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Somatic mutations in benign breast disease tissue and risk of subsequent invasive breast cancer

British Journal of Cancervolume 118pages16621664 (2018) | Download Citation



Insights into the molecular pathogenesis of breast cancer might come from molecular analysis of tissue from early stages of the disease.


We conducted a case–control study nested in a cohort of women who had biopsy-confirmed benign breast disease (BBD) diagnosed between 1971 and 2006 at Kaiser Permanente Northwest and who were followed to mid-2015 to ascertain subsequent invasive breast cancer (IBC); cases (n = 218) were women with BBD who developed subsequent IBC and controls, individually matched (1:1) to cases, were women with BBD who did not develop IBC in the same follow-up interval as that for the corresponding case. Targeted sequence capture and sequencing were performed for 83 genes of importance in breast cancer.


There were no significant case–control differences in mutation burden overall, for non-silent mutations, for individual genes, or with respect either to the nature of the gene mutations or to mutational enrichment at the pathway level. For seven subjects with DNA from the BBD and ipsilateral IBC, virtually no mutations were shared.


This study, the first to use a targeted multi-gene sequencing approach on early breast cancer precursor lesions to investigate the genomic basis of the disease, showed that somatic mutations detected in BBD tissue were not associated with breast cancer risk.

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We thank Minerva Manickchand for her dedicated work as the project coordinator for this study. We would also like to thank the following staff at the Kaiser Center for Health Research who worked on this project for several years: Nicole Bennett, Kristine Bennett, Donna Gleason, Kathy Pearson, Tracy Dodge, Stacy Harsh, and Kevin Winn.

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Author notes

  1. These authors contributed equally: Thomas E. Rohan, Christopher A. Miller.

  2. Deceased: Andrew Glass.


  1. Department of Epidemiology and Population Health, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    • Thomas E. Rohan
    •  & Mindy Ginsberg
  2. McDonnell Genome Institute, Washington University School of Medicine, St. Louis, MO, USA

    • Christopher A. Miller
    •  & Tiandao Li
  3. Department of Pathology and Laboratory Medicine, Rhode Island Hospital and Lifespan Medical Center, Warren Alpert Medical School of Brown University, Providence, RI, USA

    • Yihong Wang
  4. Hackensack University Medical Center, David Joseph Jurist Research Center, Hackensack, NJ, USA

    • Olivier Loudig
  5. Center for Health Research, Kaiser Permanente Northwest, Portland, OR, USA

    • Andrew Glass
  6. Institute for Genomic Medicine, Nationwide Children’s Hospital and The Ohio State University College of Medicine, Columbus, OH, USA

    • Elaine Mardis


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This work was supported by grants to T.E. Rohan from NIH/NCI (R01CA142942) and the Breast Cancer Research Foundation.

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The authors declare no competing interests.

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Correspondence to Thomas E. Rohan.

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