TY - JOUR
T1 - Phase II trial of neoadjuvant exemestane in combination with celecoxib in postmenopausal women who have breast cancer
AU - Lustberg, Maryam B.
AU - Povoski, Stephen P.
AU - Zhao, Weiqiang
AU - Ziegler, Rebecca M.
AU - Sugimoto, Yasuro
AU - Ruppert, Amy S.
AU - Lehman, Amy M.
AU - Shiels, Donna R.
AU - Mrozek, Ewa
AU - Ramaswamy, Bhuvaneswari
AU - Layman, Rachel M.
AU - Brueggemeier, Robert W.
AU - Shapiro, Charles L.
N1 - Funding Information:
This work was supported by the National Comprehensive Cancer Network (NCCN) from general research support provided by Pfizer, Inc. Pfizer also supplied the exemestane and celecoxib.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
KW - COX-2 inhibitor
KW - Celecoxib
KW - Estrogen receptor
KW - Exemestane
KW - Ki-67
KW - Neoadjuvant
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U2 - 10.1016/j.clbc.2011.03.022
DO - 10.1016/j.clbc.2011.03.022
M3 - Article
C2 - 21729671
AN - SCOPUS:80052711291
SN - 1526-8209
VL - 11
SP - 221
EP - 227
JO - Clinical breast cancer
JF - Clinical breast cancer
IS - 4
ER -