Chromosome instability and benefit from adjuvant anthracyclines in breast cancer

Background:

Duplication of the centromeric region of chromosome 17 (Ch17CEP) is associated with sensitivity to anthracyclines. An explanation may be chromosome instability (CIN); a frequent event in solid tumours associated with poor outcome. The predictive value of CIN seems to be drug dependent and CIN has been associated with both sensitivity and resistance to chemotherapy.

Methods:

In this study, we used fluorescent in situ hybridisation for chromosomes 1, 7, 11, 17 and 18 to identify patients with high tumour CIN% in 322 patients recruited into the BR9601 clinical trial.

Results:

High tumour CIN% was correlated to Ch17CEP (P=3.68e−7) and is associated with a reduced RFS (P=0.0011) and OS (P=0.04). Patients with high CIN had a decreased risk of death on E-CMF compared with CMF.

Conclusion:

CIN is of prognostic significance and may be of predictive value in determining anthracycline response, although further testing is required.