ESR1 Mutations in Breast Cancer: Proof-of-Concept Challenges Clinical Action

Abstract

Wang and colleagues demonstrate that digital droplet PCR (ddPCR) identified ESR1 mutations in 7% of primary breast cancers. ESR1 mutations were also readily detected in metastatic tissues and circulating tumor DNA in the blood. These results suggest that ddPCR may be amendable for monitoring tumor burden, and to predict relapse. See related article by Wang et al., p. 1130.

Fig. 1

Upon diagnosis of breast cancer, both tumor biopsies and blood samples can be collected from ER-positive breast cancer patients. Baseline biopsies could be analyzed using next generation sequencing to detect relevant mutations in breast cancer such as ESR1, PIK3CA, p53, etc. Patients can receive chemotherapy or hormonal therapy before surgery. After neoadjuvant therapies, residual tumor biopsies and liquid biopsies can be collected and analyzed using ddPCR to confirm pre-existing mutations and compare mutation frequency with matched baseline patient samples. After surgery, mutation status is monitored by collecting patient liquid biopsies. ESR1 mutations can be assessed by ddPCR and other emerging driver mutations or subclonal evolution evaluated using high throughput captured sequencing. If ESR1 mutation allele frequencies increase in the plasma DNA, hormone therapy can be tailored to emerging mutations. This approach allows precision therapy for patients. Mut, mutated; NT, negative; WT, wild type.