCCS San Raffaele Hospital, Milan, Italy.ORCID http://orcid.org/0009-0004-8934-9053
Marina FerrariniIRCCS San Raffaele Hospital, Milan, Italy.
Giancarlo BisagniAUSL - IRCCS, Reggio Emilia, Italy.
Marco ColleoniIEO, European Institute of Oncology, IRCCS, Milan, Italy.
Mauro MansuttiUdine Academic Hospital, Udine, Italy.
Claudio ZamagniIRCCS Azienda Ospedaliero Universitaria, Bologna, Italy.
Lucia Del MastroDepartment of Internal Medicine and Medical Specialties (DiMI), School of Medicine, Università di Genova, Genoa, Italy.ORCID http://orcid.org/0000-0002-9546-5841
Stefania ZambelliIRCCS San Raffaele Hospital, Milan, Italy.
Antonio FrassoldatiAzienda Ospedaliera Universitaria S. Anna, Ferrara, Italy.
Olivia BiasiIEO, European Institute of Oncology, IRCCS, Milan, Italy.
Lajos PusztaiDepartment of Internal Medicine, Section of Medical Oncology, Yale School of Medicine, New Haven, CT, USA.ORCID http://orcid.org/0000-0001-9632-6686
Pinuccia ValagussaFondazione Michelangelo, Milan, Italy.ORCID http://orcid.org/0000-0003-3590-7916
Giuseppe VialeFondazione Michelangelo, Milan, Italy.
Luca GianniFondazione Michelangelo, Milan, Italy. luca.gianni@fondazionemichelangelo.org.
Giampaolo BianchiniIRCCS San Raffaele Hospital, Milan, Italy. bianchini.giampaolo@hsr.it.ORCID http://orcid.org/0000-0002-6790-6267

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Improved outcomes in HER2+ female breast cancer have resulted from chemotherapy and anti-HER2 therapies. However, HER2+ER+ cancers exhibit lower response rates. The phase 2 NA-PHER2 trial (NCT02530424) investigated chemo-free preoperative HER2 blockade (trastuzumab + pertuzumab) and CDK4/6 inhibition (palbociclib) with or without endocrine therapy (fulvestrant) in HER2+ER+ breast cancer. Clinical endpoints (i.e. Ki67 dynamics and pathological complete response) were previously reported. Here we report on the biomarker analysis, secondary objective of the study. Through RNA sequencing and tumour infiltrating lymphocytes (TIL) assessment in serial biopsies, we identified biomarkers predictive of pCR or Day14 Ki67 response and unveiled treatment-induced molecular changes. High immune infiltration and low ER signalling correlated with pCR, while TP53 mutations associated with high Day14 Ki67. Stratification based on Ki67 at Day14 and at surgery defined three response groups (Ki67 HighHigh, LowHigh, LowLow), with divergent tumour and stroma expression dynamics. The HighHigh group showed dysfunctional immune infiltration and overexpression of therapeutic targets like PAK4 at baseline. The LowLow group exhibited a Luminal A phenotype by the end of treatment. This study expands our understanding of drivers and dynamics of HER2+ER+ tumour response, towards treatment tailoring.

Indexed as

Antineoplastic Combined Chemotherapy ProtocolsBreast NeoplasmsErb-b2 Receptor Tyrosine KinasesAntibodies, Monoclonal, HumanizedAntineoplastic Agents, HormonalBiomarkers, TumorFemaleHumansKi-67 AntigenLymphocytes, Tumor-InfiltratingMiddle AgedPiperazinesPyridinesReceptors, EstrogenTrastuzumabTreatment OutcomeAntibodies, Monoclonal, HumanizedAntineoplastic Agents, HormonalBiomarkers, TumorERBB2 protein, humanErb-b2 Receptor Tyrosine KinasesKi-67 AntigenpalbociclibpertuzumabPiperazinesPyridinesReceptors, EstrogenTP53 protein, humanTrastuzumabTumor Suppressor Protein p53

Identifiers

PMID40038334
PMCPMC11880565

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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.