Doubling back on centromere 17 in early breast cancer.

摘要

Anthracycline chemotherapy produces a modest improvement in survival for women with early-stage breast cancer.1 However, these drugs are associated with serious long-term side-effects-eg, secondary congestive heart failure and leukaemia-and careful selection is needed to ensure that anthracyclines are given only to patients who may benefit from them. A meta-analysis2 of eight randomised trials concluded that the benefit of anthracyclines was limited to patients with HER2 amplification. However, not all studies are consistent and a clear mechanistic link between HER2 amplificationand anthracycline sensitivity remains elusive. TOP2A, which neighbours HER2 on chromosome 17 (Chl7), is frequently co-amplified in HER2-positive tumours and encodes aTOP2A DNA replication protein that is inhibited by anthracycline therapy. Alterations of TOP2A have been associated with differential anthracycline benefit, although this finding has not always been recorded