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Author Spotlight: Exploring Salidroside's Molecular Mechanisms in Breast Cancer Treatment
Published on: June 9, 2023
Predictive Value of PIK3CA Mutations for Response to CDK4/6 Inhibitors in Hormone Receptor-Positive, HER2-Negative
Zaheer Qureshi1, Abdur Jamil2, Neehal Wali3
1Rowan-Virtua School of Osteopathic Medicine, Stratford, NJ.
Background:
Currently, cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors combined with hormone therapy are the standard treatment for patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) metastatic breast cancer. It remains unclear which patients benefit most from CDK4/6 inhibitors and whether predictive biomarkers exist to guide treatment decisions. Therefore, we evaluate the association between phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) mutation status and treatment response to CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer.
Methods:
We extensively searched PubMed, Web of Science, Cochrane Library, and Google Scholar databases for articles published until December 2024. The primary outcome of our study was progression-free survival (PFS), and the secondary outcomes included overall survival (OS) and objective response rate (ORR).
Results:
Seven studies-involving 2221 women with HR+/HER2 metastatic breast cancer-were systematically analyzed. The pooled results showed that patients with PIK3CA mutation had significantly poorer PFS than those with PIK3CA wild-type (hazard ratio [HR]: 1.47; 95% CI: 1.22-1.77; P<0.0001). Similarly, PIK3CA mutation was associated with significantly poorer OS than PIK3CA wild-type (HR: 1.42; 95% CI: 1.06-1.89; P=0.02). ORR was only reported in one study, with the results showing that the ORR was higher in patients with wild-type PIK3CA than in patients with PIK3CA alteration (53/180 (29%) versus 13/85 (15%).
Conclusions:
PIK3CA mutation correlates with poor PFS and OS in patients with HR+/HER2- metastatic breast cancer receiving CDK4/6 inhibitors. Therefore, PIK3CA mutation status should be considered a potential predictive biomarker of resistance to CDK4/6 inhibitors.
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