Somatic and circulating activating ESR1 mutations have been shown to be related to aromatase inhibitor (AI) resistance in hormone receptor positive (HR+) metastatic breast cancer (mBC). In a monocentric, retrospective analysis, researchers sought to evaluate the predictive and prognostic values of circulating ESR1 mutation detection at time of disease progression in patients with mBC receiving AI treatment. The researchers presented the study at the ASCO Annual Meeting.
The study included 144 consecutive patients treated with first-line AI for HR+ mBC from January 2008–December 2010. At disease progression, ESR1 circulating mutation rates were assessed by droplet digital polymerase chain reaction on plasma samples. The researchers then determined the overall survival (OS), progression-free survival (PFS), and clinical response to subsequent treatments.
The median follow-up from AI initiation was 40 months (range = 4–94 months). At progression, 30.6% of patients (n = 44) presented with at least one of the following ESR1 circulating mutations.
- D538G: 54%
- Y537S: 45%
- Y537N: 34%
- Y537C: 4%
The median OS after progression was 15 months among those with the ESR1 mutation (range, 2–44 months) compared with 24 months for patients without the mutation (range, 2–70 months; hazard ratio [HR], 1.9; p = 0.006). Among the entire patient population, performance status >1 (HR, 3; p < 0.001), circulating ESR1 mutation (HR, 1.9; p = 0.002), and high level of cell free DNA (HR, 1.8; p = 0.006) were independent prognostic factors associated with OS. Mutational status also impacted PFS (HR, 1.7; p = 0.008).
After progression, patients were treated with
- Chemotherapy (n = 56)
- Fulvestrant/tamoxifen (n = 55)
- AI plus everolimus (n = 14)
- Nothing (n = 19).
Detection of circulating ESR1 mutation was independently related to a worse OS and PFS in the chemotherapy group (HR = 2 for both OS and PFS; p = 0.04 and p = 0.03, respectively). A worse trend for OS was also indicated in mutated patients treated with fulvestrant/tamoxifen (p = 0.09), whereas no difference was observed for PFS and OS among patients with ESR1 mutations in the different treatment groups.
The researchers concluded, “Circulating ESR1 mutation detection at progression under AI is a strong and independent prognostic factor of OS in HR+ mBC patients. This detection seems predictive of a worse outcome in any subsequent treatment.”