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.


CONCLUSIONS
CIN is of prognostic significance and may be of predictive value in determining anthracycline response, although further testing is required.
Endocrine Cancer Group, Edinburgh Cancer Research UK Centre, MRC IGMM, University of Edinburgh, Crewe Road South, Edinburgh EH4 2XR, UK.
A F
AF
Munro
C
C
Twelves
J S
JS
Thomas
D A
DA
Cameron
J M S
JM
Bartlett
D000328:Adult; D000368:Aged; D018943:Anthracyclines / Q000627:therapeutic use*; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D015415:Biomarkers; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D043171:Chromosomal Instability; D002886:Chromosomes, Human, Pair 17; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D055815:Young Adult
D018943:Anthracyclines; D000903:Antibiotics, Antineoplastic; D015415:Biomarkers