Therapeutic resistance to anti-oestrogen therapy in breast cancer Review
| Authors: | Will, M.; Liang, J.; Metcalfe, C.; Chandarlapaty, S. |
| Review Title: | Therapeutic resistance to anti-oestrogen therapy in breast cancer |
| Abstract: | The hormone receptor oestrogen receptor-α (ER) orchestrates physiological mammary gland development, breast carcinogenesis and the progression of breast tumours into lethal, treatment-refractory systemic disease. Selective antagonism of ER signalling has been one of the most successful therapeutic approaches in oncology, benefiting patients as both a cancer preventative measure and a cancer treatment strategy. However, resistance to anti-oestrogen therapy is a major clinical challenge. Over the past decade, we have gained an understanding of how breast cancers evolve under the pressure of anti-oestrogen therapy. This is best depicted by the case of oestrogen-independent mutations in the gene encoding ER (ESR1), which are virtually absent in primary breast cancer but highly prevalent (20–40%) in anti-oestrogen-treated metastatic disease. These and other findings highlight the ‘evolvability’ of ER+ breast cancer and the need to understand molecular processes by which this evolution occurs. Recent development and approval of next-generation ER antagonists to target ESR1-mutant breast cancer underscores the clinical importance of this evolvability and sets a new paradigm for the treatment of ER+ breast cancers. © 2023, Springer Nature Limited. |
| Keywords: | signal transduction; genetics; review; breast cancer; estrogen; estrogens; drug resistance; pathology; drug resistance, neoplasm; breast neoplasms; cancer resistance; cancer hormone therapy; breast tumor; antineoplastic hormone agonists and antagonists; randomized controlled trial (topic); molecularly targeted therapy; phase 2 clinical trial (topic); estrogen receptor alpha; humans; human; female; evolvability |
| Journal Title: | Nature Reviews Cancer |
| Volume: | 23 |
| Issue: | 10 |
| ISSN: | 1474-175X |
| Publisher: | Nature Publishing Group |
| Date Published: | 2023-10-01 |
| Start Page: | 673 |
| End Page: | 685 |
| Language: | English |
| DOI: | 10.1038/s41568-023-00604-3 |
| PUBMED: | 37500767 |
| PROVIDER: | scopus |
| PMCID: | PMC10529099 |
| DOI/URL: | |
| Notes: | Review -- MSK Cancer Center Support Grant (P30 CA008748) acknowledged in PubMed -- MSK corresponding author is Sarat Chandarlapaty -- Source: Scopus |
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