Cyclooxygenase-2 (COX-2), aromatase and breast cancer:a possible role for COX-2 inhibitors in breast cancer chemoprevention

Abstract

Interest in chemoprevention in oncology using suppressants of prostaglandin (PG) synthesis has been stimulated by epidemiological observations that the use of aspirin and other non-steroidal inflammatory drugs (NSAIDs) is associated with reduced incidence of some cancers, including cancer of the breast. The main target of NSAID activity is the cyclooxygenase (COX) enzyme. Two isoforms of COX have been identified: COX-1, the constitutive isoform; and COX-2. the inducible form of the enzyme. COX-2 can undergo rapid induction in response to many factors such as bacterial lipopolysaccharides, growth factors, cytokines and phorbol esters. COX-2 is overexpressed in some malignancies including carcinoma of the breast. It has been suggested that such enhanced expression may lead to increased angiogenesis such that the inhibition of COX-2 might have a general anticancer effect via decreased blood vessel formation. In addition, an association between COX-2, its main product PGE2 and aromatase activity in human breast cancer suggests that such inhibitors might have an additional, specific prophylactic mechanism for this tumour. New COX-2 inhibitors are already licensed for use in the treatment of arthritis and are well tolerated. Their potential role in chemoprevention of mammary carcinogenesis in rats has already been investigated. What remains to be seen is if these findings can be extrapolated to human studies.

Low-dose aspirin use and survival in breast cancer patients: A nationwide cohort study

“…The potential anti-cancer effect of aspirin has been hypothesised to be, in part, mediated through suppression of oestrogen biosynthesis [35,36], but similar to our study, two previous cohort studies found no difference in associations by hormone receptor status [10,17].…”

COX-2 expression is associated with an aggressive phenotype in ductal carcinoma in situ

“…Inhibition of the COX-2 enzyme and attenuation of the consequential carcinogenic effects of overexpression with increased prostaglandin production (inhibition of apoptosis, stimulation of neo-angiogenesis, upregulation of intra-tumoral CYP19 aromatase; Davies et al, 2002) at this stage has the potential to prevent progression to invasion.…”

Impact of anesthesia for cancer surgery: Continuing Professional Development

“…65 A retrospective review of breast cancer patients undergoing mastectomy suggested that intraoperative ketorolac use was associated with decreased cancer recurrence. 66 Impact of anesthesia for cancer surgery 1253 RCT -randomized controlled trial.…”

“…65 Une étude rétrospective chez des patientes ayant un cancer du sein subissant une mastectomie a suggéré que l'utilisation peropératoire de kétorolac était associée à un taux de récidive moindre du cancer. 66 …”