Estrogen-dependent prognostic significance of cyclooxygenase-2 expression in early-stage invasive breast cancers treated with breast-conserving surgery and radiation.
OBJECTIVE
To evaluate the prognostic significance of cyclooxygenase-2 (COX-2) in breast cancer patients treated with conservative surgery and radiation therapy (CS+RT).


METHODS
Between 1975 and 2003, we retrieved specimens from 504 breast cancer patients treated with CS+RT. The specimens were constructed into tissue microarrays processed and stained for estrogen receptor (ER), progesterone receptor, Her2/neu, and COX-2. Each core was scored as positive or negative. All data including demographics, clinical, pathologic, staging, and outcome variables were entered into a computerized database.


RESULTS
Expression of COX-2 was positive in 58% of cases and correlated with younger age (p = 0.01) and larger tumor size (p = 0.001). Expression of COX-2 was predictive of local relapse (relative risk[RR], 3.248; 95% confidence interval [CI], 1.340-7.871; p = 0.0091), distant metastasis (RR, 2.21; 95% CI, 1.259-3.896; p = 0.0058), and decreased survival (RR, 2.321; 95% CI, 1.324-4.071; p = 0.0033). Among ER-positive patients, COX-2 expression was predictive of worse local control (85% vs. 93%, p = 0.04), distant metastasis (75% vs. 95%, p = 0.002) and worse survival (65% vs. 94%, p = 0.002). Among ER-negative tumors COX-2 expression was not significantly correlated with local control (87 vs. 95%, p = 0.12), distant metastasis (73% vs. 78%, p = 0.39), or survival (77% vs. 87%, p = 0.15).


CONCLUSIONS
In breast cancer patients treated with CS+RT, COX-2 expression is associated with younger age, larger tumor size, worse local control, distant metastasis, and worse overall survival. The significance is limited to hormone receptor-positive tumors, consistent with the known effect of COX-2/PGE2 on aromatase activity. Use of COX-2 inhibitors in estrogen-dependent breast cancers warrants further investigation.
Haffty
Bruce G
BG
Department of Radiation Oncology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School-University of Medicine and Dentistry of New Jersey, New Brunswick, NJ 08903, USA. hafftybg@umdnj.edu
Yang
Qifeng
Q
Moran
Meena S
MS
Tan
Antoinette R
AR
Reiss
Michael
M
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D015331:Cohort Studies; D003131:Combined Modality Therapy / Q000706:statistics & numerical data; D003237:Connecticut / Q000453:epidemiology; D051546:Cyclooxygenase 2 / Q000032:analysis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental / Q000706:statistics & numerical data*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000175:diagnosis* / Q000378:metabolism / Q000401:mortality / Q000628:therapy*; D017063:Outcome Assessment, Health Care / Q000379:methods*; D011379:Prognosis; D011878:Radiotherapy / Q000706:statistics & numerical data*; D011960:Receptors, Estrogen / Q000032:analysis*; D015203:Reproducibility of Results; D018570:Risk Assessment / Q000379:methods; D012307:Risk Factors; D012680:Sensitivity and Specificity; D015996:Survival Rate; D016896:Treatment Outcome
D011960:Receptors, Estrogen; D051546:Cyclooxygenase 2