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ESR1 Mutation Prevalence and Genomic Landscape Alterations in CDK4/6i-Treated HR+/HER2− Breast Cancer
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- This study analyzed tumor genomic profiles of 5910 patients with HR+/HER2− metastatic breast cancer from the Flatiron database according to treatment and endocrine therapy resistance (ETR) status. ESR1 mutations were more prevalent in patients with secondary ETR (relapse after >2 years of adjuvant ET) than in those with primary ETR (relapse after <2 years of adjuvant ET), whereas TP53 mutations were more common in patients with primary ETR. These genomic profiles transitioned when relapse occurred at approximately 1 year of adjuvant ET. Patients treated with CDK4/6 inhibitor plus aromatase inhibitor (AI) in the first-line metastatic setting developed significantly more ESR1 mutations than those treated with AI alone, especially with >1 year of treatment. Patients treated with fulvestrant-based therapy or chemotherapy showed no significant increase in ESR1 mutations.
- These data support a biological definition of primary ETR that includes patients relapsing after ≤1 year on adjuvant ET and suggest that a 1-year duration on CDK4/6 inhibitor plus AI represents a cutoff wherein higher rates of ESR1 mutations emerge.
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NPJ breast cancer
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
CDK4/6i-treated HR+/HER2- breast cancer tumors show higher ESR1 mutation prevalence and more altered genomic landscape
NPJ Breast Cancer 2024 Feb 22;10(1)15, N Chaudhary, AM Chibly, A Collier, J Martinalbo, P Perez-Moreno, HM Moore, P Luhn, C Metcalfe, M HafnerFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
The emergence of resistance to CDK4/6 inhibitors in patients with metastatic breast cancer underscores the imperative for exploring alternative therapeutic strategies. Despite the initial efficacy of existing treatment options, tumors invariably develop resistance mechanisms, resulting in disease progression. Consequently, there is a pressing need for innovative therapeutic interventions to address this clinical challenge. Research efforts are focused on elucidating the underlying mechanisms of resistance and developing novel combination therapies to overcome resistance and prolong progression-free survival. Understanding how exposure to CDK4/6 inhibitors impacts the tumor genomic landscape is important to help clarify potential future targeted treatment options. This information will also help guide future investigations, which will hopefully identify novel therapeutic strategies.
The investigators of the current study leveraged real-world data using a large database of tumor genomic profiles from nearly 6000 patients with HR+/HER2− metastatic breast cancer. The observations noted in this important study will be helpful to optimize further treatment approaches.