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William J. Gradishar, MD, FACP, FASCO


AACR 2022: Does Hormone Receptor–Positive ESR1-Mutated Breast Cancer Respond to CDK4/6 Inhibition?

By: Vanessa A. Carter, BS
Posted: Tuesday, April 19, 2022

Whether the inhibition of CDK4/6 in patients with hormone receptor–positive, ESR1-mutated metastatic breast cancer is effective in the real-world setting remains unknown. However, data supporting the use of these inhibitors were presented by Jamie O. Brett, MD, PhD, of Massachusetts General Hospital, Boston, and colleagues during the American Association for Cancer Research (AACR) Annual Meeting 2022 (Abstract 5248). They concluded that these agents appear to be effective against this aggressive type of breast cancer.

“CDK4/6 inhibition may be additionally beneficial for patients with ESR1 fusions,” added the study authors. “Future directions include expanding the ESR1-fusion cohort and deciphering the heterogeneity of CDK4/6 inhibitor responses in this patient population.”

The GuardantINFORM database of commercial payer claims and circulating tumor DNA (ctDNA) tests from more than 170,000 individuals was used to source real-world evidence. A total of 757 patients with either ESR1-mutated (n = 145) or ESR1–wild-type (n = 612) hormone receptor–positive metastatic breast cancer who began treatment with a CDK4/6 inhibitor within 30 days of ctDNA testing were analyzed for the time to next treatment. Additionally, cases with ESR1 fusions were extracted from a clinicopathologic database at an academic cancer center.

A significant difference in the time to next treatment between patients with and without these mutations was not observed. As anticipated, individuals with ESR1 mutations had a shorter overall survival than those without ESR1 mutations (2.2 vs. 5.1 months; P < .0001), even after the investigators adjusted for age and treatment (P = .002). Additionally, the lack of clinical annotation limited endocrine partner analysis to 27% of cases.

Approximately 55% of patients with ESR1–wild-type and 25% of ESR1-mutated breast cancer received aromatase inhibitors, whereas 39% and 68% of individuals received fulvestrant, respectively. Although additional stratified analyses have yet to be presented, four cases of ESR1-mutated breast cancer were identified; all patients received a CDK4/6 inhibitor.

Disclosure: For full disclosures of the study authors, visit

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