Integrating Molecular Insights into Treatment Strategies: The PI3K/AKT/mTOR Axis in HR+ Breast Cancer Management in India

Authors

Ananya Deshmukh, Department of Medical Oncology, Tata Memorial Hospital, Mumbai, India
Raghavendra B. Iyer, Division of Molecular Pathology, All India Institute of Medical Sciences (AIIMS), New Delhi, India
Priyanka Nair, Department of Biochemistry, Amrita Institute of Medical Sciences, Kochi, India
Vivek Sharma, Department of Translational Research, Kidwai Memorial Institute of Oncology, Bangalore, IndiaFollow

Article Type

Article

Abstract

Background: The PI3K/AKT/mTOR pathway plays a pivotal role in endocrine resistance among hormone receptor-positive (HR+) breast cancer patients. Despite growing global access to pathway-targeted therapies, the clinical integration of molecular diagnostics in India remains limited. This study investigates the prevalence and prognostic implications of PI3K/AKT/mTOR pathway activation in HR+ breast cancer using patient-derived tumor tissue. Methods: This prospective observational study analyzed tumor samples from 60 HR+ breast cancer patients treated at a tertiary oncology center in India. PIK3CA mutation status was assessed via PCR-based genomic testing. Protein expression of p-AKT and mTOR was evaluated using immunohistochemistry. Survival data were correlated with biomarker expression using Kaplan-Meier and chi-square analysis. Results: PIK3CA mutations were present in 40% of patients and were significantly associated with p-AKT (83.3%) and mTOR (75%) activation (p < 0.01). Patients harboring PIK3CA mutations showed reduced median overall survival (16 vs. 24 months) and event-free survival (12 vs. 20 months) compared to wild-type patients. Pathway activation was a strong predictor of endocrine resistance and early recurrence. Conclusion: Activation of the PI3K/AKT/mTOR axis, particularly in PIK3CA-mutated tumors, correlates with adverse clinical outcomes in HR+ breast cancer. These findings underscore the need to incorporate routine molecular profiling into breast cancer management in India to guide precision therapy. Broader access to affordable diagnostics and targeted inhibitors like alpelisib is critical to improving outcomes in this population.

Keywords

PI3K/AKT/mTOR pathway, Hormone receptor-positive breast cancer, PIK3CA mutation, India, Molecular profiling, Alpelisib, Endocrine resistance, Immunohistochemistry

Recommended Citation

Deshmukh, Ananya; Iyer, Raghavendra B.; Nair, Priyanka; and Sharma, Vivek (2025) "Integrating Molecular Insights into Treatment Strategies: The PI3K/AKT/mTOR Axis in HR+ Breast Cancer Management in India," Muthanna Medical Journal: Vol. 12: Iss. 1, Article 3.
Available at: https://muthmj.mu.edu.iq/journal/vol12/iss1/3

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This work is licensed under a Creative Commons Attribution 4.0 International License.