title: The prognostic impact of COX-2 expression in breast cancer depends on oral contraceptive history, preoperative NSAID use, and tumor size.
abstract: The association between tumor cyclooxygenase 2 (COX-2) expression and breast cancer prognosis has been inconsistent. The purpose of this study was to evaluate the prognostic significance of COX-2 tumor expression according to adjuvant treatment, and potential effect modifications of non-steroid anti-inflammatory drug (NSAID) use, and other tumor and lifestyle factors. A prospective cohort of 1,116 patients with primary breast cancer in Lund, Sweden, included 2002-2012 was followed until June 2014 (median 5 years). Tumor-specific COX-2 expression was evaluated on tissue microarrays using immunohistochemistry. Associations between COX-2 intensity (negative, weak-moderate, high) and patient and tumor characteristics as well as prognosis were analyzed. Tumor-specific COX-2 expression was available for 911 patients and was significantly associated with higher age at diagnosis and less aggressive tumor characteristics. Higher COX-2 expression was associated with lower risk for breast cancer events during the first five years of follow-up,adjHR 0.60 (95%CI: 0.37-0.97), per category. The association between COX-2 expression and prognosis was significantly modified by oral contraceptive (OC) use (Pinteraction= 0.048), preoperative NSAID use (Pinteraction= 0.009), and tumor size (Pinteraction= 0.039). COX-2 negativity was associated with increased risk for events during the first five years in ever OC users,adjHR 1.94 (1.01-3.72) and during the 11-year follow-up in preoperative NSAID users,adjHR 4.51 (1.18-11.44) as well as in patients with large tumors,adjHR 2.57 (1.28-5.15). In conclusion, this study, one of the largest evaluating COX-2 expression in breast cancer, indicates that the prognostic impact of COX-2 expression depends on host factors and tumor characteristics.
authors.affiliation: Faculty of Medicine, Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Simonsson
authors.affiliation: Faculty of Medicine, Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Sofie
authors.initials: S
authors.lastname: Björner
authors.affiliation: Faculty of Medicine, Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Markkula
authors.affiliation: Faculty of Medicine, Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Björn
authors.initials: B
authors.lastname: Nodin
authors.affiliation: Faculty of Medicine, Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Karin
authors.initials: K
authors.lastname: Jirström
authors.affiliation: CREATE Health and Department of Immunotechnology, Lund University, Medicon Village, Lund, Sweden.
authors.forename: Carsten
authors.initials: C
authors.lastname: Rose
authors.affiliation: Faculty of Medicine, Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden.|Oncology and Haematology, Skåne University Hospital, Sweden.
authors.forename: Signe
authors.initials: S
authors.lastname: Borgquist
authors.affiliation: Department of Clinical Sciences, Lund, Surgery, Lund University and Skåne University Hospital, Lund, Sweden.
authors.forename: Christian
authors.initials: C
authors.lastname: Ingvar
authors.affiliation: Faculty of Medicine, Department of Clinical Sciences Lund, Oncology and Pathology, Lund University, Lund, Sweden.
authors.forename: Helena
authors.initials: H
authors.lastname: Jernström
mesh_terms: D000368:Aged; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology*; D003267:Contraception; D003276:Contraceptives, Oral / Q000008:administration & dosage* / Q000494:pharmacology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D016019:Survival Analysis; D013548:Sweden; D047368:Tumor Burden; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D003276:Contraceptives, Oral; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human
keywords: breast cancer; cyclooxygenase-2; non-steroidal anti-inflammatory drugs; oral contraceptives; prognosis