Prognostic value of genomic alterations in minimal residual cancer cells purified from the blood of breast cancer patients

The prognostic value of disseminated tumour cells derived from 353 breast c ancer patients was evaluated. Disseminated tumour cells were purified from blood using a newly established method and nucleic acids were subsequently isolated. We investigated genomic imbalances (GI) such as mutation, amplifi cation and loss of heterozygosity of 13 tumour suppressor genes and 2 proto -oncogenes using DNA from isolated minimal residual cancer cells. Significa nt correlations were found between genomic alterations of the DCC- and c-er bB-2 genes in disseminated breast cancer cells and actuarial relapse-free s urvival. Furthermore, increasing numbers of genomic imbalances measured in disseminated tumour cells were significantly associated with worse prognosi s of recurrent disease. Logistic regression and Cox multivariate analysis l ed to the identification of genomic imbalances as an independent prognostic factor. Determination of disseminated tumour cells by genotyping of oncoge nes and tumour suppressor genes seems not only to be a useful adjunct in fo llow up of carcinoma patients but provides also valuable additional individ ualized prognostic and predictive information in breast cancer patients bey ond the TNM system. (C) 2000 Cancer Research Campaign.