Unknown,Transcriptomics,Genomics,Proteomics

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A nested case-control study to investigate drivers for metastatic disease in breast cancer

ABSTRACT: The purpose of this study was to improve prediction of patients at high-risk for metastatic disease utilizing a nested case-control design that uniquely enables enrichment for relevant phenotypes. We identified all women diagnosed with primary breast cancer from January 1, 1997, to December 31, 2005, in the Stockholm health care region. Patients developing distant metastatic disease (cases) were selected and controls (free from distant disease) were randomly matched by adjuvant therapy, age and calendar period at diagnosis. The nested case-control study included 768 study subjects with clinical information and gene expression arrays (Human Cancer G110). Study subjects were randomly and equally divided into training set (discovery) or testing (validation) set. Metastatic onset prediction was then compared including either clinical variables only or combining clinical and genetic information. Differentially expressed genes and pathways between cases and controls included a wide-spectrum of well known as well as candidate regulators of the metastatic cascade. The nested case-control study included 768 study subjects corresponding to 623 primary tumor samples. Details concerning case-control status are given in the samples section. Each case and its' matching controls form risk sets, indicated by the setnr variable.

ORGANISM(S): Homo sapiens

SUBMITTER: Alexandra Jauhiainen

PROVIDER: E-GEOD-48091 | 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:Using Human WG CodeLink microarrays, we established the expression profiling of 26 LARC without metastasis to gain insight into the molecular signatures associated with response to treatment after CRT. The study initially included a total of 35 consecutive patients with locally advanced rectal cancer (LARC) treated at Virgen de las Nieves Hospital from 2008 until 2010. Written informed consent was obtained from all the patients, and the study protocol was approved by the local Clinical Research (Ethics) Committee. They were distributed in two subgroups following a histological classification of response to treatment. Pretherapeutic staging was performed, including complete medical history and physical evaluation, digital rectal examination, endorectal ultrasound, rigid rectoscopy, colonoscopy, PET/TC and chest x-ray. Tumor samples were prospectively obtained during the rectoscopy. All patients subsequently received a total dose of 50.4Gy of radiatio (28 fractions of 1.8Gy) associated with capecitabine or capecitabine and oxaliplatine. Standardized surgery was performed, including total mesorectal excision, after an interval of 8 weeks after chemoradiotherapy. Tumor response was assessed in surgical specimen by semi-quantitative pathological examination (regression grade) including UICC stage. Histopathological tumor regression was graded based on the semiquantitative 5 point tumor regression grading (TRG) system: TRG1 or a TRG2 scores were considered Responders, whereas TRG3, TRG4, and TRG5 scores were classified as Non-Responders. In addition, the tumor regression or radiotherapy effects were assessed by positron emission tomography (18F-FDG PET). Tumor samples of LARC were collected from 35 patients. Nine patients were finally excluded due to the poor quality of the RNA or contradictory results of MandardM-BM-4s criteria and histopathological downstaging, resulting a total of 26 patients. Complete clinical data regarding, age, sex, stage of disease, response to therapy, and overall survival from 26 patients (10 responders and 16 non-responders) was provided in the sample characteristics field. CRT: Chemoradiation; Cap: Capecitabine; Capox: Capecitabine and Oxaliplatine; cTN: clinical stage; Surg: surgical technique; LAR: Low anterior resection; APR: Abdmino-perineal resection; HART: Hartmann, TRG: Tumor Regression Grade; Downst: Downstaging; Downs: downsizing, Resp: response, CPR: complete pathologic response

Dataset Information

A nested case-control study to investigate drivers for metastatic disease in breast cancer

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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