Unexpected doxorubicin-induced cardiomyopathy in sisters

We report the details of two unexpected cases of doxorubicin (DOX)-induced cardiac toxicity in two sisters receiving adjuvant breast cancer therapy. One at age 38 developed a cardiomyopathy resulting in cardiac transplantation 6.5 years after receiving a relatively low total dose of DOX, i.e., 280 mg/m(2). The second at age 60 also developed a severe cardiomyopathy (i.e., a ventricular ejection fraction of 22%) 6 years after receiving a total dose of DOX of only 158 mg/m(2). Twelve single nucleotide polymorphisms previously associated with doxorubicin cardiotoxicity were assessed by pyrosequencing. None of the genotypes associated with an increased risk of doxorubicin-induced cardiotoxicity were identified in these two patients.