Department of Specialized Medicine, Maccabi Healthcare Services, Tel Aviv, Israel.
Breast Cancer Res Treat. 2011 Jan;125(2):505-10. doi: 10.1007/s10549-010-1008-7. Epub 2010 Jul 1.
Endoxifen, the most active metabolite of the prodrug tamoxifen, is produced by cytochrome P450 CYP2D6. Breast cancer patients treated with tamoxifen who have reduced CYP2D6 activity, related to either genetic variation or drug inhibition, may have inferior outcomes. To assess the effect of concomitant CYP2D6 inhibiting drug use on clinical outcomes of breast cancer patients treated with adjuvant tamoxifen. We conducted a retrospective database analysis. Women with non-metastatic estrogen receptor positive tumors who had completed adjuvant tamoxifen therapy for 2 years, without treatment with adjuvant aromatase inhibitors or early relapse, were included. Patients were classified as users of CYP2D6 inhibitors if they purchased strong CYP2D6 inhibiting drugs for ≥ 4 consecutive months during tamoxifen treatment. Tumors were classified as "high risk" if adjuvant chemotherapy was prescribed. Primary endpoint was disease free (DFS) and secondary endpoint was overall survival (OS). 902 patients treated with tamoxifen (median duration, 4.9 years) were followed for a median period of 5.9 years. Fifty-nine (6.5%) patients were users of CYP2D6 inhibitors (median duration, 23 months). DFS at 3 years (corresponding to 5 years after tamoxifen initiation) did not differ between users and non-users of CYP2D6 inhibiting drugs (92.7 vs. 93.0%, respectively; adjusted P = 0.44). OS at 3 years was lower in the patients using CYP2D6 inhibiting drugs: 89.4 vs. 93.8%, but after adjustment for age and comorbidities this difference was not significant (P = 0.20). Overall recurrence rates did not differ between users and non-users of CYP2D6 inhibiting drugs (11.8 vs. 19.0% respectively, P = 0.23). Concomitant prolonged therapy with strong CYP2D6 inhibiting drugs does not affect adversely DFS and recurrence rates in tamoxifen-treated early breast cancer patients.
他莫昔芬的前药，其最活跃的代谢产物是依西美坦，由细胞色素 P450 CYP2D6 产生。接受他莫昔芬治疗的乳腺癌患者，如果 CYP2D6 活性降低，这可能与遗传变异或药物抑制有关，则可能预后较差。评估同时使用 CYP2D6 抑制药物对接受辅助他莫昔芬治疗的乳腺癌患者临床结局的影响。我们进行了一项回顾性数据库分析。纳入了完成辅助他莫昔芬治疗 2 年且未接受辅助芳香酶抑制剂治疗或早期复发的非转移性雌激素受体阳性肿瘤的女性患者。如果患者在他莫昔芬治疗期间连续购买强 CYP2D6 抑制药物≥4 个月，则将其归类为 CYP2D6 抑制剂使用者。如果患者接受辅助化疗，则将肿瘤分类为“高危”。主要终点是无病生存期（DFS），次要终点是总生存期（OS）。902 名接受他莫昔芬治疗（中位持续时间为 4.9 年）的患者接受了中位时间为 5.9 年的随访。59 名（6.5%）患者为 CYP2D6 抑制剂使用者（中位持续时间为 23 个月）。在 3 年（相当于他莫昔芬开始后 5 年）时，CYP2D6 抑制剂使用者与非使用者的 DFS 无差异（分别为 92.7%和 93.0%；调整后 P=0.44）。在 CYP2D6 抑制剂使用者中，3 年时 OS 较低：89.4%比 93.8%，但调整年龄和合并症后差异无统计学意义（P=0.20）。CYP2D6 抑制剂使用者与非使用者的总复发率无差异（分别为 11.8%和 19.0%，P=0.23）。同时延长使用强 CYP2D6 抑制药物不会对接受他莫昔芬治疗的早期乳腺癌患者的 DFS 和复发率产生不利影响。
