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Molecular Pathology: Marjanka Schmidt

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Marjanka Schmidt, Ph.D.Groupleader

About Marjanka Schmidt

Research interest: Breast cancer epidemiology

Our work focuses on the effects of genetic variants on risk of breast cancer subtypes, prognosis and long-term outcome of breast cancer. We investigate the interactions between germline variants and life style (e.g. diabetes and insulin exposure) on the incidence of specific breast cancer subtypes, and the interactions between germline variants, tumor characteristics, breast cancer treatment and lifestyle factors on breast cancer prognosis, incidence of second tumors, and mortality. A second research line focuses on patient information and consent procedures, and return of results from research using human materials. This directly relates to the first research line as increasingly studies generate genetic information about hereditary variants. This research group is based in two divisions: Molecular Pathology, and Psychosocial Research and Epidemiology.

Genetic determinants of breast cancer risk and outcome

In recent years we have as part of the Breast Cancer Association consortium (BCAC; PI: D. Easton, Cambridge, UK) identified many new breast cancer susceptibility loci. However, the genetic determinants of breast cancer prognosis are still largely unexplained. We are trying to identify those through a number of studies, among others within this large BCAC consortium. The BCAC clinico-pathological database including tumor characteristics and clinical diagnostic and treatment information as well as follow-up from 65 studies comprising ~110,000 patients is maintained by our group. We aim to identify germline variants that are important in the aetiology of breast cancer subtypes as well as variants that affect prognosis through treatment response or other mechanisms. The proof of principle is our finding that the breast cancer susceptibility variant CHEK2*1100delC also predisposes to an increased risk for contralateral breast cancer and worse breast cancer survival.

In our 'BOSOM' cohort, a nationwide consecutive breast cancer cohort of women diagnosed with breast cancer <50 years of age, we are investigating prognosis and long-term outcome of BRCA1/2 mutation carriers. For the HEBON-Resource study, a nationwide cohort of breast cancer patients from families that have been screened for BRCA1/2 mutations (coordinator: M Rookus), we are studying prognosis and treatment of familial breast cancer patients, as well as impact of prophylactic measures.

Genetic germline or tumor genetic variants or molecular tumor markers will need to be included in (online) prediction models. We are working in collaborative efforts to improve outcome predictions of online models such as Adjuvant Online! and PREDICT in order to assist fine-tuning of these prediction models for more specified groups of breast cancer patients.

Biobanking: consent procedures and return of results

In the Netherlands and many other countries, the use of residual tissues for research is regulated by an 'opt-out' procedure, in which patients can decide to disagree with the use of their tissue on the basis of written information. At present, the amount and quality of information differs widely across Dutch hospitals. Therefore, we have developed a standardized information brochure (read more).

Our previous research showed that cancer patients are unsatisfied with the current information procedure: they are mostly unaware of residual tissue storage for their own clinical benefit and possible use in research, although only a minority wishes to refuse this. We are currently surveying patients to investigate different consent procedures for the secondary use of human materials in clinical research. We examine patient satisfaction and their preference for the different procedures, and the impact of the different consent procedures on the quality of clinical research and on the medical staff.

The discussion about consent procedures, return of results and inclusion of patient advocates in the governance of biobanks has intensified over the increasing amount of genetic results generated from biobank materials. Biobank donors state to be interested in receiving research results from biobank research. In a national collaborative effort within BBMRI-NL, we aim to identify common denominators in content and context of return of results, optimal way to inform donors about research results strategies and models for the involvement of donors in the governance of biobanks.

Co-workers

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Delal Akdeniz, M.D.

Ph.D. Student

Experience

After I graduated from medical school in April 2013, I worked in the department of the internal medicine in Rotterdam. 

In October 2014 I started my PhD project which is about the development of a decision aid for the prediction of contralateral breast cancer (CBC). My focus will be on the medical part; I will investigate the risk factors involved in the development of CBC. 

The project is funded by KWF and is a collaboration with the Rotterdam Erasmus Medical Center.

 

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Linde Braaf, BSc

Coordinating technician molecular genetics - Lab Manager CF-MPB

Experience

In 2004 I got my bachelor degree in life sciences and started working at the NKI in the group of  Laura Van 't Veer, with Annegien Broeks, as a technician. I am, and have been,  involved in several molecular genetic breast cancer projects. In 2010 I joined the CFMPB as a Coordinating technician of the molecular genetics studies. In 2011 I also started as a lab manager of the division of Molecular Pathology where I am involved in the organization of this division.

 

 

 

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Sandra van den Broek, MSc

Postdoctoral fellow

Experience

From 2009-2014 I worked as a PhD student at the divisions of Psychosocial Research and Epidemiology, and Molecular Pathology, studying genetic determinants (i.e. BRCA mutations) of the survival of young breast cancer patients.

In October 2015 I started working as a postdoc at the division of Molecular Pathology, again in the Group of Marjanka Schmidt. I work on the EU-funded B-CAST project, which aim is to understand the determinants of risk and prognosis of molecular subtypes of breast cancer. This will be accomplished through large-scale pathologic-molecular analyses of over 20.000 breast tumors, and the integration with germline, lifestyle/environmental and pathologic/clinical data.

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Annegien Broeks, Ph.D.

Associate Staff Scientist, CF-MPB manager

Experience

Following my MSc. at the Free Univerity and PhD in 1997 in the group of Ronald Plasterk,  I became a postdoc/Associate-Staff-Scientist in the group of Laura van 't Veer at the NKI. I have worked on several KWF projects studying e.g. cancer susceptibility genes and radiation-induced breast cancer. In 2010 I accepted a new challenge; the development of the Core Facility Molecular Pathology and Biobanking. In addition I continued doing research in close collaboration with Marjanka Schmidt. Research projects I am involved in investigating breast tumor genomic profiles (CGH, NGS, IHC) following previous malignancies (e.g. primary bc or HL) and influences of treatment.  

   

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Postdoctoral Fellow

Experience

I received my PhD degree from Tilburg University in 2009 for my thesis on machine learning approaches to processing and understanding of natural language. Since 2009, I have been employed by the Netherlands Cancer Institute. From 2009 to 2015, I had a postdoc position in the Computational Cancer Biology group of Lodewyk Wessels, where I worked on a wide range of statistical analyses of cancer genomics data. Late 2015, I joined the group of Marjanka Schmidt at the NKI. My work in this group focuses on dissecting the role of inherited genetic variation in tumour biology and patient survival.
 

 

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Sten Cornelissen, BSc

Technician

Experience

I work at the NKI since January 2008 after I graduated at the University of Applied Sciences in Utrecht. I work on several projects investigating genetic risk factors for breast cancer (survival) and on a project in which we investigate genetic tumour profiles of diabetic women with breast cancer. Techniques I use are among others PCR, Taqman Real-time PCR, GeneScan fragment analyses, Sanger Sequencing & Next Generation Sequencing.

 

 

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Escala Garcia, Maria

Maria Escala Garcia

Ph.D. Student

Experience

In 2014 I obtained my bachelor degree in Biotechnology at the University of Barcelona. Then, I did MSc in Bioinformatics at KU Leuven, Belgium. 

In July 2016, I started my PhD in the group of Marjanka Schmidt where I am currently working on the study of patient data from the Breast Cancer Association Consortium (BCAC). Concretely, the project aims to apply statistic and bioinformatics approaches in order to investigate the association between germline variants and survival.  

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Renske Fles, MSc

Ph.D. Student

Experience

I have a Master's degree in management and policy analysis and entrepreneurship in health and life science with the specialization international public health. Having worked previously at the NKI as a technician, and as a project coordinator, I started my PhD end of 2012. This project entitled 'Optimizing Nasopharyngeal Carcinoma management through increasing awareness in Yogyakarta, Indonesia' aims to improve the treatment outcomes of patients with nasopharyngeal carcinoma in Indonesia. We focus on identifying and proposing solutions for the delay to treatment caused by the patients, medical health care workers and the system.

 

 

 

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Giardiello, Daniele

Daniele Giardiello

Ph.D. Student

Experience

I obtained my MSc in Biostatistics and Experimental Statistics at the University of Milan-Bicocca in 2012. My previous position was at the National Cancer Institute in Milan as statistician with the group of dr. Luigi Mariani, where I worked on different projects.
In November 2016, I started my PhD joining the group of dr. Marjanka Schmidt's as a statistician and working on the project of developing and validating an online decision aid for physicians and patients in order to estimate the risk of controlateral breast cancer.

 

 

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Renske Keeman, MSc

Data Manager

Experience

I have a Bachelors degree in Bio Medical Sciences at the VU University and a Masters degree in Health and Nutrition (specialization Epidemiology) at the Wageningen University. After graduation I worked as a Junior Researcher at the Pharmo Institute for Drug Outcome Research for 1.5 years. I started at the NKI in March 2012. Here I'm a data manager, primarily for the BCAC (Breast Cancer Association Consortium) and the BOSOM (Breast cancer Outcome Study Of Mutation carriers) studies. I receive, manage, clean, update and supply data from various sources. The diversity in this job is what makes it challenging.

 

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Iris Kramer

PhD student

Experience

I obtained my Bachelor degree in Health and Life Sciences at the VU University in Amsterdam (including an internship at the NKI), and my Master degree in Health Promotion at the Maastricht University.

In August 2016, I started my PhD in the group of Marjanka Schmidt. I'm working on a project concerning contralateral breast cancer (CBC). I'll be involved with the development of a decision aid for the prediction of CBC. My focus will be on the risk factors involved in the development of CBC (e.g. tumor characteristics of the primary breast cancer).

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Marcelo Sobral-Leite

Ph.D. Student

Experience

I graduated in Pharmacy in 2005, and got my post-graduation degree as an Oncology Pharmacist in 2009. Thereafter, I obtained a Masters Degree in Pharmacology in 2012 at the Federal University of Rio de Janeiro, Brazil. In October 2013 I started as a Ph.D. student at the Division of Molecular Pathology in the group of Dr. Marjanka Schmidt, with Prof. Dr. Jan Schellens as my promoter. I am continuing my search for biomarkers for breast cancer prognosis prediction, a challenge that I started in 2009 at the Brazilian National Cancer Institute (INCA) with Dr. Rosane Vianna-Jorge. She will also be involved in my current research. The large cohorts of patients with individual molecular profiles will allow the discovery and validation of new prognostic markers and models to improve treatment selection, chemotherapy tolerability and therapeutic efficacy in different groups of breast cancer patients.

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Danielle McCool

Ph.D. Student

Experience

I graduated in 2014 with my Masters in Methodology and Statistics from the University of Utrecht, and  started my PhD in the Division of Molecular Pathology NKI-AVL in January of 2015. I'm in Marjanka Schmidt's group where I'm working on a project concerning contralateral breast cancer. In the upcoming few years, I'll be involved with the development of a prediction model for contralateral breast cancer, followed by the implementation of this model in a decision aid to be used by doctors and patients.
The project is funded by KWF/Alpe d'Huzes and is a collaboration with the Rotterdam Erasmus Medical Center.

 

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Anna Morra

PhD student

Experience

I obtained my Master degree in Mathematics with specialization in Statistical sciences at the University of Leiden. As a part of my study, I did an internship within the Statistical Genetics group in the department of Medical Statistics and Bioinformatics of the Leiden University Medical Center.

In March 2016 I joined the group of Marjanka Schmidt as a research assistant and I'm currently working on statistical analyses to investigate the association of  genetics variants and pre-diagnostic risk factors with the survival of breast cancer patients, with particular interest in the associations within specific tumor and treatment subtypes. From September 2016 I started my PhD trajectory.

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Susanne Rebers, Ph.D.

Postdoctoral fellow

Experience

After obtaining my M.Sc. in Biology, I worked on an interdisciplinary research project at the Faculty of Social Sciences of the VU University, for which I received my Ph.D. degree.
My current work focuses on consent procedures for the use of residual tissues for scientific research. I mainly focus on the opinion of patients. Do they prefer an informed consent procedure, or do they think an opt-out procedure is sufficient? Ultimately, the research results will be translated into a consent procedure that best reflects the interests of patients, researchers and clinical staff.

 

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Eric Vermeulen, Ph.D.

Postdoctoral fellow

Experience

Eric is a sociologist. Currently he is working on the BBMRI.NL (Biobanking and Biomolecular Resoureces Research Infrastructure) rainbow project 'Towards a joint strategy for the return of results and optimal communication with biobank donors'. http://www.bbmri.nl/nl-nl/activiteiten/regenboogprojecten/180

The aim of this project is determine how biobanks can inform biobank donors about individual research results emanating from biobank research. The project aims to develop advice for Dutch biobanks to deal with return of results.

 

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Key publications View All Publications

  • Impact of Age at Primary Breast Cancer on Contralateral Breast Cancer Risk in BRCA1/2 Mutation Carriers

    (2016) J Clin Oncol. Feb 10;34(5):409-18. doi: 10.1200/JCO.2015.62.3942. Epub 2015 Dec 23.

    van den Broek AJ, van 't Veer LJ, Hooning MJ, Cornelissen S, Broeks A, Rutgers EJ, Smit VT, Cornelisse CJ, van Beek M, Janssen-Heijnen et al.

    Link to PubMed
  • Identification of novel genetic markers of breast cancer survival

    (2015) J Natl Cancer Inst. Apr 18;107(5). pii: djv081. doi: 10.1093/jnci/djv081. Print 2015 May.

    Guo Q*, Schmidt MK*, Kraft P, Canisius S, Chen C, Khan S, Tyrer J, Bolla MK, Wang Q, Dennis J, Michailidou K, Lush M, Kar S, Beesley J, et al.

    Link to PubMed
 
 

Recent publications View All Publications

  • Breast Cancer Survival of BRCA1/BRCA2 Mutation Carriers in a Hospital-Based Cohort of Young Women

    (2017) J Natl Cancer Inst. Aug 1;109(8). doi: 10.1093/jnci/djw329

    Schmidt MK, van den Broek AJ, Tollenaar RA, Smit VT, Westenend PJ, Brinkhuis M, Oosterhuis WJ, Wesseling J, Janssen-Heijnen ML, Jobsen...

    Link to PubMed
  • Cancer risk among insulin users: comparing analogues with human insulin in the CARING five-country cohort study

    (2017) Diabetologia. Jun 1. doi: 10.1007/s00125-017-4312-5. [Epub ahead of print]

    But A, De Bruin ML, Bazelier MT, Hjellvik V, Andersen M, Auvinen A, Starup-Linde J, Schmidt MK, Furu K, de Vries F, Karlstad Ø, Ekström...

    Link to PubMed
 

Contact

  • Office manager

    Suzanne Romijn

  • E-mail

    s.romijn@nki.nl

  • Telephone Number

    +31 20 512 9168

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'Many breast cancers have a genetic component. We try to find out how these genetic factors influence the course of the disease.
Please support our research and thereby help improving survival of breast cancer patients'

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