Association between cyclooxygenase-2 expression in atypical hyperplasia and risk of breast cancer
Visscher DW, Pankratz VS, Santisteban M, Reynolds C, Ristimäki A, Vierkant RA, Lingle WL, Frost MH, Hartmann LC.
Department of Surgical Pathology, University of Michigan, Ann Arbor, MI, USA.
The cyclooxygenase-2 (COX-2) enzyme, which is induced by inflammatory and mitogenic stimuli, plays a protumorigenic role in several human cancers. COX-2 is overexpressed in invasive and in situ breast cancers. Atypical hyperplasia in breast tissue, although benign, is associated with a high risk of breast cancer. We investigated whether COX-2 overexpression in atypical hyperplasia is associated with the risk of subsequent breast cancer.
COX-2 expression was assessed immunohistochemically in archival sections from 235 women with atypia whose biopsy specimens were obtained at the Mayo Clinic from January 1, 1967, through December 31, 1991. COX-2 expression was scored as 0 (negative), 1+ (weak), 2+ (moderate), or 3+ (strong). Risk factor information and follow-up for breast cancer events were obtained via a study questionnaire and the medical records. All statistical tests were two-sided.
Forty-one (17%) of the 235 women developed breast cancer during a median follow-up of 15 years. Moderate (category 2+) or strong (category 3+) COX-2 expression was identified in 71 (30%) and 34 (14%) of the 235 samples, respectively. The risk for developing breast cancer, relative to a control population (the Iowa Surveillance, Epidemiology, and End Results registry), increased with increasing COX-2 expression (relative risk [RR] = 2.63, 95% confidence interval [CI] = 1.56 to 4.15, for those with negative or weak COX-2 expression; RR = 3.56, 95% CI = 1.94 to 5.97, for those with moderate expression; and RR = 5.66, 95% CI = 2.59 to 10.75, for those with strong expression; P = .07). Overexpression of COX-2 was statistically significantly associated with the type of atypia (lobular vs ductal, P < .001), number of foci of atypia in the biopsy (P = .02), and older age at time of biopsy (>45 years, P = .01).
COX-2 appears to be a biomarker that further stratifies breast cancer risk among women with atypia and may be a relevant target for chemoprevention strategies.
CITATION J Natl Cancer Inst. 2008 Mar 19;100(6):421-7. Epub 2008 Mar 11