Risk of breast cancer according to use of antidepressants, phenothiazines, and antihistamines

Slone Epidemiology Unit, Boston University School of Medicine, Brookline, MA, USA.
American Journal of Epidemiology (Impact Factor: 5.23). 11/1999; 150(8):861-8.
Source: PubMed


In laboratory studies, some antidepressants caused increased growth of mammary tumors. The relation of use of these drugs to the development of breast cancer was examined in a hospital-based case-control study. Information, including lifetime medication history, was collected by interview from 5,814 women with primary breast cancer diagnosed within the previous year, 5,095 women with primary malignancies of other sites, and 5,814 women with other conditions. Relative risks were estimated by using unconditional multiple logistic regression for regular use (> or =4 days per week for > or =4 weeks beginning > or =1 year before admission) of antidepressants and structurally similar drugs. With reference to never use of each drug, relative risks were statistically compatible with 1.0 for selective serotonin reuptake inhibitors (SSRI), tricyclics, other antidepressants, phenothiazines, and antihistamines; results were very similar using both control groups. There were no significant increases in risk for any category of regular use, stratified according to cumulative duration of use or time interval since the most recent use or for any individual drug within the broader classes. However, the estimate for regular SSRI use in the previous year, 1.8, was of borderline statistical significance (95% confidence interval: 1.0, 3.3). The findings do not support an overall association between the use of antidepressants, phenothiazines, or antihistamines and breast cancer. However, the results for SSRIs are not entirely reassuring.

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Available from: Sowmya R. Rao
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    • "Results from another hospital-based case–control study (Kelly et al. 1999) in 5,814 women with breast cancer, 5,095 patients with other malignancies and 5,814 women without malignancies, researchers investigated the relative risk for developing breast cancer with regular use of antidepressants and structurally similar drugs. Though no significant increases in risk for any category of regular use were noted, the relative risk estimate for regular SSRI use in the previous year, 1.8, was of borderline statistical significance (95% confidence interval: 1.0, 3.3). "
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    ABSTRACT: The cardinal climacteric symptoms of hot flushes and night sweats affect 24-93% of all women during the physiological transition from reproductive to post-reproductive life. Though efficacious, hormonal therapy and partial oestrogenic compounds are linked to a significant increase in breast cancer. Non-hormonal treatments are thus greatly appreciated. This systematic review of published hormonal and non-hormonal treatments for climacteric, and breast and prostate cancer-associated hot flushes, examines clinical efficacy and therapy-related cancer risk modulation. A PubMed search included literature up to June 19, 2014 without limits for initial dates or language, with the search terms, (hot flush* OR hot flash*) AND (clinical trial* OR clinical stud*) AND (randomi* OR observational) NOT review). Retrieved references identified further papers. The focus was on hot flushes; other symptoms (night sweats, irritability, etc.) were not specifically screened. Included were some 610 clinical studies where a measured effect of the intervention, intensity and severity were documented, and where patients received treatment of pharmaceutical quality. Only 147 of these references described studies with alternative non-hormonal treatments in post-menopausal women and in breast and prostate cancer survivors; these results are presented in Additional file 1. The most effective hot flush treatment is oestrogenic hormones, or a combination of oestrogen and progestins, though benefits are partially outweighed by a significantly increased risk for breast cancer development. This review illustrates that certain non-hormonal treatments, including selective serotonin reuptake inhibitors, gabapentin/pregabalin, and Cimicifuga racemosa extracts, show a positive risk-benefit ratio.
    Full-text · Article · Dec 2015 · SpringerPlus
    • "Recently, the SSRI citalopram was found to reduce tumor size and metastases in a mouse model of colorectal cancer (CRC), possibly through inhibition of TGF-β (van Noort et al., 2014). Past epidemiologic studies that evaluated the association between anti-depressant exposure and breast cancer risk were inconclusive and demonstrated high (Ashbury et al., 2012; Cotterchio et al., 2000; Sharpe et al., 2002), low (Coogan et al., 2005) or no change in risk (Ashbury et al., 2010; Coogan et al., 2008; Eom et al., 2012; González-Pérez and García Rodríguez, 2005, Haque et al., 2005; Kelly et al., 1999; Moorman et al., 2003; Moorman et al., 2005; Tamim et al., 2006). Several of those studies demonstrated an association with duration of therapy (Coogan et al., 2005) or use of TCAs that were defined as genotoxic (Sharpe et al., 2002). "
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    ABSTRACT: Previous studies demonstrated a possible association between anti-depressant therapy with selective serotonin reuptake inhibitors (SSRI) and tricyclic anti-depressants (TCA), several genetic and hormonal pathways and cancer risk, with inconsistent results. Exposure to serotonin-norepinephrine reuptake inhibitors (SNRI) was not studied extensively. We sought to evaluate the association between exposure to SSRIs, TCAs and SNRIs and the five most common solid tumors. We conducted nested case-control studies using a large UK population-representative database. Cases were those with any medical code for the specific malignancy. For every case, four controls matched on age, sex, practice site, and duration of follow-up before index date were selected using incidence-density sampling. Exposure of interest was SSRI, SNRI or TCA therapy before index date. Odds ratios (ORs) and 95% CIs were estimated for each anti-depressant class using conditional logistic-regression analysis, adjusted for potential confounders, such as obesity, smoking history and alcohol consumption. 109,096 cancer patients and 426,402 matched controls were included. Current SSRI users with treatment initiation>one year before index date had modestly higher risk for lung and breast cancers with ORs of 1.27 (95% CI 1.16-1.38) and 1.12 (95% CI 1.06-1.18), respectively. Among current TCA users, there was a higher risk only for lung cancers with OR of 1.45 (95% CI 1.31-1.6). There was no statistically significant association between current SNRI therapy and cancer risk. Treatment with SSRI and TCA might be associated with increased lung cancer risk. SSRI therapy might be associated with modest increase in breast cancer risk. Copyright © 2015. Published by Elsevier B.V.
    No preview · Article · Apr 2015 · European neuropsychopharmacology: the journal of the European College of Neuropsychopharmacology
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    • "No previous peer-reviewed published studies have considered a delayed effect of SSRI exposure using similar time periods. However, results from other studies that assessed the effect of timing of SSRI use on breast cancer risk using less precise measures of past SSRI use, such as 'time since first use' or 'time since last use' [19,20,28] or 'current' versus 'former' users [22-24,27] are consistent with our null findings. "
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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.
    Full-text · Article · Dec 2010 · BMC Medicine
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