ArticleBritish journal of cancer2018
Hierarchical clustering of activated proteins in the PI3K and MAPK pathways in ER-positive, HER2-negative breast cancer with potential therapeutic consequences.
Article in British journal of cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 22 citations in OpenAlex.
- PI3K pathway protein analyses in metastatic breast cancer patients receiving standard everolimus and exemestane.Journal of cancer research and clinical oncology · 2020Trial
- In Silico Design and Evaluation of Quinone Methide Oxime Derivatives as Potential Non-Covalent Steroid Sulfatase Inhibitors.Molecules (Basel, Switzerland) · 2026Article
- Unraveling molecular interconnections and identifying potential therapeutic targets of significance in obesity-cancer link.Journal of the National Cancer Center · 2025Review
- A set of circulating microRNAs belonging to the 14q32 chromosome locus identifies two subgroups of individuals with recent-onset type 1 diabetes.Cell reports. Medicine · 2024Article
- Cyclin A2 and Ki-67 proliferation markers could be used to identify tumors with poor prognosis in African American women with breast cancer.Journal of cancer biology · 2023Article
- Article
- Resistance to endocrine therapy in HR + and/or HER2 + breast cancer: the most promising predictive biomarkers.Molecular biology reports · 2022Review
- Advances in Analyzing the Breast Cancer Lipidome and Its Relevance to Disease Progression and Treatment.Journal of mammary gland biology and neoplasia · 2021Review
- Phenomapping of Patients with Primary Breast Cancer Using Machine Learning-Based Unsupervised Cluster Analysis.Journal of personalized medicine · 2021Article
- Article
- IGF-1R pathway activation as putative biomarker for linsitinib therapy to revert tamoxifen resistance in ER-positive breast cancer.International journal of cancer · 2020Article
- Hierarchical clustering of PI3K and MAPK pathway proteins in breast cancer intrinsic subtypes.APMIS : acta pathologica, microbiologica, et immunologica Scandinavica · 2020Article
- Reprogramming of fatty acid metabolism in cancer.British journal of cancer · 2020Review
- Cancer-immune interactions in ER-positive breast cancers: PI3K pathway alterations and tumor-infiltrating lymphocytes.Breast cancer research : BCR · 2019Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe phosphatidylinositol-3-kinase (PI3K) and/or mitogen-activated protein kinase (MAPK) pathways are frequently activated in breast cancer which can result in antioestrogen resistance. Single protein markers failed to be introduced into clinical practice. We, therefore, aimed to find a better read-out of activation of the PI3K and MAPK pathways in ER+/HER2- breast cancer. Assessment of seven PI3K/MAPK proteins might better reflect pathway activation and distinguish patients without adjuvant tamoxifen benefit.
methodsTumour blocks were recollected from 293 primary postmenopausal ER+/HER2- breast cancer patients randomised between tamoxifen and no adjuvant therapy. PTEN, p-AKT(Thr308), p-AKT(Ser473), p-p70S6K, p-4EBP1, p-ERK1/2 and p-S6RP expression was assessed by immunohistochemistry followed by unsupervised hierarchical clustering. The primary endpoint was recurrence-free interval. Multivariate Cox models were used to assess tamoxifen benefit. A classification tool was developed based on protein expression profile.
resultsSubgroups were identified with preferentially activated (A) and preferentially not activated (N) proteins. Patients in group N derived significant benefit from tamoxifen (multivariate hazard ratio (HR) = 0.23, p = 0.000101), while patients from group A did not (multivariate HR = 1.37, p = 0.64), p for interaction 0.020. Our generated classification tool confirmed these results (p for interaction 0.024).
conclusionsHierarchical clustering of seven PI3K/MAPK proteins reflects pathway activation and can guide treatment decisions in primary ER+/HER2- postmenopausal breast cancer patients.
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