SAGAsafe® technology utilized in new study of ESR1 mutations in breast cancer

ESR1 mutations are found in primary breast cancers prior to therapy initiation and are associated to worse relapse-free and overall survival. These results were reported today by a group of researchers from Lund University and Skåne University Hospital in a new studied published in JNCI Cancer Spectrum.

The estrogen receptor alpha is one of the most important breast cancer biomarkers. It is encoded by the gene ESR1, which is known to be frequently mutated in metastatic breast cancers in patients who previously received hormonal treatment for primary breast cancer. Therefore, ESR1 mutation has been considered an acquired resistance mechanism to hormonal therapy.

In the new study, the largest analysis for ESR1 mutations in invasive primary breast cancer (non-metastatic), patient material from a total of 3,217 patients from within the SCAN-B trial (ClinicalTrials.gov NCT02306096) were included. RNA sequencing was performed on tumor samples obtained from these patients at initial diagnosis, prior to any systemic treatment. 30 patients (0.9% of all patients and 1.1% of all patients with ER-positive tumors) were found to have an ESR1 mutation already present in their tumor. SAGAsafe^® (previously IBSAFE) digital PCR technology was used to verify the results. For the analysis, SAGAsafe^® assays for the ESR1 variants E380Q, D538G, Y537S, Y537N, and Y537G were used to analyze patients that had tumor and germline DNA available and the mutations were confirmed in 100% (18/18) of tumor DNAs and in 100% (11/11) of cases as being somatic.

Preexisting ESR1 mutations were found to be significantly associated to poor recurrence-free interval (RFI) and overall survival (OS) in patients who received adjuvant endocrine therapy (p=0.008 and p=0.007, respectively).