LAUSR

In the last years prognosis of cancer patients (pts) has been improved, but the develop of cardiotoxicity (CTX) in pts with low CV risk treated with cumulative doses of Anthracycline (ANT) considered safe, led to investigate the possible role of the genetic profile in the onset of CTX. To study the role of some single nucleotide polymorphisms (SNPs) as predictive genetic markers of individual susceptibility to CTX induced by anticancer treatment. We have enrolled women with non-metastatic breast cancer who had to start a therapy with ANT. The presence of a known heart disease, a previous mediastinal irradiation and a previous treatment with ANT, were the main exclusion criteria. All pts underwent complete cardiological evaluation (ECG, echo) before the beginning of the therapy (T0), after each ANT cycle and every 3 months up to 1 year of follow-up after the end of treatment. During each visit, we performed the determination of troponin I (TnI) and NT-proBNP. The genetic profile of each pts was also investigated, analyzing 6 SNPs belonging to 3 different genes (two for each genes) coding for enzymes or enzyme systems involved in the metabolism of ANT. DNA extraction from blood samples was performed using the QIAamp DNA Mini kit (QIAGEN). The DNA extracted was genotyped (by performing TaqMan SNP Genotyping assays) identifying 3 possible variants for each SNPs: homozygosity for the protective and “at risk” variant and heterozygosity. 179 pts finished the follow-up and from the analysis of the trend of biomarkers we found that 53 pts (30%) showed a significant increase in TnI (>0.04ng/mL) or less than this cut-off but persistently >0.015ng/mL in at least 2 measurements (“TnI+ group”), in the remaining 126 pts the TnI remained non-measurable (“TnI− group”); 76 pts (43%) showed NT-proBNP values ≥125 ng/L in at least two consecutive determinations (“NT-proBNP + group”),in the remaining 57% of pts this increase was not detected (“NT-proBNP - group”). Comparing “TnI+ group” to “TnI− group” we observed that only the genotyping of the SNPs rs1149222 (G/T) belonging to the ABCB4 gene is distributed differently in the two groups, in particular the homozygosity for the “at risk” variant (G/G) was present in 13% of the pts of the “TnI+ group” vs 5% in the “TnI− group” (p 0.06). The results of the comparison of “NT-proBNP+ group” vs “NT-proBNP− group”, showed that the genotyping of the SNPs rs6759892 (G/T) belonging to the UGT1A6 gene was distributed differently, the homozygosity for the “at risk” variant (G/G) was present in 28% of the “NT-proBNP+ group” vs 17% in the “NT-proBNP− group” (p 0.07). Together with the baseline clinical evaluation, genetic markers could contribute to the early identification of pts at high risk of developing CTX especially following treatment with ANT and they could support future therapeutic decisions and the planning of taylored strategies for the prevention of the CTX development. Type of funding source: None