Clinical and genetic risk factors for @entity1259 -induced XXXX in early @entity0 @entity1 .

@entity1 @entity712 @entity0 @entity1115 @entity8253 @entity1002 @entity5948 @entity23873 @entity1259 @entity786 @entity72978 @entity1398 @entity11092 @entity38516 @entity16092 @entity1370 @entity7737 @entity1487
@entity5948 -induced @entity1370 (ACT) is a well-known serious adverse drug reaction leading to substantial morbidity. The purpose of this study was to assess ACT occurrence and clinical and genetic risk factors in early @entity0 @entity1 . In 6 genes of interest ( @entity11092 , @entity7737 , @entity1115 , @entity23873 , @entity16092 , @entity38516 ), 10 single nucleotide polymorphisms (SNPs) involved in ACT were selected based on a literature search. Eight hundred and seventy-seven @entity1 treated between 2000 and 2010 with 3-6 cycles of (neo) adjuvant @entity1487 , @entity1259 and @entity786 (FEC) were genotyped for these SNPs using Sequenom MassARRAY. Main outcome measures were asymptomatic decrease of @entity1002 ( @entity1002 ) > 10 % and @entity712 grade 3-5 (CTCAE 4.0). To evaluate the impact of these 10 SNPs as well as clinical factors (age, relative dose intensity of @entity1259 , left-sided radiotherapy, occurrence of @entity1398 , and planned and received cycles of @entity1259 ) on decrease of @entity1002 and @entity712 , we performed uni- and multivariable logistic regression analysis. Additionally, exploratory analyses including 11 additional SNPs related to the metabolism of @entity8253 were performed. After a median follow-up of 3.62 years (range 0.40-9.60), a @entity1002 decline of > 10 % occurred in 153 @entity1 (17.5 %) and @entity712 in 16 @entity1 (1.8 %). In multivariable analysis, six cycles of FEC compared to three cycles received and heterozygous carriers of the @entity72978 T-allele in @entity11092 relative to homozygous carriers of the T-allele were significantly associated with @entity1002 decline of > 10 % (OR 1.3, 95 % CI 1.1-1.4, p < 0.001 and OR 1.6, 95 % CI 1.1-2.3, p = 0.02). Radiotherapy for left-sided @entity0 was associated with @entity712 (OR 3.7, 95 % CI 1.2-11.5, p 0.026). The other 9 SNPs and clinical factors tested were not significantly associated. In our exploratory analysis, no other SNPs related to @entity5948 metabolism were retained in the multivariate model for prediction of @entity1002 decline. ACT in @entity0 @entity1 is related to number of received cycles of @entity1259 and left-sided radiotherapy. Additional studies should be performed to independently confirm the potential association between @entity72978 in @entity11092 and @entity1002 .
