Conclusions
This study suggests that a major defect in DNA repair occurs between preneoplasia and breast cancer. This defect is associated with changes in telomere length between the preneoplastic and the cancer stage.
Methods
We carried out a retrospective immunohistochemical analysis of pathway ataxia telangiectasia mutated (p-ATM) (series 1981) and gamma-H2AX (series 139) levels in normal breast, preneoplastic lesions, and invasive carcinoma. Fluorescent in situ hybridization was used to analyze telomere length at each stage.
Results
ATM was activated in 45% of normal tissue samples, 70% of preneoplastic lesions, and 14% of breast carcinomas. The increase in ATM activation, between normal tissues and preneoplasia, was not significant (P = 0.095), whereas, ATM repression between preneoplasia and cancer was significant (P = 0.0023). Telomeres in preneoplastic lesions were more frequently shorter than those in normal tissues (P = 0.0116). Finally, telomere lengths were long in 38.9% and very short in 38.9% of breast carcinomas (P = 0.0087 for comparisons with preneoplastic lesions). Conclusions: This study suggests that a major defect in DNA repair occurs between preneoplasia and breast cancer. This defect is associated with changes in telomere length between the preneoplastic and the cancer stage.