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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 aromatas...

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Detalles Bibliográficos
Autores principales: Ellis, Matthew J., Ma, Cynthia
Formato: Texto
Lenguaje:English
Publicado: Springer US 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2001223/
https://www.ncbi.nlm.nih.gov/pubmed/17912634
http://dx.doi.org/10.1007/s10549-007-9701-x
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author Ellis, Matthew J.
Ma, Cynthia
author_facet Ellis, Matthew J.
Ma, Cynthia
author_sort Ellis, Matthew J.
collection PubMed
description 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.
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spelling pubmed-20012232007-10-09 Letrozole in the neoadjuvant setting: the P024 trial Ellis, Matthew J. Ma, Cynthia Breast Cancer Res Treat Review 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. Springer US 2007-10-03 2007-10 /pmc/articles/PMC2001223/ /pubmed/17912634 http://dx.doi.org/10.1007/s10549-007-9701-x Text en © Springer Science+Business Media, LLC 2007
spellingShingle Review
Ellis, Matthew J.
Ma, Cynthia
Letrozole in the neoadjuvant setting: the P024 trial
title Letrozole in the neoadjuvant setting: the P024 trial
title_full Letrozole in the neoadjuvant setting: the P024 trial
title_fullStr Letrozole in the neoadjuvant setting: the P024 trial
title_full_unstemmed Letrozole in the neoadjuvant setting: the P024 trial
title_short Letrozole in the neoadjuvant setting: the P024 trial
title_sort letrozole in the neoadjuvant setting: the p024 trial
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2001223/
https://www.ncbi.nlm.nih.gov/pubmed/17912634
http://dx.doi.org/10.1007/s10549-007-9701-x
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