Androgen receptor expression in circulating tumor cells of patients with metastatic breast cancer
Autor: | Stefan Sleijfer, Paul Hamberg, Marcel Smid, Mieke Timmermans, Wendy Onstenk, John W.M. Martens, Jaco Kraan, Agnes Jager, Felix E. de Jongh, Ingeborg E. de Kruijff, Anieta M. Sieuwerts |
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Přispěvatelé: | Medical Oncology |
Rok vydání: | 2019 |
Předmět: |
Adult
Cancer Research Estrogen receptor Breast Neoplasms 03 medical and health sciences 0302 clinical medicine Circulating tumor cell Breast cancer SDG 3 - Good Health and Well-being Biomarkers Tumor medicine Humans Clinical significance Prospective Studies Neoplasm Metastasis Aged Aged 80 and over business.industry Middle Aged Neoplastic Cells Circulating medicine.disease Primary tumor Metastatic breast cancer Progression-Free Survival Androgen receptor Receptors Estrogen Oncology Receptors Androgen 030220 oncology & carcinogenesis Androgens Cancer research Biomarker (medicine) Female business |
Zdroj: | International Journal of Cancer, 145(4), 1083-1089. Wiley-Liss Inc. |
ISSN: | 1097-0215 0020-7136 |
DOI: | 10.1002/ijc.32209 |
Popis: | 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. |
Databáze: | OpenAIRE |
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