Overview of the therapeutic strategies for ER positive breast cancer

Estrogen Receptor is the driving transcription factor in about 75% of all breast cancers, which is the target of endocrine therapies, but drug resistance is a common clinical problem. ESR1 point mutations at the ligand binding domain are frequently identified in metastatic tumor and ctDNA (Circulating tumor DNA) derived from ER positive breast cancer patients with endocrine therapies. Although endocrine therapy and CDK4/6 inhibitor therapy have demonstrated preclinical and clinical benefits for breast cancer, the development of resistance remains a significant challenge and the detailed mechanisms, and potential therapeutic targets in advanced breast cancer yet to be revealed. Since a crosstalk between tumor and tumor microenvironment (TME) plays an important role to grow tumor and metastasis, this effect could serve as key regulators in the resistance of endocrine therapy and the transition of breast cancer cells to metastasis. In this article, we have reviewed recent progress in endocrine therapy and the contribution of TME to ER positive breast cancer.

Automated summary

Estrogen receptor (ER) is the main transcription factor in 75% of breast cancers, targeted by endocrine therapies. However, drug resistance is common. Frequent ESR1 mutations are found in metastatic tumors and ctDNA derived from ER positive breast cancer patients. The mechanisms of resistance and potential therapeutic targets in advanced breast cancer remain unclear. The tumor microenvironment (TME) is important in endocrine therapy resistance and breast cancer metastasis. This article reviews recent progress in endocrine therapy and the role of TME in ER positive breast cancer.