No increase in breast cancer recurrence with concurrent use of tamoxifen and some CYP2D6-inhibiting medications.

No increase in breast cancer recurrence with concurrent use of tamoxifen and some CYP2D6-inhibiting medications.
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DOI:
10.1158/1055-9965.epi-09-0516
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发表时间:
2009-09
期刊:
Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology
影响因子:
--
通讯作者:
Lash TL
Lash TL
中科院分区:
其他
文献类型:
--
作者:
Ahern TP;Pedersen L;Cronin-Fenton DP;Sørensen HT;Lash TL

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Tamoxifen reduces recurrence risk among women treated for estrogen receptor-positive breast cancer. Its effectiveness partly depends on metabolic activation via cytochrome P450 2D6 (CYP2D6). Some medications compromise CYP2D6 activity and may lower plasma concentrations of active tamoxifen metabolites. We studied the association between concurrent use of tamoxifen and CYP2D6-inhibiting medications and breast cancer recurrence among Danish women diagnosed with early-stage, estrogen receptor-positive breast cancer. Using the Danish Breast Cancer Cooperative Group (DBCG) Registry, we identified 366 cases with local or distant breast cancer recurrence and 366 matched breast cancer controls. We ascertained concurrent prescription of CYP2D6-inhibiting medications during tamoxifen treatment by linking to the national prescription database covering all Danish pharmacies. We computed the breast cancer recurrence odds ratio (OR) and 95% confidence interval (95% CI) for each medication. The pooled recurrence odds ratio was null (OR: 1.0; 95% CI: 0.8, 1.3); recurrence odds ratios for individual drugs ranged from 0.3 to 3.4. The individual odds ratios followed the pattern expected under a null-centered Gaussian distribution. Null associations were apparent for all drugs after empirical Bayes adjustment for multiple comparisons. Together, these results provide evidence for a null association between drug-compromised CYP2D6 activity and breast cancer recurrence among tamoxifen-treated women.