A B S T R A C T PurposeThe clinical efficacy of tamoxifen is suspected to be influenced by the activity of drug-metabolizing enzymes and transporters involved in the formation, metabolism, and elimination of its active forms. We investigated relationships of polymorphisms in transporter genes and CYP2D6 to clinical outcome of patients receiving tamoxifen.
Patients and MethodsWe studied 282 patients with hormone receptor-positive, invasive breast cancer receiving tamoxifen monotherapy, including 67 patients who have been previously reported. We investigated the effects of allelic variants of CYP2D6 and haplotype-tagging single nucleotide polymorphisms (tag-SNPs) of ABCB1, ABCC2, and ABCG2 on recurrence-free survival using the Kaplan-Meier method and Cox regression analysis. Plasma concentrations of tamoxifen metabolites were measured in 98 patients receiving tamoxifen 20 mg/d.
Results
CYP2D6variants were significantly associated with shorter recurrence-free survival (P ϭ .000036; hazard ratio [HR] ϭ 9.52; 95% CI, 2.79 to 32.45 in patients with two variant alleles v patients without variant alleles). Among 51 tag-SNPs in transporter genes, a significant association was found at rs3740065 in ABCC2 (P ϭ .00017; HR ϭ 10.64; 95% CI, 1.44 to 78.88 in patients with AA v GG genotypes). The number of risk alleles of CYP2D6 and ABCC2 showed cumulative effects on recurrence-free survival (P ϭ .000000055). Patients carrying four risk alleles had 45.25-fold higher risk compared with patients with Յ one risk allele. CYP2D6 variants were associated with lower plasma levels of endoxifen and 4-hydroxytamoxifen (P ϭ .0000043 and .00052), whereas no significant difference was found among ABCC2 genotype groups.
ConclusionOur results suggest that polymorphisms in CYP2D6 and ABCC2 are important predictors for the prognosis of patients with breast cancer treated with tamoxifen.
The mean ADC values for breast cancer were significantly different from that of normal breasts. The mean ADC value for breast cancer did not significantly correlate with cancer cellularity but did correlate with histological types.
The PNQ has an applicable degree of feasibility and validity, useful for the diagnosis of CIPN as well as for clinical treatment decision-making, where the development of CIPN is a potential treatment-limiting consideration. Physicians underreport and underestimate the severity of CIPN symptoms compared with patients, thereby supporting the importance of assessing patient-reported outcomes using the PNQ.
Although a number of factors have been correlated with seroma formation, strong evidence is still scarce. However, there is evidence showing that sentinel lymph node biopsy reduces seroma formation.
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