title: Physiological COX-2 expression in breast epithelium associates with COX-2 levels in ductal carcinoma in situ and invasive breast cancer in young women.
abstract: Cyclooxygenase-2 (COX-2) overexpression is implicated in increased risk and poorer outcomes in breast cancer in young women. We investigated COX-2 regulation in normal premenopausal breast tissue and its relationship to malignancy in young women. Quantitative COX-2 immunohistochemistry was performed on adjacent normal and breast cancer tissues from 96 premenopausal women with known clinical reproductive histories, and on rat mammary glands with distinct ovarian hormone exposures. COX-2 expression in the normal breast epithelium varied more than 40-fold between women and was associated with COX-2 expression levels in ductal carcinoma in situ and invasive cancer. Normal breast COX-2 expression was independent of known breast cancer prognostic indicators, including tumor stage and clinical subtype, indicating that factors regulating physiological COX-2 expression may be the primary drivers of COX-2 expression in breast cancer. Ovarian hormones, particularly at pregnancy levels, were identified as modulators of COX-2 in normal mammary epithelium. However, serial breast biopsy analysis in nonpregnant premenopausal women suggested relatively stable baseline levels of COX-2 expression, which persisted independent of menstrual cycling. These data provide impetus to investigate how baseline COX-2 expression is regulated in premenopausal breast tissue because COX-2 levels in normal breast epithelium may prove to be an indicator of breast cancer risk in young women, and predict the chemopreventive and therapeutic efficacy of COX-2 inhibitors in this population.
authors: Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Program in Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Young Women's Breast Cancer Translational Program, University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors: Jaime
authors: J
authors: Fornetti
authors: Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Young Women's Breast Cancer Translational Program, University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors: Sonali
authors: S
authors: Jindal
authors: Laboratory of Genetics, National Institutes of Aging, Baltimore, Maryland.
authors: Kara A
authors: KA
authors: Middleton
authors: Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Young Women's Breast Cancer Translational Program, University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado.
authors: Virginia F
authors: VF
authors: Borges
authors: Division of Medical Oncology, Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Program in Reproductive Sciences, University of Colorado Anschutz Medical Campus, Aurora, Colorado; Young Women's Breast Cancer Translational Program, University of Colorado Cancer Center, University of Colorado Anschutz Medical Campus, Aurora, Colorado; AMC Cancer Research Foundation, Denver, Colorado. Electronic address: pepper.schedin@ucdenver.edu.
authors: Pepper
authors: P
authors: Schedin
mesh_terms: D000328:Adult; D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000201:enzymology* / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D008875:Middle Aged; D051381:Rats; D017207:Rats, Sprague-Dawley; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2