Trial reportBreast cancer research and treatment2018
Low PTEN levels and PIK3CA mutations predict resistance to neoadjuvant lapatinib and trastuzumab without chemotherapy in patients with HER2 over-expressing breast cancer.
Trial report in Breast cancer research and treatment, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00548184 (A Phase II Trial of Lapatinib and Trastuzumab With or Without Endocrine Therapy in Locally Advanced HER2 Overexpressing Breast Cancer Patients), which is not on this map. Cited by 60 papers, 3 of them syntheses that pooled 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.
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.
A Phase II Trial of Lapatinib and Trastuzumab With or Without Endocrine Therapy in Locally Advanced HER2 Overexpressing Breast Cancer Patients
Who cites it
60 citing papers in PubMed, 3 syntheses or guidelines pooled it, 95 citations in OpenAlex.
- Comparing Biomarkers for Predicting Pathological Responses to Neoadjuvant Therapy in HER2-Positive Breast Cancer: A Systematic Review and Meta-Analysis.Frontiers in oncology · 2021Pooled it
- HER2-enriched subtype and pathological complete response in HER2-positive breast cancer: A systematic review and meta-analysis.Cancer treatment reviews · 2020Pooled it
- Pooled it
- Updated Results of TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathological Complete Response to Pertuzumab and Trastuzumab in Breast Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Evaluation of the Predictive Role of Tumor Immune Infiltrate in Patients with HER2-Positive Breast Cancer Treated with Neoadjuvant Anti-HER2 Therapy without Chemotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2020Trial
- A randomized, controlled phase II trial of neoadjuvant ado-trastuzumab emtansine, lapatinib, and nab-paclitaxel versus trastuzumab, pertuzumab, and paclitaxel in HER2-positive breast cancer (TEAL study).Breast cancer research : BCR · 2019Trial
- TBCRC026: Phase II Trial Correlating Standardized Uptake Value With Pathologic Complete Response to Pertuzumab and Trastuzumab in Breast Cancer.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2019Trial
- HER3 Expression and PIK3CA Mutational Status Predict Pathological Response of Neoadjuvant Therapy in HER2-Positive Breast Cancer Patients.Cancer research and treatment · 2026Article
- Genomic landscape, immune microenvironment and survival in male versus female breast cancer.ESMO open · 2026Article
- Addition of Ipatasertib to Dual Anti-HER2 Maintenance Therapy in HER2-Positive Metastatic Breast Tumors with PIK3CA Mutations: The Phase Ib SOLTI-1507 IPATHER Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- Article
- Immunohistochemistry for PTEN testing in HR +/HER2- metastatic breast cancer.Virchows Archiv : an international journal of pathology · 2025Review
- Metabolic hallmarks of trastuzumab resistance.Expert opinion on therapeutic targets · 2025Review
- Neoadjuvant pyrotinib and trastuzumab in HER2-positive breast cancer with no early response (NeoPaTHer): efficacy, safety and biomarker analysis of a prospective, multicentre, response-adapted study.Signal transduction and targeted therapy · 2025Article
- Clinicopathological and prognostic analysis of PIK3CA mutated invasive breast cancer in Chinese women.Clinics (Sao Paulo, Brazil) · 2025Article
- HER2-Positive Breast Cancer Treatment and Resistance.Advances in experimental medicine and biology · 2025Review
- Targeted Sequencing of HER2-Positive Breast Cancer Mutations Revealed a Potential Association between PIK3CA and Trastuzumab Resistance.Asian Pacific journal of cancer prevention : APJCP · 2024Article
- Combined transcriptome and proteome analysis reveals MSN and ARFIP2 as biomarkers for trastuzumab resistance of breast cancer.Breast cancer research and treatment · 2024Article
- PTEN deficiency induces an extrahepatic cholangitis-cholangiocarcinoma continuum via aurora kinase A in mice.Journal of hepatology · 2024Article
- The FBXW7-binding sites on FAM83D are potential targets for cancer therapy.Breast cancer research : BCR · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
24 authors at 10 institutions in 1 country.
Funding
Abstract
purposeAberrant activation of the PI3K pathway has been implicated in resistance to HER2-targeted therapy, but results of clinical trials are confounded by the co-administration of chemotherapy. We investigated the effect of perturbations of this pathway in breast cancers from patients treated with neoadjuvant anti-HER2-targeted therapy without chemotherapy. PATIENTS AND
methodsBaseline tumor samples from patients with HER2-positive breast cancer enrolled in TBCRC006 (NCT00548184), a 12-week neoadjuvant clinical trial with lapatinib plus trastuzumab [plus endocrine therapy for estrogen receptor (ER)-positive tumors], were assessed for PTEN status by immunohistochemistry and PIK3CA mutations by sequencing. Results were correlated with pathologic complete response (pCR).
resultsOf 64 evaluable patients, PTEN immunohistochemistry and PIK3CA mutation analysis were performed for 59 and 46 patients, respectively. PTEN status (dichotomized by H-score median) was correlated with pCR (32% in high PTEN vs. 9% in low PTEN, p = 0.04). PIK3CA mutations were identified in 14/46 tumors at baseline (30%) and did not correlate with ER or PTEN status. One patient whose tumor harbored a PIK3CA mutation achieved pCR (p = 0.14). When considered together (43 cases), 1/25 cases (4%) with a PIK3CA mutation and/or low PTEN expression levels had a pCR compared to 7/18 cases (39%) with wild-type PI3KCA and high PTEN expression levels (p = 0.006).
conclusionPI3K pathway activation is associated with resistance to lapatinib and trastuzumab in breast cancers, without chemotherapy. Further studies are warranted to investigate how to use these biomarkers to identify upfront patients who may respond to anti-HER2 alone, without chemotherapy.
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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.