title: COX-2 expression predicts worse breast cancer prognosis and does not modify the association with aspirin.
abstract: Some previous studies have found worse prognosis among cyclooxygenase-2 (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. Through this study 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. In this study we investigated 2,001 women presenting 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 identified 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. 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 COX-2-negative tumors; 0.64 (0.43-0.96) and 0.57 (0.44-0.74), respectively. 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. COX-2 breast cancer expression is associated with worse prognosis. If aspirin truly impacts breast cancer survival, then it is not solely via COX-2.
authors: Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 181 Longwood Avenue, Boston, MA 02115, USA. michelle.holmes@channing.harvard.edu
authors: Michelle D
authors: MD
authors: Holmes
authors: Wendy Y
authors: WY
authors: Chen
authors: Stuart J
authors: SJ
authors: Schnitt
authors: Laura
authors: L
authors: Collins
authors: Graham A
authors: GA
authors: Colditz
authors: Susan E
authors: SE
authors: Hankinson
authors: Rulla M
authors: RM
authors: Tamimi
mesh_terms: D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism; D001943:Breast Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D006801:Humans; D016015:Logistic Models; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D047368:Tumor Burden
chemical_list: D000970:Antineoplastic Agents; D001241:Aspirin; D014408:Biomarkers, Tumor; D051546:Cyclooxygenase 2; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C496540:PTGS2 protein, human; C508053:ERBB2 protein, human