Tumour aromatase as measured by immunohistochemistry in patients treated neoadjuvantly with either letrozole or tamoxifen in the P024 randomised trial—correlations with other biomarkers

Miller, Wilson H.; Tao, Tao; Ellis, MJ; Bhatnagar, Anish; Evans, DB; Sasano, Hironobu

doi:10.1016/s1359-6349(06)80346-0

Cited by 2 publications

(4 citation statements)

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“…In parallel, studies were conducted in which tumor biopsies and blood samples were taken from all patients prior to the initiation of therapy and at the end of treatment to generate a database from which changes in molecular markers could be assessed [ 37 – 41 ]. These studies were prospectively designed to assess the biological basis for letrozole efficacy.…”

Section: Trial Design and Patientsmentioning

confidence: 99%

“…Aromatase is the key enzyme responsible for estrogen biosynthesis and is present in about 70% of tumors. IHC was performed with a monoclonal aromatase antibody (677) on trial samples prior to and following letrozole or tamoxifen treatment ( n = 185); scoring was measured as a proportion of immuno-positive cells and their intensity of reactivity in malignant epithelial, stromal, adipose, and normal compartments [ 41 ].…”

Section: Trial Design and Patientsmentioning

confidence: 99%

“…Sufficient pre- and post-treatment tumor material was available from 171 cases (81 on letrozole and 90 on tamoxifen) from the P024 trial for immunohistochemistry analysis of aromatase protein expression [ 41 ]. Aromatase was detected in all tumor compartments, with the strongest staining observed in malignant epithelial cells.…”

Section: Efficacymentioning

confidence: 99%

“…Aromatase was detected in all tumor compartments, with the strongest staining observed in malignant epithelial cells. Median aromatase values did not change significantly with letrozole or tamoxifen treatment; however, changes in score did occur in individual cases, with more noticeable effects observed in letrozole-treated patients [ 41 ]. A positive correlation existed between baseline ER and aromatase staining in cancer cells, while a negative correlation was observed between baseline Ki67 and aromatase expression in cancer plus stroma.…”

Section: Efficacymentioning

confidence: 99%

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Letrozole in the neoadjuvant setting: the P024 trial

Ellis¹,

Ma²

2007

Breast Cancer Res Treat

107

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Neoadjuvant chemotherapy trials have consistently reported lower response rates in hormone receptorpositive (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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Section: Trial Design and Patientsmentioning

confidence: 99%

Section: Trial Design and Patientsmentioning

confidence: 99%

Section: Efficacymentioning

confidence: 99%

Section: Efficacymentioning

confidence: 99%

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