Comment on 'Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy'.
Comment on 'Impact of CYP2D6*10 on recurrence-free survival in breast cancer patients receiving adjuvant tamoxifen therapy'.
复制标题
评论“CYP2D6*10 对接受他莫昔芬辅助治疗的乳腺癌患者无复发生存的影响”。
DOI：
10.1111/j.1349-7006.2008.00864.x
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发表时间：
2008
期刊：
影响因子：
5.7
通讯作者：
Sørensen,HenrikToft
中科院分区：
文献类型：
--
作者：
Lash,TimothyL;Ahern,ThomasP;Cronin-Fenton,Deirdre;Garne,JensPeter;Hamilton-Dutoit,Stephen;Sørensen,HenrikToft
CYP2D6* 10 allele on recurrence-free survival in Japanese breast cancer patients receiving adjuvant tamoxifen therapy.(1) The* 10 allele causes an amino-acid substitution that reduces the enzyme’s functionality, so breast cancer patients with this allele who are treated with tamoxifen may not produce a sufficient concentration of the pharmacologically most active metabolites.(2) Indeed, compared with women who have the* 1/* 1 genotype, the authors reported a 4-fold higher rate of recurrence [95% confidence interval (95% CI) 0.41, 39.18] in women who have the* 1/* 10 genotype and a 16.63-fold higher rate of recurrence (95% CI 1.75, 158.12) in women who have the* 10/* 10 genotype.The study included 67 women (a) diagnosed with estrogen or progesterone receptor-positive invasive breast cancer after 1985 at the Tokushima Breast Care Clinic,(b) treated with five years of tamoxifen and (c) agreeing to participate and give blood for genotyping in 2007. The authors acknowledged that patients with recurrences soon after diagnosis may not have participated because they were too ill or dead by 2007. The authors may not, however, have adequately considered the potential implications of studying recurrence rates in a time period that participants must have survived to join the cohort. All participants had to survive from their breast cancer surgery until their blood draw, yet recurrences and person-time in that period were included in the analysis. Outcomes and person-time that occur before the last event required for participation in a study are ordinarily excluded from analysis to avoid bias.(3) This study’s crosssectional design most likely introduced a selection bias, which can create the appearance of an association when none exists.(4) For example, it is possible that the* 10 allele actually delayed onset of recurrence or improved survival of patients who had a recurrence. Three of five earlier studies of the effect of the functionally variant CYP2D6* 4 allele reported a lower recurrence risk in women with the variant allele.(5) The surviving breast cancer patients in 2007 would then have a higher prevalence of the* 10 allele among patients with a recurrence–exactly as observed–but this higher prevalence would result from protection against recurrence and mortality by the* 10 allele beginning at the time of diagnosis, not from a higher rate of adverse outcomes as suggested by the reported associations. Because of the study’s susceptibility to bias, one cannot unambiguously interpret its result.
