A randomized trial exploring the biomarker effects of neoadjuvant sequential treatment with exemestane and anastrozole in post-menopausal women with hormone receptor-positive breast cancer

Abstract

Several adjuvant endocrine strategies exist for postmenopausal women with breast cancer. This study compared the effect of two sequences of aromatase inhibitor use [steroidal (exemestane) and non-steroidal (anastrozole)] on serological and pathological biomarkers when given in the neoadjuvant setting to postmenopausal women with breast cancer. Thirty women were assigned to receive exemestane 25 mg or anastrozole 1 mg each given for 8 weeks in a randomized sequence. The effect of this treatment on serum estrone sulfate and estradiol levels, as well as tumor changes in the proliferation biomarker Ki67 were evaluated at baseline, 8 weeks and 16 weeks. WHO clinical response criteria, patient preference, and quality of life were also assessed. Assessable data was available from 28 patients. There were no differences in concentration changes of serum estradiol or Ki67 between patients in the two arms. Overall clinical response rate was 68% (19/28 assessable patients) and clinical benefit was 93% (26/28 assessable patients). There was no significant difference in toxicity or quality of life scores. The majority of patients expressed a personal preference for anastrozole over exemestane. Results suggest that the order of steroidal and non-steroidal aromatase inhibitors has little effect on outcome. The majority of patients express clear preferences for drug treatments.

Effects of aromatase inhibitors and body mass index on steroid hormone levels in women with early and advanced breast cancer

“…In the present study, an in‐depth SH profile comparing third‐generation AIs showed that levels of all the measured hormones were significantly higher in the exemestane group. Previously, studies have predominantly involved one of these AIs alone, reporting changes before and after treatment for oestradiol, oestrone and oestrone sulphate, or have been crossover studies with all but one comparing anastrozole and letrozole. A previous report showed that after 8 weeks of treatment with exemestane, 69 per cent of women had complete suppression of oestradiol, compared with 78 per cent of those who received anastrozole; the present findings are in line with these results.…”

Evaluating the Feasibility of Performing Window of Opportunity Trials in Breast Cancer

“…Changes in tumor Ki67 expression is a well-recognized surrogate endpoint for treatment response [ 18 – 21 ] and predictor of clinical outcome [ 22 , 23 ]. Variability in Ki67 staining can occur as a result of a number of factors, including the duration of tissue ischemia, formalin quality, duration of fixation, immunohistochemical technique used, and assessor differences.…”

Landscape of Neoadjuvant Therapy for Breast Cancer

“…Results indicated that the greatest suppression was observed in patients taking letrozole, and the least suppression was with exemestane. 55,56 Importantly, a prospective randomized, trial (MA.27) comparing anastrozole and exemestane demonstrated no difference in DFS or OS in the adjuvant setting. 57 The superiority of letrozole compared to the other AIs, in terms of long-term clinical outcomes, has not been established.…”