HER2 signaling pathway and trastuzumab cardiotoxicity

Romond EH, Perez EA, Bryant J et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N. Engl. J. Med. 353(16), 1673-1684 (2005). Trastuzumab-induced cardiotoxicity may induce reversible damage that is usually transitory and improves with trastuzumab withdrawal. In clinical trials with trastuzumab in the adjuvant setting patients with cardiac risks were not included. Subgroup analysis identified subpopulations that were most likely to experience cardiac damage upon trastuzumab exposure. Although there is a risk of cardiac toxicity with adjuvant trastuzumab, the improvement of outcome in patients treated with this drug outweighs this. It is essential, therefore, to properly assess cardiac function prior to, during and after trastuzumab therapy in all patients. The incidence of congestive heart failure in older patients treated with trastuzumab is expected to be higher than in the overall population evaluated in large clinical trials. Therefore, cardiac risk assessment, breast cancer recurrence risk, and discussion between cardiologists and oncologists should take place prior to deciding which adjuvant treatment is appropriate for a woman with early breast cancer. A longer follow-up period is recommended in order to verify whether cardiac reversibility remains and, accordingly, whether the short-term risk is exaggerated or understated. With the NSABP-B31 trial regimen, the benefit of trastuzumab definitely outweighs the risk; indeed, the occurrence of late congestive heart failure after adding trastuzumab to chemotherapy is fairly unusual. In the era of personalized medicine, efforts are needed to promote strategies for risk detection and management to avoid dangerous toxicities that may impede the development of and patient access to new agents.