Treating Breast Cancer with Mutated Estrogen Receptor with Camizestrant
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Reviewed by Dat Tien Nguyen, B.A, ScM.
Translated by Nhi Phuong Quynh Le, B.A |
Posted on September 3rd, 2025
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Aromatase inhibitor and CDK 4/6 inhibitor are frequently used as first-line treatment for breast cancer tumor expressing hormone receptors. However, mutation to the estrogen receptor might interfere with the binding of the antagonist aromatase inhibitor. To circumvent this resistance mechanism, AstraZeneca funded a study that tested camizestrant, an selective estrogen-receptor degrader, as a therapy for breast cancer.
The phase 3 clinical trial included 315 participants who had been diagnosed with locally recurrent or metastatic breast cancer tumors with estrogen-receptor but lacked human epidermal growth factor receptor 2 (HER2). 80% of the patients have one mutation to the estrogen receptor, the remaining have multiple. These patients were being treated with an aromatase inhibitor and a CDK4/6 inhibitor, with three-quarters using palbociclib, and the remaining under either ribociclib or abemaciclib.
The participants were randomly assigned to be treated with their current aromatase inhibitor or switched to camizestrant, at a daily dose of 75 mg. Camizestrant is a selective estrogen-receptor degrader. It circumvents the mutation to the estrogen receptor because it can remove the receptor. This reaction happens independently from the active site that has been mutated so the aromatase inhibitor can no longer interact with.
The researchers found that camizestrant reduced the risk of death and disease progression by 56%, and it has a progression-free survival duration by 16 months - significantly longer than the 9.2 months reported in those treated with aromatase inhibitors. The researchers noted that as disease progressed, the tumor acquired more resistance mechanisms. Thus, they recommended that selective estrogen-receptor degrader should not be kept as a second-line therapy, but should be used instead of an aromatase inhibitor as a first-line therapy.
The phase 3 clinical trial included 315 participants who had been diagnosed with locally recurrent or metastatic breast cancer tumors with estrogen-receptor but lacked human epidermal growth factor receptor 2 (HER2). 80% of the patients have one mutation to the estrogen receptor, the remaining have multiple. These patients were being treated with an aromatase inhibitor and a CDK4/6 inhibitor, with three-quarters using palbociclib, and the remaining under either ribociclib or abemaciclib.
The participants were randomly assigned to be treated with their current aromatase inhibitor or switched to camizestrant, at a daily dose of 75 mg. Camizestrant is a selective estrogen-receptor degrader. It circumvents the mutation to the estrogen receptor because it can remove the receptor. This reaction happens independently from the active site that has been mutated so the aromatase inhibitor can no longer interact with.
The researchers found that camizestrant reduced the risk of death and disease progression by 56%, and it has a progression-free survival duration by 16 months - significantly longer than the 9.2 months reported in those treated with aromatase inhibitors. The researchers noted that as disease progressed, the tumor acquired more resistance mechanisms. Thus, they recommended that selective estrogen-receptor degrader should not be kept as a second-line therapy, but should be used instead of an aromatase inhibitor as a first-line therapy.