The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer is driven by molecular features.
biomarkers
everolimus
luminal metastatic breast cancer
prognosis
Journal
The journal of pathology. Clinical research
ISSN: 2056-4538
Titre abrégé: J Pathol Clin Res
Pays: England
ID NLM: 101658534
Informations de publication
Date de publication:
May 2024
May 2024
Historique:
revised:
04
03
2024
received:
20
11
2023
accepted:
11
03
2024
medline:
2
4
2024
pubmed:
2
4
2024
entrez:
2
4
2024
Statut:
ppublish
Résumé
Everolimus is widely used in patients with advanced ER-positive, HER2-negative breast cancer. We looked at alterations in the PIK3CA/AKT/mTOR pathway in a multicenter cohort as potential biomarkers of efficacy. Patients with advanced ER-positive, HER2-negative breast cancer treated with everolimus and endocrine therapy between 2012 and 2014 in two cancer centers were included. Targeted sequencing examined mutations in PIK3CA, ESR1, and AKT1 genes. An immunochemical analysis was conducted to evaluate expression of PTEN, INPP4B, STK11, p4EBP1, and pS6. We analyzed 71 patients (44 primary tumors; 27 metastatic tissues). Median age was 63 years [58-69]. All patients had heavily pretreated advanced disease. A mutation in the PIK3CA pathway was observed in 32 samples (PIK3CA exons 10 and 21 and AKT1 exon 4 in 15.5%, 24.0%, and 5.6% of samples), and in ESR1 in 5 samples (7.0%), respectively. Most samples showed cytoplasmic expression of the PIK3CA pathway proteins. Progression-free survival was longer in patients with a pS6 or p4EBP1 histoscore ≥ median value (6.6 versus 3.7 months, p = 0.037), and in patients with a PTEN histoscore ≤ median value (7.1 versus 5.3 months, p = 0.02). Overall survival was longer in patients with pS6 ≥ 3rd quartile (27.6 versus 19.3 months, p = 0.038) and in patients with any mutation in the PIK3CA/AKT/mTOR pathway (27.6 versus 19.3 months, p = 0.011). The prognosis of patients treated with everolimus for advanced ER-positive, HER2-negative breast cancer appears primarily driven by molecular features associated with the activation of the PIK3CA/AKT/mTOR pathway.
Identifiants
pubmed: 38563252
doi: 10.1002/2056-4538.12372
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
e12372Subventions
Organisme : Novartis
Informations de copyright
© 2024 The Authors. The Journal of Pathology: Clinical Research published by The Pathological Society of Great Britain and Ireland and John Wiley & Sons Ltd.
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