RGD Reference Report - Association between cyclooxygenase-2 expression in atypical hyperplasia and risk of breast cancer. - Rat Genome Database

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

Authors: Visscher, DW  Pankratz, VS  Santisteban, M  Reynolds, C  Ristimaki, A  Vierkant, RA  Lingle, WL  Frost, MH  Hartmann, LC 
Citation: Visscher DW, etal., J Natl Cancer Inst. 2008 Mar 19;100(6):421-7. Epub 2008 Mar 11.
RGD ID: 2300129
Pubmed: PMID:18334709   (View Abstract at PubMed)
DOI: DOI:10.1093/jnci/djn036   (Journal Full-text)

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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Breast Neoplasms susceptibilityIEP 2300129 RGD 
Breast Neoplasms susceptibilityISOPTGS2 (Homo sapiens)2300129; 2300129 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Ptgs2  (prostaglandin-endoperoxide synthase 2)

Genes (Mus musculus)
Ptgs2  (prostaglandin-endoperoxide synthase 2)

Genes (Homo sapiens)
PTGS2  (prostaglandin-endoperoxide synthase 2)


Additional Information