Department of Clinical Epidemiology, Aarhus University Hospital, Denmark.
Acta Oncol. 2010 Apr;49(3):305-12. doi: 10.3109/02841860903575273.
Up to one-quarter of breast cancer patients suffer clinically significant depression in the year after diagnosis, which may respond to intervention. About half may be prescribed a psychotropic medication, such as a selective serotonin reuptake inhibitor (SSRI), while completing breast cancer therapy. Cytochrome P-450 2D6 (CYP2D6) metabolizes SSRIs and also metabolizes tamoxifen to more active forms. Therefore, concurrent use of SSRIs may reduce tamoxifen's effectiveness at preventing breast cancer recurrence. The SSRI citalopram has limited potency to inhibit CYP2D6 activity, so has been recommended for breast cancer patients taking tamoxifen. This study provides epidemiologic evidence to support this recommendation.
We conducted a case-control study of breast cancer recurrence nested in the population of female residents of Denmark who were diagnosed with non-metastatic estrogen-receptor positive breast cancers between 1994 and 2001 and who took tamoxifen for at least one year. We ascertained complete prescription histories by linking cases' and controls' civil registration numbers to the Danish national prescription registry. We estimated the association between SSRI use while taking tamoxifen and risk of recurrent breast cancer.
About the same proportion of recurrent cases (37 of 366) and matched controls (35 of 366) received at least one prescription for citalopram or its s-stereoisomer while taking tamoxifen (adjusted odds ratio = 1.1, 95% confidence interval = 0.7, 1.7). Breast cancer patients taking other SSRIs were also at no increased risk of recurrence (adjusted odds ratio = 0.9, 95% confidence interval = 0.5, 1.8).
Breast cancer patients with indications for an SSRI may be prescribed citalopram - and possibly other SSRI - without adversely affecting the outcome of adjuvant therapy with tamoxifen.
多达四分之一的乳腺癌患者在诊断后一年内会出现临床显著的抑郁，这可能需要干预。大约一半的患者可能会在接受乳腺癌治疗的同时被开一种精神药物，如选择性 5-羟色胺再摄取抑制剂（SSRIs）。细胞色素 P-450 2D6（CYP2D6）代谢 SSRIs，也代谢他莫昔芬成为更活跃的形式。因此，同时使用 SSRIs 可能会降低他莫昔芬预防乳腺癌复发的效果。SSRI 西酞普兰对 CYP2D6 活性的抑制作用有限，因此被推荐用于服用他莫昔芬的乳腺癌患者。本研究提供了支持这一建议的流行病学证据。
我们进行了一项病例对照研究，在丹麦的女性居民中，对 1994 年至 2001 年间被诊断为非转移性雌激素受体阳性乳腺癌且至少服用一年他莫昔芬的患者进行了乳腺癌复发的嵌套研究。我们通过将病例和对照的公民登记号码与丹麦国家处方登记处相链接，确定了完整的处方史。我们估计了在服用他莫昔芬的同时使用 SSRI 与乳腺癌复发风险之间的关联。
在服用他莫昔芬时，接受至少一种西酞普兰或其 S-对映异构体处方的复发病例（366 例中的 37 例）和匹配对照（366 例中的 35 例）的比例大致相同（调整后的比值比=1.1，95%置信区间=0.7，1.7）。服用其他 SSRIs 的乳腺癌患者也没有增加复发的风险（调整后的比值比=0.9，95%置信区间=0.5，1.8）。
有 SSRI 适应证的乳腺癌患者可能会被开西酞普兰-可能还有其他 SSRIs-而不会对他莫昔芬辅助治疗的结果产生不利影响。
