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Background: Antidepressants are among the most commonly prescribed drugs in the United States. Laboratory studies suggest that because certain antidepressants increase prolactin levels that they may also increase breast cancer risk. However, human studies evaluating use of antidepressants in relation to breast cancer risk have yielded inconsistent results. Methods: A population-based case-control study consisting of 975 breast cancer cases 65-79 years of age diagnosed from 1997-1999 and 1,007 age and residence-matched controls was conducted in western Washington State. Detailed information on antidepressant use was obtained through a structured in-person interview for each subject. Logistic regression was performed to analyze the relationship between antidepressant use and breast cancer risk. Results: Overall, there was no apparent association between ever use of antidepressants and breast cancer risk (odds ratio [OR] =1.2, 95% confidence interval [95% CI]: 0.9-1.6). When evaluated separately, tricyclic antidepressants (TCA), selective serotonin reuptake inhibitors (SSRI), and triazolopyridines were also each not associated with breast cancer risk. First-degree family history of breast cancer modified the association between antidepressant use and breast cancer risk (p<0.001). Ever users of antidepressants who had a first-degree family history had a decreased risk of breast cancer (OR=0.4, 95% CI: 0.2-0.9), while ever users without a family history had an increased risk of breast cancer (OR=1.5, 95% CI: 1.1-2.0) compared to never users. In addition, risk varied by hormone receptor status. Compared to never users, ever users of SSRIs had elevated risks of ER+/PR-, PR-, and ER- breast cancers (OR=2.0, 95% CI: 1.1-3.8; OR= 1.8, 95% CI: 1.1-3.6; and OR=1.6, 95% CI: 0.8-3.4, respectively, though the latter risk was within the limits of chance), but not of tumors with other hormone receptor profiles. Conclusions: Based on these results and those of previous studies, there is limited evidence that any type of antidepressant use is related to breast cancer risk overall. However, we are the first to report that a first-degree family history of breast cancer may be an important modifier of this association, and that risk may vary by hormone receptor status as SSRI users appear to have elevated risks of ER+/PR-, PR-, and ER- breast tumors. Further studies are needed to confirm these findings and to clarify the relationship between various types of antidepressants and different types of breast cancer.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]