Clinical trial · Observational
PI3K Pathway Activation Markers in ER-Positive, HER2-Negative Breast Cancer: A Clinicopathologic Study
Immunohistochemical Evaluation of p-AKT and p-S6 as Surrogate Markers of PI3K/AKT/mTOR Pathway Activation in ER-Positive, HER2-Negative Breast Carcinoma
- Source
- ClinicalTrials.gov
- Retrieved
- Sep 8, 2026
- Layer
- normalized (units and labels harmonized; values unchanged)
- Run
- ING-CLINICALTRIALS-20260908-000001
Summary
Brief summary (as posted)
The goal of this observational study is to examine whether markers of PI3K pathway activation are associated with endocrine therapy response and clinicopathologic features in estrogen receptor-positive, HER2-negative breast cancer. The main questions it aims to answer are: Are immunohistochemical levels of phosphorylated AKT (p-AKT) and phosphorylated S6 (p-S6) different between endocrine-sensitive and endocrine-resistant breast cancer cases? Do different levels of p-AKT and p-S6 show distinct clinicopathologic and histologic characteristics, including features of the tumor microenvironment? Archived tumor tissue from patients who received adjuvant endocrine therapy as part of routine clinical care will be analyzed. Biomarker expression will be correlated with clinicopathologic parameters, including tumor-infiltrating lymphocyte density, tumor budding, and other histologic features, to explore associations with tumor behavior and outcomes.
Conditions
Conditions (1)
Free-text conditions as registered, with the CancerIndex entity they were reconciled to and the match type.
| Condition (as posted) | Mapped entity | Match | Confidence |
|---|---|---|---|
| Breast Cancer - ER+, HER2-, PIK3CA Gene Mutation | Breast Neoplasm | ONTOLOGY_EXACT | 0.90 |
Interventions
Interventions (1)
| Intervention | Type | Mapped drug | Match |
|---|---|---|---|
| Not applicable- observational study | Other | — | UNRESOLVED |
Design
Arms and outcomes
Arms (2)
- label
- Endocrine-Resistant Breast Cancer
- description
- Patients with ER-positive, HER2-negative invasive breast carcinoma who developed primary or secondary resistance to adjuvant endocrine therapy.
- interventionNames
- Other: Not applicable- observational study
- label
- Endocrine-Sensitive Breast Cancer
- description
- Patients with ER-positive, HER2-negative invasive breast carcinoma who remained relapse-free during adjuvant endocrine therapy and for ≥12 months after completion, with sufficient follow-up.
- interventionNames
- Other: Not applicable- observational study
Primary outcomes (1)
- measure
- Immunohistochemical expression of PI3K pathway activation markers: p-AKT and p-S6.
- timeFrame
- At the time of immunohistochemical staining of archived tissue (single time point).
Eligibility
Eligibility (as posted)
- Sex
- All
Show eligibility criteria text
Inclusion Criteria: * Patients diagnosed with invasive breast carcinoma. * ER-positive and HER2-negative tumor status. * Received adjuvant endocrine therapy as part of routine clinical care. * Archived formalin-fixed paraffin-embedded (FFPE) tumor tissue available from excisional specimens (mastectomy). * Available medical records documenting treatment history and follow-up outcomes. Exclusion Criteria: * Cases with missing or unavailable FFPE tissue blocks. * Cases with insufficient tissue quality for immunohistochemistry (e.g., severely degraded or exhausted FFPE block). * Cases with unknown or incomplete follow-up or treatment data.
References
Publications (14)
- BACKGROUNDLv W, Du C, Zhang Y, Wu F, Jin Y, Chen X, Liu X, Feng C, Ma X, Zhang S. Clinicopathological characteristics and prognostic analysis of PIK3CA mutation in breast cancer patients in Northwest China. Pathol Res Pract. 2022 Oct;238:154063. doi: 10.1016/j.prp.2022.154063. Epub 2022 Aug 10. PMID 35994807
- BACKGROUNDAdamo B, Deal AM, Burrows E, Geradts J, Hamilton E, Blackwell KL, Livasy C, Fritchie K, Prat A, Harrell JC, Ewend MG, Carey LA, Miller CR, Anders CK. Phosphatidylinositol 3-kinase pathway activation in breast cancer brain metastases. Breast Cancer Res. 2011;13(6):R125. doi: 10.1186/bcr3071. Epub 2011 Dec 1. PMID 22132754
- BACKGROUNDMaruyama N, Miyoshi Y, Taguchi T, Tamaki Y, Monden M, Noguchi S. Clinicopathologic analysis of breast cancers with PIK3CA mutations in Japanese women. Clin Cancer Res. 2007 Jan 15;13(2 Pt 1):408-14. doi: 10.1158/1078-0432.CCR-06-0267. Epub 2007 Jan 3. PMID 17202311
- BACKGROUNDSakr RA, Weigelt B, Chandarlapaty S, Andrade VP, Guerini-Rocco E, Giri D, Ng CK, Cowell CF, Rosen N, Reis-Filho JS, King TA. PI3K pathway activation in high-grade ductal carcinoma in situ--implications for progression to invasive breast carcinoma. Clin Cancer Res. 2014 May 1;20(9):2326-37. doi: 10.1158/1078-0432.CCR-13-2267. Epub 2014 Mar 14. PMID 24634376
- BACKGROUNDRasti AR, Guimaraes-Young A, Datko F, Borges VF, Aisner DL, Shagisultanova E. PIK3CA Mutations Drive Therapeutic Resistance in Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer. JCO Precis Oncol. 2022 Mar;6:e2100370. doi: 10.1200/PO.21.00370. PMID 35357905
- BACKGROUNDPierobon M, Ramos C, Wong S, Hodge KA, Aldrich J, Byron S, Anthony SP, Robert NJ, Northfelt DW, Jahanzeb M, Vocila L, Wulfkuhle J, Gambara G, Gallagher RI, Dunetz B, Hoke N, Dong T, Craig DW, Cristofanilli M, Leyland-Jones B, Liotta LA, O'Shaughnessy JA, Carpten JD, Petricoin EF. Enrichment of PI3K-AKT-mTOR Pathway Activation in Hepatic Metastases from Breast Cancer. Clin Cancer Res. 2017 Aug 15;23(16):4919-4928. doi: 10.1158/1078-0432.CCR-16-2656. Epub 2017 Apr 26.