NSAIDs and breast cancer: a possible prevention and treatment strategy.
BACKGROUND
Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) and thereby reduce prostaglandin synthesis. Abnormally upregulated COX and prostaglandins are features of breast cancer so NSAIDs might have a role in treatment and prevention of the disease.


OBJECTIVE
To review the available epidemiological data on the relation between NSAIDs and risk of breast cancer together with interventional studies in established disease.


RESULTS
Both case-control and cohort studies indicate a moderate reduction in risk of breast cancer among women taking NSAID particularly aspirin. There may be a reduction in oestrogen receptor positive tumours in aspirin users but results are heterogeneous. It is not possible to estimate the dose-response effect for duration of use. In patients with breast cancer, aspirin increased levels of serum nitric oxide (NO) and maspin both of which inhibit growth of breast cancer cells in vitro. Furthermore, a reduced breast cancer and all-cause mortality has been reported in those taking NSAIDs after diagnosis. The cyclooxygenase 2 (COX-2) inhibitor celecoxib showed promising preliminary efficacy and acceptability in combination with exemestane in advanced breast cancer although cardiotoxicity led to discontinuation of celecoxib in a prevention trial for individuals with colonic polyps.


CONCLUSIONS
NSAIDs may reduce breast cancer risk by 20% but the optimal type, dose and duration is still undetermined together with the feasibility of such an intervention in an at risk population. There may be a role for NSAIDs in combination with endocrine therapies as either an adjuvant or palliative treatment for women with established breast cancer.
Agrawal
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A
Hedley Atkins Breast Unit, Guy's Hospital, London, UK.
Fentiman
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IS
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000517:prevention & control*; D002986:Clinical Trials as Topic; D016861:Cyclooxygenase Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D012307:Risk Factors; D015854:Up-Regulation / Q000187:drug effects
D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D011453:Prostaglandins; D011451:Prostaglandin-Endoperoxide Synthases