Antidepressants and Breast and Ovarian Cancer Risk: A Review of the Literature and Researchers’ Financial Associations with Industry

Tuesday, 03/05/2011  |   Breast Cancer, Ovarian/ Uterine Cancer  |  no comments

Antidepressant (AD) use has been purported to increase the risk of breast and ovarian cancer, although both epidemiological and pre-clinical studies have reported mixed results [1]–[6]. Previous studies in a variety of biomedical fields have found that financial ties to drug companies are associated with favorable study conclusions [7].
Reviewing the evidence is a critical public health issue in light of the increasing prevalence of AD use, especially among women, and in light of the fact that 1 in 8 women will be diagnosed with cancer of the breast during their lifetime [8]. Ovarian cancer is the second most frequently occurring female reproductive cancer and causes more deaths than any other gynecological cancer [9]. In the US alone, over 27 million people are taking an AD [10], most of whom are women, for they are twice as likely as men to be diagnosed with Major Depressive Disorder and up to three times more likely to be diagnosed with Dysthymic Disorder [11]. ADs are increasingly being prescribed for other conditions such as hot flashes, headache, back pain, neuropathy, sleep-related conditions, anxiety spectrum disorders, eating disorders, and fibromyalgia [12].
Experimental studies have demonstrated that some ADs promote tumor growth in animals [5], [6], [13] although the exact mechanism by which antidepressants may increase the risk of tumors is currently unknown. Some ADs, especially SSRIs, are potent inhibitors of the cytochrome P450 monooxygenase enzymatic system (a system that metabolizes antineoplastic as well as other agents) [14]. The expanding pre-clinical and clinical research on CYP450 enzymes and the deleterious effects of these enzymes on the metabolism and therapeutic efficacy of tamoxifen and other antineoplastic agents [15] has led to concerns that ADs may directly enhance tumor cell proliferation.
Methods and Findings
A search of English-language articles in MEDLINE, PsychINFO, the Science Citations Index and the Cochrane Central Register of Controlled Clinical Trials was done through November 2010. A total of 61 articles that assessed the relationship between breast and ovarian cancer and AD use and articles that examined the effect of ADs on cell growth were included. Multi-modal screening techniques were used to investigate researchers’ financial ties with industry. A random effects meta-analysis was used to pool the findings from the epidemiological literature. Thirty-three percent (20/61) of the studies reported a positive association between ADs and cancer. Sixty-seven percent (41/61) of the studies reported no association or antiproliferative effect. The pooled odds ratio for the association between AD use and breast/ovarian cancer in the epidemiologic studies was 1.11 (95% CI, 1.03–1.20). Researchers with industry affiliations were significantly less likely than researchers without those ties to conclude that ADs increase the risk of breast or ovarian cancer. (0/15 [0%] vs 20/46 [43.5%] (Fisher’s Exact test P = 0.0012).
Both the pre-clinical and clinical data are mixed in terms of showing an association between AD use and breast and ovarian cancer. The possibility that ADs may exhibit a bi-phasic effect, whereby short-term use and/or low dose antidepressants may increase the risk of breast and ovarian cancer, warrants further investigation. Industry affiliations were significantly associated with negative conclusions regarding cancer risk. The findings have implications in light of the 2009 USPSTF guidelines for breast cancer screening and for the informed consent process.
Future research should include a systematic review of all epidemiological data on cancer risk and AD use. Progress in the field of pharmacogenomics has led to increasing concerns about the complex relationships among serotonin, SSRIs, certain TCAs, prolactin, and tamoxifen, and how these inter-relationships affect pharmacodynamics and cancer risk [16]. It is recommended that future research examine this body of literature and investigate the association between industry funding and qualitative conclusions regarding cancer risk.
Cosgrove L, Shi L, Creasey DE, Anaya-McKivergan M, Myers JA, et al. (2011) Antidepressants and Breast and Ovarian Cancer Risk: A Review of the Literature and Researchers’ Financial Associations with Industry. PLoS ONE 6(4): e18210. doi:10.1371/journal.pone.0018210
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