Advances in the treatment of advanced oestrogen-receptor-positive breast cancer
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Published on: June 13, 2014
Nicholas C Turner1, Patrick Neven2, Sibylle Loibl3
1Royal Marsden Hospital and Institute of Cancer Research, London, UK.
Abstract:
Oestrogen-receptor-positive breast cancer is the most common subtype of breast cancer. Endocrine therapies that target the dependence of this subtype on the oestrogen receptor have substantial activity, yet the development of resistance to therapy is inevitable in advanced cancer. Major progress has been made in identifying the drivers of oestrogen-receptor-positive breast cancer and the mechanisms of resistance to endocrine therapy. This progress has translated into major advances in the treatment of advanced breast cancer, with several targeted therapies that enhance the efficacy of endocrine therapy; inhibitors of mTOR and inhibitors of the cyclin-dependent kinases CDK4 and CDK6 substantially improve progression-free survival. A new wave of targeted therapies is being developed, including inhibitors of PI3K, AKT, and HER2, and a new generation of oestrogen-receptor degraders. Considerable challenges remain in patient selection, deciding on the most appropriate order in which to administer therapies, and establishing whether cross-resistance occurs between therapies.
Insights
Oestrogen-receptor-positive breast cancer treatment has advanced with targeted therapies like CDK4/6 inhibitors, improving progression-free survival. However, overcoming resistance to endocrine therapy remains a key challenge in advanced disease.
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Oestrogen-receptor-positive (ER+) breast cancer is the most prevalent subtype.
- Endocrine therapies are effective but resistance is common in advanced stages.
- Understanding resistance mechanisms is crucial for improving treatment outcomes.
Purpose of the Study:
- To review progress in identifying drivers of ER+ breast cancer.
- To discuss mechanisms of resistance to endocrine therapy.
- To highlight advances in targeted therapies for advanced ER+ breast cancer.
Main Methods:
- Literature review of recent advancements in ER+ breast cancer research.
- Analysis of targeted therapies and their impact on progression-free survival.
- Discussion of emerging therapeutic strategies and remaining challenges.
Main Results:
- Targeted therapies, including mTOR and CDK4/6 inhibitors, significantly improve progression-free survival.
- New therapies targeting PI3K, AKT, HER2, and a new generation of oestrogen-receptor degraders are under development.
- Significant progress has been made in understanding resistance mechanisms.
Conclusions:
- Targeted therapies have substantially improved treatment for advanced ER+ breast cancer.
- Ongoing research focuses on overcoming endocrine resistance and developing novel therapeutic combinations.
- Challenges include patient selection, optimal sequencing of therapies, and understanding cross-resistance.
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