The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here:

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Åke Borg

Åke Borg

Principal investigator

Åke Borg

Whole-genome sequencing of triple-negative breast cancers in a population-based clinical study


  • Johan Staaf
  • Dominik Glodzik
  • Ana Bosch
  • Johan Vallon-Christersson
  • Christel Reuterswärd
  • Jari Häkkinen
  • Andrea Degasperi
  • Tauanne Dias Amarante
  • Lao H Saal
  • Cecilia Hegardt
  • Hilary Stobart
  • Anna Ehinger
  • Christer Larsson
  • Lisa Rydén
  • Niklas Loman
  • Martin Malmberg
  • Anders Kvist
  • Hans Ehrencrona
  • Helen R Davies
  • Åke Borg
  • Serena Nik-Zainal

Summary, in English

Whole-genome sequencing (WGS) brings comprehensive insights to cancer genome interpretation. To explore the clinical value of WGS, we sequenced 254 triple-negative breast cancers (TNBCs) for which associated treatment and outcome data were collected between 2010 and 2015 via the population-based Sweden Cancerome Analysis Network-Breast (SCAN-B) project ( ID:NCT02306096). Applying the HRDetect mutational-signature-based algorithm to classify tumors, 59% were predicted to have homologous-recombination-repair deficiency (HRDetect-high): 67% explained by germline/somatic mutations of BRCA1/BRCA2, BRCA1 promoter hypermethylation, RAD51C hypermethylation or biallelic loss of PALB2. A novel mechanism of BRCA1 abrogation was discovered via germline SINE-VNTR-Alu retrotransposition. HRDetect provided independent prognostic information, with HRDetect-high patients having better outcome on adjuvant chemotherapy for invasive disease-free survival (hazard ratio (HR) = 0.42; 95% confidence interval (CI) = 0.2-0.87) and distant relapse-free interval (HR = 0.31, CI = 0.13-0.76) compared to HRDetect-low, regardless of whether a genetic/epigenetic cause was identified. HRDetect-intermediate, some possessing potentially targetable biological abnormalities, had the poorest outcomes. HRDetect-low cancers also had inadequate outcomes: ~4.7% were mismatch-repair-deficient (another targetable defect, not typically sought) and they were enriched for (but not restricted to) PIK3CA/AKT1 pathway abnormalities. New treatment options need to be considered for now-discernible HRDetect-intermediate and HRDetect-low categories. This population-based study advocates for WGS of TNBC to better inform trial stratification and improve clinical decision-making.


  • Breastcancer-genetics
  • BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
  • Research Group Lung Cancer
  • Molecular therapeutics in breast cancer
  • Translational Oncogenomics
  • Tumor microenvironment
  • Tumor Cell Biology
  • Division of Translational Cancer Research
  • The Liquid Biopsy and Tumor Progression in Breast Cancer
  • Breast Cancer Surgery
  • Surgery (Lund)
  • Familial Breast Cancer
  • Division of Clinical Genetics

Publishing year







Nature Medicine



Document type

Journal article


Nature Publishing Group


  • Cancer and Oncology




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

Research group

  • Research Group Lung Cancer
  • Molecular therapeutics in breast cancer
  • Translational Oncogenomics
  • Tumor Cell Biology
  • The Liquid Biopsy and Tumor Progression in Breast Cancer
  • Breast Cancer Surgery
  • Familial Breast Cancer


  • ISSN: 1546-170X