Gallicchio Lisa, Lord Gwyn, Tkaczuk Katherine, Danton Malcolm, Lewis Lynn M, Lim Chang K, Flaws Jodi A
Department of Epidemiology and Preventive Medicine, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
Breast Cancer Res Treat. 2004 May;85(1):89-97. doi: 10.1023/B:BREA.0000021050.92539.b0.
The positive effects of tamoxifen (TAM) on breast cancer recurrence and survival as well as on overall mortality have led to its use as the predominant adjuvant therapy among women with breast cancer. However, the association of TAM intake with undesirable side effects has been reported in numerous studies. This analysis was carried out to assess whether the concentrations of TAM or TAM metabolites, N -desmethyltamoxifen ( N -DMT) and 4-hydroxytamoxifen (4-OHT), were associated with self-reported side effects of TAM. Participants were 99 breast cancer patients who had been taking TAM for at least 30 days. Each participant completed a questionnaire that was used to ascertain whether she experienced certain specific symptoms while taking TAM. In addition, each woman provided a blood sample that was used to measure plasma concentrations of TAM, N -DMT, and 4-OHT by high performance liquid chromatography. Results of the analysis showed that women who experienced at least one TAM-related side effect had significantly higher levels of TAM than women not experiencing any TAM-related side effects. Furthermore, women who reported experiencing visual problems had significantly higher levels of both TAM and N -DMT compared to those women who reported experiencing no visual problems. The levels of 4-OHT were negatively associated with the occurrence of vaginal discharge. The results of this study suggest that the self-reported occurrence of certain symptoms during TAM treatment is related to TAM metabolism. Future studies should assess subgroups of women with specific TAM and TAM metabolite profiles to determine whether alternate, equally effective therapies would decrease their risk of experiencing certain undesirable side effects.
他莫昔芬（TAM）对乳腺癌复发、生存以及总体死亡率具有积极影响，这使得它成为乳腺癌女性患者主要的辅助治疗药物。然而，众多研究报道了服用TAM会产生不良副作用。开展该分析是为了评估TAM或其代谢产物N -去甲基他莫昔芬（N -DMT）和4-羟基他莫昔芬（4-OHT）的浓度是否与TAM的自我报告副作用相关。研究对象为99名服用TAM至少30天的乳腺癌患者。每位参与者都完成了一份问卷，用于确定她在服用TAM期间是否出现某些特定症状。此外，每位女性都提供了一份血样，通过高效液相色谱法测定血浆中TAM、N -DMT和4-OHT的浓度。结果显示，经历至少一种与TAM相关副作用的女性，其TAM水平显著高于未经历任何与TAM相关副作用的女性。此外，报告有视觉问题的女性，其TAM和N -DMT水平均显著高于未报告有视觉问题的女性。4-OHT水平与白带的发生呈负相关。本研究结果表明，TAM治疗期间自我报告的某些症状的出现与TAM代谢有关。未来的研究应评估具有特定TAM和TAM代谢产物谱的女性亚组，以确定替代的、同样有效的治疗方法是否会降低她们出现某些不良副作用的风险。
