Abstract 2401: Evaluation of circulating serum Amphiregulin levels in patients with breast cancer.
Authors: Peterson Esther A. , Kenny Paraic A. 
Published: August 2014

Amphiregulin (AREG), a ligand for Epidermal Growth Factor Receptor (EGFR), has been implicated as an effector of ERα signaling in mammary gland development and as a candidate ERα effector in human breast cancers. Analysis of 13 luminal subtype breast cancer cell lines and human breast tumors showed a strong correlation between ERα status and high AREG levels. A pilot study using healthy and breast cancer women's serum showed that circulating AREG levels were higher in the ERα positive patients as compared to healthy individuals. Therefore we hypothesized that Amphiregulin is a potential biomarker and/or therapeutic target for ERα positive breast cancers.

To test our hypothesis, we are currently evaluating AREG as a potential serum biomarker of breast cancer progression and as an indicator of response to treatment by analyzing a cohort of breast cancer patients (n=225) stratified by stage of disease and subtypes (hormone receptor status). In this study, we want to determine if tumor-derived AREG is released into the systemic circulation and whether it may be a useful serum biomarker for the presence of breast cancer and for response to therapy. In the first phase, serum Amphiregulin was measured by an ELISA assay to establish the reference range in 125 healthy females. Fifty-five percent of the healthy women had no detectable circulating AREG (n=69), and only ten women had levels exceeding 500 pg/mL. Serum AREG levels did not vary significantly during the menstrual cycle. We determined that the 95th and 90th percentile was &gt;1575 pg/ml and &gt;471 pg/ml, respectively, to use as a comparison against the AREG levels of the breast cancer patients. We are analyzing serum AREG levels in breast cancer patient serum samples of three different cohorts: women with no evidence of disease after more than 1 year post-surgery (Cohort 1), women with locally advanced or stage IV with disease progression (Cohort 2) and women with operable disease that will have surgery and subsequent chemotherapy and/or endocrine therapy (Cohort 3). Each cohort was further stratified by hormone receptor status. In addition to determining the baseline AREG levels, for Cohort 3, AREG levels will be measured post-surgery and at different timepoints during treatment. Interim analysis of the different cohorts showed a significance difference (p&lt;0.05) between healthy individuals and patients with ERα+ breast tumors when comparing detectable versus undetectable AREG levels (threshold of detection: 20 pg/ml). Interestingly, longitudinal sampling of one patient with very high levels (18,300 pg/ml at diagnosis) showed a 37% decline following tumor resection and a 60% decline after 9 months of endocrine therapy.

In summary, determining the potential role of AREG as predictive biomarker for therapy and/or as therapeutic target by the completion of this clinical study, will contribute to the quest for better predictive biomarkers in breast cancer and better management of the disease.

Citation Format: Esther A. Peterson, Paraic A. Kenny. Evaluation of circulating serum Amphiregulin levels in patients with breast cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2401. doi:10.1158/1538-7445.AM2013-2401