ESR1 mutations

ESR1 mutations occur commonly in women with acquired hormonal resistance in endocrine breast cancer treatment.

ESR1 fusions occur in 1 to 10% of hormonally responsive positive breast cancers, including untreated, early stage breast cancers.

It is rare in de novo metastatic breast cancer.

Studies suggests 30-50% of patients with acquired endocrine resistance have this mutation.

ESR1 mutations development up to 40% of patients with ER+ breast cancer, and more than 90% of these in response to therapy.

ESR1 mutations occur in the ligand-binding domain of the estrogen receptor.

The mutations activate ER independent of ligand binding.

The presence of the mutation confers activation of the ER, which can lead to resistance to standard endocrine therapies.

ESR1 mutations associated with the worse prognosis, faster progression and poorer survival of breast cancer.

Resistance to aromatase inhibitors relates frequently to cancer subclones harboring activating mutations in ESR1, the gene that encodes estrogen receptor alpha, the main isoform of the estrogen receptor.

Cell free circulating DNA analysis show that approximately 40% of patients with advanced breast cancer that is estrogen receptor positive and HER2  negative have detectable ESR1 mutations in their blood after progression on an aromatase inhibitor.

ESR1 xmutations are largely acquired with hormonal treatment.

Fulvestrant has activity in ESR1 muted tumors, and has been the only SERD agent for decades.

CDK 4/6 inhibitors have anti-tumor activity in patients with ESR1 mutations who have progressed on prior endocrine therapy.

Resistance to aromatase inhibitors and selective estrogen receptor modulators  and degraders occur with ESR1 fusions, the functional swaps that occur may still be sensitive to CDK4/6.

Lasofoxifene may be effective in the ESR1 mutation breast cancers, as does everolimus.

Elascent is a SERD not associated with cardiac or ocular toxicity.


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