Prognostic and predictable value of COX2 expression in Russian women with stage I breast cancer.

Abstract

80 Background: Some previous studies found worse prognosis among cyclooxygenase-2 (COX2)-expressing breast cancers; we study prognostic and predictiable value of COX2 expression in breast cancer stage I. Methods: our study included Russian women with breast cancer stage I (n=315) treated in RCRC, RMAPE (1985-2009). A Tissue Micro Array (TMA) with triplicate 1 mm tumor tissue punches taken from tumor blocks was constructed in LUMC; sections were immunohistochemically stained for ER, PR, HER2-status, Ki67 (by standard morphological criteria); COX2-expression were evaluated as positive (>median; 31/309 cases, 10%) or negative (≤median; 278/209 cases, 90%). Also the histological type, grade, age and adjuvant endocrine therapy were examined. We analyzed the clinic and morphological data of COX2-positive tumors, prognostic value for survival (relapses free- RFS, overall- OS and cancer specific- CSS) and predictable value for endocrine therapy. Results: COX2-positive tumor were associated with ductal histological type (p=0,018), PR-negative status (p=0,027) and high Ki67 (p<0,0001), but not correlated (p>0,05) with age, grade, ER, HER2 status or biological subtype. In women with ER-negative tumors (104 patients, 34,1%) COX2-expression did not associate with worse survival (p>0,05). In contrast to this, in patients with ER-positive tumors (201 women, 65,9%) COX2-expression strongly correlated with worse RFS in univariate (HR 2,829, 95% CI 1,366-5,860, p=0,005) and multivariate analyses (HR=2,972, 95% CI 1,190-7,423, p=0,02). The same value of COX2-expression in women with ER-positive tumors was found for CSS (univariate: HR 3,421, 95% CI 1,436-8,149, p=0,005; multivariate: HR 4,260, 95% CI 1,344-13,504, p=0,014), but not for OS (p>0,05). In women who did not receive adjuvant endocrine therapy (145 patients, 46%) COX2 expression did not have any prognostic value for RFS, OS and CSS (p>0,05) but in patients that used adjuvant endocrine therapy (170 women, 54%) COX2-expression strongly associated with worse cancer-specific survival (HR 5,614 95% CI 1,165-27,059, p=0,032), but not with RFS and OS (p>0,05). Conclusions: COX2 expression plays a role in hormonal pathways and sensitivity for endocrine therapy.