PIK3CA mutation status, progression and survival in advanced HR + /HER2- breast cancer: a meta-analysis of published clinical trials.

Antineoplastic Combined Chemotherapy Protocols / therapeutic use Breast Neoplasms / pathology Class I Phosphatidylinositol 3-Kinases / genetics Disease-Free Survival Female Humans Mutation Phosphatidylinositol 3-Kinases / genetics Phosphatidylinositols / therapeutic use Receptor, ErbB-2 / genetics
Hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) Metastatic breast cancer (mBC) Overall survival PIK3CA Progression-free survival

Journal

BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800

Informations de publication

Date de publication:
21 Sep 2022
Historique:
received: 28 10 2021
accepted: 05 09 2022
entrez: 21 9 2022
pubmed: 22 9 2022
medline: 24 9 2022
Statut: epublish

Résumé

Approximately 40% of hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) metastatic breast cancer (mBC) patients harbor phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations. However, associations between PIK3CA mutation status and clinical outcomes among patients with HR + /HER2- mBC have been heterogeneous across clinical trials. This meta-analysis was conducted to survey recently available trial data to assess the prognostic effects of PIK3CA among patients with HR + /HER2- mBC.  METHODS: Randomized clinical trials reporting progression-free survival (PFS) or overall survival (OS) stratified by PIK3CA status in HR + /HER2- mBC were identified via systematic literature review. Trial arms receiving phosphatidylinositol 3-kinase (PI3K)-targeted therapies were excluded. Meta-regression analysis was used to estimate the association between PIK3CA status and PFS and OS among included studies. The analyzed data included 3,219 patients from 33 study arms across 11 trials (PIK3CA mutated: 1,386, wild type: 1,833). PIK3CA mutation was associated with shorter median PFS (difference [95% CI] (months): -1.8 [-3.4, -0.1], I Pooling evidence across multiple studies, PIK3CA mutation was associated with shorter PFS and OS. These findings suggest a negative prognostic value of PIK3CA mutations in patients with HR + /HER2- mBC.

Sections du résumé

BACKGROUND BACKGROUND
Approximately 40% of hormone receptor positive/human epidermal receptor 2 negative (HR + /HER2-) metastatic breast cancer (mBC) patients harbor phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutations. However, associations between PIK3CA mutation status and clinical outcomes among patients with HR + /HER2- mBC have been heterogeneous across clinical trials. This meta-analysis was conducted to survey recently available trial data to assess the prognostic effects of PIK3CA among patients with HR + /HER2- mBC.  METHODS: Randomized clinical trials reporting progression-free survival (PFS) or overall survival (OS) stratified by PIK3CA status in HR + /HER2- mBC were identified via systematic literature review. Trial arms receiving phosphatidylinositol 3-kinase (PI3K)-targeted therapies were excluded. Meta-regression analysis was used to estimate the association between PIK3CA status and PFS and OS among included studies.
RESULTS RESULTS
The analyzed data included 3,219 patients from 33 study arms across 11 trials (PIK3CA mutated: 1,386, wild type: 1,833). PIK3CA mutation was associated with shorter median PFS (difference [95% CI] (months): -1.8 [-3.4, -0.1], I
CONCLUSIONS CONCLUSIONS
Pooling evidence across multiple studies, PIK3CA mutation was associated with shorter PFS and OS. These findings suggest a negative prognostic value of PIK3CA mutations in patients with HR + /HER2- mBC.

Identifiants

DOI: 10.1186/s12885-022-10078-5 PMID: 36131248 PMC: PMC9490901
pubmed: 36131248
doi: 10.1186/s12885-022-10078-5
pii: 10.1186/s12885-022-10078-5
pmc: PMC9490901
doi:

Substances chimiques

Phosphatidylinositols 0
Class I Phosphatidylinositol 3-Kinases EC 2.7.1.137
PIK3CA protein, human EC 2.7.1.137
Receptor, ErbB-2 EC 2.7.10.1

Types de publication

Journal Article Meta-Analysis Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

1002

Informations de copyright

© 2022. The Author(s).

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Auteurs

Mirko Fillbrunn (M)

Analysis Group, Inc., Boston, Massachusetts, USA.

James Signorovitch (J)

Analysis Group, Inc., Boston, Massachusetts, USA. James.Signorovitch@analysisgroup.com.

Fabrice André (F)

Institut Gustave Roussy, Villejuif, France.

Iris Wang (I)

Novartis, East Hanover, New Jersey, USA.

Ines Lorenzo (I)

Novartis, Madrid, Spain.

Antonia Ridolfi (A)

Novartis, Paris, France.

Jinhee Park (J)

Novartis, East Hanover, New Jersey, USA.

Akanksha Dua (A)

Analysis Group, Inc., Boston, Massachusetts, USA.

Hope S Rugo (HS)

University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, California, USA.

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Classifications MeSH

questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Association de médicaments › Protocoles de polychimiothérapie antinéoplasique › PIK3CA mutation status, progression and...
questionsmedicales.fr › Maladies de la peau et du tissu conjonctif › Maladies de la peau › Maladies du sein › Tumeurs du sein › PIK3CA mutation status, progression and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphatidylinositol 3-kinases › Phosphatidylinositol-4-phosphate 3-kinase › Phosphatidylinositol 3-kinases de classe I › PIK3CA mutation status, progression and...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Statistiques comme sujet › Analyse de survie › Survie sans rechute › PIK3CA mutation status, progression and...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › PIK3CA mutation status, progression and...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › Mutation › PIK3CA mutation status, progression and...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines et peptides de signalisation intracellulaire › Phosphatidylinositol 3-kinases › PIK3CA mutation status, progression and...
questionsmedicales.fr › Lipides › Lipides membranaires › Phospholipides › Glycérophosphate › Acides phosphatidiques › Glycérophospholipides › Phosphatidyl inositols › PIK3CA mutation status, progression and...
questionsmedicales.fr › Facteurs biologiques › Marqueurs biologiques › Marqueurs biologiques tumoraux › Récepteur ErbB-2 › PIK3CA mutation status, progression and...