Single Nucleotide Polymorphisms and Anthracycline Cardiotoxicity in Children: Potential Implications for Adult Oncology

TO THE EDITOR: One of the values that Journal of Clinical Oncology brings to clinicians is the collection of content from different fields. Although I do not treat children with cancer, I make it a habit to peruse articles about pediatric oncology in the event that one of them might resonate with something of importance to my practice. Reviewing the May 1 issue of the Journal while pursuing this habit, I was rewarded by finding articles by Visscher et al and Blanco et al along with an accompanying editorial by Davies discussing the role of single nucleotide polymorphisms in predicting cardiotoxicity after anthracycline-based chemotherapy for childhood cancer. The editorial by Davies is an intelligent, balanced synthesis of the data presented in the two original articles and gives an excellent summary of their importance to the management of childhood cancer. However, the potential implications for adult cancer are entirely missed. Whereas anthracyclines may be an integral part of treatment for those childhood malignancies in which it is used, the situation is different in adults, most glaringly in breast cancer. Anthracyclines are commonly used for adjuvant therapy in early breast cancer, but the survival advantage over nonanthracycline-containing regimens is small (3% to 4% at 8-10 years of follow-up) and limited to higher-dose or prolonged treatment regimens. If we could predict which patients will develop anthracycline-induced cardiotoxicity, the risk/benefit ratio of the drugs can be more clearly conveyed to our patients. Even more important is the choice of therapy for patients with HER2/neu-amplified breast cancer. The two most popular options in this country are cyclophosphamide and doxorubicin followed by paclitaxel and trastuzumab or the simultaneous use of docetaxel, carboplatin, and trastuzumab. The former is known to have more cardiotoxicity than the latter, but it has shown somewhat better survival results. If we could predict a patient’s risk of cardiotoxicity by analyzing single nucleotide polymorphisms, we could more easily choose the regimen most likely to benefit each individual patient. I hope the studies published by Visscher et al and Blanco et al will be pursued further and extended to the study of cardiotoxicity after anthracycline-based chemotherapy for breast cancer in adults.