Breast Cancer Risk Among Users of Antidepressant Medications

Centro Español de Investigación Farmacoepidemiológica (CEIFE), Madrid, Spain.
Epidemiology (Impact Factor: 6.2). 02/2005; 16(1):101-5. DOI: 10.1097/01.ede.0000147103.92638.c0
Source: PubMed


Breast cancer is the most common cancer in women. Laboratory studies suggest that antidepressants may promote breast cancer tumor growth. Several epidemiologic studies have evaluated this association with conflicting results.
We conducted a cohort study with a secondary nested case-control analysis based on the General Practice Research Database. Our goal was to assess the association between the risk of breast cancer and use of serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants (TCAs), and other antidepressants. We calculated adjusted estimates controlling for breast cancer risk factors using unconditional logistic regression.
A total of 3708 cases of breast cancer were ascertained. Overall, antidepressant use was not associated with an increased risk of breast cancer. Current users of SSRIs had an odds ratio (OR) of 0.98 (95% confidence interval=0.81-1.19), whereas current users of TCAs had an OR of 0.86 (0.73-1.00). When only use for longer than 1 year was considered, the corresponding estimates for SSRIs and TCAs were 0.76 (0.53-1.09) and 0.87 (0.70-1.09), respectively. None of the individual drugs was associated with breast cancer risk.
Use of antidepressants was not associated with an increased risk of breast cancer regardless of duration of use, daily dose, or specific drug being used. These results, together with evidence from prior studies, support the lack of a clinically meaningful association between breast cancer risk and antidepressants.

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Available from: Luis Alberto Garcia-Rodriguez, Oct 05, 2015
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    • "In our study, age 55 was chosen as a cut-off to avoid misclassification of premenopausal cases as post-menopausal, since breast cancer cases are more likely to self-report a later age at menopause (Morabia and Flandre, 1992; Phipps et al., 2010). In addition, previous studies investigating the role of menopausal status on breast cancer risk have used similar age cut-offs to define menopausal status (Van Hoften et al., 2000; Tryggvadottir et al., 2002; Gonzalez-Perez and Garcia Rodriguez, 2005). "
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    ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs) are a widely prescribed class of antidepressants. Laboratory and epidemiologic evidence suggests that a prolactin-mediated mechanism secondary to increased serotonin levels at neuronal synapses could lead to a potentially carcinogenic effect of SSRIs. In this population-based case-control study, we evaluated the association between SSRI use and breast cancer risk as a function of their relative degree of inhibition of serotonin reuptake as a proxy for their impact on prolactin levels. Cases were 2,129 women with primary invasive breast cancer diagnosed from 2003 to 2007, and controls were 21,297 women randomly selected from the population registry. Detailed information for each SSRI prescription dispensed was compiled using the Saskatchewan prescription database. Logistic regression was used to evaluate the impact of use of high and lower inhibitors of serotonin reuptake and duration of use, as well as to assess the effect of individual high inhibitors on the risk of breast cancer. Exclusive users of high or lower inhibitors of serotonin reuptake were not at increased risk for breast cancer compared with non-users of SSRIs (OR = 1.01, CI = 0.88-1.17 and OR = 0.91, CI = 0.67-1.25 respectively), regardless of their duration of use or menopausal status. While we cannot rule out the possibility of a clinically important risk increase (OR = 1.83, CI = 0.99-3.40) for long-term users of sertraline (≥24 prescriptions), given the small number of exposed cases (n = 12), the borderline statistical significance, and the wide confidence interval, these results need to be interpreted cautiously. In this large population-based case-control study, we found no conclusive evidence of breast cancer risk associated with the use of SSRIs even after assessing the degree of serotonin reuptake inhibition and duration of use. Our results do not support the serotonin-mediated pathway for the prolactin-breast cancer hypothesis.
    Frontiers in Oncology 12/2012; 2:177. DOI:10.3389/fonc.2012.00177
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    • "However, despite these methodological improvements, our results are consistent with most other observational studies, including six that used self-reported SSRI exposure information [19-24], and four studies that ascertained SSRI use from a prescription database [25-28]. However, only three of these studies [22,24,27] had sufficient sample sizes to adequately evaluate risk associated with three or more years of combined SSRI use, and only one study [27] quantified total SSRI use with a dosage variable. "
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    ABSTRACT: Selective serotonin reuptake inhibitors (SSRIs), a popular class of antidepressants, may increase breast cancer risk by stimulating the secretion of prolactin, a potential tumour promoter. We evaluated the effects of duration of SSRI use, cumulative dose, and latency on the risk of breast cancer by conducting a population-based case-control study utilizing Saskatchewan health databases. Cases included 1,701 women with primary invasive breast cancer diagnosed from 2003 to 2006, and controls consisted of 17,017 women, randomly selected from the population registry. Use of SSRIs was compiled using the Saskatchewan prescription database. Unconditional logistic regression was conducted to evaluate the impact of duration of combined SSRI use (total number of prescriptions dispensed), cumulative dose (total dosage received) and timing of use (two or more years, two to seven years and more than seven years prior to index date) on the risk of breast cancer. Overall, SSRI use was not associated with an increased risk of breast cancer regardless of our definition of cumulative use (total number of prescriptions dispensed and total dosage). In addition, our results indicate that prolonged SSRI use does not have a latent effect on breast cancer risk. Also, our findings are not suggestive of an increased risk of breast cancer with the use of individual SSRIs. Our study improved upon most previous studies by having a longer follow-up period, a larger sample size of long-term SSRI users and consideration of risk during specific exposure time windows that take latency into account. Given the potential health benefits of using SSRIs, our results suggest that the issue of breast cancer risk may no longer be a concern for women requiring long-term SSRIs.
    BMC Medicine 12/2010; 8(1):90. DOI:10.1186/1741-7015-8-90 · 7.25 Impact Factor
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    • "This is supported by the relation with dose (where those without depression have a higher proportion of low dose and vice versa). Previous studies have examined tricyclics and the incidence of colorectal (Xu et al, 2006), prostate (Tamim et al, 2007), breast (Cotterchio et al, 2000; Gonzalez-Perez and Garcia Rodriguez, 2005; Fulton-Kehoe et al, 2006; Wernli et al, 2009) and lung cancers (Toh et al, 2007), but have shown little consistency, and significant evidence has been found to link tricyclics with cancer. A study on colorectal cancer (Xu et al, 2006) hypothesised that tricyclics are genotoxic, and therefore increase cancer risk, but, their results suggest a nonsignificant protective effect, as did another recent study (Patricia et al, 2009). "
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    ABSTRACT: Several studies suggest links between cancer and tricyclic antidepressant use. A case-control study using the General Practice Research Database examined whether previous tricyclic usage was associated with reduced incidence of brain (with glioma as a sub-category), breast, colorectal, lung and prostate cancers. Conditional logistic regression adjusted for age, gender, general practice, depression, smoking, body mass index, alcohol use and non-steroidal anti-inflammatory drug use. A total of 31 953 cancers were identified, each matched with up to two controls. We found a statistically significant reduction in tricyclic prescriptions compared with controls in glioma (odds ratio (OR) =0.59, 95% confidence interval (CI)=0.42-0.81) and colorectal cancer patients (OR=0.84, CI=0.75-0.94). These effects were dose-dependent (P-values for trend, glioma=0.0005, colorectal=0.001) and time-dependant (P-values for trend glioma=0.0005, colorectal=0.0086). The effects were cancer-type specific, with lung, breast and prostate cancers largely unaffected by antidepressant use. The biologically plausible, specific and dose- and time-dependant inverse association that we have found suggests that tricyclics may have potential for prevention of both colorectal cancer and glioma.
    British Journal of Cancer 11/2010; 104(1):193-7. DOI:10.1038/sj.bjc.6605996 · 4.84 Impact Factor
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