Effects of letrozole and anastrozole on low ER expressing invasive breast carcinomas: results from a randomised trial.

Abstract

Abstract Abstract #1065 Introduction:
 Changes in proliferation as measured by Ki67 occur within 14 days of starting treatment with an aromatase inhibitor and have been shown to be predictors of long term outcome. The biological effect of different aromatase inhibitors on low ER expressing cancers has not been studied. This study compared changes in proliferation in breast cancers expressing low levels of ER (Allred score 2-5) following 14 days of treatment with anastrozole or letrozole.
 Materials and methods:
 Thirty six postmenopausal women with invasive breast cancer, classified as estrogen receptor (ER) poor by an Allred score of 2-5 on initial core biopsy, were enrolled into a randomised pre-operative trial of 14 days treatment with either 2.5 mg of letrozole or 1 mg of anastrozole. Paired biopsy tissue was available for all patients: [15 who received anastrozole and 21 letrozole] with sufficient invasive cancer present for analysis. Assessment included ER (Allred score) and proliferation (% tumor cells Ki67 positive) by immunohistochemistry. Results are presented as means (SEM) and medians (range). Due to the non-normality of the data, pre- and post-treatment Ki67 values were transformed on the log scale. Change between pre- and post- treatment scores was calculated as the difference in the logged scores; analysis is by t-test and Fisher's Exact Test. All tests are two-sided. Results were back-transformed in order to preserve the original scale.
 Results:
 Proliferation measured by Ki67:
 Anastrozole reduced tumour cell proliferation from baseline in 10/15 cancers from a mean of 31.0% (7.1) to 20.8% (6.1). The median and mean reductions in Ki67 were 37% (range -94.0% to 92.6%) and 38% (13.9) from baseline. This equates to an average fall of 2.6 times from baseline, p=0.006, by analysis of the transformed data.
 Letrozole reduced proliferation from baseline in 17/21 cancers from a mean of 39.0% (7.3) to 25.3% (6.4). The median and mean reductions were 67% (range -115.6% to 99.6%) and 46% (10.6) from baseline. This equates to an average fall of 3.13 times from baseline, p=0.0002, by analysis of the transformed data.
 There was no evidence of a significant difference between drugs in reduction of proliferation, the number of cases showing a fall in proliferation, or the absolute Ki67 index at 14 days. Only 3/15 (anastrozole) and 2/21 (letrozole) tumours had post-treatment absolute Ki67 indices of ≤1%. There were no significant differences in changes in proliferation between tumours with ER score 2-3 vs score 4-5.
 Conclusions:
 1. Both anastrozole and letrozole significantly reduced proliferation in invasive cancers with low ER expression.
 2. There were no evident significant differences between drugs.
 3. These data suggest that aromatase inhibitors are of value even in low-ER expressing cancers, either on their own or perhaps as part of combined therapy.
 4. Analysis of more patients and of biological response according to molecular phenotype is underway. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 1065.