Longitudinal Multi-Omic Characterization of Patient Responses to Neoadjuvant HER2-Targeted Therapy
Documentation files
Documentation files
Citation and access
Citation and access
Data access level:
Creator/Principal investigator(s):
Research principal:
Data contains personal data:
Yes
Type of personal data:
The dataset does not contain direct identifiers such as names, social security numbers, or contact details. Each patient is represented by a specific ID. These specific IDs are pseudonymized and cannot be used to identify individual patients. Linkage to individual identities is only possible by the local principal investigator and designated site staff through site-specific keys, which are not shared. The metadata includes sampling time, treatment arm, which are indirect identifiers.
Code key exists:
Yes
Sensitive personal data:
Yes
Citation:
Language:
Method and outcome
Method and outcome
Population:
The research focuses on patients diagnosed with early HER2-positive breast cancer who were enrolled in the PREDIX HER2 randomized phase II clinical trial. The participants include women and men aged 18 years or older with HER2-positive tumors larger than 20 mm and/or lymph node metastases. Patients with oligometastatic disease (up to two distant metastases) were also eligible, provided all lesions could be radically treated locally. A total of 202 patients were enrolled, and the analysis specifically refers to the subset of patients who provided plasma samples for longitudinal proteomic profiling and tissue biopsies for multi-omics analysis.
Time method:
Study design:
- Experimental study
Data format/data structure:
Administrative information
Administrative information
Responsible department/unit:
Department of Oncology-Pathology [K7]
Ethical Review
Ethical Review
Reviewer:
- Stockholm Ethical Review Board
Registration number:
dnr 2014/1465-31/10
Registration number:
EudraCT-number: 2014-000808-10
Ethical review information:
Protocol - European Union and European Economic Area via the Clinical Trials Information System (CTIS).
Registration number:
EUCT number:2023-508411-23-00
Funding
Funding
Funding agency:
- Swedish Research Council
Opens a new window at ror.org.
ROR
Award number:
2018-02398_VR
Award title:
Optimizing treatment in HER2 positive breast cancer through insights in tumor biology
Funding information:
This project aims to identify predictive biomarkers and improve therapy selection and outcomes in HER2+ breast cancer (BC). The PREDIX trial comparing the standard combination of trastuzumab+pertuzumab+docetaxel vs. the antibody-drug conjugate trastuzumab-emtasine given for 6 cycles as preoperative therapy (200 patients included) will be used. The project is divided into five work packages (WP).WP1 is the primary efficacy analysis of the trial, in which the rate of pathologic complete response will be compared between the two treatment groups.In WP2, whole genome and RNA sequencing will be performed using longitudinal biopsies taken at baseline, after 2 cycles and at surgery to study mutations and differential gene expression, including their dynamic evolution during treatment.WP3 will explore the predictive role of immune microenvironment for the efficacy of anti-HER2 treatments and chemotherapy, using a multiplex immunofluorescence assay. The HER2+ subgroup (N=341) of a trial of adjuvant chemotherapy will also be used in this WP.In WP4, intra-tumor heterogeneity (ITH) will be studied as a predictor of poor drug response and clinical outcome. The serial core tumor biopsies will be used for single-cell in situ analysis of estrogen receptor, HER2, and the proliferation marker Ki67 by Single-Molecule RNA FISH and the Proximity Ligation Assay. In a subset of 20 cases, single-cell DNA and RNA sequencing will be used to study clonal evolution and mechanisms of resistance (WP5).
Funding agency:
- Swedish Research Council
Opens a new window at ror.org.
ROR
Award number:
2021-03061_VR
Award title:
Integrative digital diagnostics for therapy optimization in early breast cancer
Funding information:
Purpose and aimsThis project aims to develop tools for prediction of response to neoadjuvant (pre-operative) therapy (NAT) and prognostication of post-surgery risk of recurrence in breast cancer. To this end, input from radiology, digital pathology, genomics and informative clinical variables will be integrated using a machine learning (ML)-based multi-modal fusion strategy. Project organisation, time plan and scientific methodsThree academic clinical trials and one population-based cohort of NAT (N=2500) will be used to train single-source predictive model priors that will be ensembled into integrative multi-omics predictive models. These will be validated externally in independent cohorts of ~3000 patients.The project will be divided into work packages (WP), corresponding to each of the data modalities. WP1 data and material collection (year 1-4); WP2-3 transcriptomics and genomics in tissue and blood (y 1-3); WP4 radiomics using mammography and magnetic resonance imaging (y 1-3); WP5 pathomics (y 1-3); WP6 model integration (y 3-4); WP7 external validation (y 4-5). ImportanceThe project will contribute with novel ML methodology for clinical medicine and a precision oncology solution for optimizing NAT selection and risk stratification that will lead to less over- and under treatment, sparing patients from unnecessary toxicities and reducing financial burden to healthcare systems, and ultimately improving prognosis for patients with breast cancer.
