COX inhibitors and breast cancer

Abstract

There is considerable evidence to suggest that prostaglandins play an important role in the development and growth of cancer. The enzyme cyclo-oxygenase (COX) catalyses the conversion of arachidonic acid to prostaglandins. In recent years, there has been interest in a possible role for COX inhibitors in the prevention and treatment of malignancy. Cyclo-oxygenase-2 (COX-2) is overexpressed in several epithelial tumours, including breast cancer. Preclinical evidence favours an antitumour role for COX inhibitors in breast cancer. However, the epidemiological evidence for an association is conflicting. Trials are being conducted to study the use of COX inhibitors alone and in combination with other agents in the chemoprevention of breast cancer, and in the neoadjuvant, adjuvant, and metastatic treatment settings. In evaluating the potential use of these agents particularly in cancer chemoprophylaxis, the safety profile is as important as their efficacy. Concern over the cardiovascular safety of both selective and nonselective COX-inhibitors has recently been highlighted. Breast cancer is the most common malignancy in women in industrialised nations and the second leading cause of female cancer-related mortality. Approximately 40 000 women develop breast cancer in the UK each year. The incidence of breast cancer has increased by two-thirds over the last 15 years. Mortality rates though have fallen by one-third, and this is likely to be due to earlier detection of breast cancer because of screening, and the increased use of adjuvant therapies. In recent times, the prospect of further improvements in mortality rates has grown with hope provided by new chemotherapy agents and monoclonal antibody therapy directed at cell surface molecules. But can we do even better for women with breast cancer using cheap and simple treatments that are in current use?Nonsteroidal anti-inflammatory drugs (NSAIDs) are a group of widely available, inexpensive medicines. The analgesic, antiinflammatory, antipyretic and antithrombotic effects of salicylate in willow bark and other plant extracts were recognised in ancient Egypt and Greece. These properties have been extensively exploited in numerous fields of clinical medicine since the 19th century, and in cancer patients primarily for analgesia.

Improving Survival Rates in Two Models of Spontaneous Postoperative Metastasis in Mice by Combined Administration of a β-Adrenergic Antagonist and a Cyclooxygenase-2 Inhibitor

“…COX-2 inhibitors, which unlike COX-1 inhibitors do not increase the risk of bleeding, are used as pain relievers during surgery (47) and have been used for the prevention and treatment of malignancies (48). Furthermore, in a previous study we found that COX-2, but not COX-1 inhibition, attenuated the metastasis-promoting effects of surgery, and etodolac was more effective than the highly COX-2 selective celecoxib (22).…”

Clinical evidence of the relationship between aspirin and breast cancer risk (Review)

“…For those women who present with tumors with positive hormone receptors, the use of aspirin could contribute to the suppression of aromatase activity, reducing the intra-mammary prostaglandin production, and thus, estrogen production (59). In particular, it has been shown that E2 prostaglandin (PGE 2 ) stimulates the transcription of aromatase, increasing the estrogen levels and, moreover, contributing to the progression of estrogen-dependent BC (60). The induction and overexpression of COX-2 and its main product PGE 2 in human mammary tissue, have also been associated with aromatase-catalyzed estrogen biosynthesis (61).…”

“…Maspin protein is a tumor-suppressor serine protease, which is expressed in several tissues including mammary epithelia, prostate, epidermis, lung, and in the stromal cells of the cornea (35,36,61,62). This protein is of special interest as it is able to inhibit cellular invasion and metastasis and to act as a tumor suppressor (37,60).…”

Synthesis and Biological Evaluation of Novel Sulfonanilide Compounds as Antiproliferative Agents for Breast Cancer

“…17 A growing body of experimental and epidemiological evidence suggests that the use of NSAIDs may decrease the incidence of mammary cancer, tumor burden, and tumor volume. [18][19][20] Although this effect has been studied within the past few decades, the mechanism by which these benefits occur is unclear. Nimesulide [N-(4-nitro-2-phenoxyphenyl) methane sulfonamide] is a nonsteroidal anti-inflammatory drug with a preferential cyclooxygenase-2 inhibitory activity and has been available in some Asia and European countries since 1985.…”