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. 2010 Feb 8:340:c693.
doi: 10.1136/bmj.c693.

Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study

Catherine M Kelly  1 , David N Juurlink, Tara Gomes, Minh Duong-Hua, Kathleen I Pritchard, Peter C Austin, Lawrence F Paszat
Affiliations

Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study

Catherine M Kelly et al. BMJ. .

Abstract

Objective: To characterise whether some selective serotonin reuptake inhibitor (SSRI) antidepressants reduce tamoxifen's effectiveness by inhibiting its bioactivation by cytochrome P450 2D6 (CYP2D6).

Design: Population based cohort study.

Participants: Women living in Ontario aged 66 years or older treated with tamoxifen for breast cancer between 1993 and 2005 who had overlapping treatment with a single SSRI.

Main outcome measures: Risk of death from breast cancer after completion of tamoxifen treatment, as a function of the proportion of time on tamoxifen during which each SSRI had been co-prescribed.

Results: Of 2430 women treated with tamoxifen and a single SSRI, 374 (15.4%) died of breast cancer during follow-up (mean follow-up 2.38 years, SD 2.59). After adjustment for age, duration of tamoxifen treatment, and other potential confounders, absolute increases of 25%, 50%, and 75% in the proportion of time on tamoxifen with overlapping use of paroxetine (an irreversible inhibitor of CYP2D6) were associated with 24%, 54%, and 91% increases in the risk of death from breast cancer, respectively (P<0.05 for each comparison). By contrast, no such risk was seen with other antidepressants. We estimate that use of paroxetine for 41% of tamoxifen treatment (the median overlap in our sample) would result in one additional breast cancer death within five years of cessation of tamoxifen for every 19.7 (95% confidence interval 12.5 to 46.3) patients so treated; the risk with more extensive overlap would be greater.

Conclusion: Paroxetine use during tamoxifen treatment is associated with an increased risk of death from breast cancer, supporting the hypothesis that paroxetine can reduce or abolish the benefit of tamoxifen in women with breast cancer.

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Conflict of interest statement

Competing interests: All authors have completed the Unified Competing Interest form at www.icmje.org_disclosure.pdf (available on request from the corresponding author. During the past three years KIP has been a consultant for Sanofi-Aventis, AstraZeneca, Roche, Pfizer, Ortho-Biotech, YM Biosciences, Novartis, Abraxis, Amgen, and GlaxoSmithKline (GSK). KIP has received research funding either directly through per case funding for studies, or indirectly through the National Cancer Institute of Canada Clinical Trials Group, contracted with pharmaceutical companies including AstraZeneca, YM Biosciences, Bristol Myers, Squibb, Sanofi-Aventis, Amgen, Ortho-Biotech, Pfizer, Novartis, GlaxoSmithKline, and Ortho Biotech. KIP has received honorariums or been part of speaker’s bureaux from Sanofi-Aventis, AstraZeneca, Pfizer, Roche, YM Biosciences, and Novartis. KIP has given paid expert testimony for Sanofi-Aventis, AstraZeneca, and GlaxoSmithKline. KIP has been a member of Advisory Committees for Sanofi-Aventis, AstraZeneca, Ortho-Biotech, Roche, Pfizer, Novartis, YM Biosciences, and GlaxoSmithKline. All other authors declare (1) no support from any company for the submitted work; (2) no relationships with any companies that might have an interest in the submitted work in the previous 3 years; (3) their spouses, partners, or children have no financial relationships that may be relevant to the submitted work; and (4) no non-financial interests that may be relevant to the submitted work.

Figures

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Fig 1 Risk of breast cancer mortality associated with increasing proportions of antidepressant use during tamoxifen treatment
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Fig 2 All-cause mortality associated with increasing proportions of antidepressant use during tamoxifen therapy
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