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Published on: June 13, 2014
[Advanced luminal breast cancer (hormone receptor-positive, HER2 negative): New therapeutic options in 2015]
Hélène Vanacker1, Olivia Bally1, Loay Kassem2
1Département de médecine, Centre Léon-Bérard, Lyon, France.
Abstract:
Despite improvements in early detection, surgery and systemic therapy, metastatic breast cancer remains a major cause of death. Luminal type breast cancers expressing hormone estrogen receptor (ER) or progesterone (PR) and without HER2 overexpression are generally sensitive to endocrine therapy, but raise the issue of the occurrence of resistance to treatment, particularly at metastatic stage. A better understanding of hormone resistance may guide the development of new therapeutics. New strategies aim at enhancing and prolonging of endocrine sensitivity, by optimizing existing schemes, or by combining an endocrine therapy with a targeted therapies specific to hormone resistance pathways: ER signaling, PI3K/AKT/mTOR and Cyclin Dependent Kinase (CDK). Key corners of 2014 include confirmation of benefit of high dose fulvestrant, and commercialization of everolimus as the first mTOR inhibitor in this indication. Other strategies are being tested dealing with new endocrine therapies or new molecular targets such as PI3K inhibitors, insulin-like growth factor receptor (IGF-R) and histone deacetylase (HDAC) inhibitors. Coming years may be fruitful and might radically change our way to treat these patients.
Insights
Hormone resistance in metastatic breast cancer is a significant challenge. New therapeutic strategies combining endocrine therapy with targeted treatments show promise for improving patient outcomes.
Area of Science:
- Oncology
- Endocrinology
- Pharmacology
Background:
- Metastatic breast cancer (MBC) remains a leading cause of cancer death despite advances in treatment.
- Luminal type breast cancers, characterized by estrogen receptor (ER) or progesterone receptor (PR) expression, often develop resistance to endocrine therapy, particularly at the metastatic stage.
- Understanding the mechanisms of hormone resistance is crucial for developing novel therapeutic approaches.
Purpose of the Study:
- To review current and emerging strategies for overcoming endocrine resistance in hormone receptor-positive metastatic breast cancer.
- To highlight novel therapeutic targets and combinations aimed at enhancing or prolonging endocrine sensitivity.
- To discuss recent advancements and future directions in the treatment of ER-positive MBC.
Main Methods:
- Review of recent clinical trial data and preclinical research on endocrine resistance in breast cancer.
- Analysis of emerging targeted therapies, including inhibitors of ER signaling, PI3K/AKT/mTOR pathway, and Cyclin-Dependent Kinases (CDKs).
- Examination of novel endocrine agents and molecular targets such as PI3K, IGF-R, and HDAC inhibitors.
Main Results:
- High-dose fulvestrant has demonstrated confirmed clinical benefit.
- Everolimus, an mTOR inhibitor, has been commercialized, representing a significant advancement in targeting resistance pathways.
- Ongoing research is exploring the efficacy of various targeted agents and combination therapies.
Conclusions:
- New therapeutic strategies combining endocrine therapy with targeted agents are essential for managing hormone resistance in metastatic breast cancer.
- Targeting key resistance pathways like ER signaling, PI3K/AKT/mTOR, and CDK offers promising avenues for improving treatment outcomes.
- Future research holds the potential to significantly alter the treatment landscape for patients with ER-positive metastatic breast cancer.
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