PURPOSE: Within breast tissue, aromatase expression and activity is increased by prostaglandin E2, providing a rationale for combining the COX-2 inhibitor celecoxib with an aromatase inhibitor. To evaluate the effect of these drugs on aromatase and other biomarkers, a phase II trial of neoadjuvant exemestane followed sequentially by celecoxib plus exemestane was performed. METHODS: Postmenopausal women with estrogen receptor (ER) and/or progesterone (PR) positive stages II-III breast cancers received 8 weeks of exemestane 25 mg daily, followed by 8 weeks of exemestane 25 mg daily and celecoxib 400 mg twice daily. Core biopsies were collected pretreatment, after 8 weeks of exemestane, and at definitive breast cancer surgery. A tissue microarray was constructed and immunohistochemistry (IHC) for aromatase, ER, PR, HER-2, Ki-67, and COX-2 was performed. RESULTS: Twenty-two women were enrolled. Celecoxib was discontinued in 4 (18%) women for toxicity (all grade 1 and 2) and 2 (9%) developed serious cardiac events occurring at 1 and 4 months after completing treatment. By US, there were 8 (36%)-partial responses and 12 (55%)-stable disease. There were no pathological complete responses (pCR). There were statistically significant decreases in ER (P = .003), PR (P = .002), Ki-67 (P < .001), and COX-2 (P = .004) expression. No significant differences in aromatase or HER-2 expression were observed (P = .13 and P = .39, respectively). CONCLUSION: The addition of celecoxib to exemestane was tolerated by the majority of women and anti-tumor response was observed. Additional studies, including gene expression, are required to more fully understand the basis for the decreased expression of ER, PR, Ki-67, and COX-2.
PURPOSE: Within breast tissue, aromatase expression and activity is increased by prostaglandin E2, providing a rationale for combining the COX-2 inhibitor celecoxib with an aromatase inhibitor. To evaluate the effect of these drugs on aromatase and other biomarkers, a phase II trial of neoadjuvant exemestane followed sequentially by celecoxib plus exemestane was performed. METHODS: Postmenopausal women with estrogen receptor (ER) and/or progesterone (PR) positive stages II-III breast cancers received 8 weeks of exemestane 25 mg daily, followed by 8 weeks of exemestane 25 mg daily and celecoxib 400 mg twice daily. Core biopsies were collected pretreatment, after 8 weeks of exemestane, and at definitive breast cancer surgery. A tissue microarray was constructed and immunohistochemistry (IHC) for aromatase, ER, PR, HER-2, Ki-67, and COX-2 was performed. RESULTS: Twenty-two women were enrolled. Celecoxib was discontinued in 4 (18%) women for toxicity (all grade 1 and 2) and 2 (9%) developed serious cardiac events occurring at 1 and 4 months after completing treatment. By US, there were 8 (36%)-partial responses and 12 (55%)-stable disease. There were no pathological complete responses (pCR). There were statistically significant decreases in ER (P = .003), PR (P = .002), Ki-67 (P < .001), and COX-2 (P = .004) expression. No significant differences in aromatase or HER-2 expression were observed (P = .13 and P = .39, respectively). CONCLUSION: The addition of celecoxib to exemestane was tolerated by the majority of women and anti-tumor response was observed. Additional studies, including gene expression, are required to more fully understand the basis for the decreased expression of ER, PR, Ki-67, and COX-2.
Authors: Scott D Solomon; John J V McMurray; Marc A Pfeffer; Janet Wittes; Robert Fowler; Peter Finn; William F Anderson; Ann Zauber; Ernest Hawk; Monica Bertagnolli Journal: N Engl J Med Date: 2005-02-15 Impact factor: 91.245
Authors: J M Dixon; C D Love; C O Bellamy; D A Cameron; R C Leonard; H Smith; W R Miller Journal: Breast Cancer Res Treat Date: 2001-04 Impact factor: 4.872
Authors: B Fisher; J Bryant; N Wolmark; E Mamounas; A Brown; E R Fisher; D L Wickerham; M Begovic; A DeCillis; A Robidoux; R G Margolese; A B Cruz; J L Hoehn; A W Lees; N V Dimitrov; H D Bear Journal: J Clin Oncol Date: 1998-08 Impact factor: 44.544
Authors: Lesley-Ann Martin; Giles L S Davies; Marion T Weigel; Nadine Betambeau; Margaret J Hills; Janine Salter; Geraldine Walsh; Roger A'Hern; Mitch Dowsett Journal: Breast Cancer Res Treat Date: 2010-08-10 Impact factor: 4.872