This article is part of a series on Inflammation and breast cancer, edited by Mina J Bissell and Jeffrey W Pollard.

Review

Inflammation and breast cancer. Cyclooxygenase/prostaglandin signaling and breast cancer

Louise R Howe

Department of Cell & Developmental Biology, Weill Medical College of Cornell University, York Avenue, New York, New York 10021, USA

author email corresponding author email

Breast Cancer Research 2007, 9:210doi:10.1186/bcr1678

Published:	16 July 2007

Abstract

Many human cancers exhibit elevated prostaglandin (PG) levels due to upregulation of cyclooxygenase-2 (COX-2), a key enzyme in eicosanoid biosynthesis. COX-2 over-expression has been observed in about 40% of cases of invasive breast carcinoma and at a higher frequency in preinvasive ductal carcinoma in situ tumors, Extensive pharmacologic and genetic evidence implicates COX enzymes in neoplasia. Epidemiologic analyses demonstrate a protective effect of COX-inhibiting nonsteroidal anti-inflammatory drugs with respect to human cancer. Complementary experimental studies have established that both conventional nonsteroidal anti-inflammatory drugs and selective COX-2 inhibitors suppress mammary tumor formation in rodent breast cancer models. Furthermore, knocking out Cox-2 reduces mammary tumorigenesis and angiogenesis, and, conversely, transgenic COX-2 over-expression induces tumor formation. The utility of COX/PG signaling as a target for chemoprevention has been established by randomized controlled clinical trials. However, these studies also identified increased cardiovascular risk associated with use of selective COX-2 inhibitors. Thus, current efforts are directed toward identifying safer approaches to antagonizing COX/PG signaling for cancer prevention and treatment, with a particular focus on PGE₂ regulation and signaling, because PGE₂ is a key protumorigenic prostanoid.