The spectrum of ATM missense variants and their contribution to contralateral breast cancer

Breast Cancer Res Treat. 2008 Jan;107(2):243-8. doi: 10.1007/s10549-007-9543-6. Epub 2007 Mar 28.


Heterozygous carriers of ATM mutations are at increased risk of breast cancer. In this case-control study, we evaluated the significance of germline ATM missense variants to the risk of contralateral breast cancer (CBC). We have determined the spectrum and frequency of ATM missense variants in 443 breast cancer patients diagnosed before age 50, including 247 patients who subsequently developed CBC. Twenty-one per cent of the women with unilateral breast cancer and 17% of the women with CBC had at least one ATM germline missense variant, indicating no significant difference in variant frequency between these two groups. We have found that carriers of an ATM missense mutation, who were treated with radiotherapy for the first breast tumour, developed their second tumour on average in a 92-month interval compared to a 136-month mean interval for those CBC patients who neither received RT nor carried a germline variant, (p = 0.029). Our results indicate that the presence of ATM variants does not have a major impact on the overall risk of CBC. However, the combination of RT and (certain) ATM missense variants seems to accelerate tumour development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Ataxia Telangiectasia Mutated Proteins
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / metabolism*
  • Cell Cycle Proteins / genetics*
  • DNA Mutational Analysis
  • DNA-Binding Proteins / genetics*
  • Female
  • Genetic Predisposition to Disease
  • Genetic Variation
  • Germ-Line Mutation
  • Heterozygote
  • Humans
  • Middle Aged
  • Mutation
  • Mutation, Missense*
  • Protein-Serine-Threonine Kinases / genetics*
  • Risk
  • Treatment Outcome
  • Tumor Suppressor Proteins / genetics*


  • Cell Cycle Proteins
  • DNA-Binding Proteins
  • Tumor Suppressor Proteins
  • ATM protein, human
  • Ataxia Telangiectasia Mutated Proteins
  • Protein-Serine-Threonine Kinases