The Role of NSAIDs in Breast Cancer Prevention and Relapse: Current Evidence and Future Perspectives

Moris, Demetrios; Kontos, Michalis; Spartalis, Eleftherios; Fentiman, Ian S.

doi:10.1159/000452315

Cited by 52 publications

(48 citation statements)

References 60 publications

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“…3 Ever use was defined as two or more prescriptions filled after the first breast cancer diagnosis. 4 Duration was defined as the period between the first and the last postdiagnosis prescription plus the duration of the last prescription and categorized into tertiles among NA-NSAID users. 5 Intensity was and defined as the cumulated number of DDDs divided by duration of postdiagnosis use in days and categorized into tertiles among NA-NSAID users.…”

Section: Resultsmentioning

confidence: 99%

“…3 1,306 first breast cancers with unknown or missing ER status not included. 4 Defined in the period from 10 years prior to until 1 year after the first breast cancer diagnosis.…”

Section: Discussionmentioning

confidence: 99%

“…2 Intention to treat: treatment prescribed according to DBCG's guidelines 3 Comorbid diseases were selected from Charlson's index and defined in the period from 10 years prior to and 1 year after the first breast cancer diagnosis. 4 Prediagnosis use was defined as two or more prescriptions prior to the first breast cancer diagnosis.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…2,3 Nonsteroidal anti-inflammatory drugs (NSAIDs) inhibit the COX-enzymes and are thus considered as potential preventive agents against breast cancer. 4 So far, however, findings from epidemiological studies have been equivocal. 5 A possible explanation for the inconsistent results may be that various pharmacological subgroups of NSAIDs have different therapeutic effects, indications and user patterns, and inhibit the COX-enzymes to a varying degree.…”

Section: Introductionmentioning

confidence: 99%

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Nonaspirin NSAIDs and contralateral breast cancer risk

Bens

Cronin‐Fenton

Dehlendorff

et al. 2018

Intl Journal of Cancer

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Laboratory studies suggest that inhibition of the cyclooxygenase (COX)-2 enzymes inhibits breast cancer development. We aimed to evaluate whether postdiagnosis use of COX-2 selective or other nonaspirin nonsteroidal anti-inflammatory drugs (NSAIDs) reduce the risk of contralateral breast cancer (CBC) among Danish breast cancer patients. From the clinical database of the Danish Breast Cancer Group, we identified 52,723 women diagnosed with breast cancer between 1996 and 2012. Data on nonaspirin NSAID use, CBC and potential confounding variables were obtained from nationwide registries. We defined postdiagnosis use (two or more prescriptions) as a time-varying covariate with a one-year lag. Cox proportional hazard regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for CBC associated with nonaspirin NSAID use. During a median follow-up of 4.8 years (interquartile range: 2.3-9 years), 1,444 patients were diagnosed with CBC. Overall, postdiagnosis use of nonaspirin NSAID was associated with an adjusted HR for CBC of 0.98 (95% CI: 0.87-1.11). The HRs did not vary substantially with duration or intensity of nonaspirin NSAID use. Moreover, similar associations were found for COX-2 selective (HR: 1.02; 95% CI: 0.85-1.23) and nonselective (HR: 0.96; 95% CI: 0.82-1.13) nonaspirin NSAIDs. In conclusion, our nationwide cohort study of breast cancer patients does not suggest a reduced risk of CBC with nonaspirin NSAID use regardless of the COX-2 selectivity.

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Section: Resultsmentioning

confidence: 99%

“…3 1,306 first breast cancers with unknown or missing ER status not included. 4 Defined in the period from 10 years prior to until 1 year after the first breast cancer diagnosis.…”

Section: Discussionmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nonaspirin NSAIDs and contralateral breast cancer risk

Bens

Cronin‐Fenton

Dehlendorff

et al. 2018

Intl Journal of Cancer

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“…In fact, regular use of aspirin and possibly other NSAIDs seem to decrease breast cancer risk [64], while ibuprofen exerts a protective but marginal effect regarding recurrence [65]. The fact that increased expression of COX-2 has [66][67][68], while epidemiological studies on use of NSAIDs in breast cancer are conflicting, rendering further experimental investigation imperative [65].…”

Section: Nsaidsmentioning

confidence: 99%

Targeting Inflammation to Improve Tumor Drug Delivery

2017

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Inefficient delivery of drugs is a main cause of chemotherapy failure in hypo-perfused tumors. To enhance perfusion and drug delivery in these tumors, two strategies have been developed: vascular normalization, aiming at normalizing tumor vasculature and blood vessel leakiness; and stress alleviation, aiming at decompressing tumor vessels. Vascular normalization is based on antiangiogenic drugs, whereas stress alleviation on stroma-depleting agents. Here, an alternatively approach to normalize vessels is presented, considering that malignant tumors tend to develop at chronic inflammation sites. Similarly to tumor vessel leakiness, inflammation is also characterized by vascular hyper-permeability. Therefore, testing the ability of anti-inflammatory agents, such as non-steroidal anti-inflammatory drugs or inflammation resolution mediators, as an alternative way to increase tumor drug delivery, might prove promising.Keywords stress alleviation; vascular normalization; tumor perfusion; anti-inflammatory agents; inflammation resolution The Tumor microenvironment and drug deliveryTumors are complex tissues consisting of cancer cells and their microenvironment [1,2], which includes structural and cellular components. Structural components of the tumor microenvironment comprise tumor blood and lymphatic vessels, and the extracellular matrix (ECM) (see Glossary); while the stromal cell constituents [3] include angiogenic vascular cells (endothelial cells and pericytes), infiltrating immune cells, and cancer-associated fibroblasts (CAFs). Naturally, interactions between cancer cells and the various components of tumor microenvironment affect fundamental cancer cell properties such as proliferation, apoptosis, migration and invasion.It has been postulated that components and features of the tumor microenvironment may also set certain barriers with regard to the effective delivery of therapeutic agents, resulting in compromised therapeutic outcomes and decreased survival [4]. Chemotherapeutic drugs are, without a doubt, potent cytotoxic agents. However, they often fail to cure cancer due to the fact that they are unable to reach cancer cells within the tumor in sufficient amounts [5,6]. Hence, the discovery of more efficient approaches to enhance tumor drug delivery is imperative. Here, the main obstacles in drug delivery to the tumor are presented along with the approaches currently used to overcome them. Furthermore, the use of anti-inflammatory agents is proposed as a promising alternative approach to normalize vessels and improve therapy. Europe PMC Funders Group Causes of insufficient drug delivery to tumorsInefficient drug delivery may arise due to barriers posed by abnormal structure and function of tumor stroma, known as desmoplasia. Desmoplastic tumors are characterized by a dense ECM, containing increased levels of total fibrillar collagen, hyaluronan, fibronectin, proteoglycans and tenascin C [4], which also provides the tumor with a reservoir of growth factors eventually promoting its growth. The dense ...

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Complex roles of the old drug aspirin in cancer chemoprevention and therapy

Hua

Zhang

Kong

et al. 2018

Medicinal Research Reviews

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The nonsteroidal anti-inflammatory agent aspirin is widely used for preventing and treating cardiovascular and cerebrovascular diseases. In addition, epidemiologic evidences reveal that aspirin may prevent a variety of human cancers, while data on the association between aspirin and some kinds of cancer are conflicting. Preclinical studies and clinical trials also reveal the therapeutic effect of aspirin on cancer. Although cyclooxygenase is a well-known target of aspirin, recent studies uncover other targets of aspirin and its metabolites, such as AMP-activated protein kinase, cyclin-dependent kinase, heparanase, and histone. Accumulating evidence demonstrate that aspirin may act in different cell types, such as epithelial cell, tumor cell, endothelial cell, platelet, and immune cell. Therefore, aspirin acts on diverse hallmarks of cancer, such as sustained tumor growth, metastasis, angiogenesis, inflammation, and immune evasion. In this review, we focus on recent progress in the use of aspirin for cancer chemoprevention and therapy, and integratively analyze the mechanisms underlying the anticancer effects of aspirin and its metabolites. We also discuss mechanisms of aspirin resistance and describe some derivatives of aspirin, which aim to overcome the adverse effects of aspirin.

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The Role of NSAIDs in Breast Cancer Prevention and Relapse: Current Evidence and Future Perspectives

Cited by 52 publications

References 60 publications

Nonaspirin NSAIDs and contralateral breast cancer risk

Nonaspirin NSAIDs and contralateral breast cancer risk

Targeting Inflammation to Improve Tumor Drug Delivery

Complex roles of the old drug aspirin in cancer chemoprevention and therapy

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