Jamie Brett

Jamie Brett, resident in internal medicine at Massachusetts General Hospital, discusses the similarities and differences between 

 mutations and fusions and why they are grouped together.

 mutations and fusions are grouped together as they are the same gene and have similar overall effects. However, all 

 mutations occur in roughly 20%-40% of patients with metastatic breast cancer treated with an aromatase inhibitor, and are not typically found in other settings. Then, ESR1 fusions occur in approximately 1%-10% of new or treated breast cancers, mostly as a luminal B type.

 We group them together because it's the same gene and they have similar overall effects, but the whole space of 

 mutations are point mutations in the ligand binding domain of the estrogen receptor. They are known to occur in about 20% to 40% of patients with metastatic breast cancer who have been treated with an aromatase inhibitor in the metastatic setting and do not really occur in other settings. These mutations make the estrogen receptor independent of estrogen and they create complete aromatase inhibition resistance and some relative resistance to other estrogen receptor targeted therapies.

 fusions that are less studied overall. They are thought to occur roughly in the range of 1% to 10% of new breast cancer or treated breast cancer, mostly a luminal B type. They are heterogeneous, so they cause different effects. The 2 main categories are that you can swap the ligand binding domain of the estrogen receptor for that of a different protein, and then you create sort of a hyperactive ligand independent estrogen receptor, or you can have the other protein, which is typically 

, become altered by the fusion to the estrogen receptor.

Videos

Jamie Brett discusses the similarities and differences between ESR1 mutations and fusions and why they are grouped together.

Examining ESR1 Alterations in HR-Positive Metastatic Breast Cancer

Jamie Brett, resident in internal medicine at Massachusetts General Hospital, discusses the effectiveness of CDK4/6 for patients with hormone receptor-positive metastatic breast cancer (MBC) with 

Within a presentation at the AACR Annual Meeting 2022, Brett evaluated patients with MBC who started on a CDK4/6 inhibitor within 30 days of ctDNA testing and analyzed their time-to-next-treatment data.

Findings revealed there to be no significant difference in time to next treatment between those with ESR1 fusions and wild type status. While future studies plan to expand this research, this trial showed those with ESR1 mutations to have shorter overall survival (HR, 0.58; 95% CI, 0.42 - 0.82, 

 We used our own MGH database to look for patients with 

 fusions. What we found is that in the real-world setting, CDK 4/6 inhibitors can be useful patients with 

 mutations. In fact, these patients do very similarly in terms of time to next treatment as patients with 

 wild type status. CDK 4/6 inhibitors also seem to be beneficial in each of the cases that we found of patients with 

 The summary result is that in the real-world setting, CDK 4/6 inhibitors seem to be a useful strategy of therapy for patients with 

 alterations that are otherwise very hard to treat because of endocrine resistance. There's a lot of future directions that I think include expanding the 

 fusion case series to include a lot more patients. They're looking into the garden data in terms of which patients really do well with CDK 4/6 inhibitors and which patients do not do well, and why there's still some differences in survival long term with these patients despite similar outcomes in terms of time to next treatment on CDK 4/6 inhibitors.

Articles

Jamie Brett, resident in internal medicine at Massachusetts General Hospital, discusses the effectiveness of CDK4/6 for patients with hormone receptor-positive metastatic breast cancer (MBC) with ESR1 mutations and fusions.

Jamie Brett | Authors

Articles

Examining ESR1 Alterations in HR-Positive Metastatic Breast Cancer

CDK 4/6 Inhibitors Show Efficacy in HR+ MBC With ESR1 Mutations