他莫昔芬作为最常用的非甾体类抗雌激素药物，被广泛用于雌激素受体阳性乳腺癌患者的内分泌辅助治疗。CYP2D6作为他莫昔芬的主要代谢酶之一，参与其代谢形成活性代谢物。对于CYP2D6编码基因存在某些突变的患者，他莫昔芬的治疗效果较差。托瑞米芬的代谢途径不同于他莫昔芬，不通过CYP2D6代谢，可以安全有效地取代他莫昔芬用于乳腺癌患者内分泌辅助治疗，对于某些亚组患者可能优于他莫昔芬，例如接受他莫昔芬辅助治疗时获益较少的CYP2D6 * 10（c.100 C>T）T/T基因型（占中国总人口大约五分之一）中国女性。
2018年7月6日，国际抗癌联盟官方期刊《国际癌症杂志》在线发表中国医学科学院北京协和医学院肿瘤医院中国癌症中心徐兵河、马飞等学者的研究报告，对国家癌症中心230例接受术后他莫昔芬（115例）或托瑞米芬（115例）内分泌辅助治疗的早期乳腺癌患者进行了深入分析。
结果发现，对于不同CYP2D6*10基因型患者，接受托瑞米芬治疗的无病生存相似（P = 0.737）。托瑞米芬与他莫昔芬相比，患者接受治疗后的5年无病生存率较高（89.6%比80.9%，P = 0.009）。
根据多因素分析，排除其他因素的影响后，托瑞米芬与他莫昔芬相比，仍为治疗后无病生存的独立预后标志，复发死亡风险低49%（风险比：0.51，P = 0.014）。
对于所有50例CYP2D6*10T/T基因型患者，托瑞米芬与他莫昔芬相比，5年无病生存率显著较高（90.9%比67.9%，P = 0.031）。
对于剩余170例CYP2D6*10C/C或C/T基因型患者，托瑞米芬与他莫昔芬相比，5年无病生存率相似（89.2%比85.1%，P = 0.188）。
因此，该研究结果表明，对于CYP2D6*10T/T基因型中国乳腺癌患者，托瑞米芬可能显著优于他莫昔芬。对于该亚组中国患者，托瑞米芬可能是内分泌辅助治疗的良好选择。
Int J Cancer. 2018 Jul 6. [Epub ahead of print]
Toremifene, rather than tamoxifen, might be a better option for the adjuvant endocrine therapy in CYP2D6*10 T/T genotype breast cancer patients in China.
Lan B, Ma F, Chen S, Wang W, Li Q, Fan Y, Luo Y, Cai R, Wang J, Yuan P, Zhang P, Li Q, Xu B.
National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, China.
Toremifene (TOR) is a valid and safe alternative to tamoxifen (TAM) for adjuvant endocrine therapy in breast cancer patients with a metabolic pathway that differs from that of TAM. TOR might have a therapeutic advantage in certain subgroups of patients, such as Chinese women with the CYP2D6 *10 (c.100C>T) T/T genotype, who would get less benefit when receiving adjuvant TAM treatment. A total of 230 breast cancer patients who received adjuvant TAM (n=115) or TOR (n=115) at the National Cancer Center were analyzed. The CYP2D6 *10 genotype was not significantly associated with DFS in patients who received TOR (p=0.737). Patients treated with TOR had a higher 5-year disease-free survival (DFS) rate than those treated with TAM (89.6% versus 80.9%, p=0.009). TOR treatment remained an independent prognostic marker of DFS in multivariate analysis compared with TAM (hazard ratio=0.51; p=0.014). For all of the 50 CYP2D6 *10 T/T genotype patients, TOR treatment group had a significantly higher 5-year DFS rate than TAM group (90.9% versus 67.9%, p=0.031). For the remaining 170 CYP2D6 *10 C/C or C/T genotype patients, there was no significant difference between the 5-year DFS rates of the TOR and TAM groups (89.2% versus 85.1%, p=0.188). The advantage of adjuvant TOR over TAM in Chinese breast cancer patients might be caused by the significant benefit obtained by the CYP2D6 *10 T/T patients, who accounted for one-fifth of the overall population. TOR might be a good option for adjuvant endocrine therapy in this subgroup of patients in China.
KEYWORDS: CYP2D6; SNP; TAM; TOR; breast cancer
PMID: 29978573
DOI: 10.1002/ijc.31639
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