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Åke Borg

Åke Borg

Principal investigator

Åke Borg

Preexisting Somatic Mutations of Estrogen Receptor Alpha (ESR1) in Early-Stage Primary Breast Cancer


  • Malin Dahlgren
  • Anthony George
  • Christian Brueffer
  • Sergii Gladchuk
  • Yilun Chen
  • Johan Vallon-Christersson
  • Cecilia Hegardt
  • Jari Häkkinen
  • Lisa Ryden
  • Martin Malmberg
  • Christer Larsson
  • Sofia Gruvberger
  • Anna Ehinger
  • Niklas Loman
  • Åke Borg
  • Lao Saal

Summary, in English

More than three-quarters of primary breast cancers are positive for estrogen receptor alpha (ER; encoded by the gene ESR1), the most important factor for directing anti-estrogenic endocrine therapy (ET). Recently, mutations in ESR1 were identified as acquired mechanisms of resistance to ET, found in 12% to 55% of metastatic breast cancers treated previously with ET. We analyzed 3217 population-based invasive primary (nonmetastatic) breast cancers (within the SCAN-B study, NCT02306096), sampled from initial diagnosis prior to any treatment, for the presence of ESR1 mutations using RNA sequencing. Mutations were verified by droplet digital polymerase chain reaction on tumor and normal DNA. Patient outcomes were analyzed using Kaplan-Meier estimation and a series of 2-factor Cox regression multivariable analyses. We identified ESR1 resistance mutations in 30 tumors (0.9%), of which 29 were ER positive (1.1%). In ET-treated disease, presence of ESR1 mutation was associated with poor relapse-free survival and overall survival (2-sided log-rank test P < .001 and P = .008, respectively), with hazard ratios of 3.00 (95% confidence interval = 1.56 to 5.88) and 2.51 (95% confidence interval = 1.24 to 5.07), respectively, which remained statistically significant when adjusted for other prognostic factors. These population-based results indicate that ESR1 mutations at diagnosis of primary breast cancer occur in about 1% of women and identify for the first time in the adjuvant setting that such preexisting mutations are associated to eventual resistance to standard hormone therapy. If replicated, tumor ESR1 screening should be considered in ER-positive primary breast cancer, and for patients with mutated disease, ER degraders such as fulvestrant or other therapeutic options may be considered as more appropriate.


  • Transl oncogenomics
  • LUCC: Lund University Cancer Centre
  • Translational Oncogenomics
  • Breastcancer-genetics
  • Breast cancer treatment
  • The Liquid Biopsy and Tumor Progression in Breast Cancer
  • Breast Cancer Surgery
  • Surgery (Lund)
  • Tumor Cell Biology
  • Division of Translational Cancer Research
  • Division of Clinical Genetics
  • Familial Breast Cancer

Publishing year





JNCI Cancer Spectrum





Document type

Journal article


Oxford University Press


  • Cancer and Oncology
  • Bioinformatics and Systems Biology
  • Bioinformatics (Computational Biology)


  • ESR1
  • Mutation
  • RNA-seq
  • dPCR
  • Endocrine therapy
  • Therapy resistance
  • Breast cancer




  • Sweden Cancerome Analysis Network - Breast (SCAN-B): a large-scale multicenter infrastructure towards implementation of breast cancer genomic analyses in the clinical routine

Research group

  • Translational Oncogenomics
  • The Liquid Biopsy and Tumor Progression in Breast Cancer
  • Breast Cancer Surgery
  • Tumor Cell Biology
  • Familial Breast Cancer


  • ISSN: 2515-5091