A new study has reported that treating mice known to develop ductal carcinoma in situ (DCIS)-like lesions with a Cox-2 inhibitor failed to reduce mammary tumor development or prevent metastasis. Several molecular changes have been identified in DCIS. Among them, cyclooxygenase 2 (Cox-2) overexpression has been reported in 60% to 80% of DCIS cases. The mouse model used in the study exhibits a similar phenotype to human solid-pattern DCIS.

Celecoxib is a nonsteroidal anti-inflammatory drug (NSAID) that selectively inhibits Cox-2. Compared with untreated mice, mice given celecoxib were not found to have fewer tumors. Nor was celecoxib able to delay tumor appearance in the treated mice. Celecoxib given early in tumorigenesis also did not reduce the progression of DCIS-like tumors to invasive tumors, nor prevent lung metastasis. However, celecoxib did reduce prostaglandin levels in the mouse mammary tumors, as well as increasing apoptosis and inhibiting vascular endothelial growth factor expression in treated mice. The authors remark that their results contradict some previously published studies and highlight the complexity of the relationship between Cox-2 and breast cancer.

Cox-2 and breast cancer

Cox-2 is an important enzyme in fatty acid metabolism and inflammation. Although most primary breast tumors normally in themselves do not involve significant inflammation, it has long been thought that chronic inflammation might increase the risk of breast cancer dissemination and recurrence. Inflammation has been shown to facilitate tumor growth and metastasis by altering tumor cell biology and the tumor microenvironment. Systemic inflammation may also facilitate the growth and migration of micrometastases or reactivate dormant tumors at distant sites. Cox-2 has been found to be overexpressed in breast cancer and is associated with worse survival independent of known prognostic factors. However, long-term use of Cox-2 inhibitors, a group of non-steroidal drugs used to treat inflammation and pain, often has adverse effects, including an increased incidence of heart attack and other cardiovascular events.

Certain foods can reduce Cox-2 expression

Certain foods contain components that can reduce Cox-2 expression. Consuming such foods does not carry the cardiovascular risks of NSAIDs and provides chemopreventive compounds that may act synergistically to reduce cancer risk. The following foods have been found to inhibit Cox-2 expression and have also been found to be associated with reduced risk of breast cancer:

Arugula Basil Blackberries Blueberries Bok choy Broccoli Brussels sprouts Cabbage Cauliflower Celery Cherries & sour cherries Collard greens Cranberries Edamame

Flaxseed Garlic Herring Horseradish Kale Kefir Mackerel Mushrooms Mustard Mustard greens Olive oil Parsley Pumpkins Raspberries

Rice, brown Salmon, wild Soybeans Tomatoes Turmeric Walnuts Wasabi Watercress Tofu Watermelon Yogurt, lowfat Zucchini

The following foods also have been found to inhibit Cox-2 expression, but population studies have not been performed to assess any association between their consumption and risk of breast cancer:

Cashew nuts

Dandelion greens

Ginger

Macadamia nuts

Pineapple

Wheat bran

On the other hand, irradiation of meat has been shown to lead to the formation of a class of compounds known as alkylcyclobutanones, some of which have been shown to stimulate Cox-2 expression. There is also some evidence that oils with high linoleic acid content such as corn oil, safflower oil, soybean oil, and sunflower oil may stimulate Cox-2 mediated progression of breast cancer.