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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.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Bundred, Nigel J. Cramer, Angela Morris, Julie L. Renshaw, Lorna Cheung, Kwok-Leung Flint, Pamela J. Johnson, Rachael Young, Oliver Landberg, Goeran Grassby, S. Turner, Lorraine Baildam, Andrew D. Barr, Lester Dixon, J. Michael |
| Copyright Year | 2010 |
| Abstract | 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 x 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. |
| File Format | PDF HTM / HTML |
| DOI | 10.1158/1078-0432.CCR-09-1623 |
| PubMed reference number | 20179229 |
| Journal | Medline |
| Volume Number | 16 |
| Issue Number | 5 |
| Alternate Webpage(s) | http://clincancerres.aacrjournals.org/content/clincanres/16/5/1605.full.pdf |
| Alternate Webpage(s) | http://clincancerres.aacrjournals.org/content/clincanres/early/2010/02/22/1078-0432.CCR-09-1623.full.pdf |
| Alternate Webpage(s) | https://doi.org/10.1158/1078-0432.CCR-09-1623 |
| Journal | Clinical cancer research : an official journal of the American Association for Cancer Research |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
