TY - JOUR
T1 - A randomized, placebo-controlled, phase II, presurgical biomarker trial of Celecoxib versus exemestane in postmenopausal breast cancer patients
AU - Aristarco, Valentina
AU - Serrano, Davide
AU - Gandini, Sara
AU - Johansson, Harriet
AU - Macis, Debora
AU - Guerrieri-Gonzaga, Aliana
AU - Lazzeroni, Matteo
AU - Feroce, Irene
AU - Pruneri, Giancarlo
AU - Pagani, Gianmatteo
AU - Toesca, Antonio
AU - Caldarella, Pietro
AU - DeCensi, Andrea
AU - Bonanni, Bernardo
PY - 2016/5/1
Y1 - 2016/5/1
N2 - In breast cancer presurgical trials, the Ki-67 labeling index predicts disease outcome and offers clues to the preventive potential of drugs. We conducted a placebo-controlled trial to evaluate the activity of exemestane and celecoxib before surgery. The main endpoint was the change in Ki-67. Secondary endpoints were the modulation of circulating biomarkers. Postmenopausal women with histologically confirmed estrogen receptor-positive breast cancer were randomly assigned to exemestane 25 mg/day (n = 50), or celecoxib 800 mg/day (n = 50), or placebo (n = 25) for 6 weeks before surgery. Changes in biomarkers were analyzed through an ANCOVA model adjusting for baseline values. Exemestane showed a median absolute 10% reduction in Ki-67 [from22 (interquartile range, IQR, 16-27), to 8 (IQR 5-18)], and a 15% absolute reduction in PgR expression [from 50 (IQR 3-90) to 15 (IQR-0-30)] after 6 weeks of treatment. Exemestane significantly increased testosterone [median change 0.21 ng/mL, (IQR 0.12-0.35)], decreased SHBG [median change-14.6 nmol/L, (IQR-23.1 to-8.6)], decreased total and HDL cholesterol by-10 mg/dL (IQR-21-2) and-7 mg/dL, (IQR-14 to-2), respectively. Triglycerides were reduced by both agents [median change-0.5 mg/dL (IQR-17.5-13.5) and-8 mg/dL (IQR-28-9) for celecoxib and exemestane, respectively]. Exemestane showed a remarkable antiproliferative effect on breast cancer, whereas celecoxib did not affect breast cancer proliferation. Given the proven preventive efficacy of exemestane, these findings support the use of Ki-67 to explore the optimal exemestane dose and schedule in the prevention setting. Cancer Prev Res; 9(5); 349-56.
AB - In breast cancer presurgical trials, the Ki-67 labeling index predicts disease outcome and offers clues to the preventive potential of drugs. We conducted a placebo-controlled trial to evaluate the activity of exemestane and celecoxib before surgery. The main endpoint was the change in Ki-67. Secondary endpoints were the modulation of circulating biomarkers. Postmenopausal women with histologically confirmed estrogen receptor-positive breast cancer were randomly assigned to exemestane 25 mg/day (n = 50), or celecoxib 800 mg/day (n = 50), or placebo (n = 25) for 6 weeks before surgery. Changes in biomarkers were analyzed through an ANCOVA model adjusting for baseline values. Exemestane showed a median absolute 10% reduction in Ki-67 [from22 (interquartile range, IQR, 16-27), to 8 (IQR 5-18)], and a 15% absolute reduction in PgR expression [from 50 (IQR 3-90) to 15 (IQR-0-30)] after 6 weeks of treatment. Exemestane significantly increased testosterone [median change 0.21 ng/mL, (IQR 0.12-0.35)], decreased SHBG [median change-14.6 nmol/L, (IQR-23.1 to-8.6)], decreased total and HDL cholesterol by-10 mg/dL (IQR-21-2) and-7 mg/dL, (IQR-14 to-2), respectively. Triglycerides were reduced by both agents [median change-0.5 mg/dL (IQR-17.5-13.5) and-8 mg/dL (IQR-28-9) for celecoxib and exemestane, respectively]. Exemestane showed a remarkable antiproliferative effect on breast cancer, whereas celecoxib did not affect breast cancer proliferation. Given the proven preventive efficacy of exemestane, these findings support the use of Ki-67 to explore the optimal exemestane dose and schedule in the prevention setting. Cancer Prev Res; 9(5); 349-56.
UR - http://www.scopus.com/inward/record.url?scp=84969922808&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84969922808&partnerID=8YFLogxK
U2 - 10.1158/1940-6207.CAPR-15-0311
DO - 10.1158/1940-6207.CAPR-15-0311
M3 - Article
AN - SCOPUS:84969922808
VL - 9
SP - 349
EP - 356
JO - Cancer Prevention Research
JF - Cancer Prevention Research
SN - 1940-6207
IS - 5
ER -