(252) Effect of Drug-Drug Interaction Between Tamoxifen and CYP2D6-inhibiting Antidepressants on Cancer Recurrence and Mortality of Women with Breast Cancer: a Systematic Review
PhD Student in Epidemiology Federal University of Rio Grande do Sul, Brazil
Background: Tamoxifen (TMX) is a prodrug metabolized to endoxifen by enzyme cytochrome P450 2D6 (CYP2D6). The use of CYP2D6 inhibitors antidepressants with tamoxifen can impact clinical outcomes in breast cancer.
Objectives: To summarize the evidence on the effect of the interaction between TMX and CYP2D6-inhibiting antidepressants on cancer recurrence and mortality in breast cancer patients.
Methods: We performed a systematic review by searching 11 electronic databases (Medline, Embase, Cinahl, Cochrane Central, Clinical Trials, SciELO, Lilacs, Scopus, Web of Science, Oasisbr, and Open Gray). Two independent reviewers identified studies, extracted data, and assessed the risk of bias using the National Institutes of Health (NIH) tools. We used a descriptive-analytical approach to synthesize the results. Due to the substantial heterogeneity between included studies, it is not meaningful to meta-analyze the extracted data. The protocol was registered with PROSPERO (CRD42020212914).
Results: The eight studies included in this review are observational (four retrospective cohort studies, two case-control, and two nested case-control studies), published between 2009 and 2019. The cohort studies showed better overall quality than case-control studies. The most significant limitation was the non-adjustment of the measures for the pre-established prognostic variables. The majority assessed the selective serotonin reuptake inhibitors (SSRI) effect use, presenting results by drug or drug class. Vast differences regarding exposure definitions were found among the studies. Only one study identified an increased risk of mortality. No increased risk of cancer recurrence was found, irrespective of the power of antidepressive CYP2D6 inhibition.
Conclusions: This systematic review could not find an association between cancer recurrence and death in breast cancer patients using TMX and CYP2D6-inhibiting antidepressants. However, the methodological limitations identified compromise the clinical practice applicability of this finding. Considering that other antidepressants with less or any effect on CYP2D6 are available, doctors should be warned to avoid prescribing antidepressants classified as strong CYP2D6 inhibitors for patients taking TMX.
