Concurrent use of tamoxifen with CYP2D6 inhibitors and the risk of breast cancer recurrence

Abstract

Concurrent use of tamoxifen and cytochrome P450 2D6 (CYP2D6) inhibitors, such as selective serotonin reuptake inhibitors, has been shown to decrease plasma concentrations of tamoxifen metabolites. However, it is still unclear whether such concurrent use affects tamoxifen's effectiveness. Thus, the objective of this study is to determine whether concurrent use of tamoxifen with CYP2D6 inhibitors increases the risk of recurrence in patients newly diagnosed with breast cancer. We conducted a nested case-control analysis within a population-based cohort from the UK General Practice Research Database. The cohort included women with a first-ever diagnosis of breast cancer who were prescribed tamoxifen between January 1, 1998 and June 30, 2008. Cases consisted of all patients with a breast cancer recurrence occurring during follow-up. Up to ten controls were matched to each case on year of birth, date of cohort entry, and duration of follow-up. Conditional logistic regression was used to estimate rate ratios (RR) of breast cancer recurrence in patients who concurrently used tamoxifen with CYP2D6 inhibitors, compared to patients who only used tamoxifen. The cohort included 9,209 incident users of tamoxifen, of whom 807 were diagnosed with a breast cancer recurrence. Concurrent use was not associated with an increased incidence of breast cancer recurrence (adjusted RR 1.07, 95% 0.88, 1.30). Type and strength of CYP2D6 inhibitors, as well as duration of concurrent use did not affect breast cancer recurrence. These results remained consistent after performing sensitivity analyses. The results of this large population-based study indicate that concurrent use of tamoxifen with CYP2D6 inhibitors does not increase the risk of recurrence.

Antidepressant use and risk of central nervous system metastasis

“…The effect of tamoxifen was reduced in patients taking antidepressants resulting in a significantly higher 2-year breast cancer recurrence rate, 13.9% compared to 7.5% in patients not taking antidepressants with tamoxifen (HR 1.92, 95% CI 1.33-2.76, p < 0.001) [277]. In contrast to these findings, many studies suggest no association between antidepressants and breast cancer recurrence, even though this contradicts the biology [258,272,278,279]. Reasons for this inconsistency in previous studies include differences in SSRI inhibition ability, genomic differences, differences in data collection, limited information on tamoxifen compliance, and small sample size [274].…”

“…The idea that the decrease in tamoxifen activity by antidepressants affects breast cancer recurrence has been widely debated [258,272,274,[277][278][279]. The effect of tamoxifen was reduced in patients taking antidepressants resulting in a significantly higher 2-year breast cancer recurrence rate, 13.9% compared to 7.5% in patients not taking antidepressants with tamoxifen (HR 1.92, 95% CI 1.33-2.76, p < 0.001) [277].…”

“…Studies exist determining if an association exists between antidepressant use and cancer risk [264][265][266][267][268][269][270]283] and antidepressant use and recurrence of cancer [258,272,277,278], but to our knowledge, no studies exist determining if antidepressant use is associated with an increase in brain metastasis in humans. Shapovalov et al found an association between pretreatment with fluoxetine, a selective serotonin reuptake inhibitor (SSRI), and an increase in brain metastasis from breast cancer in mice [14].…”

Impact of CYP2D6 polymorphism on tamoxifen therapy: where are we?

“…However, evidence is weak with only one trial showing an increased risk of recurrence [53]. By contrast, in two recent retrospective analyses of about 10,000 tamoxifen-treated early breast cancer patients, recurrence rates were not affected by prolonged concomitant use of CYP2D6 inhibiting drugs [54,55]. However, data from prospective studies are currently lacking.…”

Traitement des bouffées de chaleur après cancer du sein

“…Il existe des arguments théoriques, soutenus par des études pharmacoépidémiologiques [65][66][67], suggérant une moindre efficacité du TMX en cas d'association à un inhibiteur puissant du CYP2D6. Les publications les plus récentes ne soutiennent pas cette hypothèse [68][69][70]. Dans un point d'information du 22 juin 2010, l'Afssaps, conjointement avec l'INCa, « recommande de ne pas utiliser la fluoxétine ou la paroxétine en cas de traitement par le TMX, et de recourir à d'autres antidépresseurs ».…”