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

Use of antidepressant medications in relation to the incidence of breast cancer

Although associations have been reported between antidepressant use and risk of breast cancer, the findings have been inconsistent. We conducted a population-based case–control study among women enrolled in Group Health Cooperative (GHC), a health maintenance organization in Washington State. Women with a first primary breast cancer diagnosed between 1990 and 2001 were identified (N=2904) and five controls were selected for each case (N=14396). Information on antidepressant use was ascertained through the GHC pharmacy database and on breast cancer risk factors and screening mammograms from GHC records. Prior to one year before diagnosis of breast cancer, about 20% of cases and controls had used tricyclic antidepressants (adjusted odds ratio=1.06, 95% CI 0.94–1.19) and 6% of each group had used selective serotonin reuptake inhibitors (OR=0.98, 95% CI 0.80–1.18). There also were no differences between cases and controls with regard to the number of prescriptions filled or the timing of use. Taken as a whole, the results from this and other studies to date do not indicate an altered risk of breast cancer associated with the use of antidepressants overall, by class, or for individual antidepressants

Use of non-steroidal anti-inflammatory drugs and risk of breast cancer: The Spanish Multi-Case-control (MCC) study

Background: The relationship between non-steroidal anti-inflammatory drug (NSAID) consumption and breast cancer has been repeatedly studied, although the results remain controversial. Most case-control studies reported that NSAID consumption protected against breast cancer, while most cohort studies did not find this effect. Most studies have dealt with NSAIDs as a whole group or with specific drugs, such aspirin, ibuprofen, or others, but not with NSAID subgroups according to the Anatomical Therapeutic Chemical Classification System; moreover, scarce attention has been paid to their effect on different tumor categories (i.e.: ductal/non-ductal, stage at diagnosis or presence of hormonal receptors). Methods: In this case-control study, we report the NSAID – breast cancer relationship in 1736 breast cancer cases and 1895 healthy controls; results are reported stratifying by the women’s characteristics (i.e.: menopausal status or body mass index category) and by tumor characteristics. Results: In our study, NSAID use was associated with a 24 % reduction in breast cancer risk (Odds ratio [OR] = 0.76; 95 % Confidence Interval [CI]: 0.64–0.89), and similar results were found for acetic acid derivatives, propionic acid derivatives and COXIBs, but not for aspirin. Similar results were found in postmenopausal and premenopausal women. NSAID consumption also protected against hormone + or HER2+ cancers, but not against triple negative breast cancers. The COX-2 selectivity showed an inverse association with breast cancer (i.e. OR < 1), except in advanced clinical stage and triple negative cancers. Conclusion: Most NSAIDs, but not aspirin, showed an inverse association against breast cancer; this effect seems to be restricted to hormone + or HER2+ cancers. Keywords: Breast cancer, Non-steroidal anti-inflammatory drug, Hormone receptor positive breast cancer, HER2 positive breast cancer, Triple negative breast cance

Prescriptions for selective cyclooxygenase-2 inhibitors, non-selective non-steroidal anti-inflammatory drugs, and risk of breast cancer in a population-based case-control study

INTRODUCTION. Non-steroidal anti-inflammatory drugs (NSAIDs) prevent the growth of mammary tumours in animal models. Two population-based case-control studies suggest a reduced risk of breast cancer associated with selective cyclooxygenase-2 (sCox-2) inhibitor use, but data regarding the association between breast cancer occurrence and use of non-selective NSAIDs are conflicting. METHODS. We conducted a population-based case-control study using Danish healthcare databases to examine if use of NSAIDs, including sCox-2 inhibitors, was associated with a reduced risk of breast cancer. We included 8,195 incident breast cancer cases diagnosed in 1991 through 2006 and 81,950 population controls. RESULTS. Overall, we found no reduced breast cancer risk in ever users (>2 prescriptions) of sCox-2 inhibitors (odds ratio (OR) = 1.08, 95% confidence interval (95% CI) = 0.99, 1.18), aspirin (OR = 0.98, 95% CI = 0.90-1.07), or non-selective NSAIDs OR = 1.04, (95% CI = 0.98, 1.10)). Recent use (>2 prescriptions within two years of index date) of sCox-2 inhibitors, aspirin, or non-selective NSAIDs was likewise not associated with breast cancer risk (Ors = 1.06 (95% CI = 0.96, 1.18), 0.96 (95% CI = 0.87, 1.06) and 0.99 (95% CI = 0.85, 1.16), respectively). Risk estimates by duration (<10, 10 to 15, 15+ years) or intensity (low/medium/high) of NSAID use were also close to unity. Regardless of intensity, shorter or long-term NSAID use was not significantly associated with breast cancer risk. CONCLUSIONS. Overall, we found no compelling evidence of a reduced risk of breast cancer associated with use of sCox-2 inhibitors, aspirin, or non-selective NSAIDs.Karen Elise Jensen Foundatio

Second-hand smoke exposure in adulthood and lower respiratory health during 20 year follow up in the European Community Respiratory Health Survey

Background: Early life exposure to tobacco smoke has been extensively studied but the role of second-hand smoke (SHS) for new-onset respiratory symptoms and lung function decline in adulthood has not been widely investigated in longitudinal studies. Our aim is to investigate the associations of exposure to SHS in adults with respiratory symptoms, respiratory conditions and lung function over 20 years. Methods: We used information from 3011 adults from 26 centres in 12 countries who participated in the European Community Respiratory Health Surveys I-III and were never or former smokers at all three surveys. Associations of SHS exposure with respiratory health (asthma symptom score, asthma, chronic bronchitis, COPD) were analysed using generalised linear mixed-effects models adjusted for confounding factors (including sex, age, smoking status, socioeconomic status and allergic sensitisation). Linear mixed-effects models with additional adjustment for height were used to assess the relationships between SHS exposure and lung function levels and decline. Results: Reported exposure to SHS decreased in all 26 study centres over time. The prevalence of SHS exposure was 38.7% at baseline (1990-1994) and 7.1% after the 20-year follow-up (2008-2011). On average 2.4% of the study participants were not exposed at the first, but were exposed at the third examination. An increase in SHS exposure over time was associated with doctor-diagnosed asthma (odds ratio (OR): 2.7; 95% confidence interval (95%-CI): 1.2-5.9), chronic bronchitis (OR: 4.8; 95%-CI: 1.6-15.0), asthma symptom score (count ratio (CR): 1.9; 95%-CI: 1.2-2.9) and dyspnoea (OR: 2.7; 95%-CI: 1.1-6.7) compared to never exposed to SHS. Associations between increase in SHS exposure and incidence of COPD (OR: 2.0; 95%-CI: 0.6-6.0) or lung function (β: - 49 ml; 95%-CI: -132, 35 for FEV1 and β: - 62 ml; 95%-CI: -165, 40 for FVC) were not apparent. Conclusion: Exposure to second-hand smoke may lead to respiratory symptoms, but this is not accompanied by lung function changes

Risco de câncer associado ao uso de antidepressivos Risk of cancer associated with the use of antidepressants

INTRODUÇÃO: Alguns estudos sugerem que o uso de antidepressivos poderia aumentar o risco de câncer. Este estudo visa realizar uma revisão sobre o tema. MÉTODO: Foi feita uma busca nas bases de dados MEDLINE e LILACS, utilizando como palavras de busca antidepressant, cancer e nomes das diferentes drogas antidepressivas. RESULTADOS: Onze artigos foram selecionados. Foram encontrados seis artigos sugerindo uma associação positiva fraca entre o uso de antidepressivos e o crescimento tumoral e cinco artigos que não sugeriam a associação. Discussão: Os resultados dos estudos com relação ao risco de câncer associado ao uso de antidepressivos são ainda conflitantes. Na maioria dos estudos, a análise multivariada não mostra associação positiva em uso de antidepressivos e câncer, a não ser em casos específicos, como linfoma de Hodgkin.<br>INTRODUCTION: Some studies suggest that the use of antidepressants could increase the risk of cancer. This study aims at performing a review on this subject. METHOD: A search was performed in the MEDLINE and LILACS databases using the keywords antidepressant, cancer and names of varied antidepressant drugs. RESULTS: Eleven articles were selected. Six articles were found suggesting a positive weak association between use of antidepressants and tumoral growth. In five articles this association was not found. DISCUSSION: The results of studies on increased risk of cancer associated with antidepressants are still conflicting. In most studies the multivariate analysis did not show positive association between use of antidepressants and cancer, unless in specific cases, such as Hodgkin's lymphoma

Hydrothermal Prospection in the Red Sea Rift: Geochemical Messages from Basalts

Hydrothermal circulation at mid-ocean ridges and assimilation of hydrothermally altered crust or hydrothermal fluids by rising magma can be traced by measuring chlorine (Cl) excess in erupted lavas. The Red Sea Rift provides a unique opportunity to study assimilation of hydrothermally altered crust at an ultra-slow spreading ridge (maximum 1.6 cm yr−1 full spreading rate) by Cl, due to its saline seawater (40–42‰, cf. 35‰ in open ocean water), the presence of (hot) brine pools (up to 270‰ salinity and 68 °C) and the thick evaporite sequences that flank the young rift. Absolute chlorine concentrations (up to 1300 ppm) and Cl concentrations relative to minor or trace elements of similar mantle incompatibility (e.g., K, Nb) are much higher in Red Sea basalts than in basalts from average slow spreading ridges. Mantle Cl/Nb concentrations can be used to calculate the Cl-excess, above the magmatic Cl, that is present in the samples. Homogeneous within-sample Cl concentrations, high Cl/H2O, the decoupling of Cl-excess from other trace elements and its independence of the presence of highly saline seafloor brines at the site of eruption indicate that Cl is not enriched at the seafloor. Instead we find basaltic Cl-excess to be spatially closely correlated with evidence of hydrothermal activity, suggesting that deeper assimilation of hydrothermal Cl is the dominant Cl-enrichment process. A proximity of samples to both evaporite outcrops and bathymetric signs of volcanism on the seafloor enhance Cl-excess in basalts. The basaltic Cl-excess can be used as a tracer together with new bathymetric maps as well as indications of hydrothermal venting (hot brine pools, metalliferous Hydrothermal circulation at mid-ocean ridges and assimilation of hydrothermally altered crust or hydrothermal fluids by rising magma can be traced by measuring chlorine (Cl) excess in erupted lavas. The Red Sea Rift provides a unique opportunity to study assimilation of hydrothermally altered crust at an ultra-slow spreading ridge (maximum 1.6 cm yr−1 full spreading rate) by Cl, due to its saline seawater (40–42‰, cf. 35‰ in open ocean water), the presence of (hot) brine pools (up to 270‰ salinity and 68 °C) and the thick evaporite sequences that flank the young rift. Absolute chlorine concentrations (up to 1300 ppm) and Cl concentrations relative to minor or trace elements of similar mantle incompatibility (e.g., K, Nb) are much higher in Red Sea basalts than in basalts from average slow spreading ridges. Mantle Cl/Nb concentrations can be used to calculate the Cl-excess, above the magmatic Cl, that is present in the samples. Homogeneous within-sample Cl concentrations, high Cl/H2O, the decoupling of Cl-excess from other trace elements and its independence of the presence of highly saline seafloor brines at the site of eruption indicate that Cl is not enriched at the seafloor. Instead we find basaltic Cl-excess to be spatially closely correlated with evidence of hydrothermal activity, suggesting that deeper assimilation of hydrothermal Cl is the dominant Cl-enrichment process. A proximity of samples to both evaporite outcrops and bathymetric signs of volcanism on the seafloor enhance Cl-excess in basalts. The basaltic Cl-excess can be used as a tracer together with new bathymetric maps as well as indications of hydrothermal venting (hot brine pools, metalliferous sediments) to predict where hydrothermal venting or now inactive hydrothermal vent fields can be expected. Sites of particular interest for future hydrothermal research are the Mabahiss Deep, the Thetis-HadarbaHatiba Deeps and Shagara-Aswad-Erba Deeps (especially their large axial domes), and Poseidon Deep. Older hydrothermal vent fields may be present at the Nereus and Suakin Deeps. These sites significantly increase the potential of hydrothermal vent field prospection in the Red Sea