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


LUND, Sweden — /April 22, 2021/ — 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 ( 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).


The results suggest that ESR1 mutations at diagnosis of untreated primary breast cancer occur in about 1% of patients and confirms that such mutations are predictive of resistance to standard hormone therapy. If replicated, ESR1 mutations will have important clinical ramifications for adjuvant treatment of ESR1-mutant primary breast cancer. It may become important to screen breast tumors for ESR1 mutation already at initial diagnosis, in which case a SAGAsafe® mutation test would be a rapid and cost-effective option.
CEO Lao Saal, MD PhD


The study was published on 22 April 2021 in JNCI Cancer Spectrum (open access): “Preexisting Somatic Mutations of Estrogen Receptor Alpha (ESR1) in Early-Stage Primary Breast Cancer




CEO Lao Saal, MD PhD.  [email protected]  Phone: +46 (0) 733 01 7242


About SAGA Diagnostics AB
SAGA Diagnostics is a personalized cancer genomics and disease monitoring company that offers molecular genetic testing of tissue biopsies and non-invasive “liquid biopsies” such as blood samples. SAGA helps pharmaceutical companies, scientists, and healthcare providers to detect actionable mutations, stratify patient groups, and monitor treatment response more accurately and to an industry-leading lower limit of detection of 0.001%. Analysis of circulating tumor DNA using its proprietary technologies gives SAGA unique ultrasensitivity, and provides the basis for optimal decision-making.