Breast cancer recurrence risk related to concurrent use of SSRI antidepressants and tamoxifen

Lash, Timothy L.; Cronin‐Fenton, Deirdre; Ahern, Thomas P.; Rosenberg, Carol L.; Lunetta, Kathryn L.; Silliman, Rebecca A.; Hamilton-Dutoit, Stephen; Garne, Jens Peter; Ewertz, Marianne; Sørensen, Henrik Toft; Pedersen, Lars

doi:10.3109/02841860903575273

Cited by 88 publications

(77 citation statements)

References 24 publications

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“…Although some studies have reported an association between antidepressants and the risk of breast cancer (Lawlor et al, 2003;Lash et al, 2010), other preclinical studies indicate that antidepressants display anticancer activities (Xia et al, 1999;Coogan et al, 2009;Cloonan and Williams, 2011). These discordant observations may relate to the activity of the individual antidepressants.…”

Section: Discussionmentioning

confidence: 54%

The Tricyclic Antidepressant Amitriptyline Inhibits d-Cyclin Transactivation and Induces Myeloma Cell Apoptosis by Inhibiting Histone Deacetylases: In Vitro and In Silico Evidence

Mao

Hou²,

Cao³

et al. 2011

Mol Pharmacol

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Amitriptyline is a classic tricyclic antidepressant (TCA) and has been used to treat the depression and anxiety of patients with cancer, but its relevance to cancer cell apoptosis is not known. In the present study, we demonstrated that amitriptyline inhibited cyclin D2 transactivation and displayed potential antimyeloma activity by inhibiting histone deacetylases (HDACs). Amitriptyline markedly decreased cyclin D2 promoter-driven luciferase activity, reduced cyclin D2 expression, and arrested cells at the G 0 /G 1 phase of the cell cycle. Amitriptyline-induced apoptosis was confirmed by Annexin V staining, and cleavage of caspase-3 and poly(ADP-ribose) polymerase-1. D-Cyclin expression is reported to be epigenetically regulated by histone acetylation. Thus, we examined the effects of amitriptyline on histone 3 (H3) acetylation and demonstrated that amitriptyline increased acetylation of H3 and expression of p27 and p21. Further studies indicated that amitriptyline interfered with HDAC function by down-regulation of HDAC3, -6, -7, and -8, but not HDAC2, and by interacting with HDAC7. Molecular docking analysis and molecular dynamics simulations revealed that amitriptyline bound to HDAC7 and formed strong van der Waals interactions with five residues of HDAC7, including Phe162, His192, Phe221, Leu293, and His326, thus inhibiting HDAC activity. Therefore, we found that amitriptyline inhibited cyclin D2 transactivation and HDAC activity and could be a promising treatment for multiple myeloma.

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Section: Discussionmentioning

confidence: 54%

The Tricyclic Antidepressant Amitriptyline Inhibits d-Cyclin Transactivation and Induces Myeloma Cell Apoptosis by Inhibiting Histone Deacetylases: In Vitro and In Silico Evidence

Mao

Hou²,

Cao³

et al. 2011

Mol Pharmacol

View full text Add to dashboard Cite

show abstract

“…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].…”

Section: Antidepressant Usementioning

confidence: 98%

“…Since SSRIs inhibit cytochrome P-450 2D6 (CYP2D6), the enzyme that metabolizes tamoxifen, they decrease the amount of tamoxifen metabolites in the blood [272]. Some SSRIs inhibit CYP2D6 more than others.…”

Section: Antidepressant Usementioning

confidence: 99%

“…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].…”

Section: Antidepressant Usementioning

confidence: 99%

“…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].…”

Section: Antidepressant Usementioning

confidence: 99%

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