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

BACKGROUND: 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. Previous studies in a variety of biomedical fields have found that financial ties to drug companies are associated with favorable study conclusions. METHODS AND FINDINGS: We searched English-language articles in MEDLINE, PsychINFO, the Science Citations Index and the Cochrane Central Register of Controlled Clinical Trials (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). CONCLUSIONS: 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

The effect of osteoporotic vertebral fracture on predicted spinal loads in vivo

The aetiology of osteoporotic vertebral fractures is multi-factorial, and cannot be explained solely by low bone mass. After sustaining an initial vertebral fracture, the risk of subsequent fracture increases greatly. Examination of physiologic loads imposed on vertebral bodies may help to explain a mechanism underlying this fracture cascade. This study tested the hypothesis that model-derived segmental vertebral loading is greater in individuals who have sustained an osteoporotic vertebral fracture compared to those with osteoporosis and no history of fracture. Flexion moments, and compression and shear loads were calculated from T2 to L5 in 12 participants with fractures (66.4 ± 6.4 years, 162.2 ± 5.1 cm, 69.1 ± 11.2 kg) and 19 without fractures (62.9 ± 7.9 years, 158.3 ± 4.4 cm, 59.3 ± 8.9 kg) while standing. Static analysis was used to solve gravitational loads while muscle-derived forces were calculated using a detailed trunk muscle model driven by optimization with a cost function set to minimise muscle fatigue. Least squares regression was used to derive polynomial functions to describe normalised load profiles. Regression co-efficients were compared between groups to examine differences in loading profiles. Loading at the fractured level, and at one level above and below, were also compared between groups. The fracture group had significantly greater normalised compression (p = 0.0008) and shear force (p < 0.0001) profiles and a trend for a greater flexion moment profile. At the level of fracture, a significantly greater flexion moment (p = 0.001) and shear force (p < 0.001) was observed in the fracture group. A greater flexion moment (p = 0.003) and compression force (p = 0.007) one level below the fracture, and a greater flexion moment (p = 0.002) and shear force (p = 0.002) one level above the fracture was observed in the fracture group. The differences observed in multi-level spinal loading between the groups may explain a mechanism for increased risk of subsequent vertebral fractures. Interventions aimed at restoring vertebral morphology or reduce thoracic curvature may assist in normalising spine load profiles. © 2006 Springer-Verlag