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Recommendations for genetic testing to reduce the incidence of anthracycline‐induced cardiotoxicity
Author(s) -
Aminkeng Folefac,
Ross Colin J. D.,
Rassekh Shahrad R.,
Hwang Soomi,
Rieder Michael J.,
Bhavsar Amit P.,
Smith Anne,
Sanatani Shubhayan,
Gelmon Karen A.,
Bernstein Daniel,
Hayden Michael R.,
Amstutz Ursula,
Carleton Bruce C.
Publication year - 2016
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/bcp.13008
Subject(s) - medicine , guideline , anthracycline , cardiotoxicity , genetic testing , pharmacogenomics , oncology , intensive care medicine , bioinformatics , cancer , pharmacology , pathology , chemotherapy , biology , breast cancer
Aims Anthracycline‐induced cardiotoxicity (ACT) occurs in 57% of treated patients and remains an important limitation of anthracycline‐based chemotherapy. In various genetic association studies, potential genetic risk markers for ACT have been identified. Therefore, we developed evidence‐based clinical practice recommendations for pharmacogenomic testing to further individualize therapy based on ACT risk. Methods We followed a standard guideline development process, including a systematic literature search, evidence synthesis and critical appraisal, and the development of clinical practice recommendations with an international expert group. Results RARG rs2229774, SLC28A3 rs7853758 and UGT1A6 rs17863783 variants currently have the strongest and the most consistent evidence for association with ACT. Genetic variants in ABCC1 , ABCC2 , ABCC5 , ABCB1 , ABCB4 , CBR3 , RAC2 , NCF4 , CYBA , GSTP1 , CAT , SULT2B1 , POR , HAS3 , SLC22A7 , SCL22A17 , HFE and NOS3 have also been associated with ACT, but require additional validation. We recommend pharmacogenomic testing for the RARG rs2229774 (S427L), SLC28A3 rs7853758 (L461L) and UGT1A6 * 4 rs17863783 (V209V) variants in childhood cancer patients with an indication for doxorubicin or daunorubicin therapy (Level B – moderate). Based on an overall risk stratification, taking into account genetic and clinical risk factors, we recommend a number of management options including increased frequency of echocardiogram monitoring, follow‐up, as well as therapeutic options within the current standard of clinical practice. Conclusions Existing evidence demonstrates that genetic factors have the potential to improve the discrimination between individuals at higher and lower risk of ACT. Genetic testing may therefore support both patient care decisions and evidence development for an improved prevention of ACT.