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Pathways to Endocrine Therapy Resistance in Breast Cancer
Md Moquitul Haque1, Kartiki V Desai1
1Department of Cancer Genomics and Epigenomics, National Institute of Biomedical Genomics, Kalyani, India.
Abstract:
Breast cancers with positive expression of Estrogen Receptor (ER+) are treated with anti-hormone/endocrine therapy which targets the activity of the receptor, the half-life of the receptor or the availability of estrogen. This has significantly decreased mortality in women with ER+ breast cancer, however, about 25-30% of treated women run the risk or recurrence due to either intrinsic or acquired resistance to endocrine therapies. While ER itself is a predictor of response to such therapies, there exists a need to find more biomarkers and novel targets to treat resistant tumors. In this review, we summarize the known mechanisms and describe the ability of genomics in unraveling rare mutations and gene rearrangements that may impact the development of resistance and therefore treatment of ER+ breast cancer in the near future.
Insights
Estrogen Receptor-positive breast cancer treatment faces resistance in 25-30% of patients. Genomics research is uncovering rare mutations and gene rearrangements to overcome endocrine therapy resistance.
Area of Science:
- Oncology
- Genomics
- Endocrinology
Background:
- Estrogen Receptor-positive (ER+) breast cancer is commonly treated with endocrine therapy.
- While effective, 25-30% of patients develop intrinsic or acquired resistance.
- Novel biomarkers and therapeutic targets are needed for resistant ER+ breast cancer.
Purpose of the Study:
- To review mechanisms of endocrine therapy resistance in ER+ breast cancer.
- To highlight the role of genomics in identifying resistance mechanisms.
- To discuss future therapeutic strategies based on genomic findings.
Main Methods:
- Literature review of mechanisms of endocrine resistance.
- Analysis of genomic studies identifying mutations and rearrangements in resistant breast cancer.
- Synthesis of current knowledge on ER+ breast cancer treatment resistance.
Main Results:
- Endocrine therapy resistance involves complex intrinsic and acquired mechanisms.
- Genomic analyses reveal rare mutations and gene rearrangements contributing to resistance.
- These genomic alterations offer potential new targets for therapeutic intervention.
Conclusions:
- Genomics plays a crucial role in understanding and overcoming endocrine resistance in ER+ breast cancer.
- Identifying specific mutations and rearrangements can guide personalized treatment strategies.
- Further research into genomic alterations will advance the treatment of resistant ER+ breast cancer.
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