Breast Cancer Liquid Biopsy Stratification

NCT03992521 | Unknown

• 1 other identifier: BreastctDNA01
• Study Type: observational
• Target: 59
• Locations: 1 country
• Sites: 1

Brief Summary

Breast cancer is the most common cancer in Austrian women. Estimation of prognosis and treatment strategies is increasingly being dependent on stratification of tumors into different entities or classes. Currently, clinical routine stratification of tumors is mostly based on hormone receptor, HER2 status, and estimation of proliferation. However, a more robust and objective classification of tumors can be achieved by elucidation of further biological properties, which is also of increasing significance, as novel anticancer therapies are based on biological mechanisms. Consequently, available information from molecular analyses is increasingly being implemented in routine diagnostic assays with the aim to improve stratification for optimal treatment selection. To date the most extensive molecular-based taxonomy of breast cancer has been achieved by a classification based on combining gene expression and somatic copy number alterations (SCNAs), referred to as integrative clusters. Tissue biopsies are the current gold standard to attain such a classification. However, they can often be difficult to obtain in the metastatic setting and are subject to sampling bias due to intratumor heterogeneity. "Liquid biopsies" are, among other analytes, based on the analysis of cell-free DNA (cfDNA) which contains circulating tumor DNA (ctDNA), i.e. DNA fragments shed from normal and tumor cells into the blood, in patients with cancer. cfDNA can be obtained minimally invasive with a blood draw, allows for the "real time" analysis of tumor DNA from the circulation, and blood samples can be repeated at any time point, which is especially important for monitoring response to therapy. The investigator's group has extensive expertise in the analysis of cfDNA and has developed a plethora of approaches for ctDNA analysis. Recently, the investigators have developed a new approach, which relates to nucleosome positions and gene expression. cfDNA fragments have been associated with the release of DNA from apoptotic cells after enzymatic processing and hence consist mainly of mono-nucleosomal DNA. By performing whole-genome sequencing of cfDNA the investigators could demonstrate that at transcriptional start sites, the nucleosome occupancy results in different read-depth coverage patterns in expressed and silent genes. By employing machine learning for gene classification, the investigators were able to classify genes in cells releasing their DNA into the circulation as expressed. The main hypothesis of the project is that integrative breast cancer clusters can be established from directly blood without the need for an invasive tissue biopsy. Hence, the study aims include refining stratification of patients for an improved selection of treatment strategies. Furthermore, the investigators will obtain novel insights into the biology of metastatic breast cancer, so that this project will have important implications for patients, clinical oncologists, pathologists, pharmacologists, and all basic researchers interested in cancer.

Conditions

Breast Cancer

Outcome Measures

Primary Outcomes (1)

• Evaluating as proof-of-concept the ability to stratify patients solely based on a detailed plasma DNA analysis

  Clinico-pathological characteristics including prior and subsequent therapies were recorded for each patient. For each patient a standard classification into luminal, basal, ERBB2/HER2 was conducted and is available.

  Three years

Interventions

Nucleosome positioning GENETIC

Stratification of patients based on nucleosome positioning from plasma DNA.

Eligibility Criteria

• Age: 18 Years - 99 Years
• Gender Eligibility Details: Females with breast cancer
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

The study includes women with proven histological diagnosis of breast cancer and appropriate clinical data. Participants were recruited at the Medical University Hospital of Graz.

You may qualify if:

• Histological diagnosis of breast cancer, availability of primary tumor tissue and plasma DNA with a high ctDNA content.

You may not qualify if:

• Patient rejects the participation.

Sponsors & Collaborators

• Medical University of Graz: lead

Study Sites (1)

Medical University of Graz

Graz, 8010, Austria

Location

Related Publications (4)

• Ulz P, Thallinger GG, Auer M, Graf R, Kashofer K, Jahn SW, Abete L, Pristauz G, Petru E, Geigl JB, Heitzer E, Speicher MR. Inferring expressed genes by whole-genome sequencing of plasma DNA. Nat Genet. 2016 Oct;48(10):1273-8. doi: 10.1038/ng.3648. Epub 2016 Aug 29.

  PMID: 27571261 BACKGROUND

• Heitzer E, Haque IS, Roberts CES, Speicher MR. Current and future perspectives of liquid biopsies in genomics-driven oncology. Nat Rev Genet. 2019 Feb;20(2):71-88. doi: 10.1038/s41576-018-0071-5.

  PMID: 30410101 BACKGROUND

• Ulz P, Belic J, Graf R, Auer M, Lafer I, Fischereder K, Webersinke G, Pummer K, Augustin H, Pichler M, Hoefler G, Bauernhofer T, Geigl JB, Heitzer E, Speicher MR. Whole-genome plasma sequencing reveals focal amplifications as a driving force in metastatic prostate cancer. Nat Commun. 2016 Jun 22;7:12008. doi: 10.1038/ncomms12008.

  PMID: 27328849 BACKGROUND

• Ulz P, Heitzer E, Speicher MR. Co-occurrence of MYC amplification and TP53 mutations in human cancer. Nat Genet. 2016 Feb;48(2):104-6. doi: 10.1038/ng.3468. No abstract available.

  PMID: 26813759 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Plasma DNA and DNA from primary tumors

MeSH Terms

Conditions

Breast Neoplasms

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Study Officials

• Michael R Speicher, MD

  Medical University of Graz

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 18, 2019
• First Posted: June 20, 2019
• Study Start: October 1, 2018
• Primary Completion: October 1, 2023
• Study Completion: October 1, 2023
• Last Updated: October 10, 2022

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

AU (1)