Ignite Creation Date:
2026-03-26 @ 3:14 PM
Ignite Modification Date:
2026-03-31 @ 4:50 AM
Study NCT ID:
NCT07387861
Status:
NOT_YET_RECRUITING
Last Update Posted:
2026-02-04
First Post:
2026-01-25
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
PI3K Pathway Activation Markers in ER-Positive, HER2-Negative Breast Cancer: A Clinicopathologic Study
Sponsor:
Assiut University
Organization:
Study Overview
Official Title:
Immunohistochemical Evaluation of p-AKT and p-S6 as Surrogate Markers of PI3K/AKT/mTOR Pathway Activation in ER-Positive, HER2-Negative Breast Carcinoma
Status:
NOT_YET_RECRUITING
Status Verified Date:
2026-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
p-AKT p-S6
Brief Summary:
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.
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.
Detailed Description:
Endocrine therapy is the cornerstone of treatment for estrogen receptor-positive breast cancer; however, a substantial proportion of patients develop resistance during the disease course. Activation of the PI3K/AKT/mTOR signaling pathway has been implicated as a key mechanism underlying resistance to endocrine therapy and disease progression. While genomic alterations in PI3K pathway-related genes are commonly assessed, they do not consistently reflect pathway activation or predict therapeutic response, highlighting the need for practical surrogate biomarkers.
The aim of this study is to evaluate immunohistochemical markers of PI3K pathway activation in estrogen receptor-positive, HER2-negative invasive breast carcinoma and to explore their associations with endocrine therapy response and clinicopathologic characteristics. Specifically, the study examines whether levels of phosphorylated AKT (p-AKT) and phosphorylated S6 (p-S6) differ between endocrine-sensitive and endocrine-resistant cases and whether these markers correlate with histologic features related to tumor biology and the tumor microenvironment.
This is a retrospective observational study including patients with estrogen receptor-positive, HER2-negative invasive breast carcinoma who received adjuvant endocrine therapy as part of routine clinical care. Archived formalin-fixed, paraffin-embedded (FFPE) tissue blocks from excisional surgical specimens will be retrieved, and clinicopathologic and follow-up data will be collected from medical records.
Cases will be classified into endocrine-sensitive and endocrine-resistant groups based on international consensus definitions using the timing of disease recurrence relative to endocrine therapy. Immunohistochemical staining for p-AKT and p-S6 will be performed on FFPE tissue sections and evaluated using a semi-quantitative scoring system. Histopathologic assessment will include standard reporting parameters as well as additional features such as tumor-infiltrating lymphocyte density, tumor budding, lymphovascular invasion, perineural invasion, and tumoral necrosis. Associations between biomarker expression, clinicopathologic features, and follow-up outcomes will be explored.
The aim of this study is to evaluate immunohistochemical markers of PI3K pathway activation in estrogen receptor-positive, HER2-negative invasive breast carcinoma and to explore their associations with endocrine therapy response and clinicopathologic characteristics. Specifically, the study examines whether levels of phosphorylated AKT (p-AKT) and phosphorylated S6 (p-S6) differ between endocrine-sensitive and endocrine-resistant cases and whether these markers correlate with histologic features related to tumor biology and the tumor microenvironment.
This is a retrospective observational study including patients with estrogen receptor-positive, HER2-negative invasive breast carcinoma who received adjuvant endocrine therapy as part of routine clinical care. Archived formalin-fixed, paraffin-embedded (FFPE) tissue blocks from excisional surgical specimens will be retrieved, and clinicopathologic and follow-up data will be collected from medical records.
Cases will be classified into endocrine-sensitive and endocrine-resistant groups based on international consensus definitions using the timing of disease recurrence relative to endocrine therapy. Immunohistochemical staining for p-AKT and p-S6 will be performed on FFPE tissue sections and evaluated using a semi-quantitative scoring system. Histopathologic assessment will include standard reporting parameters as well as additional features such as tumor-infiltrating lymphocyte density, tumor budding, lymphovascular invasion, perineural invasion, and tumoral necrosis. Associations between biomarker expression, clinicopathologic features, and follow-up outcomes will be explored.
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?: