Neoadjuvant Tamoxifen Therapy Synchronizes Er Alpha Binding And Gene Expression Profiles

Background: The majority of breast cancer patients are diagnosed with ERα-positive breast cancer. Most ERα-positive patients are treated with adjuvant endocrine therapy — typically tamoxifen or aromatase inhibitors — to block cellular proliferation. Although these treatments are considered successful, resistance is common. Notably, cross-resistance between the two types of therapies is not always observed suggesting molecular heterogeneity and underlining the need for development of personalized treatments. The Anastrozole, Fulvestrant or Tamoxifen Exposure — Response in molecular profile study (AFTER study, NCT00738777) aims to investigate prospectively whether short-term treatment can induce molecular changes indicative of pre-operative therapy response. Study Design: ERα-positive breast cancer patients are included in this open-label multicenter study. Post-menopausal patients are randomized between tamoxifen, anastrozole and fulvestrant and pre-menopausal and male patients receive tamoxifen. Treatment occurs during the pre-operative window between diagnosis and surgery (4±2 weeks). Clinical characteristics collected are ERα/PR and HER2 status as well as lymph-node status. The primary endpoint is the decrease in tumor cell proliferation, as assessed by Ki67 gene expression and published cell proliferation gene expression signatures. All data are collected from both pre- and post-treatment samples. Additionally, we will compare the changes induced by treatment in gene expression, ERα/DNA binding interactions, DNA copy number, endoxifen and estradiol levels. Results: Among 67 patients currently enrolled, we examined the data from the subset of 28 tamoxifen treated patients. ERα and PR levels did not differ significantly between pre- and post-treatment. All tumors were HER2-negative. Proliferation examined by Ki67 (IHC and gene expression, MKI67) was significantly lower in post-treatment samples (P Citation Format: Linn SC, Severson TM, Nevedomskaya E, Peeters J, van Rossum A, Kuilman T, Krijgsman O, Goossens I, Glas A, Koornstra R, Peeper D, Wesseling J, Simon I, Wessels L, Zwart W. Neoadjuvant tamoxifen therapy synchronizes ERα binding and gene expression profiles. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P6-08-06.