Dataset Information

AR Expression in Breast Cancer CTCs Associates with Bone Metastases.

ABSTRACT: Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing was performed of circulating tumor cells (CTC) isolated from blood samples of women with metastatic estrogen receptor (ER)+ breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7. AR expression within CTCs is correlated with the duration of treatment with aromatase inhibitors, suggesting that it contributes to acquired resistance to endocrine therapy. In an established breast cancer xenograft model, a bone-tropic derivative displays increased AR expression, whose genetic or pharmacologic suppression reduces metastases to bone but not to lungs. Together, these observations identify AR signaling in CTCs from women with bone-predominant ER+ breast cancer, and provide a rationale for testing androgen inhibitors in this subset of patients.Implications: This study highlights a role for the AR in breast cancer bone metastasis, and suggests that therapeutic targeting of the AR may benefit patients with metastatic breast cancer. Mol Cancer Res; 16(4); 720-7. ©2018 AACR.

SUBMITTER: Aceto N

PROVIDER: S-EPMC5882540 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature

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AR Expression in Breast Cancer CTCs Associates with Bone Metastases.

Aceto Nicola N Bardia Aditya A Wittner Ben S BS Donaldson Maria C MC O'Keefe Ryan R Engstrom Amanda A Bersani Francesca F Zheng Yu Y Comaills Valentine V Niederhoffer Kira K Zhu Huili H Mackenzie Olivia O Shioda Toshi T Sgroi Dennis D Kapur Ravi R Ting David T DT Moy Beverly B Ramaswamy Sridhar S Toner Mehmet M Haber Daniel A DA Maheswaran Shyamala S

Molecular cancer research : MCR 20180216 4

Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing was performed of circulating tumor cells (CTC) isolated from blood samples of women with metastatic estrogen receptor (ER)<sup>+</sup> breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene ...[more]

PMID: 29453314

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Project description:BackgroundBone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone.Methods/designThe B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases.DiscussionThe B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the potential of metabolomic profiles for risk assessment and early detection and the signalling pathways controlling the metastatic tumour microenvironment. There is substantial synergy between the four projects and it is hoped that this integrated program of research will advance our understanding of key aspects of bone metastases from breast cancer to improve the prevention, prediction, detection, and treatment of these lesions.

Dataset Information

AR Expression in Breast Cancer CTCs Associates with Bone Metastases.

Publications

AR Expression in Breast Cancer CTCs Associates with Bone Metastases.

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