TY - JOUR
T1 - A two-by-two factorial trial comparing oral with transdermal estrogen therapy and fenretinide with placebo on breast cancer biomarkers
AU - Decensi, Andrea
AU - Bonanni, Bernardo
AU - Baglietto, Laura
AU - Guerrieri-Gonzaga, Aliana
AU - Ramazzotto, Francesca
AU - Johansson, Harriet
AU - Robertson, Chris
AU - Marinucci, Irene
AU - Mariette, Frederique
AU - Sandri, Maria Teresa
AU - Daldoss, Cristina
AU - Bianco, Vanda
AU - Buttarelli, Marco
AU - Cazzaniga, Massimiliano
AU - Franchi, Dorella
AU - Cassano, Enrico
AU - Omodei, Umberto
PY - 2004/7/1
Y1 - 2004/7/1
N2 - Purpose: Oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) increase breast cancer risk, whereas the effect of transdermal estradiol (E2) and MPA is less known. Fenretinide may decrease second breast malignancies in premenopausal women but not in post-menopausal women, suggesting a hormone-sensitizing effect. We compared the 6 and 12-month changes in insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), IGF-I:IGFBP-3 ratio, sex-hormone binding-globulin, and computerized mammographic percent density during oral CEE or transdermal E2 with sequential MPA and fenretinide or placebo. Experimental Design: A total of 226 recent postmenopausal healthy women were randomly assigned in a two-by-two factorial design to either oral CEE 0.625 mg/day (n = 111) or transdermal E2, 50 μg/day (n = 115) and to fenretinide 100 mg/twice a day (n = 112) or placebo (n = 114) for 12 months. Treatment effects were investigated by the Kruskall-Wallis test and analysis of covariance. P values were two-sided. Results: After 12 months, oral CEE decreased IGF-I by 26% [95% confidence interval (CI), 22-30%] and increased sex-hormone binding-globulin by 96% (95% CI, 79-112%) relative to baseline, whereas no change occurred with transdermal E2 (P <0.001 between groups). Fenretinide decreased IGFBP-3 relative to placebo (P = 0.04). Percentage of breast density showed an absolute increase of 3.5% (95% CI, 2.5-4.6%) during hormone therapy without differences between groups (P = 0.39). Conclusions: Oral CEE has more favorable changes than transdermal E2 on circulating breast cancer risk biomarkers but gives similar effects on mammographic density. Fenretinide exerted little modulation on most biomarkers. The clinical implications of these findings require additional studies.
AB - Purpose: Oral conjugated equine estrogen (CEE) and medroxyprogesterone acetate (MPA) increase breast cancer risk, whereas the effect of transdermal estradiol (E2) and MPA is less known. Fenretinide may decrease second breast malignancies in premenopausal women but not in post-menopausal women, suggesting a hormone-sensitizing effect. We compared the 6 and 12-month changes in insulin-like growth factor-I (IGF-I), IGF-binding protein-3 (IGFBP-3), IGF-I:IGFBP-3 ratio, sex-hormone binding-globulin, and computerized mammographic percent density during oral CEE or transdermal E2 with sequential MPA and fenretinide or placebo. Experimental Design: A total of 226 recent postmenopausal healthy women were randomly assigned in a two-by-two factorial design to either oral CEE 0.625 mg/day (n = 111) or transdermal E2, 50 μg/day (n = 115) and to fenretinide 100 mg/twice a day (n = 112) or placebo (n = 114) for 12 months. Treatment effects were investigated by the Kruskall-Wallis test and analysis of covariance. P values were two-sided. Results: After 12 months, oral CEE decreased IGF-I by 26% [95% confidence interval (CI), 22-30%] and increased sex-hormone binding-globulin by 96% (95% CI, 79-112%) relative to baseline, whereas no change occurred with transdermal E2 (P <0.001 between groups). Fenretinide decreased IGFBP-3 relative to placebo (P = 0.04). Percentage of breast density showed an absolute increase of 3.5% (95% CI, 2.5-4.6%) during hormone therapy without differences between groups (P = 0.39). Conclusions: Oral CEE has more favorable changes than transdermal E2 on circulating breast cancer risk biomarkers but gives similar effects on mammographic density. Fenretinide exerted little modulation on most biomarkers. The clinical implications of these findings require additional studies.
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U2 - 10.1158/1078-0432.CCR-04-0087
DO - 10.1158/1078-0432.CCR-04-0087
M3 - Article
C2 - 15240527
AN - SCOPUS:19244366072
VL - 10
SP - 4389
EP - 4397
JO - Clinical Cancer Research
JF - Clinical Cancer Research
SN - 1078-0432
IS - 13
ER -