Key opinion leaders explore the mechanisms of resistance that can develop after endocrine therapy and CDK4/6 inhibitor treatment in HR+/HER2- breast cancer, emphasizing the uncertain etiology of resistance and current hypotheses, while also examining biomarkers that may predict resistance to CDK4/6 inhibitors and endocrine therapy.
Please provide an overview of the mechanisms of resistance that can emerge following endocrine therapy and CDK4/6 inhibitors in HR+/HER2- breast cancer.
What are the major pathways implicated in resistance to ET and CDK4/6i?
Are there any biomarkers that predict resistance to CDK4/6 inhibitors and ET?
What other genetic alterations may be implicated in resistance?
Could you discuss the role of the PI3K/AKT/PTEN pathway in driving resistance and progression after first-line treatment with CDK4/6i + ET?
In normal cells, what is the role of the PI3K/AKT/PTEN pathway?
How might aberrations in PI3K, AKT, or PTEN and dysregulation of this pathway contribute to treatment resistance and progression in HR+/HER2-locally advanced or metastatic breast cancer?
How might alterations in PI3K/AKT/PTEN impact patient outcomes and treatment strategies in HR+/HER2- locally advanced or metastatic breast cancer?
Please discuss the frequency of dysregulation in the PI3K/AKT/mTOR pathway in HR+/HER2- locally advanced or metastatic breast cancer patients?