The PIK3CA Mutation in Advanced Breast Cancer Chemoresistance and Recurrence
Movchan Oleksii Volodimirovich 1*, Smolanka Ivan Ivanovich 1, Lyashenko Andriy Oleksandrovich 1, Loboda Anton Dmitrovich 1, Dosenko Irina Viktorivna 1, Dosenko Irina Viktorivna 1, Ivankova Oksana Mykolaivna 1
Journal of Angiotherapy 8(4) 1-8 https://doi.org/10.25163/angiotherapy.849552
Submitted: 02 March 2024 Revised: 03 April 2024 Published: 06 April 2024
Abstract
Background: The molecular mechanisms facilitating the resurgence of critical breast tumor cells and their potential to engender malignant lesions remain elusive. Several carcinogenic pathways contribute to the progression, chemoresistance, and recurrence of primary breast cancer (BC), among which is the PIK3CA mutation within the PI3K-AKT-mTOR pathway. Drug resistance poses a significant challenge to effective therapy for advanced breast cancer (ABC). This study aimed to assess the PIK3CA mutation as a diagnostic marker for disease prognosis and the prediction of treatment response. Methods: Ninety patients with advanced resistant BC were stratified into two groups: 1) 45 patients with PIK3CA mutation; 2) 45 patients with 'wild-type' PIK3CA. Patient data were collected regarding overall survival and relapse-free status. All patients received comprehensive treatment according to generally accepted standards for their respective subtypes. Results: Seventy percent of lesions associated with chemoresistance and recurrence exhibited high levels of the PIK3CA mutation. Among PIK3CA mutation lesions, 40% were HER2-positive. Analysis of immunohistochemistry data from 30 patients and matched pairings revealed that 18 patients with HER2-positive/PIK3CA mutation exhibited high expression of acquired hormone status, with 35% of patients presenting with ER-negative disease. Conclusions: Women with HER2-positive/PIK3CA mutation lesions demonstrated a threefold higher frequency of subsequent hormone status compared to those with HER2-negative/PIK3CA wild-type lesions. HER2-positive/PIK3CA mutation was associated with ER-negative disease, chemoresistance, and recurrence. These findings underscore the importance of evaluating the protein expression of HER2 and PIK3CA mutations in ABC patients post-diagnosis and intensifying anti-relapse therapy.
Keywords: PIK3CA Mutation, Advanced breast cancer, Chemoresistance, Disease recurrence.
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