Association between cyclooxygenase-2 expression in atypical hyperplasia and risk of breast cancer.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Visscher
Daniel W
DW
Department of Surgical Pathology, University of Michigan, Ann Arbor, MI, USA.
Pankratz
V Shane
VS
Santisteban
Marta
M
Reynolds
Carol
C
Ristimäki
Ari
A
Vierkant
Robert A
RA
Lingle
Wilma L
WL
Frost
Marlene H
MH
Hartmann
Lynn C
LC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001940:Breast / Q000201:enzymology* / Q000473:pathology*; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D005260:Female; D005500:Follow-Up Studies; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006965:Hyperplasia / Q000175:diagnosis / Q000201:enzymology; D015994:Incidence; D008875:Middle Aged; D011230:Precancerous Conditions / Q000201:enzymology*; D011237:Predictive Value of Tests; D012107:Research Design; D018570:Risk Assessment; D012307:Risk Factors
D051546:Cyclooxygenase 2