Androgen receptor expression in circulating tumor cells of metastatic breast cancer patients.

Authors

null

Ingeborg Elisabeth de Kruijff

Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands

Ingeborg Elisabeth de Kruijff , Anieta M. Sieuwerts , Wendy Onstenk , A. Jager , Paul Hamberg , Felix De Jongh , Marcel Smid , Mieke A. Timmermans , John W.M. Martens , Stefan Sleijfer

Organizations

Department of Medical Oncology, Erasmus MC Cancer Institute, Erasmus University Medical Center, Rotterdam, Netherlands, Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, Netherlands, Department of Internal Medicine, Franciscus Gasthuis & Vlietland, Rotterdam, Netherlands, Department of Internal Medicine, Ikazia Hospital, Rotterdam, Netherlands

Research Funding

Other

Background: The androgen receptor (AR) is of clinical relevance in metastatic breast cancer (mBC): AR has been associated with resistance to endocrine therapy and could be a potential target for therapy, especially in the triple negative (TN) subtype. A minimal-invasive way to determine AR expression is by characterization of circulating tumor cells (CTCs). We therefore assessed AR mRNA expression in CTCs (CTC-AR) from mBC patients representing different breast cancer subtypes in relation to outcome on endocrine therapy and 25 genes related to the ER and AR pathways. Furthermore, we assessed AR in matched primary tumors and CTC samples taken at advanced disease. Methods:AR and AR- and ER-related gene expression levels were measured in CellSearch-enriched CTCs from 133 mBC patients with ≥5 CTCs and in 48 matched formalin-fixed paraffin embedded primary tissues using quantitative reverse-transcriptase PCR. AR was considered positive if the expression was 1 standard deviation higher than the expression measured in 12 healthy blood donors. mBC subtypes were established based on ER, PR and HER2-status of the primary tumor (9 unknowns). Results: 31% of the CTC samples were AR-positive (AR+). The HER2+ subtype had most frequently AR+ CTCs (4/8, 50%), which was significantly higher than observed in the TN subtype (2/16, 13%) (p = 0.046). The ER+/HER2- subtype had 35% (27/78) AR+ samples and the ER+/HER2+ 23% (5/22). There was no significant difference between PFS in ER-targeting treated patients and CTC-AR-status (17 AR+ / 41 AR-negative (AR-) cases, p = 0.991). 65% of the matched CTC samples and primary tissues were discordant with respect to AR, observing both switches from AR+ to AR- and vice versa. Conclusions:AR can be determined in RNA isolated from CTCs from different mBC subtypes, with in our set 31% AR-positive samples. Because there was a 65% discordancy between AR in CTC samples and the primary tumor, it seems that AR should be determined in CTCs, but more research should be conducted in a larger set. In our current analysis patients had similar outcome on ER-targeting therapy regardless of their CTC-AR status. Thus, determination of AR expression in CTCs might be a promising tool to select mBC patients for AR inhibiting agents.

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2018 ASCO Annual Meeting

Session Type

Poster Session

Session Title

Breast Cancer—Metastatic

Track

Breast Cancer

Sub Track

Other Breast Cancer Subtypes

Citation

J Clin Oncol 36, 2018 (suppl; abstr 1087)

DOI

10.1200/JCO.2018.36.15_suppl.1087

Abstract #

1087

Poster Bd #

168

Abstract Disclosures