Androgen receptor expression in circulating tumor cells of patients with metastatic breast cancer. Issue 4 (27th February 2019)

• Record Type: Journal Article
• Authors: de Kruijff, Ingeborg E.; Sieuwerts, Anieta M.; Onstenk, Wendy; Jager, Agnes; Hamberg, Paul; de Jongh, Felix E.; Smid, Marcel; Kraan, Jaco; Timmermans, Mieke A.; Martens, John W. M.; Sleijfer, Stefan
• Is Part Of: International journal of cancer. Volume 145:Issue 4(2019)
• Page Start: 1083
• Page End: 1089
• Publication Date: 2019-02-27
• Subjects: androgen receptor -- circulating tumor cells -- CTCs -- metastatic breast cancer -- biomarker; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.32209
• Languages: English
• ISSNs: 0020-7136

Abstract

Abstract : The androgen receptor (AR) has potential clinical relevance in metastatic breast cancer (mBC) since it might be a treatment target and has been associated with endocrine resistance. A minimal‐invasive way to determine AR expression on metastatic tumor cells is by characterization of circulating tumor cells (CTCs). Here, we assessed AR mRNA expression in CTCs (CTC‐ AR ) and in matched primary tumor samples from mBC patients representing different breast cancer subtypes. In addition, we explored CTC‐ AR ‐status in relation to outcome on endocrine therapy. AR, and 92 AR or estrogen receptor ( ER ) related genes, were measured in CellSearch‐enriched CTCs from 124 mBC patients and in 52 matched FFPE primary tissues using quantitative reverse‐transcriptase PCR. AR in CTCs was considered positive if the expression was 1 standard deviation higher than the expression measured in 11 healthy blood donors. A total of 31% of the mBC patients had AR ‐positive ( AR +) CTCs. 58% of the matched CTC and primary tumor samples were discordant with respect to AR status, observing both switches from AR + to AR ‐negative ( AR ‐) and vice versa . There was no statistically significant difference in progression‐free survival for patients treated with ER‐targeting drugs and CTC‐ AR ‐status (13 AR +/ 37 AR ‐ cases, p = 0.28). Thus, AR can be determined in RNA isolated from CTCs, with in our set 31% AR ‐positive samples. Given the discordance between AR status in CTC samples and corresponding primary tumors, determination of AR expression in CTCs might be a promising tool to select mBC patients for AR inhibiting agents. Abstract : What's new? Some patients with metastatic breast cancer respond well to drugs that target the androgen receptor (AR). Biomarkers are needed to identify these patients, but testing for AR on the primary tumor is not predictive enough. Here, the authors analyzed whether circulating tumor cells could provide better information about AR expression. Primary tumors and circulating tumor cells differed in AR expression in 58% of cases, they found, and CTCs are known to better represent the metastases. One of the next steps will also be to test a larger cohort to see whether patients with AR expressing CTCs respond less well to ER‐targeting therapy.