Selective serotonin reuptake inhibitors and breast cancer mortality in women receiving tamoxifen: a population based cohort study.
OBJECTIVE
To characterise whether some selective serotonin reuptake inhibitor (SSRI) antidepressants reduce tamoxifen's effectiveness by inhibiting its bioactivation by cytochrome P450 2D6 (CYP2D6).


METHODS
Population based cohort study.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Department of Medicine, Sunnybrook Health Sciences Centre, Toronto, Canada.
Catherine M
CM
Kelly
David N
DN
Juurlink
Tara
T
Gomes
Minh
M
Duong-Hua
Kathleen I
KI
Pritchard
Peter C
PC
Austin
Lawrence F
LF
Paszat
D000368:Aged; D000369:Aged, 80 and over; D018687:Antidepressive Agents, Second-Generation / Q000009:adverse effects*; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000401:mortality*; D015331:Cohort Studies; D003866:Depressive Disorder / Q000188:drug therapy; D004347:Drug Interactions; D005260:Female; D006801:Humans; D009864:Ontario / Q000453:epidemiology; D017374:Paroxetine / Q000009:adverse effects*; D012307:Risk Factors; D017367:Selective Serotonin Reuptake Inhibitors / Q000009:adverse effects*; D013629:Tamoxifen / Q000627:therapeutic use*
D018687:Antidepressive Agents, Second-Generation; D018931:Antineoplastic Agents, Hormonal; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D013629:Tamoxifen