Selective serotonin reuptake inhibitor use and breast cancer survival: a population-based cohort study

Abstract

BackgroundNearly 50% of breast cancer patients suffer from depression or anxiety. Selective serotonin reuptake inhibitors (SSRIs), the first-line pharmacological treatment for depression, have been implicated in breast cancer development through increased prolactin levels and tamoxifen metabolism inhibition. Previous studies of breast cancer progression have focused on tamoxifen users, or have been limited by their small sample size and methodology. Therefore, we used UK population-based data to more robustly investigate the association between SSRI use and cancer-specific mortality.MethodsA cohort of patients with newly-diagnosed breast cancer between 1998 and 2012 was selected from English cancer registries and linked to prescription records from the Clinical Practice Research Datalink, and to death records from the Office for National Statistics. We used Cox regression models to calculate hazard ratios (HRs) comparing mortality between post-diagnostic SSRI users and non-users (using time-dependant covariates), after adjusting for demographics, comorbidities and pre-diagnosis use of hormone replacement therapy or oral contraceptives. We conducted several additional analyses to assess causality.ResultsOur cohort included 23,669 breast cancer patients, of which 2672 used SSRIs and 3053 died due to their breast cancer during follow-up. After adjustment, SSRI users had higher breast cancer-specific mortality than non-users (HR = 1.27; 95% confidence interval (CI) 1.16, 1.40). However, this association was attenuated when restricting to patients with a prior history of depression (HR = 1.14; 95% CI 0.98, 1.33), and when comparing to users of other antidepressant medications (HR = 1.06; 95% CI 0.93, 1.20). There was some evidence of higher mortality among long-term SSRI users, even when restricting to patients with prior depression (HR = 1.54; 95% CI 1.03, 2.29).ConclusionsIn this large breast cancer cohort, SSRI use was associated with a 27% increase in breast cancer mortality. The cause of this is unknown; however, confounding by indication seems likely as it was largely attenuated when restricting to patients with prior depression, or when comparing SSRIs to other antidepressant medications. Clinicians should not be unduly concerned when prescribing SSRIs to breast cancer patients, but the increase in mortality among long-term SSRI users warrants further investigation.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0928-0) contains supplementary material, which is available to authorized users.

Implications of Antidepressants Use in Breast Cancer: A Brief Review

“…SSRIs users had a higher breast cancer-specific mortality than non-users with no apparent dose-response relationship. Nonetheless, data are lacking about patients' adherence to SSRI and anti-cancer treatment (1).…”

“…The potential relationship between depression and breast cancer has been extensively explored over the last decades. The assumed biological rationale behind this association leans to an intricate network involving the nervous, immune and endocrine system (1). In fact, reduced cytotoxic T lymphocytes, Natural Killers and inflammatory cytokines activity, along with higher cortisol levels typically associated with depression, may represent a proliferative drive for cancer cells.…”

Effect of SSRI exposure on the proliferation rate and glucose uptake in breast and ovary cancer cell lines

“…Results obtained vary significantly between studies that are oftentimes limited by small sample sizes and low number of events, especially when the effects of specific antidepressants are investigated. While a population-based retrospective cohort study by Chubak and colleagues found no increase in mortality but reported an augmented recurrence risk for patients that received paroxetine, a recent meta-analysis by Busby and colleagues reported an increase in mortality by 27% in breast cancer patients that received SSRIs for antidepressant treatment 12 , 13 . Interestingly, Busby et al also reported that different SSRIs appeared to differentially affect the outcome of breast cancer patients and pointed out that the obtained results warranted further investigations concerning the effect of SSRIs in the context of breast cancer 13 .…”

“…While a population-based retrospective cohort study by Chubak and colleagues found no increase in mortality but reported an augmented recurrence risk for patients that received paroxetine, a recent meta-analysis by Busby and colleagues reported an increase in mortality by 27% in breast cancer patients that received SSRIs for antidepressant treatment 12 , 13 . Interestingly, Busby et al also reported that different SSRIs appeared to differentially affect the outcome of breast cancer patients and pointed out that the obtained results warranted further investigations concerning the effect of SSRIs in the context of breast cancer 13 . Concerning SSRI treatment of patients with epithelial ovarian cancer, a recent study found that SSRI use was associated with a significant decrease in time to disease progression while overall survival was not affected 14 .…”

Should the Same Safety Scrutiny of Antiobesity Medications be Applied to Other Chronic Usage Drugs?

“…Conversely, any concern with a serotoninergic drug should be shared with other drugs that act similarly, such as many antidepressants. Actually, there have been some studies that raised the possibility of an increased risk of cancer with selective serotonin receptor inhibitors (7). Although these studies are observational and far from conclusive, there has never been, to our knowledge, any need for a long-term safety trial with any selective serotonin receptor inhibitors.…”