Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Expression data from fine-needle aspiration biopsies of breast cancer metastases from different anatomical sites

ABSTRACT: To determine whether breast cancer molecular subtypes and tumor characteristics with demonstrated significance in a primary tumor setting can also confer clinically relevant information in breast cancer metastases. We assessed previously published gene expression modules of seven biological processes and the intrinsic subtypes (PAM50). The translational aspect of the Swedish randomized TEX trial included 112 patients with at least one biopsy from morphologically confirmed loco-regional or distant breast cancer metastasis diagnosed from December 2002 until June 2007. All patients had detailed clinical information, complete follow-up and metastasis gene expression information (Affymetrix array GPL10379). We performed global gene expression profiling on fine-needle aspirates of metastatic lesions from different anatomical sites obtained from breast cancer patients treated within the Swedish randomized trial (TEX) of first-line chemotherapy for locally advanced or metastatic breast cancer. Samples were collected before commencement of treatment.

ORGANISM(S): Homo sapiens

SUBMITTER: Nicholas Tobin

PROVIDER: E-GEOD-56493 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival.

Tobin N P NP Harrell J C JC Lövrot J J Egyhazi Brage S S Frostvik Stolt M M Carlsson L L Einbeigi Z Z Linderholm B B Loman N N Malmberg M M Walz T T Fernö M M Perou C M CM Bergh J J Hatschek T T Lindström L S LS

Annals of oncology : official journal of the European Society for Medical Oncology 20141031 1

<h4>Background</h4>We and others have recently shown that tumor characteristics are altered throughout tumor progression. These findings emphasize the need for re-examination of tumor characteristics at relapse and have led to recommendations from ESMO and the Swedish Breast Cancer group. Here, we aim to determine whether tumor characteristics and molecular subtypes in breast cancer metastases confer clinically relevant prognostic information for patients.<h4>Patients and methods</h4>The transla ...[more]

PMID: 25361981

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Project description:Gene Expression Profiling of Breast Cancer Patients with Brain Metastases Brain metastases confer the worst prognosis of breast cancer as no therapy exists that prevents or eliminates the cancer from spreading to the brain. We developed a new computational modeling method to derive specific downstream signaling pathways that reveal unknown target-disease connections and new mechanisms for specific cancer subtypes. The model enables us to reposition drugs based on available gene expression data of patients. We applied this model to repurpose known or shelved drugs for brain, lung, and bone metastases of breast cancer with the hypothesis that cancer subtypes have their own specific signaling mechanisms. To test the hypothesis, we addressed the specific CSBs for each metastasis that satisfy that (1) CSB proteins are activated by the maximal number of enriched signaling pathways specific to this metastasis, and (2) CSB proteins involve in the most differential expressed coding-genes specific to the specific breast cancer metastasis. The identified signaling networks for the three types of metastases contain 31, 15, and 18 proteins, respectively, and are used to reposition 15, 9, and 2 drug candidates for the brain, lung, and bone metastases of breast cancer. We performed in vitro and in vivo preclinical experiments as well as analysis on patient tumor specimens to evaluate the targets and repositioned drugs. Two known drugs, Sunitinib (FDA approved for renal cell carcinoma and imatinib-resistant gastrointestinal stromal tumor) and Dasatinib (FDA approved for chronic myelogenous leukemia (CML) after imatinib treatment and Philadelphia chromosome-positive acute lymphoblastic leukemia), were shown to prohibit the metastatic colonization in brain. The TMH-52 cohort includes 11 patients who were examined with brain metastasis at the time of breast cancer diagnosis. The other 41 patients were examined with other organ metastasis at the time of breast cancer diagnosis.

Dataset Information

Expression data from fine-needle aspiration biopsies of breast cancer metastases from different anatomical sites

Publications

Molecular subtype and tumor characteristics of breast cancer metastases as assessed by gene expression significantly influence patient post-relapse survival.

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