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document
Letrozole in the neoadjuvant setting : the P024 trial . Neoadjuvant chemotherapy trials have consistently reported lower response rates in hormone receptor-positive ( HR+ ) breast cancer when compared with HR- cases . Preoperative endocrine therapy has therefore become a logical alternative and has gained considerable momentum from the finding that aromatase inhibitors ( AIs ) are more effective than tamoxifen for HR+ breast cancer in both the neoadjuvant and adjuvant settings . The most convincing neoadjuvant trial to demonstrate the superiority of an AI versus tamoxifen was the P024 study , a large multinational double-blind trial in postmenopausal women with HR+ breast cancer ineligible for breast-conserving surgery . The overall response rate ( ORR ) was 55 % for letrozole and 36 % for tamoxifen ( P < 0.001 ) . Significantly more letrozole-treated patients underwent breast-conserving surgery ( 45 vs. 35 % , respectively ; P=0.022 ) . In addition , ORR was significantly higher with letrozole than tamoxifen in the human epidermal growth factor receptor HER1/HER2+ subgroup ( P=0.0004 ) . The clinical efficacy of letrozole in HER2+ breast cancer was confirmed by fluorescent in situ hybridization analysis and was found to be comparable to that of HER2- cases ( ORR 71 % in both subsets ) . Biomarker studies confirmed the superiority of letrozole in centrally assessed estrogen receptor-positive ( ER+ ) tumors and found a strong relationship with the degree of ER positivity for both agents . Interestingly , letrozole was effective even in marginally ER+ tumors and , unlike tamoxifen , consistently reduced the expression from estrogen-regulated genes ( progesterone receptor and trefoil factor 1 ) . Furthermore , when analyzed by Ki67 immunohistochemistry , letrozole was significantly more effective than tamoxifen in reducing tumor proliferation ( P=0.0009 ) . Thus , neoadjuvant letrozole is safe and superior to tamoxifen in the treatment of postmenopausal women with HR+ locally advanced breast cancer .
32783
Intervention_Pharmacological
Letrozole
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Intervention_Pharmacological
Neoadjuvant chemotherapy
32785
Intervention_Pharmacological
Preoperative endocrine therapy
32786
Intervention_Pharmacological
aromatase inhibitors
32787
Intervention_Pharmacological
tamoxifen
32788
Intervention_Pharmacological
AI
32789
Intervention_Pharmacological
tamoxifen
32790
Intervention_Surgical
breast-conserving surgery
32791
Intervention_Pharmacological
letrozole
32792
Intervention_Pharmacological
tamoxifen
32793
Intervention_Surgical
breast-conserving surgery
32794
Intervention_Pharmacological
tamoxifen
32795
Intervention_Pharmacological
letrozole
32796
Intervention_Pharmacological
letrozole
32797
Intervention_Pharmacological
letrozole
32798
Intervention_Pharmacological
letrozole
32799
Intervention_Pharmacological
tamoxifen
32800
Outcome_Other
response rates
32801
Outcome_Other
overall response rate ( ORR )
32802
Outcome_Other
underwent breast-conserving surgery
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Outcome_Other
ORR
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Outcome_Other
clinical efficacy
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Outcome_Other
Biomarker studies
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Outcome_Other
degree of ER positivity
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Outcome_Physical
expression from estrogen-regulated genes
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Outcome_Physical
tumor proliferation
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Participant_Condition
multinational
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Participant_Condition
postmenopausal women with HR+ breast cancer ineligible for breast-conserving surgery .