COX-2 expression predicts worse breast cancer prognosis and does not modify the association with aspirin

Abstract

Background Some studies have found worse prognosis among COX-2 expressing breast cancers. Aspirin and NSAIDs inhibit COX-2. Three studies, including ours, have reported a survival advantage among women with breast cancer who take either aspirin or NSAIDs. We hypothesized that in the Nurses’ Health Study (NHS), COX-2 expression would be associated with worse prognosis, and aspirin use would be associated with better survival particularly among women with COX-2 positive tumors. Methods We studied 2,001 women with invasive breast cancers stained for COX-2 by immunohistochemistry. Tumor prognostic factors were from medical records. Aspirin use was assessed at least 12 months after diagnosis and updated. Cause of death was from death certificates. Statistical analyses included logistic regression of prognostic factors with COX-2 status as the outcome, and proportional hazards regression with breast cancer death as the outcome. Results Tumor COX-2 expression was associated with higher diagnostic stage. Compared with stage I, the RR(95% CI) for stages II-IV were 1.16(0.93–1.45), 1.68(1.27–2.22), and 1.76(0.93–3.32). COX-2 expression was associated with lobular compared with ductal histology, (1.40[1.02–1.92]), and estrogen receptor positive compared with negative (2.22[1.66–2.95]). The RR(95% CI) of breast cancer death for current aspirin use was similar for women with COX-2 positive and negative tumors; 0.64(0.43–0.96) and 0.57(0.44–0.74) respectively. Conclusions In the NHS, COX-2 breast cancer expression was associated with higher stage at diagnosis. The survival benefit associated with aspirin use did not differ by COX-2 status. Impact COX-2 breast cancer expression is associated with worse prognosis. If aspirin truly impacts breast cancer survival, it is not solely via COX-2.

New Insights on COX-2 in Chronic Inflammation Driving Breast Cancer Growth and Metastasis

“…In several breast cancer studies examining COX-2 expression (mRNA and/or protein by immunohistochemistry), COX-2 was only expressed in tumor, not normal breast tissue, and overall its expression in tumors predicted a worse prognosis [59][60][61][62][63][64][65][66][67]. COX-2 expression was used to predict whether tumors were likely to metastasize or, in the case of ductal carcinoma in situ (DCIS), to recur.…”

Down-regulation of cyclooxygenase-2 (COX-2) by cannabidiolic acid in human breast cancer cells

“…COX-2 is expressed in approximately 40% of human invasive breast cancers (Singh et al, 2007;Holmes et al, 2011), and may be actively involved in breast cancer metastasis to bones and the lungs (Yoshinaka et al, 2006;Singh et al, 2007). Thus, one strategy to reduce the risk of breast cancer including metastasis involves COX-2 inhibitors.…”

Cyclooxygenase-2 utilizes Jun N-terminal kinases to induce invasion, but not tamoxifen resistance, in MCF-7 breast cancer cells

“…In conclusion, we found that COX-2 increased the activity of JNKs to mediate invasion, but not tamoxifen resistance, in MCF-7 breast cancer cells. In breast cancer, COX-2 expression is a predictor of poor disease-free and overall survival (4)(5)(6)(7)(8)(9) and has been implicated as a marker of high metastatic potential (11,12). Pharmacological inhibition aiming at JNKs may have potential therapeutic benefit in patients with ERα-positive COX-2-overexpressing breast tumors by reducing tumor invasiveness and metastatic potential.…”

“…In breast cancer, COX-2 expression is a predictor of poor disease-free and overall survival (4)(5)(6)(7)(8)(9). In a retrospective study of 1,576 invasive breast tumors, Ristimaki et al (4) found that elevated COX-2 expression was associated with a lower survival rate in patients with estrogen receptor α (ERα)-positive breast tumors.…”