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Randomized Controlled Trial
. 2007;105 Suppl 1(Suppl 1):33-43.
doi: 10.1007/s10549-007-9701-x. Epub 2007 Oct 3.

Letrozole in the Neoadjuvant Setting: The P024 Trial

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Free PMC article
Randomized Controlled Trial

Letrozole in the Neoadjuvant Setting: The P024 Trial

Matthew J Ellis et al. Breast Cancer Res Treat. .
Free PMC article

Erratum in

  • Breast Cancer Res Treat. 2008 Nov;112(2):371

Abstract

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.

Figures

Fig. 1
Fig. 1
Patient disposition [21]
Fig. 2
Fig. 2
Clinical response rate versus estrogen receptor (ER) Allred score for letrozole and tamoxifen. The P value for a linear logistic model was 0.0013 for letrozole and 0.0061 for tamoxifen according the Wald test. In this analysis, ER−, PgR+ cases (determined by conventional cut points) were excluded. Reprinted from [37] with permission from the American Society of Clinical Oncology
Fig. 3
Fig. 3
A box plot of before and after treatment Ki67 values in the estrogen-receptor-positive, human epidermal growth factor receptor (HER) 1/2+ subset. With letrozole (n = 15), 11 showed a decrease, one exhibited no change, and three showed an increase, of which only one was >2-fold (0.1–0.3%). With tamoxifen (n = 17), ten showed a decrease and seven an increase, of which three were relatively dramatic (9.5–22.7, 20.9–40.7, and 0.1–17.3%). Reprinted from [38] with permission from the American Association for Cancer Research

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