Abstract P1-05-02: COX-2 expression in normal mammary epithelium is estrogen responsive and predicts expression in DCIS and invasive ductal carcinoma

Background: Cyclooxygenase-2 (COX-2) overexpression is implicated in the poor prognosis of young women9s breast cancer. Understanding the regulation of COX-2 expression in normal premenopausal breast tissue and its relationship to malignancy is anticipated to provide insight into COX-2 as a potential therapeutic target for young breast cancer patients. Methods: To investigate COX-2 regulation and expression, quantitative COX-2 immunohistochemistry was performed on adjacent normal and breast cancer tissues from 83 premenopausal women with known clinical reproductive histories as well as on rat mammary glands with distinct estradiol and progesterone exposures. To determine the stability of COX-2 expression over time, a small cohort of women with serial breast biopsies 2-3 weeks apart was evaluated. Results: COX-2 expression in normal adjacent breast tissue was predominantly epithelial, varied >40-fold between individual women, and was independent of proximity to tumor and tumor biology. COX-2 upregulation occurred in alveoli during pregnancy and with estradiol and progesterone exposure in the rat. Though these data demonstrate ovarian hormone regulation, COX-2 expression was relatively stable for each individual premenopausal woman over a 2-3 week assessment window. Furthermore, COX-2 expression levels in normal epithelium independently predicted COX-2 expression levels in tumors. Conclusions : COX-2 expression in the adjacent normal breast epithelium is highly variable across premenopausal women, and may be further modified by ovarian hormone exposure. Moreover, COX-2 expression in the normal breast independently predicts COX-2 expression in tumors, implicating women with high COX-2 expression in the normal breast epithelium as high risk patients who may benefit from COX-2 inhibitor therapy. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P1-05-02.