ArticleThe American journal of pathology2010
PTEN, PIK3CA, p-AKT, and p-p70S6K status: association with trastuzumab response and survival in patients with HER2-positive metastatic breast cancer.
Article in The American journal of pathology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 155 papers, 4 of them syntheses that pooled it.
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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.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
155 citing papers in PubMed, 4 syntheses or guidelines pooled it, 285 citations in OpenAlex.
- Pooled it
- The association between phosphatase and tensin homolog hypermethylation and patients with breast cancer, a meta-analysis and literature review.Scientific reports · 2016Pooled it
- Diagnostic Accuracy of PIK3CA Mutation Detection by Circulating Free DNA in Breast Cancer: A Meta-Analysis of Diagnostic Test Accuracy.PloS one · 2016Pooled it
- A pharmacogenomic method for individualized prediction of drug sensitivity.Molecular systems biology · 2011Pooled it
- Methods for Estimating Long-Term Outcomes for Trastuzumab Deruxtecan in HER2-Positive Unresectable or Metastatic Breast Cancer After Two or More Anti-HER2 Therapies.Targeted oncology · 2022Trial
- Low PTEN levels and PIK3CA mutations predict resistance to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2 over-expressing breast cancer.Breast cancer research and treatment · 2018Trial
- Efficacy and safety of everolimus in combination with trastuzumab and paclitaxel in Asian patients with HER2+ advanced breast cancer in BOLERO-1.Breast cancer research : BCR · 2017Trial
- Relationship between Tumor Biomarkers and Efficacy in EMILIA, a Phase III Study of Trastuzumab Emtansine in HER2-Positive Metastatic Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Trial
- Benefit to neoadjuvant anti-human epidermal growth factor receptor 2 (HER2)-targeted therapies in HER2-positive primary breast cancer is independent of phosphatase and tensin homolog deleted from chromosome 10 (PTEN) status.Annals of oncology : official journal of the European Society for Medical Oncology · 2015Trial
- PTEN Loss Is Associated with Worse Outcome in HER2-Amplified Breast Cancer Patients but Is Not Associated with Trastuzumab Resistance.Clinical cancer research : an official journal of the American Association for Cancer Research · 2015Trial
- Impact of PTEN protein expression on benefit from adjuvant trastuzumab in early-stage human epidermal growth factor receptor 2-positive breast cancer in the North Central Cancer Treatment Group N9831 trial.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2013Trial
- An open-label safety study of lapatinib plus trastuzumab plus paclitaxel in first-line HER2-positive metastatic breast cancer.The oncologist · 2013Trial
- A phase I/II prospective, single arm trial of gefitinib, trastuzumab, and docetaxel in patients with stage IV HER-2 positive metastatic breast cancer.Breast cancer research and treatment · 2012Trial
- Phase I/II study of trastuzumab in combination with everolimus (RAD001) in patients with HER2-overexpressing metastatic breast cancer who progressed on trastuzumab-based therapy.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2011Trial
- HER2 targeted therapy resistance in breast cancer: from molecular landscape to clinical aspects.Science China. Life sciences · 2026Review
- Phylogeography of Bone Metastasis: Clonal Evolution, Skeletal Niche Adaptation, and Clinical Implications.International journal of molecular sciences · 2026Review
- Immunohistochemistry for PTEN testing in HR +/HER2- metastatic breast cancer.Virchows Archiv : an international journal of pathology · 2025Review
- The Underlying Mechanisms and Emerging Strategies to Overcome Resistance in Breast Cancer.Cancers · 2025Review
- A phase I study of AZD8186 in combination with docetaxel in patients with PTEN-mutated or PIK3CB-mutated advanced solid tumors.ESMO open · 2025Article
95 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
Abstract
Phosphatase and tensin homolog (PTEN) is a key modulator of trastuzumab sensitivity in HER2-overexpressing breast cancer. Because PTEN opposes the downstream signaling of phosphoinositide 3-kinase (PI3K), we investigated the role of PTEN and other components of the PI3K pathway in trastuzumab resistance. We analyzed the status of PTEN, p-AKT-Ser473, and p-p70S6K-Thr389 using immunohistochemistry. PIK3CA mutation status was analyzed by direct sequencing. Primary tumor tissue was available from 137 patients with HER2-overexpressing metastatic breast cancer who had received trastuzumab-based chemotherapy. We observed that each of the four biomarkers alone did not significantly correlate with trastuzumab response, whereas PTEN loss alone significantly correlated with shorter survival times (P = 0.023). PI3K pathway activation, defined as PTEN loss and/or PIK3CA mutation, was associated with a poor response to trastuzumab (P = 0.047) and a shorter survival time (P = 0.015). PTEN loss was significantly associated with a poor response to trastuzumab (P = 0.028) and shorter survival time (P = 0.008) in patients who had received first-line trastuzumab and in patients with estrogen receptor- (P = 0.029) and progesterone receptor-negative tumors (P = 0.033). p-AKT-Ser473 and p-p70S6K-Thr389 each had a limited correlation with trastuzumab response. When these markers were combined with PTEN loss, an increased correlation with patient outcome was observed. In conclusion, PI3K pathway activation plays a pivotal role in trastuzumab resistance. Our findings may facilitate the evaluation of tumor response to trastuzumab-based and targeted therapies.
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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.