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Cyclooxygenase-2 Expression in Postmastectomy Chest Wall Relapse

Authors' Affiliations: Departments of ¹ Therapeutic Radiology, ² Pathology, and ³ Surgery, Yale University School of Medicine, New Haven, Connecticut and ⁴ Department of Radiation Oncology, Robert Wood Johnson Medical School, New Brunswick, New Jersey

Requests for reprints: Bruce G. Haffty, Robert Wood Johnson Medical School, Cancer Institute of New Jersey, 195 Little Albany Street, New Brunswick, NJ 08903-2681. Phone: 732-235-5203; Fax: 732-235-7493; E-mail: hafftybg{at}umdnj.edu.

Purpose: Cyclooxygenase-2 (COX-2) expression has been shown to be associated with radiation resistance, which theoretically could be overcome with the use of COX-2 inhibitors. The purpose of this study was to assess the prognostic significance and clinical correlations of COX-2 expression (COX) in a cohort of patients treated with radiation for postmastectomy chest wall relapse.

Experimental Design: Between 1975 and 1999, 113 patients were treated for isolated postmastectomy chest wall relapse. All patients were treated with biopsy and/or excision of the chest wall recurrence followed by radiation therapy. Median follow-up was 10 years. All clinical data, including demographics, pathology, staging, receptor status, HER-2/neu status, and adjuvant therapy, were entered into a computerized database. Paraffin-embedded chest wall recurrence specimens were retrieved from 42 patients, of which 38 were evaluated, created into a tissue microarray, stained by immunohistochemical methods for COX, and graded 0 to 3+. A score of 2 to 3+ was considered positive.

Results: Overall survival from original diagnosis for entire cohort was 44% at 10 years. Survival rate after chest wall recurrence was 28% at 10 years. The distant metastasis-free survival rate after chest wall recurrence was 40% at 10 years. Local-regional control of disease was achieved in 79% at 10 years after chest wall recurrence. COX was considered positive in 13 of 38 cases. COX was inversely correlated with estrogen receptor (P = 0.045) and progesterone receptor (P = 0.028), and positively correlated with HER-2/neu (P = 0.003). COX was also associated with a shorter time to postmastectomy chest wall relapse. The distant metastasis-free rate for COX-negative patients was 70% at 10 years, compared with 31% at 10 years for COX-2–positive patients (P = 0.029). COX positive had a poorer local-regional progression-free rate of 19% at 10 years, compared with 81% at 10 years for COX negative. This was of high statistical significance with a P value of 0.003.

Conclusions: Outcome following radiation therapy for postmastectomy chest wall relapse is relatively poor. Positive COX correlated with other markers of poor outcome, including a shorter time to local relapse, negative estrogen receptor/progesterone receptor, and positive Her-2/neu status. Positive COX correlated with higher distant metastasis and lower local-regional control of disease. If confirmed with larger studies, these data have implications with respect to the concurrent use of COX-2 inhibitors and radiation for postmastectomy chest wall relapse.