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Mismatch repair defective breast cancer in the hereditary nonpolyposis colorectal cancer syndrome

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Abstract

Whether or not breast cancer can be a feature of the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome has been debated. In order to clarify if defective mismatch repair (MMR) may indeed play a role in breast cancer, we used the Danish HNPCC register to identify all breast cancers that occurred in MMR gene mutation carriers. In total, 20 female mutation carriers were diagnosed with breast cancer at mean 50 years of age. These tumors were predominantly ductal carcinomas with extensive lymphocytic reactions in 8/14 evaluated tumors. MMR protein immunostaining showed loss of expression of MLH1, MSH2 or MSH6 corresponding to the mutations identified in 7 of the 16 cases investigated, and these tumors were diagnosed at mean 50 (33–66) years of age. The demonstration of defective MMR in a substantial proportion of the breast cancers studied links yet another tumor type to HNPCC. Though the low number do not motivate surveillance, our observation supports a role for defective MMR in breast cancer progression in HNPCC, presumably through accelerated accumulation of mutations in breast cancer-associated genes.

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Acknowledgments

Financial support was granted from the Danish Cancer Fund and the Lundbeck Foundation. We acknowledge Eva Rambech, Lund University, Sweden for performing the MSI analyses.

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Authors and Affiliations

  1. Department of Clinical Genetics, Århus University Hospital, The Bartholin Building, Wilhelm Meyers Alle, University Park, 8000, Århus, Denmark

    Uffe Birk Jensen & Lone Sunde

  2. Department of Pathology, Helsingborg Hospital, Helsingborg, Sweden

    Britta Halvarsson

  3. Clinical Research Centre, Hvidovre Hospital, Copenhagen University, Hvidovre, Denmark

    Anja Nissen & Mef Nilbert

  4. HNPCC-register, Hvidovre Hospital, Copenhagen University, Hvidovre, Denmark

    Susanne Timshel & Inge Bernstein

Authors
  1. Uffe Birk Jensen
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  2. Lone Sunde
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  3. Susanne Timshel
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  4. Britta Halvarsson
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  5. Anja Nissen
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  7. Mef Nilbert
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Correspondence to Uffe Birk Jensen.

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Jensen, U.B., Sunde, L., Timshel, S. et al. Mismatch repair defective breast cancer in the hereditary nonpolyposis colorectal cancer syndrome. Breast Cancer Res Treat 120, 777–782 (2010). https://doi.org/10.1007/s10549-009-0449-3

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  • DOI: https://doi.org/10.1007/s10549-009-0449-3

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