Cyclooxygenase-2 Inhibition Does Not Improve the Reduction in Ductal Carcinoma In situ Proliferation with Aromatase Inhibitor Therapy: Results of the ERISAC Randomized Placebo-Controlled Trial
| Autor: | Andrew D Baildam, Pamela J. Flint, Kwok-Leung Cheung, Sue Grassby, Julie Morris, Göran Landberg, O. Young, Nigel J Bundred, Lorraine Turner, Lorna Renshaw, R. Johnson, A. Cramer, J Michael Dixon, Lester Barr |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Oncology
Cancer Research medicine.medical_specialty Receptor ErbB-2 medicine.drug_class Estrogen receptor Apoptosis Breast Neoplasms Placebos chemistry.chemical_compound Breast cancer Exemestane Internal medicine Antineoplastic Combined Chemotherapy Protocols medicine Humans Aromatase skin and connective tissue diseases neoplasms Cell Proliferation Sulfonamides Aromatase inhibitor biology Aromatase Inhibitors business.industry Carcinoma Ductal Breast Cancer Ductal carcinoma medicine.disease Immunohistochemistry Androstadienes Ki-67 Antigen Endocrinology Receptors Estrogen chemistry Celecoxib Cyclooxygenase 2 biology.protein Pyrazoles Female Receptors Progesterone business Carcinoma in Situ Tamoxifen medicine.drug |
| Zdroj: | Clinical Cancer Research. 16:1605-1612 |
| ISSN: | 1557-3265 1078-0432 |
| DOI: | 10.1158/1078-0432.ccr-09-1623 |
| Popis: | Purpose: Tamoxifen reduces risk of recurrence after breast conservation surgery for ductal carcinoma in situ (DCIS), but no data exists on the effectiveness of aromatase inhibitors for DCIS. Cyclooxygenase-2 (COX-2) is overexpressed in DCIS, representing another potential therapeutic target. The aim of the study was to determine the effect of aromatase and/or COX-2 inhibition on epithelial proliferation and apoptosis in a presurgical study of estrogen receptor (ER)–positive DCIS. Methods: Postmenopausal women with ER-positive DCIS diagnosed by core biopsy were randomized to a 2 × 2 design of either 14 days of exemestane or placebo and celecoxib, or placebo immediately before surgery. Paired baseline and end point biopsies were analyzed for proliferation (Ki67), apoptosis, human epidermal growth factor receptor 2 (HER2), COX-2, and progesterone receptor (PR) expression by immunohistochemistry. The primary end point was a decrease in Ki67 between diagnosis and surgical excision. Results: Ninety women were randomized: all were ER positive, 49 (54%) had grade III tumors, and 29 (32%) were HER2 positive (3+). Exemestane reduced proliferation compared with placebo with a median reduction of 9% (95% confidence interval, 6-14; P < 0.001). Progesterone receptor was reduced by exemestane (mean decrease, 19%; 95% confidence interval, 9-28; P = 0.011). The effect of exemestane on proliferation was seen regardless of grade, HER2, or PR expression. Celecoxib had no effect on proliferation or apoptosis alone, or in combination with exemestane. Conclusions: Exemestane reduces proliferation in ER-positive DCIS. Aromatase inhibition is a potential alternative to tamoxifen in patients who have undergone breast conservation for ER-positive DCIS. Clin Cancer Res; 16(5); 1605–12 |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|