PhD Scientific Days 2026

Theoretical and Translational Medicine 2.

Investigating the Efficacy and Safety of PI3K/AKT Pathway Inhibitors in Metastatic or Locally Advanced Breast Cancer with PIK3CA Mutations: A Systematic Review and Meta-Analysis

Name of the presenter

Pallagi, Zsuzsanna

Institute/workplace of the presenter

Semmelweis University Centre for Translational Medicine

Authors

Dr. Zsuzsanna Pallagi¹, Prof. Dr. Dezső Csupor², Dr. Darius-Valentin Sandu¹, Prof. Dr. Zsuzsanna Kahán³, Mikolt Bakony¹, Dr. Sunaina Wadhwa⁴
1: Semmelweis University Centre for Translational Medicine
2: University of Szeged Institute of Clinical Pharmacy
3: University of Szeged, Albert Szent-Györgyi Health Centre, Department of Oncotherapy
4: Medical University of Vienna Department of Gynecologic Oncology

Text of the abstract

Introduction:
Breast cancer is one of the leading causes of death. The PI3K/AKT/mTOR signalling pathway is overactivated in approximately 50% of cases, and PIK3CA mutations can be detected in 40% of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancers, leading to increased resistance to standard therapies. The combination of PI3K/AKT inhibitors with endocrine therapy is considered a promising therapeutic option.
Aims:
We aim to assess the therapeutic value of PI3K/AKT inhibitors combined with endocrine therapy.
Methods:
We investigated the efficacy and safety of PI3K/AKT inhibitors in combination with endocrine therapy through a systematic review and meta-analysis. After submitting the PROSPERO protocol (CRD420251181854), we conducted a systematic search in PubMed, Embase, and CENTRAL databases. Title/abstract and full-text screening were performed independently by two investigators. Appropriate statistical methods were used to assess efficacy (progression-free survival, overall survival, clinical benefit, and objective response) and safety (adverse events, treatment discontinuation, and dose reduction). Risk of bias assessment was performed independently by two authors. The GRADE assessment was performed using the GRADEpro tool. The manuscript writing is currently ongoing.
Results:
The pooled hazard ratio for progression-free survival was 0.61 (95% CI, 0.52-0.73). Overall survival also showed improvement in the intervention group (HR: 0.73, 95% CI 0.50-1.08); however, the result was not statistically significant. The risk of developing severe hyperglycemia was higher in the intervention arm (RR 25.90, 95% CI, 11.85-56.59).
Conclusions:
The combination of PI3K/AKT inhibitors and endocrine therapy improved treatment efficacy in breast cancer with PIK3CA mutation. However, healthcare professionals should be aware of possible adverse events and appropriate strategies for managing them.
Funding:
Supported by the Semmelweis University Research Development and Innovation Fund.