SNPMiner Trials (Home Page)
Report for Mutation I665V
 Developed by Shray Alag, 2020.
SNP Clinical Trial Gene 
There is one clinical trial. 
Clinical Trials
      Breast cancer patients undergoing trastuzumab-based HER2-directed therapy are at risk of
      heart function decline or heart failure symptoms, but it is unknown if, when, and for how
      long cardiovascular protective strategies, e.g. with a beta-blocker, could help. This study
      randomly assigns those taking curative-intent trastuzumab-based HER2-directed therapy to the
      beta-blocker carvedilol—either when significant heart function decline or subtle early signs
      of heart injury (either by elevation of a cardiac blood biomarker, i.e. cardiac troponin, or
      by an abnormal heart ultrasound marker, i.e. global longitudinal strain) are noted, or
      preventatively before beginning trastuzumab-based HER2-directed therapy. This study will
      further randomly assign those patients on carvedilol to either discontinuation at the end of
      trastuzumab-based HER2-directed therapy or continuation for another year, providing much
      needed clinical trial data on what the best strategy ("tactic") for those at risk of
      cardiotoxicity with trastuzumab-based HER2-directed therapy is.
    
Correlation of absolute delta change in GLS and LVEF while on trastuzumab and after stopping trastuzumab with the frequency of the following SNPs: trastuzumab-related: p<1x10-5 hits from Norton GWAS (six loci) 130 HER 2 Ile665Val, HER2 Pro1170Ala125, 126, 130, anthracycline-related: ABCB1 rs1128503, ABCB4 rs1149222, ABCC1 rs45511401, ABCC2 res17222723, CAT rs10836235, CBR3 rs1056892, CYBA rs4673, CYP3A4*22 rs35599367, NCF4 rs1883112, RAC2 rs13058338, RARG rs2229774, SLC28A3 rs7853758, TOP2B rs10865801, and UGT 1A6*4 rs1786378374, 150-152, beta-blocker-related: β2-AR Gln27Gln, β1-AR Arg389Arg 80-82 and CYP2D6 polymorphisms (CYP2D6 alleles (*1, *2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *15, *17, *19, *20, *29, *35, *36, *40 and *41), as well as 7 CYP2D6 gene duplications (*1 9 N, *2 9 N, *4 9 N, *10 9 N, *17 9 N, *35 9 N and *41 9 N) by use of the AmpliChip CYP450 GeneChip. --- Ile665Val --- 
  Primary Outcomes 
 Description: Incidence of heart failure or asymptomatic decline in left-ventricular ejection fraction (LVEF) by >10% in patients whose LVEF is ≥50% or LVEF drop ≥5% in those with a decrease to <50% (primary outcome measure)
 Measure: Rate of asymptomatic and symptomatic cardiac dysfunction
 Time: 1 year
 Description: Reversible LVEF decline to within 5% of baseline (secondary primary outcome measure)
 Measure: Rate of reversible cardiac function decline
 Time: 1 year
  Secondary Outcomes 
 Description: Delta change in LVEF from completion to one year after completion of trastuzumab-based HER2-directed therapy
 Measure: Cardiac function changes after completion of HER2-directed therapy
 Time: 1 year
 Description: Correlation of absolute delta change in GLS and LVEF while on trastuzumab and after stopping trastuzumab with the frequency of the following SNPs: trastuzumab-related: p<1x10-5 hits from Norton GWAS (six loci) 130 HER 2 Ile665Val, HER2 Pro1170Ala125, 126, 130, anthracycline-related: ABCB1 rs1128503, ABCB4 rs1149222, ABCC1 rs45511401, ABCC2 res17222723, CAT rs10836235, CBR3 rs1056892, CYBA rs4673, CYP3A4*22 rs35599367, NCF4 rs1883112, RAC2 rs13058338, RARG rs2229774, SLC28A3 rs7853758, TOP2B rs10865801, and UGT 1A6*4 rs1786378374, 150-152, beta-blocker-related: β2-AR Gln27Gln, β1-AR Arg389Arg 80-82 and CYP2D6 polymorphisms (CYP2D6 alleles (*1, *2, *3, *4, *5, *6, *7, *8, *9, *10, *11, *15, *17, *19, *20, *29, *35, *36, *40 and *41), as well as 7 CYP2D6 gene duplications (*1 9 N, *2 9 N, *4 9 N, *10 9 N, *17 9 N, *35 9 N and *41 9 N) by use of the AmpliChip CYP450 GeneChip
 Measure: Gene variants and risk of cardiotoxicity and response to therapy
 Time: 2 years
HPO Nodes
Cardiomyopathy 
Genes 711
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